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1. Cortical thickness across the lifespan

Author: Simon E. Fisher, Eveline A. Crone, Dominik Grotegerd, Jilly Naaijen, Anders M. Dale, Sean N. Hatton, Ramona Baur-Streubel, Anthony A. James, Daniel Brandeis, Andrew J. Kalnin, Andreas Reif, Hans-Jörgen Grabe, Pieter J. Hoekstra, Lars Nyberg, Fleur M. Howells, Moji Aghajani, Randy L. Buckner, Daniel A. Rinker, Steven G. Potkin, Dennis van 't Ent, Rachel M. Brouwer, Sophia Frangou, Yang Wang, Nhat Trung Doan, Theodore D. Satterthwaite, Christine Lochner, Geraldo F. Busatto, Lars T. Westlye, Lara M. Wierenga, Calhoun Vd, Henry Brodaty, Carles Soriano-Mas, Annette Conzelmann, Christian K. Tamnes, Julian N. Trollor, Nicholas G. Martin, Neeltje E.M. van Haren, René S. Kahn, Irina Lebedeva, Philip Asherson, Suzanne C. Swagerman, John A. Joska, Theophilus N. Akudjedu, Kang Sim, Lachlan T. Strike, Patricia Gruner, Brenna C. McDonald, Thomas Frodl, Edith Pomarol-Clotet, Víctor Ortiz-García de la Foz, Margaret J. Wright, Norbert Hosten, Jean-Paul Fouche, Bernd Weber, Salvador Sarró, Wei Wen, Dag Alnæs, Greig I. de Zubicaray, Iris E. C. Sommer, Marise W. J. Machielsen, Knut Schnell, Dara M. Cannon, Paola Fuentes-Claramonte, Josiane Bourque, Andreas Meyer-Lindenberg, Anton Albajes-Eizagirre, Sarah Hohmann, Erin W. Dickie, Theo G.M. van Erp, Micael Andersson, Paul Pauli, Thomas Espeseth, Heather C. Whalley, Victoria Chubar, Ruben C. Gur, Tomohiro Nakao, Xavier Caseras, Alessandro Bertolino, Ignacio Martínez-Zalacaín, Katharina Wittfeld, Erick J. Canales-Rodríguez, David C. Glahn, Neda Jahanshad, Jiyang Jiang, Katie L. McMahon, Stefan Borgwardt, Erlend S. Dørum, Jaap Oosterlaan, Won Hee Lee, Alan Breier, Steven Williams, Aristotle N. Voineskos, Bernard Mazoyer, Jordan W. Smoller, Nancy C. Andreasen, Ilya M. Veer, Tiffany M. Chaim-Avancini, Sophie Maingault, Paul M. Thompson, Eco J. C. de Geus, Luisa Lázaro, Giulio Pergola, Efstathios Papachristou, Beng-Choon Ho, David Mataix-Cols, Esther Walton, Ben J. Harrison, Dirk J. Heslenfeld, Pablo Najt, Helena Fatouros-Bergman, Derrek P. Hibar, Gunter Schumann, Raymond Salvador, Lieuwe de Haan, Henry Völzke, Joaquim Radua, Henk Temmingh, Lianne Schmaal, Martine Hoogman, Daniel H. Wolf, Georg C. Ziegler, Marieke Klein, Barbara Franke, Erik G. Jönsson, Laura Koenders, Stefan Ehrlich, Oliver Gruber, Ingrid Agartz, Kun Yang, Ryota Kanai, Sarah Baumeister, Colm McDonald, Annabella Di Giorgio, Amanda Worker, Anne Uhlmann, Marcus V. Zanetti, Danai Dima, Matthew D. Sacchet, Sarah E. Medland, Aurora Bonvino, Benedicto Crespo-Facorro, Jan Egil Nordvik, Joshua L. Roffman, Yannis Paloyelis, Jessica A. Turner, T. P. Klyushnik, Christopher G. Davey, Rachel E. Gur, Ian B. Hickie, Christopher R.K. Ching, Jonna Kuntsi, Tobias Banaschewski, Chaim Huyser, Amirhossein Modabbernia, John D. West, Fabrice Crivello, Núria Bargalló, Patricia J. Conrod, Nic J.A. van der Wee, Mauricio H. Serpa, Thomas H. Wassink, Kathryn I. Alpert, Dick J. Veltman, Andrew J. Saykin, Genevieve McPhilemy, Perminder S. Sachdev, Vincent P. Clark, Ian H. Gotlib, Susanne Erk, Henrik Walter, Dennis van den Meer, Simon Cervenka, Oliver Grimm, Andrew M. McIntosh, Alexander Tomyshev, Francisco X. Castellanos, Bernd Kramer, Klaus-Peter Lesch, Odile A. van den Heuvel, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Terry L. Jernigan, Yulyia Yoncheva, Anouk den Braber, Jim Lagopoulos, Maria J. Portella, Ole A. Andreassen, Gaelle E. Doucet, Avram J. Holmes, Nynke A. Groenewold, Pedro G.P. Rosa, Hilleke E. Hulshoff Pol, Sanne Koops, José M. Menchón, Jan K. Buitelaar, Dan J. Stein, Dorret I. Boomsma, Lei Wang, C.A. Hartman, Pascual Sánchez-Juan, Andreas Heinz, European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Karolinska Schizophrenia Project (KaSP), Ontwikkelingspsychologie (Psychologie, FMG), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Epidemiology and Data Science, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Brain Imaging, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Biological Psychology, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, and APH - Personalized Medicine
Subjects: Male, Aging, Neurologi, Audiology, Trajectories, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], Child, Research Articles, Cerebral Cortex, Psychiatry, Aged, 80 and over, Radiological and Ultrasound Technology, Fractional polynomial, 05 social sciences, Radiology, Nuclear Medicine & Medical Imaging, 1. No poverty, Cognition, Middle Aged, Cerebral cortex, Regression, 3. Good health, Escorça cerebral, Neurology, Radiology Nuclear Medicine and imaging, Healthy individuals, Child, Preschool, anatomy & histology [Cerebral Cortex], Female, Analysis of variance, Anatomy, Life Sciences & Biomedicine, Trajectorie, Research Article, Neuroinformatics, Adult, medicine.medical_specialty, Adolescent, Human Development, Clinical Neurology, BF, Neuroimaging, Biology, Development, 050105 experimental psychology, Psykiatri, Cortical thickness, 03 medical and health sciences, Young Adult, Neuroimaging genetics, Envelliment, medicine, Humans, trajectories, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, development, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Brain morphometry, aging, Neurosciences, cortical thickness, Cross-Sectional Studies, RC0321, Neurology (clinical), Neurosciences & Neurology, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract: Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)
Published: 2022

2. Greater male than female variability in regional brain structure across the lifespan

Author: Erick J. Canales-Rodríguez, Hans J. Grabe, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Daniel Brandeis, Yang Wang, Henry Brodaty, Ruben C. Gur, Iris E. C. Sommer, Paul M. Thompson, Knut K. Kolskår, Christopher G. Davey, Dick J. Veltman, Eco J. C. de Geus, Tobias Banaschewski, Greig I. Zubicaray, Xavier Caseras, Sarah Baumeister, Raquel E. Gur, Vincent P. Clark, Maria J. Portella, Simon E. Fisher, Christopher R.K. Ching, Lars T. Westlye, Laura Koenders, Vince D. Calhoun, Carles Soriano-Mas, Nicholas G. Martin, Stefan Ehrlich, Fleur M. Howells, Catharina A. Hartman, Matthew D. Sacchet, Ole A. Andreassen, Josiane Bourque, Fabrice Crivello, Annette Conzelmann, Jaap Oosterlaan, Brenna C. McDonald, Gaelle E. Doucet, Avram J. Holmes, José M. Menchón, Danai Dima, Moji Aghajani, Joshua L. Roffman, Steven Williams, Lei Wang, David Mataix-Cols, Philip R. Szeszko, Bernd Weber, Tiril P. Gurholt, Sarah Hohmann, Ian H. Gotlib, Patricia Gruner, Anthony C. James, Paul Pauli, Lara M. Wierenga, Andrew M. McIntosh, Andrew J. Kalnin, Jim Lagopoulos, Henrik Walter, Andreas Reif, Andrew Simmons, Norbert Hosten, Pieter J. Hoekstra, Aristotle Voineskos, Alexander Tomyshev, Anton Albajes-Eizagirre, Jean-Paul Fouche, Dara M. Cannon, Ignacio Martínez‐Zalacaín, Geneviève Richard, Theophilus N. Akudjedu, David C. Glahn, Patricia J. Conrod, Ben J. Harrison, Alan Anticevic, Martine Hoogman, Francisco X. Castellanos, Bernd Kramer, Neda Jahanshad, Lieuwe de Haan, Dennis van der Meer, John D. West, Alan Breier, Jordan W. Smoller, P. G. P. Rosa, Katharina Wittfeld, Dan J. Stein, Jiyang Jiang, Jilly Naaijen, Christine Lochner, Dorret I. Boomsma, Alessandro Bertolino, Marise W. J. Machielsen, Hilleke E. Hulshoff Pol, Henry Völzke, Christian K. Tamnes, Ingrid Agartz, Georg C. Ziegler, Marieke Klein, Lars Nyberg, Perminder S. Sachdev, Philip Asherson, I.M. Veer, Sean N. Hatton, Núria Bargalló, Annabella Di Giorgio, Henk Temmingh, John A. Joska, Odile A. van den Heuvel, Wei Wen, Eveline A Crone, Kang Sim, Kathryn I. Alpert, Dennis van 't Ent, Jan K. Buitelaar, Joaquim Radua, Julian N. Trollor, B Mazoyer, Chaim Huyser, H. C. Whalley, Irina Lebedeva, Erin W. Dickie, Marcus Vinicus Zanetti, Stefan Borgwardt, Theodore D. Satterthwaite, Daniel H Wolf, Sophia I. Thomopoulos, Giulio Pergola, Luisa Lazaro, Ramona Baur-Streubel, Beathe Haatveit, Yannis Paloyelis, Ian B. Hickie, Jonna Kuntsi, Sophia Frangou, R. Salvador, Geraldo F. Busatto, Margaret J. Wright, Aurora Bonvino, Edith Pomarol-Clotet, Anouk den Braber, Lachlan T. Strike, Phil Lee, Anne Uhlmann, Yuliya N. Yoncheva, Mauricio H. Serpa, Dag Alnæs, Paola Fuentes-Claramonte, Katie L. McMahon, Andrew J. Saykin, Genevieve McPhilemy, Tiffany M. Chaim-Avancini, Sophie Maingault, Barbara Franke, Colm McDonald, Rachel M. Brouwer, Salvador Sarró, Department of Psychology, Education and Child Studies, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, AMS - Ageing & Vitality, AMS - Sports, APH - Personalized Medicine, Cognitive Psychology, Clinical Neuropsychology, IBBA, Karolinska Schizophrenia Project (KaSP) Consortium, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Amsterdam Neuroscience, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Movement Disorder (MD), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Pediatric surgery, and Amsterdam Neuroscience - Brain Imaging
Subjects: Male, Netherlands Twin Register (NTR), SEGMENTATION, Vulnerability, Disease, HM, 0302 clinical medicine, Anàlisi de variància, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], sexual characteristics, Analysis of variance, nuclear magnetic resonance imaging, Cervell, Research Articles, Cerebral Cortex, Sex Characteristics, Radiological and Ultrasound Technology, 05 social sciences, Brain, clinical trial, Brain Structure, Magnetic Resonance Imaging, Early life, Adolescence, medicine.anatomical_structure, Neurology, Cerebral cortex, Healthy individuals, X-CHROMOSOME, anatomy & histology [Cerebral Cortex], Evolution of the brain, Female, Anatomy, Neurovetenskaper, Research Article, Radiology, Nuclear Medicine and Medical Imaging, Neuroinformatics, SEX-DIFFERENCES, diagnostic imaging, brain, Human Development, BF, Neuroimaging, SURFACE-AREA, Evolució del cervell, Regional area, Biology, MULTISAMPLE, 050105 experimental psychology, brain cortex, 03 medical and health sciences, CEREBRAL-CORTEX, Sex differences, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, human, ddc:610, Cortical surface, GENERAL INTELLIGENCE, diagnostic imaging [Brain], METAANALYSIS, biological variation, HUMAN HIPPOCAMPUS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], physiology [Biological Variation, Population], Neurosciences, Gender, Brain Cortical Thickness, multicenter study, Biological Variation, Population, Diferències entre sexes, physiology, RC0321, Radiologi och bildbehandling, Neurology (clinical), anatomy & histology [Brain], 170 000 Motivational & Cognitive Control, 030217 neurology & neurosurgery, anatomy and histology, meta analysis, physiology [Human Development], Demography
Abstract: Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022

3. Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders: Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group

Author: Meng Li, Thomas Frodl, Lyubomir I. Aftanas, Ben J. Harrison, Frank P. MacMaster, Jair C. Soares, Axel Krug, Benson Mwangi, Christopher G. Davey, Sean N. Hatton, Nynke A. Groenewold, Giovana Zunta-Soares, Angela Carballedo, Bonnie Klimes-Dougan, Katharina Wittfeld, Ilya M. Veer, Philipp G. Sämann, Nils Opel, Ramona Leenings, Yuri Milaneschi, Ian B. Hickie, Dominik Grotegerd, Kathryn R. Cullen, Heather C. Whalley, Henry Völzke, Bernhard T. Baune, Maike Richter, Lianne Schmaal, Andrew M. McIntosh, Jim Lagopoulos, Dan J. Stein, Brenda W.J.H. Penninx, Mon-Ju Wu, Ivan V. Brak, Anouk Schrantee, André Aleman, Georg Woditsch, Janik Goltermann, Elena Pozzi, Kang Sim, Norbert Hosten, Liesbeth Reneman, Hans J. Grabe, Bryon A. Mueller, Klaus Berger, Udo Dannlowski, Martin Walter, Anbupalam Thalamuthu, Tim Hahn, Paul M. Thompson, Igor Nenadic, Laura Nawijn, Evgeniy A. Osipov, Claas Flint, Dick J. Veltman, Tilo Kircher, Henrik Walter, Mathew A. Harris, Marco Hermesdorf, Elena Filimonova, Sandra Van der Auwera, Matthew D. Sacchet, Neda Jahanshad, Ian H. Gotlib, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, APH - Mental Health, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, APH - Personalized Medicine, APH - Global Health, APH - Digital Health, Radiology and Nuclear Medicine, ANS - Brain Imaging, ANS - Compulsivity, Impulsivity & Attention, and Ontwikkelingspsychologie (Psychologie, FMG)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Multivariate statistics, Overweight, 03 medical and health sciences, Cellular and Molecular Neuroscience, genetics [Obesity], 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Obesity, ddc:610, diagnostic imaging [Brain], Molecular Biology, Stroke, Pathological, Depression (differential diagnoses), Aged, Cerebral Cortex, Depressive Disorder, Major, business.industry, Brain, genetics [Depressive Disorder, Major], medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, Major depressive disorder, medicine.symptom, business, Body mass index, 030217 neurology & neurosurgery
Abstract: Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.
Published: 2021

4. Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group

Author: Thomas Frodl, Eduard Vieta, Sean N. Hatton, Sophia I. Thomopoulos, Jens Sommer, Fábio L.S. Duran, Pauline Favre, Cynthia H.Y. Fu, Tony T. Yang, Knut Schnell, Tilo Kircher, Gloria Roberts, Lyubomir I. Aftanas, Norbert Hosten, Elena Pozzi, Henrik Walter, Pedro G.P. Rosa, Oliver Gruber, Colm G. Connolly, Klaus Berger, Jonathan Repple, Geraldo Busatto Filho, Tomas Hajek, Bernd Kramer, Salvador Sarró, Ulrik Fredrik Malt, Richard Dinga, Danai Dima, Mikael Landén, Laura K.M. Han, Jonathan Savitz, Peter R. Schofield, Axel Krug, Maria M. Rive, Caterina del Mar Bonnín, Edith Pomarol-Clotet, Olaf Steinsträter, Chantal Henry, Udo Dannlowski, Henricus G. Ruhé, Mauricio H. Serpa, Quinn McLellan, Benson Mwangi, Philipp G. Saemann, Christopher G. Davey, Marie-José van Tol, Mircea Polosan, Torbjørn Elvsåshagen, Nynke A. Groenewold, Marcus V. Zanetti, Claas Kähler, Jair C. Soares, Steven J.A. van der Werff, Kathryn R. Cullen, Lachlan T. Strike, Ilya M. Veer, Beata R. Godlewska, Giovana Zunta-Soares, Xavier Caseras, Janice M. Fullerton, Bronwyn Overs, Tiffany M. Chaim-Avancini, Lisa T. Eyler, Theodore D. Satterthwaite, Martin Ingvar, Ramona Leenings, Angela Carballedo, Brenda W.J.H. Penninx, Ian B. Hickie, James H. Cole, Elena Filimonova, Márcio Gerhardt Soeiro-de-Souza, Rayus Kuplicki, Leila Nabulsi, Ben J. Harrison, Aart H. Schene, Ivan V. Brak, Nic J.A. van der Wee, Hans J. Grabe, Katharina Wittfeld, Anouk Schrantee, Matthew D. Sacchet, Margaret J. Wright, Dan J. Stein, Erlend Bøen, Heather C. Whalley, Egle Simulionyte, Fleur M. Howells, Tim Hahn, Lianne Schmaal, Garrett M. Timmons, Bartholomeus C M Haarman, Kang Sim, Andrew M. McIntosh, Moji Aghajani, Jim Lagopoulos, Anne Uhlmann, Rodrigo Machado-Vieira, Jose Manuel Goikolea, Mon-Ju Wu, Christopher R.K. Ching, Dara M. Cannon, Liesbeth Reneman, Andreas Jansen, Josselin Houenou, Ian H. Gotlib, Bonnie Klimes-Dougan, Raymond Salvador, Maria J. Portella, Ole A. Andreassen, Greig I. de Zubicaray, Robert Vermeiren, Bryon A. Mueller, Nils R. Winter, Dick J. Veltman, Neda Jahanshad, Stefan Frenzel, Philip B. Mitchell, Colm McDonald, Henry Völzke, Daniel H. Wolf, Katie L. McMahon, Evgeny Osipov, Marco Hermesdorf, Tiffany C. Ho, Bernhard T. Baune, Paul M. Thompson, Glenda MacQueen, Andre F. Marquand, Maria Concepcion Garcia Otaduy, Vasileios Zannias, Christoph Abé, Ashley N. Sutherland, Sarah E. Medland, Beny Lafer, Erick J. Canales-Rodríguez, Geoffrey B. Hall, Martin Alda, Henk Temmingh, Sonya Foley, Verena Enneking, Frank P. MacMaster, Dominik Grotegerd, Joaquim Radua, Baptiste Couvy-Duchesne, André Aleman, Radiology and Nuclear Medicine, ANS - Brain Imaging, ANS - Compulsivity, Impulsivity & Attention, APH - Personalized Medicine, APH - Mental Health, Ontwikkelingspsychologie (Psychologie, FMG), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Radiology and nuclear medicine, Pediatric surgery, Amsterdam Reproduction & Development (AR&D), Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Complex Trait Genetics, and APH - Digital Health
Subjects: Adult, Male, medicine.medical_specialty, Aging, Adolescent, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], BF, Health outcomes, Article, Cellular and Molecular Neuroscience, 03 medical and health sciences, Lateral ventricles, Young Adult, 0302 clinical medicine, Atrophy, Internal medicine, medicine, Humans, ddc:610, Longitudinal Studies, Molecular Biology, diagnostic imaging [Brain], Brain aging, Depression (differential diagnoses), 030304 developmental biology, Aged, 0303 health sciences, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, Depression, 220 Statistical Imaging Neuroscience, Brain, Chronological age, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Increased risk, RC0321, Major depressive disorder, Female, Age of onset, business, 030217 neurology & neurosurgery, Neuroscience
Abstract: BackgroundMajor depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in MDD patients, and whether this process is associated with clinical characteristics in a large multi-center international dataset.MethodsWe performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 29 samples worldwide. Normative brain aging was estimated by predicting chronological age (10-75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 1,147 male and 1,386 female controls from the ENIGMA MDD working group. The learned model parameters were applied to 1,089 male controls and 1,167 depressed males, and 1,326 female controls and 2,044 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain predicted age difference (brain-PAD).FindingsOn average, MDD patients showed a higher brain-PAD of +0.90 (SE 0.21) years (Cohen’s d=0.12, 95% CI 0.06-0.17) compared to controls. Relative to controls, first-episode and currently depressed patients showed higher brain-PAD (+1.2 [0.3] years), and the largest effect was observed in those with late-onset depression (+1.7 [0.7] years). In addition, higher brain-PAD was associated with higher self-reported depressive symptomatology (b=0.05, p=0.004).InterpretationThis highly powered collaborative effort showed subtle patterns of abnormal structural brain aging in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the predictive value of these brain-PAD estimates.FundingThis work was supported, in part, by NIH grants U54 EB020403 and R01 MH116147.
Published: 2021

5. Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia

Author: Alexandre Reymond, Borja Rodriguez-Herreros, Stefan Ehrlich, Tiago Reis Marques, Roberto Roiz-Santiañez, Barbara Franke, Henry Brodaty, Ryota Hashimoto, Tobias Kaufmann, Thomas Gareau, Gary Donohoe, Masataka Kikuchi, David Ames, Greig I. de Zubicaray, Vince D. Calhoun, Zdenka Pausova, Anouk den Braber, Laurena Holleran, Katharina Wittfeld, Roel A. Ophoff, G. Bragi Walters, Sandra Martin-Brevet, Karen A. Mather, Dan J. Stein, Costin Leu, Rachel M. Brouwer, Norman Delanty, Nicholas G. Martin, Arvid Lundervold, Jean Shin, Geneviève Richard, Dorret I. Boomsma, Gudrun A. Jonsdottir, Emma Knowles, Margie Wright, Magnus O. Ulfarsson, Yunpeng Wang, Thomas W. Mühleisen, Vincent Frouin, Andrew J. Schork, Peter R. Schofield, Michael Andersson, Katrin Amunts, Hans J. Grabe, Wei Wen, Manon Bernard, James Rucker, Anbu Thalamuthu, Hans-Richard Brattbak, Joanne E. Curran, Hidenaga Yamamori, Bruce Pike, Brenda W.J.H. Penninx, Derek W. Morris, Masaki Fukunaga, Aiden Corvin, René S. Kahn, John Blangero, Yuri Milaneschi, Nynke A. Groenewold, Mark McCormack, Allan F. McRae, Clara Moreau, Gunter Schumann, Robin M. Murray, Bogdan Draganski, Simone Ciufolini, Carlos Prieto, Diana Tordesillas-Gutiérrez, Astri J. Lundervold, Sinead Kelly, Simon E. Fisher, Erik G. Jönsson, Stefan Johansson, Neda Jahanshad, Elena Shumskaya, Christopher D. Whelan, Tomáš Paus, Evangelos Vassos, Tetyana Zayats, Sébastien Jacquemont, Benedicto Crespo-Facorro, Erin Burke Quinlan, Anja Vaskinn, Ingrid Agartz, Knut K. Kolskår, Robin Bülow, Alexander Teumer, Sven Cichon, Neeltje E.M. van Haren, Jayne Y. Hehir-Kwa, Anders M. Dale, Nhat Trung Doan, Stephanie Le Hellard, John B.J. Kwok, Lars Nyberg, Sigrid Botne Sando, Omar Gustafsson, Gianpiero L. Cavalleri, Andreas Heinz, Ida E Sønderby, Sonja M C de Zwarte, Hreinn Stefansson, Derrek P. Hibar, Daniel Quintana, Vidar M. Steen, Jouke-Jan Hottenga, Paola Dazzan, David C. Glahn, Shareefa Dalvie, Lars T. Westlye, Nicholas B. Blackburn, Loes M. Olde Loohuis, Kari Stefansson, Dennis van der Meer, Lianne Schmaal, Anne Uhlmann, Nicola J. Armstrong, Stacy Steinberg, Christiane Jockwitz, Jarek Rokicki, Hilleke E Hulshoff, Sanjay M. Sisodiya, Anne-Marthe Sanders, Jan Haavik, Perminder S. Sachdev, Asta Håberg, Samuel R. Mathias, Dennis van 't Ent, Torill Ueland, Per Hoffmann, Terry L. Jernigan, Abdel Abdellaoui, Svenja Caspers, Sylvane Desrivières, Ole A. Andreassen, Masashi Ikeda, Paul M. Thompson, Eco J. C. de Geus, Céline S. Reinbold, Jingyu Liu, Juan M. Peralta, Sara Pudas, Jan Egil Nordvik, Srdjan Djurovic, David Mothersill, Lachlan T. Strike, Chi-Hua Chen, Jessica A. Turner, Manon H.J. Hillegers, Thomas Espeseth, Janita Bralten, Katie L. McMahon, APH - Methodology, APH - Mental Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Rafmagns- og tölvuverkfræðideild (HÍ), Faculty of Electrical and Computer Engineering (UI), Læknadeild (HÍ), Faculty of Medicine (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, 16p11.2 European Consortium, for the ENIGMA-CNV working group, Child and Adolescent Psychiatry / Psychology, Epidemiology and Data Science, Neurology, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, and APH - Digital Health
Subjects: Male, 0301 basic medicine, Netherlands Twin Register (NTR), genetics [Chromosome Disorders], Pathology, Databases, Factual, Autism, Taugasjúkdómar, methods [Magnetic Resonance Imaging], 0302 clinical medicine, pathology [Basal Ganglia], pathology [Brain], methods [Image Processing, Computer-Assisted], Chromosome Duplication, Basal ganglia, pathology [Globus Pallidus], genetics [Schizophrenia], Copy-number variation, pathology [Putamen], medicine.diagnostic_test, Einhverfa, Gen, genetics [Neurodevelopmental Disorders], Putamen, Neurodevelopmental disorders, Middle Aged, Microdeletion syndrome, 3. Good health, Psychiatry and Mental health, genetics [Chromosomes, Human, Pair 16], Globus pallidus, Schizophrenia, genetics [Autism Spectrum Disorder], Female, Chromosome Deletion, Medical Genetics, Adult, Neuroinformatics, medicine.medical_specialty, genetics [DNA Copy Number Variations], Article, genetics [Autistic Disorder], 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 17 - Partnerships for the Goals, Geðklofi, medicine, Humans, ddc:610, Molecular Biology, Medicinsk genetik, CNVs, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genetics [Organ Size], business.industry, Brain morphometry, Magnetic resonance imaging, medicine.disease, 030104 developmental biology, genetics [Intellectual Disability], business, Psychiatric disorders, 030217 neurology & neurosurgery, Neuroscience
Abstract: Publisher's version (útgefin grein), Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10− 9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes., 1000BRAINS: 1000BRAINS is a population-based cohort based on the Heinz-Nixdorf Recall Study and is supported in part by the German National Cohort. We thank the Heinz Nixdorf Foundation (Germany) for their generous support in terms of the Heinz Nixdorf Study. The HNR study is also supported by the German Ministry of Education and Science (FKZ 01EG940), and the German Research Council (DFG, ER 155/6-1). The authors are supported by the Initiative and Networking Fund of the Helmholtz Association (Svenja Caspers) and the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 7202070 (Human Brain Project SGA1; Katrin Amunts, Sven Cichon). This work was further supported by the German Federal Ministry of Education and Research (BMBF) through the Integrated Network IntegraMent (Integrated Understanding of Causes and Mechanisms in Mental Disorders) under the auspices of the e:Med Program (grant 01ZX1314A to M.M.N. and S.C.), and by the Swiss National Science Foundation (SNSF, grant 156791 to S.C.). 16p.11.2 European Consortium: B.D. is supported by the Swiss National Science Foundation (NCCR Synapsy, project grant Nr 32003B_159780) and Foundation Synapsis. LREN is very grateful to the Roger De Spoelberch and Partridge Foundations for their generous financial support. This work was supported by grants from the Simons Foundation (SFARI274424) and the Swiss National Science Foundation (31003A_160203) to A.R. and S.J. Betula: The relevant Betula data collection and analyses were supported by a grant from the Knut & Alice Wallenberg (KAW) to L. Nyberg. Brainscale: the Brainscale study was supported by the Netherlands Organization for Scientific Research MagW 480-04-004 (Dorret Boomsma), 51.02.060 (Hilleke Hulshoff Pol), 668.772 (Dorret Boomsma & Hilleke Hulshoff Pol); NWO/SPI 56-464-14192 (Dorret Boomsma), the European Research Council (ERC-230374) (Dorret Boomsma), High Potential Grant Utrecht University (Hilleke Hulshoff Pol), NWO Brain and Cognition 433-09-220 (Hilleke Hulshoff Pol). Brain Imaging Genetics (BIG): This work makes use of the BIG database, first established in Nijmegen, The Netherlands, in 2007. This resource is now part of Cognomics (www.cognomics.nl), a joint initiative by researchers of the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud university medical centre and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative has received supported from the participating departments and centres and from external grants, i.e., the Biobanking and Biomolecular Resources Research Infrastructure (the Netherlands) (BBMRI-NL), the Hersenstichting Nederland, and the Netherlands Organisation for Scientific Research (NWO). The research leading to these results also receives funding from the NWO Gravitation grant ‘Language in Interaction’, the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreements n° 602450 (IMAGEMEND), n°278948 (TACTICS), and n°602805 (Aggressotype) as well as from the European Community’s Horizon 2020 programme under grant agreement n° 643051 (MiND) and from ERC-2010-AdG 268800-NEUROSCHEMA. In addition, the work was supported by a grant for the ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative of a cross-NIH partnership. COBRE: This work was supported by a NIH COBRE Phase I grant (1P20RR021938, Lauriello, PI and 2P20GM103472, Calhoun, PI) awarded to the Mind Research Network. We wish to express our gratitude to numerous investigators who were either external consultants to the Cores and projects, mentors on the projects, members of the external advisory committee and members of the internal advisory committee. Decode: The research leading to these results has received financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007–2013), EU-FP7 funded grant no. 602450 (IMAGEMEND) as well as support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no.115300 (EUAIMS). DemGene: Norwegian Health Association and Research Council of Norway. Dublin: Work was supported by Science Foundation Ireland (SFI grant 12/IP/1359 to Gary Donohoe and SFI08/IN.1/B1916-Corvin to Aidan C Corvin) and the European Research Council (ERC-StG-2015-677467). EPIGEN-UK (SMS, CL): The work was partly undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health’s NIHR Biomedical Research Centres funding scheme. We are grateful to the Wolfson Trust and the Epilepsy Society for supporting the Epilepsy Society MRI scanner, and the Epilepsy Society for supporting CL. Haavik: The work at the K.G.Jebsen center for neuropsychiatric disorders at the University of Bergen, Norway, was supported by Stiftelsen K.G. Jebsen, European Community’s Seventh Framework Program under grant agreement no 602805 and the H2020 Research and Innovation Program under grant agreement numbers 643051 and 667302. HUNT: The HUNT Study is a collaboration between HUNT Research Centre (Faculty of Medicine, Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Health Authority, and the Norwegian Institute of Public Health. HUNT-MRI was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian National Advisory Unit for functional MRI. IMAGEN: The work received support from the European Union-funded FP6Integrated Project IMAGEN (Reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), the FP7 projects IMAGEMEND (602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152; 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL), the Deutsche Forschungsgemeinschaft (DFG grants SM 80/7-1, SM 80/7-2, SFB 940/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01—WM2NA, and ANR-12-SAMA-0004), the Fondation de France, the Fondation pour la Recherche Médicale, the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1), and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. MCIC: This work was supported primarily by the Department of Energy DE-FG02-99ER62764 through its support of the Mind Research Network and the consortium as well as by the National Association for Research in Schizophrenia and Affective Disorders (NARSAD) Young Investigator Award (to SE) as well as through the Blowitz-Ridgeway and Essel Foundations, and through NWO ZonMw TOP 91211021, the DFG research fellowship (to SE), the Mind Research Network, National Institutes of Health through NCRR 5 month-RR001066 (MGH General Clinical Research Center), NIMH K08 MH068540, the Biomedical Informatics Research Network with NCRR Supplements to P41 RR14075 (MGH), M01 RR 01066 (MGH), NIBIB R01EB006841 (MRN), R01EB005846 (MRN), 2R01 EB000840 (MRN), 1RC1MH089257 (MRN), as well as grant U24 RR021992. NCNG: this sample collection was supported by grants from the Bergen Research Foundation and the University of Bergen, the Dr Einar Martens Fund, the K.G. Jebsen Foundation, the Research Council of Norway, to SLH, VMS and TE. The Bergen group was supported by grants from the Western Norway Regional Health Authority (Grant 911593 to AL, Grant 911397 and 911687 to AJL). NESDA: Funding for NESDA was obtained from the Netherlands Organization for Scientific Research (Geestkracht program grant 10-000-1002); the Center for Medical Systems Biology (CSMB, NWO Genomics), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL), VU University’s Institutes for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam, University Medical Center Groningen, Leiden University Medical Center, National Institutes of Health (NIH, R01D0042157-01A, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health.Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. NTR: The NTR study was supported by the Netherlands Organization for Scientific Research (NWO), MW904-61-193 (Eco de Geus & Dorret Boomsma), MaGW-nr: 400-07- 080 (Dennis van ‘t Ent), MagW 480-04-004 (Dorret Boomsma), NWO/SPI 56-464-14192 (Dorret Boomsma), the European Research Council, ERC-230374 (Dorret Boomsma), and Amsterdam Neuroscience. OATS: OATS (Older Australian Twins Study) was facilitated by access to Twins Research Australia, which is funded by a National Health and Medical Research Council (NHMRC) Enabling Grant 310667. OATS is also supported via a NHMRC/Australian Research Council Strategic Award (401162) and a NHMRC Project Grant (1045325). DNA extraction was performed by Genetic Repositories Australia, which was funded by a NHMRC Enabling Grant (401184). OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organisation Flagship Collaboration Fund Grant. PAFIP: PAFIP data were collected at the Hospital Universitario Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Carlos III Health Institute PIE14/00031 and SAF2013-46292-R and SAF2015-71526-REDT. We wish to acknowledge IDIVAL Neuroimaging Unit for imaging acquirement and analysis.We want to particularly acknowledge the patients and the BioBankValdecilla (PT13/0010/0024) integrated in the Spanish National Biobanks Network for its collaboration. QTIM: The QTIM study was supported by grants from the US National Institute of Child Health and Human Development (R01 HD050735) and the Australian National Health and Medical Research Council (NHMRC) (486682, 1009064). Genotyping was supported by NHMRC (389875). Lachlan Strike is supported by an Australian Postgraduate Award (APA). AFM is supported by NHMRC CDF 1083656. We thank the twins and siblings for their participation, the many research assistants, as well as the radiographers, for their contribution to data collection and processing of the samples. SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, 01ZZ0403 and 01ZZ0701), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. Whole-body MR imaging was supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH. StrokeMRI: StrokeMRI has been supported by the Research Council of Norway (249795), the South-Eastern Norway Regional Health Authority (2014097, 2015044, 2015073) and the Norwegian ExtraFoundation for Health and Rehabilitation. TOP: TOP is supported by the Research Council of Norway (223273, 213837, 249711), the South East Norway Health Authority (2017-112), the Kristian Gerhard Jebsen Stiftelsen (SKGJ‐MED‐008) and the European Community’s Seventh Framework Programme (FP7/2007–2013), grant agreement no. 602450 (IMAGEMEND). We acknowledge the technical support and service from the Genomics Core Facility at the Department of Clinical Science, the University of Bergen
Published: 2020

6. Association of childhood traumatization and neuropsychiatric outcomes with altered plasma micro RNA-levels

Author: Hani Najafi-Shoushtari, Sabine Ameling, Sandra Van der Auwera, Jaicy Methew, Hans J. Grabe, Katharina Wittfeld, Karsten Suhre, Uwe Völker, Matthias Nauck, Vimal Ramachandran, Robin Bülow, Henry Völzke, and Enrique d'Harcourt Rowold
Subjects: Adult, Male, Population, Disease, Bioinformatics, Hippocampus, Article, Epigenesis, Genetic, Young Adult, 03 medical and health sciences, 0302 clinical medicine, pathology [Gray Matter], Adverse Childhood Experiences, microRNA, Gene expression, Humans, Medicine, ddc:610, Epigenetics, Gray Matter, Young adult, education, Depression (differential diagnoses), Epigenesis, Pharmacology, education.field_of_study, business.industry, blood [MicroRNAs], Middle Aged, 030227 psychiatry, MicroRNAs, Psychiatry and Mental health, pathology [Hippocampus], Female, business, 030217 neurology & neurosurgery
Abstract: Childhood traumatization (CT) is associated with the development of several neuropsychiatric disorders in later life. Experimental data in animals and observational data in humans revealed evidence for biological alterations in response to CT that may contribute to its long-term consequences. This includes epigenetic changes in miRNA levels that contribute to complex alterations of gene expression. We investigated the association between CT and 121 miRNAs in a target sample of N = 150 subjects from the general population and patients from the Department of Psychiatry. We hypothesized that CT exhibits a long-term effect on miRNA plasma levels. We supported our findings using bioinformatics tools and databases. Among the 121 miRNAs 22 were nominally significantly associated with CT and four of them (let-7g-5p, miR-103a-3p, miR-107, and miR-142-3p) also after correction for multiple testing; most of them were previously associated with Alzheimer's disease (AD) or depression. Pathway analyses of target genes identified significant pathways involved in neurodevelopment, inflammation and intracellular transduction signaling. In an independent general population sample (N = 587) three of the four miRNAs were replicated. Extended analyses in the general population sample only (N = 687) showed associations of the four miRNAs with gender, memory, and brain volumes. We gained increasing evidence for a link between CT, depression and AD through miRNA alterations. We hypothesize that depression and AD not only share environmental factors like CT but also biological factors like altered miRNA levels. This miRNA pattern could serve as mediating factor on the biological path from CT to adult neuropsychiatric disorders.
Published: 2019

7. The Impact of Childhood Trauma and Depressive Symptoms on Body Mass Index

Author: Katharina Wittfeld, Nele Friedrich, Deborah Janowitz, Lara N. Schulze, Henry Völzke, Sandra Van der Auwera, Johannes Hertel, René Walk, and Hans J. Grabe
Subjects: medicine.medical_specialty, business.industry, medicine.disease, Obesity, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, Psychiatry, business, Body mass index, 030217 neurology & neurosurgery, Depressive symptoms, Depression (differential diagnoses)
Abstract: Objectives Obesity is associated with several somatic diseases and increased psychological burden. This study focused on two potential psychological predictors of the body mass index (BMI), childhood trauma and depressive symptoms. Methods We used three independent populations: two general population samples (Study of Health in Pomerania, SHIP-2, N = 1,657; SHIP-TREND-0, N = 3,278) and one patient sample (GANI_MED, N = 1,742). Childhood trauma was measured with the childhood trauma questionnaire (CTQ) and depression with the Beck Depression Inventory (BDI-II) in SHIP-2 and the Patient Health Questionnaire (PHQ-9) in SHIP-TREND-0 and GANI_MED. We investigated the impact of childhood trauma and depression on BMI. Furthermore, we used mediation analysis to assess whether depression was a significant mediator on the path from childhood trauma to adult BMI in each of the three samples. Results In all the three populations, depressive symptoms exhibited a significant association towards higher BMI (p < 0.05). Childhood trauma was positively associated with BMI with significant associations in SHIP-TREND-0 (p < 0.001) and GANI_MED (p = 0.005). The relationship between CTQ and BMI was significantly partially mediated (p < 0.05) by depressive symptoms in SHIP-TREND-0 (38.0%) and GANI_MED (16.4%), in SHIP-2 results pointed in the same direction. All the trauma sub-dimensions, except sexual abuse, exhibited at least one significant association towards increased BMI in one of the samples. Conclusions Childhood trauma and depressive symptoms may be considered as causes of obesity. These results suggest that psychological treatments against obesity should address childhood maltreatment as well as depressive symptoms in their diagnostic assessment and could facilitate psychotherapeutic treatment when necessary.
Published: 2019

8. Full exploitation of high dimensionality in brain imaging: The JPND working group statement and findings

Author: Neda Jahanshad, Paul M. Thompson, Gennady V. Roshchupkin, Reinhold Schmidt, Hans J. Grabe, Claudia L. Satizabal, Sarah E. Medland, Wiro J. Niessen, Meike W. Vernooij, Mohamad Habes, Barbara Franke, Sudha Seshadri, Alexander Teumer, M. Arfan Ikram, Charles DeCarli, Katharina Wittfeld, Hieab H.H. Adams, Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Jovicich, Jorge, and Frisoni, Giovanni B
Subjects: Computer science, Omics, Harmonization, Bioengineering, Neuroimaging, lcsh:Geriatrics, Neurodegenerative, lcsh:RC346-429, Multimodality, Special Section: Working Group Summaries for the European Joint Programme for Neurodegenerative Disease Research (JPND). (Guest Editors: Jorge Jovicich & Giovanni B. Frisoni), 03 medical and health sciences, 0302 clinical medicine, Rare Diseases, Medical imaging, Genetics, Leverage (statistics), ddc:610, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Statement (computer science), High‐dimensional, 0303 health sciences, Data collection, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurosciences, Voxel-based morphometry, Data science, Voxel‐based morphometry, High-dimensional, Brain Disorders, lcsh:RC952-954.6, Psychiatry and Mental health, Neurological, Neurology (clinical), Generic health relevance, Voxels, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 206505.pdf (Publisher’s version ) (Open Access) Advances in technology enable increasing amounts of data collection from individuals for biomedical research. Such technologies, for example, in genetics and medical imaging, have also led to important scientific discoveries about health and disease. The combination of multiple types of high-throughput data for complex analyses, however, has been limited by analytical and logistic resources to handle high-dimensional data sets. In our previous EU Joint Programme-Neurodegenerative Disease Research (JPND) Working Group, called HD-READY, we developed methods that allowed successful combination of omics data with neuroimaging. Still, several issues remained to fully leverage high-dimensional multimodality data. For instance, high-dimensional features, such as voxels and vertices, which are common in neuroimaging, remain difficult to harmonize. In this Full-HD Working Group, we focused on such harmonization of high-dimensional neuroimaging phenotypes in combination with other omics data and how to make the resulting ultra-high-dimensional data easily accessible in neurodegeneration research.
Published: 2019

9. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Tiffany M. Chaim-Avancini, Suzanne C. Swagerman, Sophie Maingault, Mauricio H. Serpa, Kang Sim, Patricia Gruner, Dara M. Cannon, Esther Walton, Gunter Schumann, Christopher R.K. Ching, Simon E. Fisher, Tomohiro Nakao, Nhat Trung Doan, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Ilya M. Veer, Lieuwe de Haan, Paul Pauli, Derrek P. Hibar, Kun Yang, Dan J. Stein, Dominik Grotegerd, Víctor Ortiz-García de la Foz, Daniel Brandeis, Sarah Baumeister, Xavier Caseras, Fabrice Crivello, Vincent P. Clark, Maria J. Portella, Salvador Sarró, Dorret I. Boomsma, Henry Völzke, Daniel H. Wolf, Lianne Schmaal, Yannis Paloyelis, Barbara Franke, Matthew D. Sacchet, Anne Uhlmann, Yulyia Yoncheva, Ole A. Andreassen, Erick J. Canales-Rodríguez, Ingrid Agartz, Anouk den Braber, Colm McDonald, Edith Pomarol-Clotet, Anders M. Dale, Calhoun Vd, David Mataix-Cols, Ignacio Martínez-Zalacaín, Joshua L. Roffman, Andrew J. Kalnin, Anton Albajes-Eizagirre, Andreas Reif, Won Hee Lee, Gaelle E. Doucet, Hans-Jörgen Grabe, Pieter J. Hoekstra, Avram J. Holmes, Theophilus N. Akudjedu, Ian H. Gotlib, Fleur M. Howells, Andrew J. Saykin, Genevieve McPhilemy, Moji Aghajani, David C. Glahn, Rachel M. Brouwer, Núria Bargalló, Knut Schnell, Katharina Wittfeld, Thomas Frodl, Josiane Bourque, Ryota Kanai, Raymond Salvador, Sean N. Hatton, Terry L. Jernigan, Helena Fatouros-Bergman, Oliver Grimm, Marise W. J. Machielsen, Victoria Chubar, Henk Temmingh, Andrew M. McIntosh, Georg C. Ziegler, Marieke Klein, T. P. Klyushnik, Iris E. C. Sommer, Heather C. Whalley, Rachel E. Gur, Alan Breier, Jordan W. Smoller, Kathryn I. Alpert, Dick J. Veltman, Neda Jahanshad, Sophia Frangou, Jiyang Jiang, Jessica A. Turner, Eveline A. Crone, Thomas Espeseth, Alexander Tomyshev, Christine Lochner, Anthony A. James, Aristotle N. Voineskos, Julian N. Trollor, Efstathios Papachristou, Beng-Choon Ho, Pablo Najt, Christian K. Tamnes, Geraldo F. Busatto, Stefan Borgwardt, Andreas Meyer-Lindenberg, Philip Asherson, Francisco X. Castellanos, Bernd Kramer, Jim Lagopoulos, Marcus V. Zanetti, Joaquim Radua, John A. Joska, Giulio Pergola, Nynke A. Groenewold, Erlend S. Dørum, Henrik Walter, Jan Egil Nordvik, Alessandro Bertolino, Wei Wen, Klaus-Peter Lesch, Ian B. Hickie, Pedro G.P. Rosa, Randy L. Buckner, Daniel A. Rinker, Hilleke E. Hulshoff Pol, Steven G. Potkin, Odile A. van den Heuvel, Nancy C. Andreasen, Sanne Koops, Amanda Worker, Susanne Erk, Lei Wang, Norbert Hosten, Jean-Paul Fouche, Dennis van 't Ent, Jonna Kuntsi, Dennis van den Meer, Simon Cervenka, C.A. Hartman, Nicholas G. Martin, Carles Soriano-Mas, Neeltje E.M. van Haren, Pascual Sánchez-Juan, Andreas Heinz, Brenna C. McDonald, Thomas H. Wassink, José M. Menchón, Katie L. McMahon, Jan K. Buitelaar, Sarah E. Medland, Aurora Bonvino, Patricia J. Conrod, Nic J.A. van der Wee, Paul M. Thompson, Micael Andersson, Perminder S. Sachdev, Lars Nyberg, Eco J. C. de Geus, Ramona Baur-Streubel, Lachlan T. Strike, Dag Alnæs, Paola Fuentes-Claramonte, Ben J. Harrison, Martine Hoogman, Lars T. Westlye, Annette Conzelmann, Annabella Di Giorgio, Benedicto Crespo-Facorro, Sarah Hohmann, Jilly Naaijen, Yang Wang, Henry Brodaty, Greig I. de Zubicaray, Laura Koenders, Ruben C. Gur, Stefan Ehrlich, Danai Dima, Christopher G. Davey, Tobias Banaschewski, Amirhossein Modabbernia, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Theodore D. Satterthwaite, René S. Kahn, Margaret J. Wright, Jaap Oosterlaan, Steven Williams, Bernard Mazoyer, Lara M. Wierenga, Bernd Weber, Luisa Lázaro, Irina Lebedeva, Erin W. Dickie, Chaim Huyser, John D. West, Theo G.M. van Erp, National Institute of Mental Health (US), Karolinska Institute, Stockholm County Council, South-Eastern Norway Regional Health Authority, German Centre for Cardiovascular Research, Siemens Healthcare, University of Queensland, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Health and Medical Research Council (Australia), National Institute on Drug Abuse (US), Indiana State Department of Health, Parents of children with epilepsy, Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures, Epilepsy Foundation, American Epilepsy Society, Knut and Alice Wallenberg Foundation, European Commission, Dutch Research Council, Netherlands Organization for Scientific Research, Netherlands Brain Foundation, Utrecht University, European Research Council, National Center for Advancing Translational Sciences (US), National Institutes of Health (US), National Center for Research Resources (US), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, Kings College London, South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre (UK), National Institute for Health Research (UK), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Karolinska Schizophrenia Project (KaSP), Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, APH - Personalized Medicine, Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Brain Imaging
Subjects: Male, diagnostic imaging [Corpus Striatum], Physiology, Hippocampus, Edat, Morfologia (Biologia), Lateral ventricles, anatomy & histology [Corpus Striatum], 0302 clinical medicine, Thalamus, 130 000 Cognitive Neurology & Memory, Basal ganglia, diagnostic imaging [Amygdala], Child, Cervell, Research Articles, diagnostic imaging [Hippocampus], Aged, 80 and over, Radiological and Ultrasound Technology, Putamen, Radiology, Nuclear Medicine & Medical Imaging, 05 social sciences, ENIGMA, Multisi, Brain, Middle Aged, Amygdala, 3. Good health, Neurology, Child, Preschool, Brain size, Female, Anatomy, Life Sciences & Biomedicine, Neurovetenskaper, Research Article, Neuroinformatics, Adult, Adolescent, anatomy & histology [Hippocampus], Human Development, multisite, BF, Neuroimaging, Nucleus accumbens, Biology, Brain morphometry, Morphology (Biology), 050105 experimental psychology, Young Adult, 03 medical and health sciences, Age, Longitudinal trajectories, brain morphometry, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, anatomy & histology [Thalamus], Aged, diagnostic imaging [Thalamus], Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Neurosciences, Corpus Striatum, nervous system, anatomy & histology [Amygdala], RC0321, Neurosciences & Neurology, longitudinal trajectories, Neurology (clinical), 030217 neurology & neurosurgery, physiology [Human Development]
Abstract: Special Issue: The ENIGMA Consortium: the first 10 years.-- Karolinska Schizophrenia Project (KaSP)., Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., National Institute of Mental Health, Grant/Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research.
Published: 2021

10. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author: James Rucker, Carlos Prieto, Elena Shumskaya, Masaki Fukunaga, Vince D. Calhoun, Anne Uhlmann, Jeremy Hall, Evangelos Vassos, Andrew J. Schork, Erik G. Jönsson, Jayne Y. Hehir-Kwa, Sébastien Jacquemont, Erin Burke Quinlan, Paul M. Thompson, Jouke-Jan Hottenga, Paola Dazzan, Stefan Ehrlich, Alexander Teumer, Eco J. C. de Geus, Kari Stefansson, Sandra Martin-Brevet, Claudia Modenato, Tomáš Paus, Tiago Reis Marques, Benedicto Crespo-Facorro, Katrin Amunts, Marianne Bernadette van den Bree, Jingyu Liu, Niklas Rye Jørgensen, Oleksandr Frei, G. Bruce Pike, Lars Nyberg, Jan Haavik, Katharina Wittfeld, Else Eising, Jennifer Monereo Sánchez, Allan F. McRae, Simone Ciufolini, Samuel R. Mathias, Lars T. Westlye, Loes M. Olde Loohuis, Sigrid Botne Sando, Nicholas G. Martin, Ingrid Agartz, Ana I. Silva, Bogdan Draganski, Tian Ge, Emma Knowles, Micael Andersson, Kim Fejgin, Dennis van 't Ent, Dan J. Stein, Costin Leu, Henry Brodaty, Thomas Espeseth, Gunter Schumann, Gary Donohoe, Stephanie Le Hellard, Dorret I. Boomsma, Simon E. Fisher, Greig I. de Zubicaray, Shareefa Dalvie, Ida E Sønderby, Roel A. Ophoff, Derek W. Morris, Margaret J. Wright, Katie L. McMahon, Georg Homuth, Tobias Kaufmann, David C. Glahn, Nicholas B. Blackburn, Nicola J. Armstrong, Ikuo K. Suzuki, Dennis van der Meer, Clara Moreau, Per Hoffmann, Christiane Jockwitz, Pierre Vanderhaeghen, Jacob Nielsen, Anders M. Dale, David Ames, Sarah E. Medland, Torgeir Moberget, Robin M. Murray, Maria Ellegaard, Srdjan Djurovic, Nynke A. Groenewold, Laurena Holleran, Neda Jahanshad, Lachlan T. Strike, John Blangero, Jean Shin, Arvid Lundervold, Sanjay M. Sisodiya, Wiepke Cahn, Vincent Frouin, Christopher R.K. Ching, Astri J. Lundervold, Karen A. Mather, Manon H.J. Hillegers, Asta Håberg, Hans J. Grabe, Kuldeep Kumar, Derrek P. Hibar, Christian K. Tamnes, David Edmund Johannes Linden, Wei Wen, Joanne E. Curran, Ryota Hashimoto, Masataka Kikuchi, Zdenka Pausova, Peter R. Schofield, Joanne L. Doherty, Thomas Gareau, Anbupalam Thalamuthu, Rachel M. Brouwer, Magnus O. Ulfarsson, Thomas W. Mühleisen, G. Bragi Walters, Abdel Abdellaoui, Svenja Caspers, Sylvane Desrivières, Ole A. Andreassen, Masashi Ikeda, Avram J. Holmes, Hilleke E. Hulshoff Pol, Céline S. Reinbold, Juan M. Peralta, Tormod Fladby, Jan Egil Nordvik, Manon Bernard, Anne M. Maillard, Michael John Owen, Omar Gustafsson, Diana Tordesillas-Gutiérrez, Robin Bülow, Sven Cichon, Rune Boen, Andreas Meyer-Lindenberg, Sonja M C de Zwarte, Vidar M. Steen, Perminder S. Sachdev, Stefan Johansson, Hreinn Stefansson, ENIGMA-CNV working group, van der Meer, D., de Geus, EJC, de Zubicaray, G.I., de Zwarte, SMC, Le Hellard, S., van 't Ent, D., van den Bree, MBM, the ENIGMA-CNV working group, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, RS: MHeNs - R3 - Neuroscience, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Beeldvorming, Adult Psychiatry, Child and Adolescent Psychiatry / Psychology, Psychiatry, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Helmholtz Association, European Commission, Netherlands Organization for Scientific Research, European Research Council, Knut and Alice Wallenberg Foundation, Innovative Medicines Initiative, European Federation of Pharmaceutical Industries and Associations, Science Foundation Ireland, Medical Research Council (UK), Wellcome Trust, Waterloo Foundation, National Institute of Mental Health (US), National Institutes of Health (US), Department of Health & Social Care (UK), NIHR Biomedical Research Centre (UK), NHS Foundation Trust, Harvard University, Massachusetts General Hospital, Swedish Research Council, Norwegian University of Science and Technology, Swedish Research Council for Sustainable Development, Kings College London, Federal Ministry of Education and Research (Germany), German Research Foundation, Agence Nationale de la Recherche (France), Fondation de France, Fondation pour la Recherche Médicale, Research Council of Norway, University of Bergen, European Science Foundation, National Health and Medical Research Council (Australia), Australian Research Council, Japan Agency for Medical Research and Development, Instituto de Salud Carlos III, Fundación Marques de Valdecilla, National Institute on Drug Abuse (US), Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), University of Greifswald, Mecklenburg-Western Pomerania, and University of Oslo
Subjects: 0301 basic medicine, Male, genetic structures, PHENOTYPE, 0302 clinical medicine, Cognition, DUPLICATIONS, Gene duplication, Medicine, genetics [Schizophrenia], Copy-number variation, BRAIN, Psychiatry, ABNORMALITIES, REARRANGEMENTS, Brain, EXPANSION, 3. Good health, GENOME, Psychiatry and Mental health, Schizophrenia, Medical genetics, Female, medicine.symptom, Chromosome Deletion, Life Sciences & Biomedicine, Medical Genetics, Neuroinformatics, endocrine system, medicine.medical_specialty, Elementary cognitive task, MICRODUPLICATION, DNA Copy Number Variations, Molecular neuroscience, Psykiatri, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Humans, Clinical genetics, ddc:610, diagnostic imaging [Brain], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Cognitive deficit, Medicinsk genetik, Science & Technology, business.industry, CHROMOSOME 1Q21.1, medicine.disease, MICRODELETIONS, eye diseases, 030104 developmental biology, Autism, sense organs, Psychiatric disorders, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: ENIGMA-CNV working group., Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function., 1000BRAINS: The 1000BRAINS study was funded by the Institute of Neuroscience and Medicine, Research Center Juelich, Germany. We thank the Heinz Nixdorf Foundation (Germany) for the generous support of the Heinz Nixdorf Recall Study on which 1000BRAINS is based. We also thank the scientists and the study staff of the Heinz Nixdorf Recall Study and 1000BRAINS. Funding was also granted by the Initiative and Networking Fund of the Helmholtz Association (Caspers) and the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement 945539 (Human Brain Project SGA3; Amunts, Caspers, Cichon). Brainscale: The Brainscale study was supported by the Netherlands Organization for Scientific Research MagW 480-04-004 (Dorret I. Boomsma), 51.02.060 (Hilleke E. Hulshoff Pol), 668.772 (Dorret I. Boomsma and Hilleke E. Hulshoff Pol); NWO/SPI 56-464-14192 (Dorret I. Boomsma), the European Research Council (ERC-230374) (Dorret I. Boomsma), High Potential Grant Utrecht University (Hilleke E.Hulshoff Pol) and NWO Brain and Cognition 433-09-220 (Hilleke E.Hulshoff Pol). Betula: The Betula study was funded by the Knut and Alice Wallenberg (KAW) foundation (Nyberg). The Freesurfer segmentations on the Betula sample were performed on resources provided by the Swedish National Infrastructure for Computing (SNIC) at HPC2N (in Umeå, Sweden), partially funded by the Swedish Research Council through grant agreement no. 2018-05973. Brain Imaging Genetics (BIG): This work makes use of the BIG database, first established in Nijmegen, The Netherlands, in 2007. This resource is now part of Cognomics (www.cognomics.nl), a joint initiative by researchers from the Donders Centre for Cognitive Neuroimaging, the Human Genetics and Cognitive Neuroscience departments of the Radboud University Medical Centre and the Max Planck Institute for Psycholinguistics in Nijmegen. The Cognomics Initiative has received support from the participating departments and centres and from external grants, that is, the Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL), the Hersenstichting Nederland and the Netherlands Organization for Scientific Research (NWO). The research leading to these results also receives funding from the NWO Gravitation grant ‘Language in Interaction’, the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement nos. 602450 (IMAGEMEND), 278948 (TACTICS) and 602805 (Aggressotype), as well as from the European Community’s Horizon 2020 programme under grant agreement no. 643051 (MiND) and from ERC-2010-AdG 268800-NEUROSCHEMA. In addition, the work was supported by a grant for the ENIGMA Consortium (grant number U54 EB020403) from the BD2K Initiative of a cross-NIH partnership. deCODE genetics: deCODE genetics acknowledges support from the Innovative Medicines Initiative Joint Undertaking under grant agreement nos. 115008 (NEWMEDS) and 115300 (EUAIMS), of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007-2013), EU-FP7-funded grant agreement no. 602450 (IMAGEMEND) and EU-funded FP7-People-2011-IAPP grant agreement no. 286213 (PsychDPC). Dublin: This work was supported by Science Foundation Ireland (SFI grant 12/IP/1359 to Gary Donohoe and grant SFI08/IN.1/B1916-Corvin to Aidan C. Corvin). ECHO-DEFINE: The ECHO study acknowledges funding from a Medical Research Council (MRC) Centre Grant to Michael J. Owen (G0801418), the Wellcome Trust (Institutional Strategic Support Fund (ISSF) to van den Bree and Clinical Research Training Fellowship to Joanne L. Doherty), the Waterloo Foundation (WF 918-1234 to van den Bree), the Baily Thomas Charitable Fund (2315/1 to van den Bree), National Institute of Mental Health (NIMH 5UO1MH101724 to van den Bree and Michael J. Owen), the IMAGINE-2 study (funded by the MRC (MR/T033045/1) to van den Bree, Jeremy Hall and Michael J. Owen), the IMAGINE-ID study (funded by MRC (MR/N022572/1) to Jeremy Hall, van den Bree and Owen). The DEFINE study was supported by a Wellcome Trust Strategic Award (100202/Z/12/Z) to Michael J. Owen. ENIGMA: ENIGMA is supported in part by NIH grants U54 EB20403, R01MH116147 and R56AG058854. NIA T32AG058507; NIH/NIMH 5T32MH073526. EPIGEN-Dublin: The EPIGEN-Dublin cohort was supported by a Science Foundation Ireland Research Frontiers Programme award (08/RFP/GEN1538). EPIGEN-UK (Sisodiya): The work was partly undertaken at UCLH/UCL, which received a proportion of funding from the UK Department of Health’s NIHR Biomedical Research Centres funding scheme. We are grateful to the Wolfson Trust and the Epilepsy Society for supporting the Epilepsy Society MRI scanner. GAP: This work was supported by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, Psychology and Neuroscience, King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. GOBS: The GOBS study data collection was supported in part by the National Institutes of Health (NIH) grants: R01 MH078143, R01 MH078111 and R01 MH083824, with work conducted in part in facilities constructed under the support of NIH grant C06 RR020547. GSP: Data were in part provided by the Brain Genomics Superstruct Project (GSP) of Harvard University and Massachusetts General Hospital (MGH) (Principal Investigators: Randy Buckner, Jordan Smoller and Joshua Roffman), with support from the Center for Brain Science Neuroinformatics Research Group, Athinoula A. Martinos Center for Biomedical Imaging, Center for Genomic Medicine and Stanley Center for Psychiatric Research. Twenty individual investigators at Harvard and MGH generously contributed data to the overall project. We would like to thank Randy Buckner for insightful comments and feedback on this work. HUBIN: The HUBIN study was financed by the Swedish Research Council (K2010-62X-15078-07-2, K2012-61X-15078-09-3, 521-2014-3487 K2015-62X-15077-12-3, 2017-00949), the regional agreement on medical training and clinical research between Stockholm County Council and the Karolinska Institutet. HUNT: The HUNT study is a collaboration between HUNT Research Centre (Faculty of Medicine and Movement Sciences, NTNU—Norwegian University of Science and Technology), Nord-Trøndelag County Council, Central Norway Health Authority and the Norwegian Institute of Public Health. HUNT-MRI was funded by the Liaison Committee between the Central Norway Regional Health Authority and the Norwegian University of Science and Technology, and the Norwegian National Advisory Unit for functional MRI. IMAGEN: This work received support from the following sources: the European Union-funded FP6 Integrated Project IMAGEN (reinforcement-related behaviour in normal brain function and psychopathology) (LSHM-CT- 2007-037286), the Horizon 2020 funded ERC Advanced Grant ‘STRATIFY’ (Brain network based stratification of reinforcement-related disorders) (695313), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004), BRIDGET (JPND: BRain Imaging, cognition Dementia and next generation GEnomics) (MR/N027558/1), Human Brain Project (HBP SGA 2, 785907),the FP7 projects IMAGEMEND(602450; IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EUAIMS (115300-2), the Medical Research Council Grant ‘c-VEDA’ (Consortium on Vulnerability to Externalizing Disorders and Addictions) (MR/N000390/1), the Swedish Research Council FORMAS, the Medical Research Council, the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152, 01EV0711; eMED SysAlc01ZX1311A; Forschungsnetz AERIAL 01EE1406A, 01EE1406B), the Deutsche Forschungsgemeinschaft (DFG grants, SM 80/7-2, SFB 940/2), the Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1). Further support was provided by grants from: ANR (project AF12-NEUR0008-01—WM2NA, ANR-12-SAMA-0004), the Eranet Neuron (ANR-18-NEUR00002-01), the Fondation de France (00081242), the Fondation pour la Recherche Médicale (DPA20140629802), the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA), the Assistance-Publique-Hôpitaux-de-Paris and INSERM (interface grant), Paris Sud University IDEX 2012, the Fondation de l’Avenir (grant AP-RM-17-013), the Fédération pour la Recherche sur le Cerveau; the National Institutes of Health, Science Foundation Ireland (16/ERCD/3797), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1) and by NIH Consortium grant U54 EB020403, supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence. Lifespan: The study is funded by the Research Council of Norway (230345, 288083 and 223273). NCNG: NCNG sample collection was supported by grants from the Bergen Research Foundation and the University of Bergen, the Dr Einar Martens Fund, the Research Council of Norway, to le Hellard, Steen and Espeseth. The Bergen group was supported by grants from the Western Norway Regional Health Authority (Grant 911593 to Arvid Lundervold, Grant 911397 and 911687 to Astri Johansen Lundervold). NTR: The NTR cohort was supported by the Netherlands Organization for Scientific Research (NWO) and The Netherlands Organisation for Health Research and Development (ZonMW) grants 904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004,463-06-001, 451-04-034, 400-05-717, Addiction-31160008, 016-115-035, 481-08-011, 056-32-010, Middelgroot-911-09-032, OCW_NWO Gravity programme—024.001.003, NWO-Groot 480-15-001/674, Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007 and 184.033.111); Spinozapremie (NWO-56-464-14192), KNAW Academy Professor Award (PAH/6635) and University Research Fellow grant (URF) to Dorret I. Boomsma; Amsterdam Public Health research institute (former EMGO+), Neuroscience Amsterdam research institute (former NCA); the European Science Foundation (ESF, EU/QLRT-2001-01254), the European Community’s Seventh Framework Programme (FP7- HEALTH-F4-2007-2013, grant 01413: ENGAGE and grant 602768: ACTION); the European Research Council (ERC Starting 284167, ERC Consolidator 771057, ERC Advanced 230374), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the National Institutes of Health (NIH, R01D0042157-01A1, R01MH58799-03, MH081802, DA018673, R01 DK092127-04, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995); the Avera Institute for Human Genetics, Sioux Falls, South Dakota (USA). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health. Computing was supported by NWO through grant 2018/EW/00408559, BiG Grid, the Dutch e-Science Grid and SURFSARA. OATS: The OATS study has been funded by a National Health & Medical Research Council (NHMRC) and Australian Research Council (ARC) Strategic Award Grant of the Ageing Well, Ageing Productively Programme (ID No. 401162) and NHMRC Project Grants (ID Nos. 1045325 and 1085606). This research was facilitated through Twins Research Australia, a national resource in part supported by an NHMRC Centre for Research Excellence Grant (ID No.: 1079102). We thank the participants for their time and generosity in contributing to this research. We acknowledge the contribution of the OATS research team (https://cheba.unsw.edu.au/project/older-australian-twins-study) to this study. OATS genotyping was partly funded by a Commonwealth Scientific and Industrial Research Organization Flagship Collaboration Fund Grant. Osaka: Osaka study was supported by the Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS: Grant Number JP18dm0207006), Brain/MINDS& beyond studies (Grant Number JP20dm0307002) and Health and Labour Sciences Research Grants for Comprehensive Research on Persons with Disabilities (Grant Number JP20dk0307081) from the Japan Agency for Medical Research and Development (AMED), Grants-in-Aid for Scientific Research (KAKENHI; Grant Numbers JP25293250 and JP16H05375). Some computations were performed at the Research Center for Computational Science, Okazaki, Japan. PAFIP: The PAFIP study was supported by Instituto de Salud Carlos III, FIS 00/3095, 01/3129, PI020499, PI060507, PI10/00183, the SENY Fundació Research Grant CI2005-0308007 and the FundaciónMarqués de Valdecilla API07/011. Biological samples from our cohort were stored at the Valdecilla Biobank and genotyping services were conducted at the Spanish ‘Centro Nacional de Genotipado’ (CEGEN-ISCIII). MCIC/COBRE: The study is funded by the National Institutes of Health studies R01EB006841, P20GM103472 and P30GM122734 and Department of Energy DE-FG02-99ER62764. PING: Data collection and sharing for the Paediatric Imaging, Neurocognition and Genetics (PING) Study (National Institutes of Health Grant RC2DA029475) were funded by the National Institute on Drug Abuse and the Eunice Kennedy Shriver National Institute of Child Health & Human Development. A full list of PING investigators is at http://pingstudy.ucsd.edu/investigators.html. QTIM: The QTIM study was supported by the National Institute of Child Health and Human Development (R01 HD050735) and the National Health and Medical Research Council (NHMRC 486682, 1009064), Australia. Genotyping was supported by NHMRC (389875). Medland is supported in part by an NHMRC fellowship (APP1103623). SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grant nos. 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genome-wide single-nucleotide polymorphism typing in SHIP and MRI scans in SHIP and SHIP-TREND have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. StrokeMRI: StrokeMRI was supported by the Norwegian ExtraFoundation for Health and Rehabilitation(2015/FO5146), the Research Council of Norway (249795, 262372), the South-Eastern Norway Regional Health Authority (2014097, 2015044, 2015073) and the Department of Psychology, University of Oslo. Sydney MAS: The Sydney Memory and Aging Study (Sydney MAS) is funded by National and HealthMedical Research Council (NHMRC) Programme and Project Grants (ID350833, ID568969 and ID109308). We also thank the Sydney MAS participants and the Research Team. SYS: The SYS Study is supported by Canadian Institutes of Health Research. TOP: Centre of Excellence: RCN #23273 and RCN #226971. Part of this work was performed on the TSD (Tjeneste for Sensitive Data) facilities, owned by the University of Oslo, operated and developed by the TSD service group at the University of Oslo, IT-Department (USIT) (tsd-drift@usit.uio.no). The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-COFUND) under grant agreement no. 609020—Scientia Fellows; the Research Council of Norway (RCN) #276082—A lifespan perspective on mental illness: toward precision medicine using multimodal brain imaging and genetics. Ida E. Sønderby and Rune Bøen are supported by South-Eastern Norway Regional Health Authority (#2020060). Ida E. Sønderby and Ole A. Andreassen have received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant agreement no. 847776 (CoMorMent project) and the KG Jebsen Foundation (SKGJ-MED-021). UCLA_UMCU: The UCLA_UMCU cohort comprises of six studies which were supported by National Alliance for Research in Schizophrenia and Affective Disorders (NARSAD) (20244 to Prof. Hillegers), The Netherlands Organisation for Health Research and Development (ZonMw) (908-02-123 to Prof. Hulshoff Pol), and Netherlands Organisation for Scientific Research (NWO 9120818 and NWO-VIDI 917-46-370 to Prof. Hulshoff Pol). The GROUP study was funded through the Geestkracht programme of the Dutch Health Research Council (ZonMw, grant number 10-000-1001), and matching funds from participating pharmaceutical companies (Lundbeck, AstraZeneca, Eli Lilly and Janssen Cilag) and universities and mental health care organizations (Amsterdam: Academic Psychiatric Centre of the Academic Medical Center and the mental health institutions: GGZ inGeest, Arkin, Dijk en Duin, GGZ Rivierduinen, Erasmus Medical Centre, GGZ Noord-Holland-Noord. Groningen: University Medical Center Groningen and the mental health institutions: Lentis, GGZ Friesland, GGZ Drenthe, Dimence, Mediant, GGNet Warnsveld, Yulius Dordrecht and Parnassia Psycho-medical Center, The Hague. Maastricht: Maastricht University Medical Centre and the mental health institutions: GGzE, GGZ Breburg, GGZ Oost-Brabant, Vincent van Gogh, voor Geestelijke Gezondheid, Mondriaan, Virenzeriagg, Zuyderland GGZ, MET ggz, Universitair Centrum Sint-JozefKortenberg, CAPRI University of Antwerp, PC Ziekeren Sint-Truiden, PZ Sancta Maria Sint-Truiden, GGZ Overpelt, OPZ Rekem. Utrecht: University Medical Center Utrecht and the mental health institutions: Altrecht, GGZ Centraal and Delta.). UK Biobank: This work made use of data sharing from UK Biobank (under project code 27412). Others: Work by Pierre Vanderhaeghen was funded by Grants of the European Research Council (ERC Adv Grant GENDEVOCORTEX), the EOS Programme, the Belgian FWO, the AXA Research Fund and the Belgian Queen Elizabeth Foundation. Ikuo K. Suzuki was supported by a postdoctoral fellowship of the FRS/FNRS.
Published: 2021

11. Lack of association between proton pump inhibitor use and brain aging: a cross-sectional study

Author: Jakob Linseisen, Katharina Wittfeld, Christa Meisinger, Ute Amann, Ulf Schminke, Henry Völzke, Hans J. Grabe, Robin Bülow, Markus M. Lerch, Ina-Maria Rückert-Eheberg, Stefan Frenzel, Jean-François Chenot, Sebastian E. Baumeister, Michael Nolde, and Nayeon Ahn
Subjects: Adult, Male, medicine.medical_specialty, Aging, Cross-sectional study, Pharmacoepidemiology and Prescription, Proton pump inhibitors, Brain Volume, Cognitive Impairment, Dementia, Magnetic Resonance Imaging, Proton Pump Inhibitors, Population, Verbal learning, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Cognition, Magnetic resonance imaging, Internal medicine, Germany, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, ddc:610, education, Aged, Pharmacology, Aged, 80 and over, education.field_of_study, Brain volume, business.industry, Confounding, Brain, administration & dosage [Proton Pump Inhibitors], General Medicine, Middle Aged, medicine.disease, Confidence interval, drug effects [Aging], Cross-Sectional Studies, Cognitive impairment, Study of Health in Pomerania, Brain size, drug effects [Cognition], drug effects [Brain], Female, business, 030217 neurology & neurosurgery, adverse effects [Proton Pump Inhibitors]
Abstract: PurposeDue to conflicting scientific evidence for an increased risk of dementia by intake of proton pump inhibitors (PPIs), this study investigates associations between PPI use and brain volumes, estimated brain age, and cognitive function in the general population.MethodsTwo surveys of the population-based Study of Health in Pomerania (SHIP) conducted in Northeast Germany were used. In total, 2653 participants underwent brain magnetic resonance imaging (MRI) and were included in the primary analysis. They were divided into two groups according to their PPI intake and compared with regard to their brain volumes (gray matter, white matter, total brain, and hippocampus) and estimated brain age. Multiple regression was used to adjust for confounding factors. Cognitive function was evaluated by the Verbal Learning and Memory Test (VLMT) and the Nuremberg Age Inventory (NAI) and put in relation to PPI use.ResultsNo association was found between PPI use and brain volumes or the estimated brain age. The VLMT score was 1.11 lower (95% confidence interval: − 2.06 to − 0.16) in immediate recall, and 0.72 lower (95% CI: − 1.22 to − 0.22) in delayed recall in PPI users than in non-users. PPI use was unrelated to the NAI score.ConclusionsThe present study does not support a relationship between PPI use and brain aging.
Published: 2021

12. Correction: Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders

Author: Henry Völzke, Ben J. Harrison, Bonnie Klimes-Dougan, Bernhard T. Baune, Mon-Ju Wu, Jair C. Soares, Yuri Milaneschi, Norbert Hosten, Meng Li, Maike Richter, Janik Goltermann, Axel Krug, Benson Mwangi, Giovana Zunta-Soares, Martin Walter, Katharina Wittfeld, Thomas Frodl, Ramona Leenings, Christopher G. Davey, Lyubomir I. Aftanas, Ian B. Hickie, Udo Dannlowski, Anbupalam Thalamuthu, Nils Opel, Ilya M. Veer, Angela Carballedo, Mathew A. Harris, Marco Hermesdorf, Georg Woditsch, Elena Pozzi, Lianne Schmaal, Kang Sim, Heather C. Whalley, Paul M. Thompson, Laura Nawijn, Liesbeth Reneman, Claas Flint, Dominik Grotegerd, Bryon A. Mueller, Klaus Berger, Kathryn R. Cullen, Hans J. Grabe, Elena Filimonova, Sandra Van der Auwera, Matthew D. Sacchet, Tim Hahn, Frank P. MacMaster, Sean N. Hatton, Neda Jahanshad, André Aleman, Dick J. Veltman, Igor Nenadic, Evgeniy A. Osipov, Tilo Kircher, Henrik Walter, Dan J. Stein, Andrew M. McIntosh, Ian H. Gotlib, Nynke A. Groenewold, Philipp G. Sämann, Brenda W.J.H. Penninx, Ivan V. Brak, Anouk Schrantee, and Jim Lagopoulos
Subjects: 0301 basic medicine, business.industry, Physiology, Genetic data, medicine.disease, Obesity, Left fusiform gyrus, 03 medical and health sciences, Cellular and Molecular Neuroscience, Psychiatry and Mental health, 030104 developmental biology, 0302 clinical medicine, medicine, Major depressive disorder, Polygenic risk score, ddc:610, Genetic risk, business, Molecular Biology, Pathological, 030217 neurology & neurosurgery
Abstract: Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = −0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.
Published: 2021

13. ENIGMA and global neuroscience:A decade of large-scale studies of the brain in health and disease across more than 40 countries

Author: Frank G. Hillary, Esther Walton, Gunter Schumann, Sophia I. Thomopoulos, Patricia J. Conrod, Nic J.A. van der Wee, Daqiang Sun, Charlotte A.M. Cecil, Robin Bülow, Henry Völzke, Rachel M. Brouwer, Yann Chye, Katrina L. Grasby, Ingrid Agartz, Bernhard T. Baune, Josselin Houenou, Simon E. Fisher, Mark S. Shiroishi, Daan van Rooij, Miguel E. Rentería, Yanli Zhang-James, Courtney A. Filippi, Stephen V. Faraone, Sara Bertolín, Elisabeth A. Wilde, Eus J.W. Van Someren, Christopher R.K. Ching, Iliyan Ivanov, Barbara Franke, Derrek P. Hibar, Tiffany C. Ho, Hilleke E. Hulshoff Pol, Norbert Hosten, Ilya M. Veer, Daniel Garijo, Jean-Paul Fouche, Inga K. Koerte, Hans J. Grabe, Carles Soriano-Mas, Lianne Schmaal, Brenda Bartnik-Olson, Amanda K. Tilot, Sinead Kelly, Ysbrand D. van der Werf, Anderson M. Winkler, Henrik Walter, Hugh Garavan, Max A. Laansma, Agnes B. McMahon, Laura K.M. Han, Natalia Shatokhina, Scott Mackey, David F. Tate, Jason L. Stein, Thomas Frodl, Tiril P. Gurholt, Carrie E. Bearden, Katharina Wittfeld, Carrie R. McDonald, Andrew R. Mayer, Yolanda Gil, Jun Soo Kwon, Tomas Hajek, Jan K. Buitelaar, Moji Aghajani, Bhim M. Adhikari, Premika S.W. Boedhoe, Graeme Fairchild, Maria Jalbrzikowski, Alexander Olsen, Carolien G.F. de Kovel, Talia M. Nir, Mojtaba Zarei, Karen Caeyenberghs, Dirk J.A. Smit, Fabio Macciardi, Jeanne Leerssen, Margaret J. Wright, Eduard T. Klapwijk, Elena Pozzi, Lisa T. Eyler, Abraham Nunes, Sanjay M. Sisodiya, Clyde Francks, Emily L. Dennis, Rajendra A. Morey, Pauline Favre, Sophia Frangou, Boris A. Gutman, Merel Postema, Ida E Sønderby, Ian H. Harding, Julio E. Villalon-Reina, Sook-Lei Liew, Peter Kochunov, Celia van der Merwe, Je-Yeon Yun, David C. Glahn, Stefan Ehrlich, George A Karkashadze, Jian Chen, Nils Opel, Tianye Jia, Peristera Paschou, Xiangzhen Kong, Marieke Klein, Leyla Namazova-Baranova, Sylvane Desrivières, Danai Dima, Masoud Tahmasian, Dennis Hernaus, Sven C. Mueller, Gemma Modinos, Guido van Wingen, Ulrike Lueken, Ole A. Andreassen, Jonathan D. Rohrer, Lauren E. Salminen, Laura A. Berner, Eileen Luders, Georg Homuth, Stephane A. De Brito, Martine Hoogman, Federica Piras, Carrie Esopenko, Laura S van Velzen, Janna Marie Bas-Hoogendam, Udo Dannlowski, Mark W. Logue, Willem B Bruin, André Aleman, Sarah E. Medland, Neeltje E.M. van Haren, Theo G.M. van Erp, Sean N. Hatton, Laurena Holleran, Gary Donohoe, Alexander P. Lin, Rebecca C. Knickmeyer, Leonardo Tozzi, Fabrizio Pizzagalli, Kevin Hilbert, Sonja M C de Zwarte, Dick J. Veltman, Gianfranco Spalletta, Daniel S. Pine, Tim Hahn, Pratik Mukherjee, Alexander Teumer, Joanna Bright, Andre Altmann, Neda Jahanshad, James H. Cole, Arielle R. Baskin-Sommers, Odile A. van den Heuvel, Dan J. Stein, Vladimir Zelman, Lei Wang, Ronald A. Cohen, Joseph O' Neill, David Baron, Fabrizio Piras, Robert R. Althoff, Nynke A. Groenewold, Philipp G. Sämann, Christopher D. Whelan, Jessica A. Turner, Janita Bralten, Guohao Zhang, Paul M. Thompson, and Netherlands Institute for Neuroscience (NIN)
Subjects: DISORDER, Scientific community, Review Article, bepress|Life Sciences|Neuroscience and Neurobiology, 0302 clinical medicine, SCHIZOPHRENIA, Medicine and Health Sciences, GENETIC INFLUENCES, ENDOPHENOTYPE CONCEPT, Cervell, VOLUMES, RISK, Psychiatry, 0303 health sciences, 05 social sciences, Brain, Genomics, Magnetic Resonance Imaging, WORKING, 3. Good health, ALZHEIMERS-DISEASE, Psychiatry and Mental health, Eating disorders, Dissociative identity disorder, Biometris, Neurology, Conduct disorder, Schizophrenia, Major depressive disorder, Anxiety, medicine.symptom, Psychology, Neuroinformatics, Neuroimaging, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, lcsh:RC321-571, Neurologia, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, MEGA-ANALYSIS, medicine, Life Science, Humans, 0501 psychology and cognitive sciences, ddc:610, Psiquiatria, Bipolar disorder, diagnostic imaging [Brain], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, bepress|Life Sciences|Neuroscience and Neurobiology|Other Neuroscience and Neurobiology, Biological Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genetics [Depressive Disorder, Major], Reproducibility of Results, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, PsyArXiv|Neuroscience, PsyArXiv|Neuroscience|Other Neuroscience and Neurobiology, RC0321, HERITABILITY ANALYSIS, Autism, Psychiatric disorders, Neuroscience, Biomarkers, 030217 neurology & neurosurgery
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.
Published: 2020

14. ENIGMA-anxiety working group: Rationale for and organization of large-scale neuroimaging studies of anxiety disorders

Author: Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., Agosta, F., Ahs, F., An, I., Alberton, B. A. V., Andreescu, C., Asami, T., Assaf, M., Avery, S. N., Nicholas, L., Balderston, Barber, J. P., Battaglia, M., Bayram, A., Beesdo-Baum, K., Benedetti, F., Berta, R., Bjorkstrand, J., Blackford, J. U., Blair, J. R., Karina, S., Blair, Boehme, S., Brambilla, P., Burkhouse, K., Cano, M., Canu, E., Cardinale, E. M., Cardoner, N., Clauss, J. A., Cividini, C., Critchley, H. D., Udo, Dannlowski, Deckert, J., Demiralp, T., Diefenbach, G. J., Domschke, K., Doruyter, A., Dresler, T., Erhardt, A., Fallgatter, A. J., Fananas, L., Brandee, Feola, Filippi, C. A., Filippi, M., Fonzo, G. A., Forbes, E. E., Fox, N. A., Fredrikson, M., Furmark, T., Ge, T., Gerber, A. J., Gosnell, S. N., Grabe, H. J., Grotegerd, D., Gur, R. E., Gur, R. C., Harmer, C. J., Harper, J., Heeren, A., Hettema, J., Hofmann, D., Hofmann, S. G., Jackowski, A. P., Andreas, Jansen, Kaczkurkin, A. N., Kingsley, E., Kircher, T., Kosti c, M., Kreifelts, B., Krug, A., Larsen, B., Lee, S. -H., Leehr, E. J., Leibenluft, E., Lochner, C., Maggioni, E., Makovac, E., Mancini, M., Manfro, G. G., Mansson, K. N. T., Meeten, F., Michalowski, J., Milrod, B. L., Muhlberger, A., Lilianne, R., Mujica-Parodi, Munjiza, A., Mwangi, B., Myers, M., Igor Nenadi, C., Neufang, S., Nielsen, J. A., Oh, H., Ottaviani, C., Pan, P. M., Pantazatos, S. P., Martin, P., Paulus, Perez-Edgar, K., Penate, W., Perino, M. T., Peterburs, J., Pfleiderer, B., Phan, K. L., Poletti, S., Porta-Casteras, D., Price, R. B., Pujol, J., Andrea, Reinecke, Rivero, F., Roelofs, K., Rosso, I., Saemann, P., Salas, R., Salum, G. A., Satterthwaite, T. D., Schneier, F., Schruers, K. R. J., Schulz, S. M., Schwarzmeier, H., Seeger, F. R., Smoller, J. W., Soares, J. C., Stark, R., Stein, M. B., Straube, B., Straube, T., Strawn, J. R., Suarez-Jimenez, B., Boris, Suchan, Sylvester, C. M., Talati, A., Tamburo, E., Tukel, R., van den Heuvel, O. A., Van der Auwera, S., van Nieuwenhuizen, H., van Tol, M. -J., van Velzen, L. S., Bort, C. V., Vermeiren, R. R. J. M., Visser, R. M., Volman, I., Wannemuller, A., Wendt, J., Werwath, K. E., Westenberg, P. M., Wiemer, J., Katharina, Wittfeld, M. -J., Wu, Yang, Y., Zilverstand, A., Zugman, A., Zwiebel, H. L., Bas-Hoogendam, J. M., Groenewold, N. A., Aghajani, M., Freitag, G. F., Harrewijn, A., Hilbert, K., Jahanshad, N., Thomopoulos, S. I., Thompson, P. M., Veltman, D. J., Winkler, A. M., Lueken, U., Pine, D. S., van der Wee, N. J. A., Stein, D. J., ENIGMA-anxiety working, Group, Filippi, M, and UCL - SSH/IPSY - Psychological Sciences Research Institute
Subjects: Córtex pré-frontal, Review Article, Anxiety, Prefrontal cortex, Specific phobia, 0302 clinical medicine, limbic system, magnetic resonance imaging, Multicenter Studies as Topic, genetics, Review Articles, prefrontal cortex, neuroimaging, Radiological and Ultrasound Technology, 05 social sciences, Social anxiety, amygdala, Amygdala, Anxiety Disorders, Transtornos de ansiedade, Neurology, multicentric network, Anatomy, medicine.symptom, Psychology, Neurovetenskaper, Clinical psychology, endocrine system, Generalized anxiety disorder, brain, Neuroimaging, Sistema límbico, 050105 experimental psychology, 03 medical and health sciences, Global mental health, Limbic system, Magnetic resonance imaging, Imatges per ressonància magnètica, medicine, Genetics, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Neuroimagem, Psykologi (exklusive tillämpad psykologi), Panic disorder, neurosciences, Imageamento por ressonância magnética, Tonsila do cerebelo, medicine.disease, anxiety disorders, Genética, Psychology (excluding Applied Psychology), Ansietat, Neurology (clinical), Working group, 030217 neurology & neurosurgery, Anxiety disorders
Abstract: Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders., Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.
Published: 2020

15. Global and regional development of the human cerebral cortex: Molecular architecture and occupational aptitudes

Author: M. Arfan Ikram, Lukas Pirpamer, Daniel E. Vosberg, Edith Hofer, David Ames, Sandra van der Auwera-Palitschka, Zdenka Pausova, Xueqiu Jian, Henry Brodaty, André M. M. Sousa, Linda Ding, Tavia E. Evans, William S. Kremen, Jean Shin, Steven Tilley, Fabrice Crivello, Christophe Tzourio, Karen A. Mather, Peter R. Schofield, Joanna M. Wardlaw, Joshua C. Bis, Tomáš Paus, Bernard Mazoyer, Myriam Fornage, Thomas H. Mosley, Natalie Terzikhan, Nathan A. Gillespie, Hans J. Grabe, Michelle Luciano, Mathew A. Harris, Nenad Sestan, Wei Wen, Sherif Karama, Reinhold Schmidt, Shaojie Ma, Katharina Wittfeld, Lindsay B. Lewis, Arno Villringer, Hieab H.H. Adams, Sudha Seshadri, Neda Jahanshad, Jiyang Jiang, Sophie Maingault, Yasaman Saba, Qiong Yang, Frauke Beyer, Stéphanie Debette, Nicola J. Armstrong, Markus Scholz, Carol E. Franz, Margaret J. Wright, Shuo Li, Rebecca F. Gottesman, Aniket Mishra, Perminder S. Sachdev, Yash Patel, John B.J. Kwok, Anbupalam Thalamuthu, Helena Schmidt, Amaia Carrion-Castillo, Robin Bülow, Mark E. Bastin, Markus Loeffler, Ian E. Deary, Stefan Frenzel, Julian N. Trollor, Gennady V. Roshchupkin, A. Veronica Witte, Epidemiology, Medical Informatics, Radiology & Nuclear Medicine, Neurology, the ENIGMA Consortium, for the neuroCHARGE Working Group, and the neuroCHARGE Working Group
Subjects: rho GTP-Binding Proteins, Male, Aptitude, Genome-wide association study, brain development, cortical surface area, 0302 clinical medicine, Form perception, Intracranial volume, genetics [RNA-Binding Proteins], genetics [Form Perception], Visual Cortex, media_common, Cerebral Cortex, Aged, 80 and over, 0303 health sciences, Principal Component Analysis, Career Choice, Microfilament Proteins, genomeide association study, RNA-Binding Proteins, Gene Expression Regulation, Developmental, Cognition, growth & development [Visual Cortex], Middle Aged, medicine.anatomical_structure, VINTAGE, Cerebral cortex, growth & development [Cerebral Cortex], Original Article, Female, Adult, endocrine system, Adolescent, Cognitive Neuroscience, media_common.quotation_subject, tau Proteins, Biology, occupational aptitude, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Regional development, medicine, Humans, ddc:610, 030304 developmental biology, Genetic association, Aged, physiology [Aptitude], genome-wide association study, 9. Industry and infrastructure, cortical thickness, Brain Cortical Thickness, Form Perception, genetics [tau Proteins], genetics [rho GTP-Binding Proteins], genetics [Microfilament Proteins], Transcriptome, Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade—albeit in a very limited manner—to behaviors as complex as the choice of one’s occupation.
Published: 2020

16. Brain correlates of suicide attempt in 18,925 participants across 18 international cohorts

Author: Sean N. Hatton, Aditya Singh, Ronny Redlich, Matthew A. Harris, Tiffany C. Ho, Axel Krug, Cynthia H.Y. Fu, Robin Bülow, Simon Schmitt, Frank P. MacMaster, Dominik Grotegerd, Heather C. Whalley, Tracy Erwin-Grabner, Jennifer W. Evans, Nic J.A. van der Wee, Mark Adams, Susanne Meinert, Tony T. Yang, Ian B. Hickie, Margaret J. Wright, Lena Waltemate, Kang Sim, Tina Meller, Ian H. Gotlib, Hans J. Grabe, Tilo Kircher, Sarah E. Medland, Nils Opel, Andrew M. McIntosh, Liesbeth Reneman, Adrian I. Campos, Jonathan Repple, Colm G. Connolly, Katharina Wittfeld, Danai Dima, Frederike Stein, Hannah Lemke, Udo Dannlowski, Anouk Schrantee, Greig I. de Zubicaray, Ben J. Harrison, Carlos A. Zarate, Igor Nenadic, Steven J.A. van der Werff, Christopher G. Davey, Katharina Brosch, Roberto Goya-Maldonado, Elena Pozzi, Nicholas G. Martin, Lianne Schmaal, Laura S. van Veltzen, Bernhard T. Baune, Dick J. Veltman, Klaus Berger, Miguel E. Rentería, Matthew D. Sacchet, Neda Jahanshad, Katie L. McMahon, Marco Hermesdorf, Paul M. Thompson, Henry Völzke, Lachlan T. Strike, Jim Lagopoulos, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Radiology and nuclear medicine, Radiology and Nuclear Medicine, APH - Mental Health, APH - Personalized Medicine, ANS - Brain Imaging, and ANS - Compulsivity, Impulsivity & Attention
Subjects: 0301 basic medicine, BF, Neuroimaging, Suicide, Attempted, Major depressive disorder, diagnostic imaging [Depressive Disorder, Major], Suicide prevention, Article, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), Healthy control, Suicide attempt, medicine, Humans, Pooled data, ddc:610, diagnostic imaging [Brain], Biological Psychiatry, Depression (differential diagnoses), Structural magnetic resonance imaging, Suicide attempters, Depressive Disorder, Major, Brain, Control subjects, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, 030104 developmental biology, Suicidal behavior, RC0321, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: SUMMARYBackgroundSuicidal behavior is highly heterogeneous and complex. A better understanding of its biological substrates and mechanisms could inform the design of more effective suicide prevention and intervention strategies. Neuroimaging studies of suicidality have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD working group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior.MethodsHere, we pool data from eighteen international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy controls and 6,448 people with depression, of whom 694 had attempted suicide). We compare regional cortical thickness and surface area, and measures of subcortical, lateral ventricular and intracranial volumes between suicide attempters, clinical controls (non-attempters with depression) and healthy controls.FindingsWe identified 25 regions of interest with statistically significant (FDRPost-hoc examinations identified neuroimaging markers associated with suicide attempt over and above the effects of depression, including smaller volumes of the left and right thalamus and the right pallidum, and lower surface area of the left inferior parietal lobe.InterpretationThis study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt, and further demonstrates the need for well-powered samples and collaborative efforts to avoid reaching biased or misleading conclusions. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidality may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.
Published: 2020

17. Cortical Thickness Trajectories across the Lifespan: Data from 17,075 healthy individuals aged 3-90 years

Author: Stefan Ehrlich, Danai Dima, Nhat Trung Doan, Simon E. Fisher, Dominik Grotegerd, Nicholas G. Martin, Tiffany M. Chaim-Avancini, Sophie Maingault, Sean N. Hatton, Derrek P. Hibar, Vincent P. Clark, Anders M. Dale, Iris E. C. Sommer, Ben J. Harrison, Annabella Di Giorgio, Benedicto Crespo-Facorro, Ian H. Gotlib, Andrew J. Kalnin, Andreas Reif, Edith Pomarol-Clotet, Thomas Espeseth, Theodore D. Satterthwaite, Pieter J. Hoekstra, René S. Kahn, Margaret J. Wright, Núria Bargalló, Maria J. Portella, Thomas Frodl, Lianne Schmaal, Chaim Huyser, Sophia I. Thomopoulos, Odille A van den Heuvel, Rachel M. Brouwer, Rachel E. Gur, Stefan Borgwardt, Marise W. J. Machielsen, Kathryn I. Alpert, Dick J. Veltman, Sim Kang, Irina V. Lebedeva, Marcus V. Zanetti, Anne Uhlmann, Christopher R.K. Ching, John D. West, Paul Pauli, Susanne Erk, Xavier Caseras, Kun Yang, Randy L. Buckner, Julian N. Trollor, Katharina Wittfeld, Fabrice Crivello, Theo G.M. van Erp, Luisa Lázaro, Jan Egil Nordvik, Sarah Baumeister, Steven G. Potkin, Calhoun Vd, Ian B. Hickie, Giulio Pergola, Henrik Walter, Katie L. McMahon, Theophilus N. Akudjedu, Patricia J. Conrod, Nic J.A. van der Wee, Won Hee Lee, Dennis van 't Ent, Barbara Franke, Knut Schnell, Josiane Bourque, Matthew D. Sacchet, Perminder S. Sachdev, Esther Walton, Raymond Salvador, Colm McDonald, Gunter Schumann, Paul M. Thompson, Georg C. Ziegler, Erin W. Dickie, Christine Lochner, Andreas Meyer-Lindenberg, Eco J. C. de Geus, Ole A. Andreassen, Joshua L. Roffman, Oliver Grimm, Andrew M. McIntosh, Ryota Kanai, Mauricio H. Serpa, Dennis van den Meer, Jessica A. Turner, Simon Cervenka, Alexander Tomyshev, Lara M. Wierenga, Francisco X. Castellanos, Bernd Kramer, Erlend S. Dørum, Alessandro Bertolino, P. G. P. Rosa, Avram J. Holmes, Klaus-Peter Lesch, Norbert Hosten, Hilleke E. Hulshoff Pol, Jean-Paul Fouche, Neda Jahanshad, Daniel Brandeis, José M. Menchón, Jiyang Jiang, Jan K. Buitelaar, Andrew J. Saykin, Genevieve McPhilemy, Efstathios Papachristou, Hans-Jörgen Grabe, Bernd Weber, Beng-Choon Ho, Pablo Najt, Fleur M. Howells, Yannis Paloyelis, Lieuwe de Haan, Lachlan T. Strike, Dag Alnæs, David Mataix-Cols, Henry Völzke, Daniel H. Wolf, Suzanne C. Swagerman, Paola Fuentes-Claramonte, Marieke Klein, Patricia Gruner, Anthony A. James, Ingrid Agartz, Dara M. Cannon, Jim Lagopoulos, Geraldo F. Busatto, Tomohiro Nakao, Dan J. Stein, Gaelle E Doucet, Erick J. Canales-Rodríguez, Cristopher Davey, Tatyana P Klushnik, Jaap Oosterlaan, Ilya M. Veer, Steven Williams, Bernard Mazoyer, Helena Fatouros-Bergman, Yulyia Yoncheva, Ramona Baur-Streubel, Anouk den Braber, Nynke A. Groenewold, Salvador Sarró, Ignacio Martínez-Zalacaín, Sanne Koops, M. Aghajani, Lei Wang, Sarah E. Medland, C.A. Hartman, Aurora Bonvino, Pascual Sánchez-Juan, Andreas Heinz, Tobias Banaschewski, Amirhossein Modabbernia, Jilly Naaijen, Yang Wang, Sophia Frangou, Henry Brodaty, Henk Temmingh, Greig I. de Zubicaray, Nancy C. Andreasen, Carles Soriano-Mas, Neeltje E.M. van Haren, Brenna C. McDonald, Ruben C. Gur, Micael Andersson, Dorret I. Boomsma, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Víctor Ortiz-García de la Foz, Anton Albajes-Eizagirre, David C. Glahn, Alan Breier, Heather C. Whalley, Jordan W. Smoller, Joaquim Radua, Christian K. Tamnes, Eveline A. Crone, Philip Asherson, John A. Joska, Wei Wen, Jonna Kuntsi, Lars Nyberg, Thomas H. Wassink, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Annette Conzelmann, Sarah Hohmann, and Laura Koenders
Subjects: 0303 health sciences, medicine.medical_specialty, Fractional polynomial, Cognition, Audiology, Biology, Regression, Pooling data, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging genetics, Healthy individuals, medicine, General pattern, Analysis of variance, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Delineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 individuals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-individual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life; thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-individual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results reconcile uncertainties about age-related trajectories of cortical thickness; the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.
Published: 2020

18. Subcortical Volume Trajectories across the Lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Lara M. Wierenga, Iris E. C. Sommer, Edith Pomarol-Clotet, Erick J. Canales-Rodríguez, van Erp Tg, Lars T. Westlye, van Haren Ne, Francisco X. Castellanos, P. G. P. Rosa, Kang S, van der Wee Nj, Joaquim Radua, Jim Lagopoulos, José M. Menchón, Helena Fatouros-Bergman, Jan K. Buitelaar, Bernd Weber, Annette Conzelmann, Núria Bargalló, S. E. Medland, Maria J. Portella, Patricia J. Conrod, Amanda Worker, Klaus-Peter Lesch, Jonna Kuntsi, S.G. Potkin, R. Salvador, Knut Schnell, Stefan Borgwardt, Katharina Wittfeld, Kathryn I. Alpert, Dick J. Veltman, de Geus Ej, Ole A. Andreassen, Sophia Frangou, Di Giorgio A, Avram J. Holmes, Rachel M. Brouwer, Thomas Frodl, Lachlan T. Strike, Anton Albajes-Eizagirre, Giulio Pergola, van den Heuvel Oa, Perminder S. Sachdev, Esther Walton, Josiane Bourque, Dag Alnæs, David C. Glahn, Ramona Baur-Streubel, Laura Koenders, Christian K. Tamnes, Alan Breier, Jordan W. Smoller, Yulyia Yoncheva, Marise W. J. Machielsen, Sarah Hohmann, Magnus Andersson, Paola Fuentes-Claramonte, David Mataix-Cols, Salvador Sarró, Stefan Ehrlich, John A. Joska, Marieke Klein, Mauricio H. Serpa, den Braber A, Henry Völzke, Jilly Naaijen, de Haan L, Thomas H. Wassink, Daniel H. Wolf, Thomas Espeseth, Yang Wang, Henrik Walter, Wei Wen, Calhoun, Dan J. Stein, Simon E. Fisher, Eveline A. Crone, Ingrid Agartz, Susanne Erk, Oliver Grimm, Andrew M. McIntosh, Dominik Grotegerd, Henry Brodaty, Katie L. McMahon, Jaap Oosterlaan, Danai Dima, Aurora Bonvino, Anders M. Dale, Alexander Tomyshev, Ignacio Martínez-Zalacaín, Anthony A. James, Andrew J. Kalnin, Barbara Franke, Theophilus N. Akudjedu, Andreas Reif, Pieter J. Hoekstra, Nordvik Je, Lars Nyberg, Bernard Mazoyer, Paul M. Thompson, Andrew J. Saykin, Genevieve McPhilemy, Nhat Trung Doan, Geraldo F. Busatto, Colm McDonald, van ’t Ent D, Sophia I. Thomopoulos, Derrek P. Hibar, Neda Jahanshad, Norbert Hosten, Ryota Kanai, Ruben C. Gur, D.I. Boomsma, Lianne Schmaal, Jean-Paul Fouche, Anne Uhlmann, Jessica A. Turner, Fabrice Crivello, P. Asherson, de la Foz Vo, Heather C. Whalley, C.A. Hartman, Ching Cr, Dirk J. Heslenfeld, Jiyang Jiang, Pascual Sánchez-Juan, Andreas Heinz, Simon Cervenka, Irina V. Lebedeva, Nancy C. Andreasen, Erik G. Jönsson, Oliver Gruber, Ben J. Harrison, Tiffany M. Chaim-Avancini, Sophie Maingault, Efstathios Papachristou, Beng-Choon Ho, Marcus V. Zanetti, Doucet Ge, Nynke A. Groenewold, Sacchet, Andreas Meyer-Lindenberg, Bernhard K. Krämer, M. Aghajani, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lu Wang, Pablo Najt, van den Meer D, Christopher G. Davey, Theodore D. Satterthwaite, René S. Kahn, Margaret J. Wright, N. G. Martin, G. Schumann, Tobias Banaschewski, Amirhossein Modabbernia, Benedicto Crespo-Facorro, Ian B. Hickie, Alessandro Bertolino, Sanne Koops, Sean N. Hatton, Georg C. Ziegler, Carles Soriano-Mas, Kun Yang, Brenna C. McDonald, Sarah Baumeister, Scr Williams, Julian N. Trollor, Paul Pauli, Joshua L. Roffman, Xavier Caseras, Won Hee Lee, Henk Temmingh, Rachel E. Gur, Randy L. Buckner, Vincent P. Clark, Daniel Brandeis, Ian H. Gotlib, Hulshoff Pol He, Hans-Jörgen Grabe, Fleur M. Howells, Christine Lochner, Yannis Paloyelis, Erlend S. Dørum, Suzanne C. Swagerman, Patricia Gruner, Dara M. Cannon, Tomohiro Nakao, Tatyana P Klushnik, Ilya M. Veer, de Zubicaray Gi, Chaim Huyser, John D. West, Luisa Lázaro, and Erin W. Dickie
Subjects: 0303 health sciences, Putamen, Thalamus, Brain morphometry, Hippocampus, Nucleus accumbens, Biology, 03 medical and health sciences, Lateral ventricles, 0302 clinical medicine, nervous system, Brain size, Basal ganglia, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalised on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine the age-related morphometric trajectories of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum early in life; the volume of the basal ganglia showed a gradual monotonic decline thereafter while the volumes of the thalamus, amygdala and the hippocampus remained largely stable (with some degree of decline in thalamus) until the sixth decade of life followed by a steep decline thereafter. The lateral ventricles showed a trajectory of continuous enlargement throughout the lifespan. Significant age-related increase in inter-individual variability was found for the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to derive risk predictions for the early identification of diverse clinical phenotypes.
Published: 2020

19. Age-dependent genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: Philip R. Jansen, Erlend Bøen, Erin Burke Quinlan, Javier Vázquez-Bourgon, Celso Arango, Sonja M C de Zwarte, Andrea Parolin Jackowski, Mohammad Arfan Ikram, Dennis van der Meer, Clara Alloza, Matthew S. Panizzon, Ryan L. Muetzel, Vidar M. Steen, Lars T. Westlye, Joanna Bright, Walter Heindel, Marcella Rietschel, Wei Wen, Frauke Nees, Daniel Keeser, Sintia Iole Belangero, Philip Shaw, Tiago Reis Marques, Neda Jahanshad, Jiyang Jiang, Benedicto Crespo Facorro, Tilo Kircher, David Ames, Dan J. Stein, Ulrik Fredrik Malt, Axel Krug, Kang Sim, Gaia Bonfiglio, Nhat Trung Doan, Katrin Amunts, John B.J. Kwok, Pedro Mario Pan, Udo Dannlowski, Markus M. Nöthen, Elena Shumskaya, Simon R. Cox, Sarah J. Heany, Perminder S. Sachdev, Aad van der Lugt, Mark E. Bastin, Brenda W.J.H. Penninx, Catherine Morgan, Elizabeth E.L. Buimer, Henrik Walter, Dara M. Cannon, Hugo G. Schnack, Sarah Hohmann, Evangelos Vassos, Shun Takahashi, Gloria Roberts, Simone Ciufolini, Loes M. Olde Loohuis, Penny A. Gowland, Joost Janssen, Michael N. Smolka, Temmuz Karali, Robin M. Murray, Herve Lemaitre, Karen A. Mather, Dennis van 't Ent, Derek W. Morris, William S. Kremen, Peter Falkai, Berend Malchow, Tim Hahn, Dag Alnæs, Ronny Redlich, Ingrid Agartz, Fabian Streit, João P.O.F.T. Guimarães, Nils Opel, Bernhard T. Baune, Marie-Laure Paillère Martinot, Catharina A. Hartman, Alexander Teumer, Frederike Stein, André Zugman, Nikita Setiaman, Jalmar Teeuw, Isabella A. Breukelaar, Vicente Medel, Stephanie H. Witt, Christienne G. Damatac, Nicolas Crossley, Luise Poustka, Hieab H.H. Adams, Linda Ding, Jonathan Repple, Jacqueline Hoare, Eric Artiges, Manon H.J. Hillegers, Andreas Heinz, Susanne Meinert, Tianye Jia, Diana Tordesillas-Gutiérrez, Marieke Klein, Herta Flor, Joanna M. Wardlaw, Roel A. Ophoff, Rodrigo A. Bressan, Antoine Grigis, Marcos L. Santoro, Javier González-Peñas, Thomas Espeseth, Torbjørn Elvsåshagen, Kristel R. van Eijk, Hilleke E. Hulshoff Pol, Sophia I. Thomopoulos, Gustavo Sudre, Juliane H. Fröhner, Rhoshel K. Lenroot, Bernd Ittermann, René S. Kahn, Gareth J. Barker, Wiepke Cahn, Yuri Milaneschi, Margaret J. Wright, Janita Bralten, Gail Davies, Elisabet Blok, Janice M. Fullerton, Jouke-Jan Hottenga, Paola Dazzan, Andreas J. Forstner, Leila Nabulsi, Christopher D. Whelan, Katharina Wittfeld, Mathew A. Harris, Julian N. Trollor, Mayuresh S. Korgaonkar, Igor Nenadic, Nitin Gogtay, Laura K.M. Han, Robin Bülow, Moji Aghajani, Leonard H. van den Berg, Marta Di Forti, Bronwyn Overs, Paul M. Thompson, Rick M. Tankard, Sven Cichon, Jason L. Stein, Jaap Oosterlaan, Jan K. Buitelaar, Jean-Luc Martinot, René C.W. Mandl, Victor Ortiz-García de la Foz, Robert Whelan, Svenja Caspers, Rosa Ayesa-Arriola, Sylvane Desrivières, Covadonga M. Díaz-Caneja, Ole A. Andreassen, Gunter Schumann, Arun L.W. Bokde, Alyssa H. Zhu, Henk-Jan Westeneng, Emma Sprooten, Sergi Papiol, Giovanni Abrahão Salum, Neeltje E.M. van Haren, Simon E. Fisher, Dominik Grotegerd, Casper L. de Mol, Alzheimer’s Disease Neuroimaging Initiative, Dorret I. Boomsma, Gennady V. Roshchupkin, Pieter J. Hoekstra, Andreas Jansen, Peter R. Schofield, Tonya White, Maria J. Knol, Rachel M. Brouwer, Martijn G.J.C. Koevoets, Thomas W. Mühleisen, Katharina Dohm, Barbara Franke, Philip B. Mitchell, Colm McDonald, Anbupalam Thalamuthu, Henry Brodaty, Gary Donohoe, Stephanie Le Hellard, Shareefa Dalvie, Georg Homuth, Jan H. Veldink, Nicola J. Armstrong, Christiane Jockwitz, Sarah E. Medland, Katrina L. Grasby, Tobias Banaschewski, Hans J. Grabe, Hugh Garavan, Dirk J. Heslenfeld, Erik G. Jönsson, Carol E. Franz, and Janik Goltermann
Subjects: 2. Zero hunger, Apolipoprotein E, 0303 health sciences, Brain morphometry, Human brain, Biology, medicine.disease, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Atrophy, Schizophrenia, Ageing, medicine, Cognitive skill, Neuroscience, 030217 neurology & neurosurgery, Depression (differential diagnoses), 030304 developmental biology
Abstract: SummaryHuman brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. Here, we identified common genetic variants that affect rates of brain growth or atrophy, in the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal MRI data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genesGPR139, DACH1andAPOEare associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene-set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and ageing.
Published: 2020

20. Polygenic Architecture of Human Neuroanatomical Diversity

Author: Matthias Nauck, Maria del C. Valdés Hernández, Susana Muñoz Maniega, Natalie A. Royle, Benjamin S. Aribisala, Katharina Wittfeld, Ian J. Deary, Nicolas Traut, Saskia P. Hagenaars, Joanna M. Wardlaw, Hidenaga Yamamori, Uwe Völker, Thomas Bourgeron, Ryota Hashimoto, Alexander Teumer, Masataka Kikuchi, Roberto Toro, Anne Biton, Mark E. Bastin, Simon R. Cox, Robin Bülow, Hans J. Grabe, Alzheimer’s Disease Neuroimaging Initiative, Jean-Baptiste Poline, Masaki Fukunaga, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Lagos State University (LASU), Brain Research Imaging Center (BRIC), University of Medicine Greifswald, National Institute for Physiological Sciences, Graduate University for Advanced Studies [Hayama] (SOKENDAI), Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, National Center of Neurology and Psychiatry [Tokyo, Japan], Graduate School of Medicine [Osaka], Osaka University [Osaka], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Institute of Clinical Chemistry and Laboratory Medicine, Universität Greifswald - University of Greifswald, Institute for Community Medicine, University Medicine Greifswald, Greifswald, Interfaculty Institute of Genetics and Functional Genomics, Centre de Recherches Interdisciplinaires [Paris] (CRI), Institut Pasteur, Center for Research and Interdisciplinarity, Centre National de la Recherche Scientifique, the University Paris Diderot, the Fondation pour la Recherche Médicale [DBI20141231310], the European Commission Horizon 2020 [COSYN], The Human Brain Project, the European Commission Innovative Medicines Initiative [AIMS2-TRIALS, No. 777394], the Cognacq-Jay foundation, the Bettencourt-Schueller foundation, the Orange foundation, the FondaMental foundation, the Conny-Maeva foundation, and the Agence Nationale de la Recherche (ANR) [SynPathy], the Laboratory of Excellence GENMED (Medical Genomics) (grant no. ANR-10-LABX-0013, Bio-Psy, by the INCEPTION program ANR-16-CONV-0005, managed by the ANR part of the Investment for the Future program).NIH-NIBIB P41 EB019936 (ReproNim) NIH-NIMH R01 MH083320 (CANDIShare) and NIH 5 U24 DA039832 (NIF), as well as the Canada First Research Excellence Fund, awarded to McGill University for the Healthy Brains for Healthy Lives initiative (to J.-B.P.).The Study of Health in Pomerania (SHIP) is part of the Community Medicine Research net (http://www.medizin.uni-greifswald.de/icm) of the University Medicine Greifswald, which is supported by the German Federal State of Mecklenburg-West Pomerania. MRI scans in SHIP and SHIP-TREND have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany, and the Federal State of Mecklenburg-West Pomerania. This study was further supported by the EU-JPND Funding for BRIDGET (FKZ:01ED1615)., Alzheimer’s Disease Neuroimaging Initiative - Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu).Assuch, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysisor writing of this report. A complete listing of ADNI investigators can be found at:http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf, ANR-15-NEUR-0007,SynPathy,Key Determinants of Synaptic Excitation-Inhibition Imbalance in Autism Spectrum Disorders - From Genetic Animal Models to Human Patients(2015), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 667301,H2020,H2020-PHC-2015-two-stage,COSYN(2016), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: trends [Magnetic Resonance Imaging], Cognitive Neuroscience, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Single-nucleotide polymorphism, Biology, heritability, Genome, Genetic correlation, Correlation, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, polygenic architecture, Pleiotropy, Genetic variation, subcortical structures, Humans, SNP, genetics, ddc:610, Gene, diagnostic imaging [Brain], genetics [Multifactorial Inheritance], 030304 developmental biology, 0303 health sciences, neuroimaging, Chromosome, trends [Genome-Wide Association Study], Replicate, Heritability, genetics [Genetic Variation], Minor allele frequency, Evolutionary biology, Brain size, genetics [Polymorphism, Single Nucleotide], Gene-Environment Interaction, 030217 neurology & neurosurgery
Abstract: We analysed the genomic architecture of neuroanatomical diversity using magnetic resonance imaging and single nucleotide polymorphism (SNP) data from >26,000 individuals from the UK Biobank project and 5 other projects that had previously participated in the ENIGMA consortium. Our results confirm the polygenic architecture of neuroanatomical diversity, with SNPs capturing from 40% to 54% of regional brain volume variance. Chromosomal length correlated with the amount of phenotypic variance captured, r∼0.64 on average, suggesting that at a global scale causal variants are homogeneously distributed across the genome. At a local scale, SNPs within genes (∼51%) captured ∼1.5 times more genetic variance than the rest; and SNPs with low minor allele frequency (MAF) captured less variance than the rest: the 40% of SNPs with MAFG∼0.45. Genetic correlations were similar to phenotypic and environmental correlations, however, genetic correlations were often larger than phenotypic correlations for the left/right volumes of the same region. The heritability of differences in left/right volumes was generally not statistically significant, suggesting an important influence of environmental causes in the variability of brain asymmetry. Our code is available at https://github.com/neuroanatomy/genomic-architecture.
Published: 2020

21. Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: Mega-analytic findings from a large multi-site cohort

Author: Hans J. Grabe, Brenda W.J.H. Penninx, Olaf Steinsträter, Tilo Kircher, Nic J.A. van der Wee, James H. Cole, Kaja Z. LeWinn, Carsten Konrad, Samantha J. Brooks, Paul M. Thompson, Henrik Walter, Dominik Grotegerd, Deborah Janowitz, Henry Völzke, Tim Hahn, Tony T. Yang, Bartosz Zurowski, Bernhard T. Baune, D. Schoepf, Henrik Dobrowolny, Cynthia H.Y. Fu, Ronny Redlich, Robin Bülow, Thomas Frodl, Neda Jahanshad, Jim Lagopoulos, Nynke A. Groenewold, Katharina Wittfeld, Sean N. Hatton, Derrek P. Hibar, Elisabeth Schramm, Axel Krug, Dick J. Veltman, Johanna Klinger-König, Lisa Garczarek, Nils Opel, Igor Nenadic, Dan J. Stein, Leonardo Tozzi, Alan N. Simmons, Daniella Vuletic, Tiffany C. Ho, Lauren E. Salminen, Dario Zaremba, Colm G. Connolly, Meng Li, Angela Carballedo, Lianne Schmaal, Anne Uhlmann, Marie-José van Tol, Knut Schnell, Harald Kugel, Ian B. Hickie, Danai Dima, Udo Dannlowski, Theo G.M. van Erp, Ilya M. Veer, Dilara Jüksel, Martin Walter, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Anatomy and neurosciences, and APH - Digital Health
Subjects: Child abuse, Male, DISORDER, ‘for the ENIGMA-MDD Consortium’, Precuneus, NEURAL DEVELOPMENT DEPRIVATION, Audiology, MATTER VOLUME, Cohort Studies, 0302 clinical medicine, Supramarginal gyrus, Parietal Lobe, 80 and over, 2.1 Biological and endogenous factors, Psychology, Child Abuse, Aetiology, Prefrontal cortex, Child, Applied Psychology, Default mode network, ASSOCIATIONS, Aged, 80 and over, Cerebral Cortex, Violence Research, Pediatric, Psychiatry, 0303 health sciences, pathology [Depressive Disorder, Major], Depression, MEDIAL PREFRONTAL CORTEX, ABNORMALITIES, Parietal lobe, Age Factors, ENIGMA, pathology [Parietal Lobe], Superior temporal sulcus, Middle Aged, EMOTION REGULATION, Magnetic Resonance Imaging, Temporal Lobe, Psychiatry and Mental health, medicine.anatomical_structure, Mental Health, pathology [Gyrus Cinguli], Public Health and Health Services, Female, CA3 PYRAMIDAL NEURONS, Adult, medicine.medical_specialty, DIMENSIONS, Adolescent, BF, Prefrontal Cortex, Child Abuse and Neglect Research, Gyrus Cinguli, Temporal lobe, 03 medical and health sciences, Young Adult, Childhood maltreatment, Clinical Research, Behavioral and Social Science, medicine, Humans, ddc:610, 030304 developmental biology, Aged, Depressive Disorder, Major, Depressive Disorder, major depressive disorder, Neurosciences, Major, pathology [Temporal Lobe], cortical thickness, Brain Cortical Thickness, pathology [Prefrontal Cortex], Brain Disorders, Case-Control Studies, RC0321, MORPHOLOGY, pathology [Cerebral Cortex], 030217 neurology & neurosurgery
Abstract: BackgroundChildhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.MethodsWithin the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.ResultsCM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.ConclusionsSeverity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Published: 2020

22. Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia

Author: Simone Ciufolini, Anja Vaskinn, Nhat Trung Doan, John B.J. Kwok, Derrek P. Hibar, Carlos Prieto, Elena Shumskaya, Jarek Rokicki, Omar Gustafsson, Sanjay M. Sisodiya, Gianpiero L. Cavalleri, Andreas Heinz, Asta Håberg, Lianne Schmaal, David Ames, Benedicto Crespo-Facorro, Robin M. Murray, Evangelos Vassos, Anne Uhlmann, Aiden Corvin, Nynke A. Groenewold, Astri J. Lundervold, Christopher D. Whelan, Ingrid Agartz, Céline S. Reinbold, Juan M. Peralta, Allan F. McRae, Hilleke E Hulshoff, Jean Shin, Alexander Teumer, Nicholas G. Martin, Geneviève Richard, Jan Egil Nordvik, Sébastien Jacquemont, Gunter Schumann, Emma Knowles, Ida E Sønderby, Alexandre Reymond, Barbara Franke, Simon E. Fisher, Erin Burke Quinlan, Andrew J. Schork, Borja Rodriguez-Herreros, Hreinn Stefansson, Stefan Ehrlich, Anouk den Braber, David C. Glahn, Jayne Y. Hehir-Kwa, Nicholas B. Blackburn, Jan Haavik, Per Hoffmann, Dennis van der Meer, G. Bragi Walters, Dan J. Stein, Costin Leu, Dorret I. Boomsma, Tobias Kaufmann, Vince D. Calhoun, Robin Bülow, Yunpeng Wang, Sonja M C de Zwarte, Sven Cichon, Samuel R. Mathias, Daniel Quintana, Tiago Reis Marques, Vidar M. Steen, Dennis van 't Ent, Torill Ueland, Hans-Richard Brattbak, Hidenaga Yamamori, Katrin Amunts, Katharina Wittfeld, Thomas Gareau, Arvid Lundervold, Margie Wright, Anbu Thalamuthu, Stefan Johansson, Vincent Frouin, Anders M. Dale, Brenda W.J.H. Penninx, Derek W. Morris, Rachel M. Brouwer, Norman Delanty, John Blangero, Roberto Roiz-Santiañez, Anne-Marthe Sanders, Sigrid Botne Sando, Magnus O. Ulfarsson, Perminder S. Sachdev, Laurena Holleran, Thomas W. Mühleisen, Jouke-Jan Hottenga, Paola Dazzan, Kari Stefansson, Roel A. Ophoff, Peter R. Schofield, Manon Bernard, Gudrun A. Jonsdottir, Wei Wen, Joanne E. Curran, Bogdan Draganski, Karen A. Mather, Ryota Hashimoto, René S. Kahn, Yuri Milaneschi, Mark McCormack, Masataka Kikuchi, Hans J. Grabe, Zdenka Pausova, Sinead Kelly, Stephanie Le Hellard, Shareefa Dalvie, Nicola J. Armstrong, Stacy Steinberg, Christiane Jockwitz, Thomas Espeseth, Janita Bralten, Katie L. McMahon, Srdjan Djurovic, David Mothersill, Lachlan T. Strike, Knut K. Kolskår, Chi-Hua Chen, Jessica A. Turner, Manon H.J. Hillegers, Paul M. Thompson, Eco J. C. de Geus, Henry Brodaty, Gary Donohoe, Greig I. de Zubicaray, Jingyu Liu, Sara Pudas, Bruce Pike, Terry L. Jernigan, Masaki Fukunaga, Clara Moreau, Abdel Abdellaoui, Erik G. Jönsson, Svenja Caspers, Sylvane Desrivières, Ole A. Andreassen, Masashi Ikeda, Sandra Martin-Brevet, Michael Andersson, Neda Jahanshad, Diana Tordesillas-Gutiérrez, Lars T. Westlye, Loes M. Olde Loohuis, Tetyana Zayats, Neeltje E.M. van Haren, Lars Nyberg, James Rucker, and Tomáš Paus
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, DNA Copy Number Variations, Databases, Factual, Autism Spectrum Disorder, Chromosome Disorders, Globus Pallidus, Basal Ganglia, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Intracranial volume, Intellectual Disability, Chromosome Duplication, Image Processing, Computer-Assisted, Medicine, Humans, ddc:610, Copy-number variation, Autistic Disorder, Molecular Biology, business.industry, Published Erratum, Putamen, Correction, Brain, Organ Size, Middle Aged, Magnetic Resonance Imaging, Data set, Psychiatry and Mental health, 030104 developmental biology, Neurodevelopmental Disorders, Schizophrenia, Female, Radiology, Chromosome Deletion, business, 030217 neurology & neurosurgery, Chromosomes, Human, Pair 16
Abstract: Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10
Published: 2020

23. A Biomarker for Alzheimer’s Disease Based on Patterns of Regional Brain Atrophy

Author: Katharina Wittfeld, Henry Völzke, Hans J. Grabe, Stefan Frenzel, Johanna Klinger-König, Robin Bülow, and Mohamad Habes
Subjects: medicine.medical_specialty, lcsh:RC435-571, FreeSurfer, 03 medical and health sciences, 0302 clinical medicine, Atrophy, Neuroimaging, lcsh:Psychiatry, Internal medicine, medicine, magnetic resonance imaging, Dementia, ddc:610, Original Research, Psychiatry, medicine.diagnostic_test, Recall, business.industry, Magnetic resonance imaging, Alzheimer's disease, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, machine learning, Study of Health in Pomerania, Biomarker (medicine), Verbal memory, business, 030217 neurology & neurosurgery, dementia
Abstract: Introduction: It has been shown that Alzheimer's disease (AD) is accompanied by marked structural brain changes that can be detected several years before clinical diagnosis via structural magnetic resonance (MR) imaging. In this study, we developed a structural MR-based biomarker for in vivo detection of AD using a supervised machine learning approach. Based on an individual's pattern of brain atrophy a continuous AD score is assigned which measures the similarity with brain atrophy patterns seen in clinical cases of AD. Methods: The underlying statistical model was trained with MR scans of patients and healthy controls from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1 screening). Validation was performed within ADNI-1 and in an independent patient sample from the Open Access Series of Imaging Studies (OASIS-1). In addition, our analyses included data from a large general population sample of the Study of Health in Pomerania (SHIP-Trend). Results: Based on the proposed AD score we were able to differentiate patients from healthy controls in ADNI-1 and OASIS-1 with an accuracy of 89% (AUC = 95%) and 87% (AUC = 93%), respectively. Moreover, we found the AD score to be significantly associated with cognitive functioning as assessed by the Mini-Mental State Examination in the OASIS-1 sample after correcting for diagnosis, age, sex, age·sex, and total intracranial volume (Cohen's f2 = 0.13). Additional analyses showed that the prediction accuracy of AD status based on both the AD score and the MMSE score is significantly higher than when using just one of them. In SHIP-Trend we found the AD score to be weakly but significantly associated with a test of verbal memory consisting of an immediate and a delayed word list recall (again after correcting for age, sex, age·sex, and total intracranial volume, Cohen's f2 = 0.009). This association was mainly driven by the immediate recall performance. Discussion: In summary, our proposed biomarker well differentiated between patients and healthy controls in an independent test sample. It was associated with measures of cognitive functioning both in a patient sample and a general population sample. Our approach might be useful for defining robust MR-based biomarkers for other neurodegenerative diseases, too.
Published: 2020

24. ENIGMA MDD: seven years of global neuroimaging studies of major depression through worldwide data sharing

Author: Thomas Frodl, Kathryn R. Cullen, Liliana Capitão, Ben J. Harrison, Dan J. Stein, Meng Li, Tessa F. Blanken, Carlos A. Zarate, Klaus Berger, Matthew D. Sacchet, Axel Krug, Kang Sim, Baptiste Couvy-Duchesne, Tilo Kircher, Lybomir Aftanas, Brenda W.J.H. Penninx, Sophia I. Thomopoulos, Henrik Walter, Sean N. Hatton, Liesbeth Reneman, André Aleman, Paul M. Thompson, Christopher G. Davey, Bonnie Klimes-Dougan, David M. A. Mehler, Cynthia H.Y. Fu, Dick J. Veltman, Anouk Schrantee, Tracy Erwin-Grabner, Dominik Grotegerd, Udo Dannlowski, Igor Nenadic, Ian H. Gotlib, Leonardo Tozzi, Frank P. MacMaster, Benson Irungu, Nils Inge Landrø, Sarah Whittle, Sinead Kelly, Jair C. Soares, Neda Jahanshad, Hans J. Grabe, Martin Walter, Beata R. Godlewska, Nic J.A. van der Wee, Rune Jonassen, Andrew M. McIntosh, Jennifer W. Evans, Nynke A. Groenewold, Tony T. Yang, Jeanne Leerssen, Margaret J. Wright, Lianne Schmaal, Philipp G. Sämann, Elena Pozzi, David Edmund Johannes Linden, Ilya M. Veer, Marco Hermesdorf, Roberto Goya-Maldonado, Boris A. Gutman, Tiffany C. Ho, Marie-José van Tol, Ian B. Hickie, Oliver Gruber, Eus J.W. Van Someren, Heather C. Whalley, Nils Opel, Laura S van Velzen, Laura K.M. Han, Maria J. Portella, Yolanda Vives-Gilabert, Jim Lagopoulos, Geoffrey B. Hall, Katharina Wittfeld, Bernhard T. Baune, Miguel E. Rentería, Robert Vermeiren, Eva Hilland, and Netherlands Institute for Neuroscience (NIN)
Subjects: PsyArXiv|Neuroscience|Clinical Neuroscience, MEDLINE, Neuroimaging, Disease, Review Article, Affect (psychology), diagnostic imaging [Depressive Disorder, Major], behavioral disciplines and activities, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, bepress|Life Sciences|Neuroscience and Neurobiology, 0302 clinical medicine, SDG 17 - Partnerships for the Goals, mental disorders, medicine, bepress|Medicine and Health Sciences|Medical Specialties|Psychiatry, Humans, ddc:610, diagnostic imaging [Brain], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Depression (differential diagnoses), Psychiatry, Depressive Disorder, Major, business.industry, Information Dissemination, Depression, Brain, Brain alterations, Major depressive disorders, medicine.disease, Mental health, 030227 psychiatry, 3. Good health, Data sharing, Psychiatry and Mental health, PsyArXiv|Neuroscience, Study cohorts, PsyArXiv|Psychiatry, Major depressive disorder, business, 030217 neurology & neurosurgery, Clinical psychology, Neuroscience
Abstract: A key objective in the field of translational psychiatry over the past few decades has been to identify the brain correlates of major depressive disorder (MDD). Identifying measurable indicators of brain processes associated with MDD could facilitate the detection of individuals at risk, and the development of novel treatments, the monitoring of treatment effects, and predicting who might benefit most from treatments that target specific brain mechanisms. However, despite intensive neuroimaging research towards this effort, underpowered studies and a lack of reproducible findings have hindered progress. Here, we discuss the work of the ENIGMA Major Depressive Disorder (MDD) Consortium, which was established to address issues of poor replication, unreliable results, and overestimation of effect sizes in previous studies. The ENIGMA MDD Consortium currently includes data from 45 MDD study cohorts from 14 countries across six continents. The primary aim of ENIGMA MDD is to identify structural and functional brain alterations associated with MDD that can be reliably detected and replicated across cohorts worldwide. A secondary goal is to investigate how demographic, genetic, clinical, psychological, and environmental factors affect these associations. In this review, we summarize findings of the ENIGMA MDD disease working group to date and discuss future directions. We also highlight the challenges and benefits of large-scale data sharing for mental health research. ENIGMA MDD work is supported by NIH grants U54 EB020403 (Thompson), R01 MH116147 (Thompson), and R01 MH117601 (Jahanshad & Schmaal). LS was supported by an NHMRC Career Development Fellowship (1140764). AFFDIS cohort: this study was funded by the University Medical Center Goettingen (UMG Startfoerderung) and the research team is supported by German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung, BMBF: 01 ZX 1507, “PreNeSt - e:Med”). Barcelona cohort: MJP is funded by the Ministerio de Ciencia e Innovación of the Spanish Government and by the Instituto de Salud Carlos III through a ‘Miguel Servet’ research contract (CP16–0020); National Research Plan (Plan Estatal de I + D + I 2016–2019); and co-financed by the European Regional Development Fund (ERDF). BRC DeCC cohort: CHYF is supported by NIHR BRC. Calgary cohort: supported by Canadian Institutes for Health Research, Branch Out Neurological Foundation. Cardiff cohort: supported by the Medical Research Council (grant G 1100629) and the National Center for Mental Health (NCMH), funded by Health Research Wales (HS/14/20). CLING cohort: this study was partially supported by the Deutsche Forschungsgemeinschaft (DFG) via grants to OG (GR1950/5–1 and GR1950/10–1). CODE cohort: Henrik Walter is supported by a grant of the Deutsche Forschungsgemeinschaft (WA 1539/4–1). The CODE cohort was collected from studies funded by Lundbeck and the German Research Foundation (WA 1539/4–1, SCHN 1205/3–1, SCHR443/11–1). DIP-Groningen cohort: this study was supported by the Gratama Foundation, the Netherlands (2012/35 to NG). Edinburgh cohort: The research leading to these results was supported by IMAGEMEND, which received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 602450. This paper reflects only the author’s views and the European Union is not liable for any use that may be made of the information contained therein. This work was also supported by a Wellcome Trust Strategic Award 104036/Z/14/Z. FOR2107-Marburg cohort: funded by the German Research Foundation (DFG, grant FOR2107 KR 3822/7–2 to AK; FOR2107 KI 588/14–2 to TK and FOR2107 JA 1890/7–2 to AJ). Houston cohorts: supported in part by NIMH grant R01 085667 and the Dunn Research Foundation. JCS is supported by the Pat Rutherford, Jr. Endowed Chair in Psychiatry. IMH Study cohort: supported by funding from NHG (SIG/15012) and NMRC CISSP (2018). Melbourne cohort: funded by National Health and Medical Research Council of Australia (NHMRC) Project Grants 1064643 (Principal Investigator BJH) and 1024570 (Principal Investigator CGD). Minnesota cohort: the study was funded by the National Institute of Mental Health (K23MH090421; Dr. Cullen) and Biotechnology Research Center (P41 RR008079; Center for Magnetic Resonance Research), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, and the Minnesota Medical Foundation. This work was carried out in part using computing resources at the University of Minnesota Supercomputing Institute. Münster cohort: funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5–1 and DA1151/5–2 to UD; SFB-TRR58, Projects C09 and Z02 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD). NESDA cohort: The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (Zon-Mw, grant number 10–000–1002) and is supported by participating universities (VU University Medical Center, GGZ inGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen) and mental health care organizations, see www.nesda.nl. Pharmo cohort: supported by ERA-NET PRIOMEDCHILD FP 6 (EU) grant 11.32050.26. PSYABM-NORMENT: supported by the Research Council of Norway (project number 229135). The South East Norway Health Authority Research Funding (project number 2015052). The Department of Psychology, University of Oslo, Norway. San Francisco cohort: supported by NIH/NCCIH 1R61AT009864–01A1. NIMH R01MH085734. SHIP and SHIP-trend cohorts: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. MRI scans in SHIP and SHIP-TREND have been supported by a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. Stanford cohorts: this work was supported by NIH grant R37 MH101495. The BiDirect Study was supported by grants from the German Federal Ministry of Education and Research (BMBF; grants FKZ-01ER0816 and FKZ-01ER1506). MDS is partially supported by an award funded by the Phyllis and Jerome Lyle Rappaport Foundation. TCH is supported by NIMH grant 5K01MH117442. EJWVS, JL, and TFB are supported by European Research Council grant no. ERC-ADG-2014–671084 INSOMNIA. TFB is supported by a VU University Amsterdam University Research Fellowship 2016–2017. JL is supported by a VU University Amsterdam University Research Fellowship 2017–2018.
Published: 2020

25. Corticosteroids and Regional Variations in Thickness of the Human Cerebral Cortex across the Lifespan

Author: Leon French, Nadine Parker, Bernard Mazoyer, Anders M. Fjell, Henry Völzke, Reinhold Schmidt, Ian J. Deary, Perminder S. Sachdev, Aniket Mishra, Jean Shin, Kristine B. Walhovd, Norbert Hosten, Katharina Wittfeld, Qiong Yang, Gunter Schumann, Stéphanie Debette, Sudha Seshadri, Tomáš Paus, Claudia L. Satizabal, Simon R. Cox, Maria J. Knol, Hans J. Grabe, Jiyang Jiang, Hieab H.H. Adams, Henry Brodaty, Helena Schmidt, Stefan Frenzel, Zdenka Pausova, Giovanni Abrahão Salum, Wei Wen, Didac Vidal-Piñeiro, Mohammad Arfan Ikram, Epidemiology, Radiology & Nuclear Medicine, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Rotman Research Institute at the Baycrest Centre (RRI), Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Metacohorts Consortium, Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Institute for Community Medicine, Universität Greifswald - University of Greifswald, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), and University of Washington [Seattle]
Subjects: Male, Aging, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gene Expression, 0302 clinical medicine, Glucocorticoid receptor, metabolism [Receptors, Mineralocorticoid], Gene expression, Child, metabolism [Receptors, Glucocorticoid], Aged, 80 and over, Cerebral Cortex, 0303 health sciences, Microglia, Human brain, Middle Aged, physiology [Aging], medicine.anatomical_structure, VINTAGE, Cerebral cortex, Child, Preschool, anatomy & histology [Cerebral Cortex], Corticosteroid, Female, Original Article, Glucocorticoid, medicine.drug, Adult, medicine.medical_specialty, Adolescent, medicine.drug_class, Cognitive Neuroscience, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Receptors, Glucocorticoid, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, ddc:610, Gene, 030304 developmental biology, Aged, metabolism [Cerebral Cortex], Endocrinology, Receptors, Mineralocorticoid, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 030217 neurology & neurosurgery
Abstract: Exposures to life stressors accumulate across the lifespan, with possible impact on brain health. Little is known, however, about the mechanisms mediating age-related changes in brain structure. We use a lifespan sample of participants (n = 21 251; 4–97 years) to investigate the relationship between the thickness of cerebral cortex and the expression of the glucocorticoid- and the mineralocorticoid-receptor genes (NR3C1 and NR3C2, respectively), obtained from the Allen Human Brain Atlas. In all participants, cortical thickness correlated negatively with the expression of both NR3C1 and NR3C2 across 34 cortical regions. The magnitude of this correlation varied across the lifespan. From childhood through early adulthood, the profile similarity (between NR3C1/NR3C2 expression and thickness) increased with age. Conversely, both profile similarities decreased with age in late life. These variations do not reflect age-related changes in NR3C1 and NR3C2 expression, as observed in 5 databases of gene expression in the human cerebral cortex (502 donors). Based on the co-expression of NR3C1 (and NR3C2) with genes specific to neural cell types, we determine the potential involvement of microglia, astrocytes, and CA1 pyramidal cells in mediating the relationship between corticosteroid exposure and cortical thickness. Therefore, corticosteroids may influence brain structure to a variable degree throughout life.
Published: 2020

26. The informative error: A framework for the construction of individualized phenotypes

Author: Georg Fuellen, Birte Holtfreter, Johannes Hertel, Hans J. Grabe, Katharina Wittfeld, Matthias Nauck, Maik Pietzner, Stefan Frenzel, Henry Völzke, Nele Friedrich, Thomas Kocher, and Johanna König
Subjects: Statistics and Probability, Epidemiology, Computer science, Population, epidemiology [Germany], Machine learning, computer.software_genre, 01 natural sciences, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Health Information Management, Germany, statistics & numerical data [Precision Medicine], Humans, ddc:610, Obesity, 030212 general & internal medicine, Precision Medicine, 0101 mathematics, education, education.field_of_study, epidemiology [Obesity], Models, Statistical, Operationalization, business.industry, Phenotype, Variable (computer science), Workflow, Research Design, Personalized medicine, Artificial intelligence, Epidemiologic Methods, Construct (philosophy), business, computer, Predictive modelling
Abstract: For the goal of individualized medicine, it is critical to have clinical phenotypes at hand which represent the individual pathophysiology. However, for most of the utilized phenotypes, two individuals with the same phenotype assignment may differ strongly in their underlying biological traits. In this paper, we propose a definition for individualization and a corresponding statistical operationalization, delivering thereby a statistical framework in which the usefulness of a variable in the meaningful differentiation of individuals with the same phenotype can be assessed. Based on this framework, we develop a statistical workflow to derive individualized phenotypes, demonstrating that under specific statistical constraints the prediction error of prediction scores contains information about hidden biological traits not represented in the modeled phenotype of interest, allowing thereby internal differentiation of individuals with the same assigned phenotypic manifestation. We applied our procedure to data of the population-based Study of Health in Pomerania to construct a refined definition of obesity, demonstrating the utility of the definition in prospective survival analyses. Summarizing, we propose a framework for the individualization of phenotypes aiding personalized medicine by shifting the focus in the assessment of prediction models from the model fit to the informational content of the prediction error.
Published: 2018

27. Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives

Author: Sandra Van der Auwera, Katharina Wittfeld, Georg Homuth, Nele Friedrich, Matthias Nauck, Maik Pietzner, Sönke Langner, Tim Kacprowski, Henry Völzke, Hans Joergen Grabe, Uwe Völker, Johanna König, Anna Artati, Anja Kretschmer, Karsten Suhre, Johannes Hertel, Jerzy Adamski, Gabi Kastenmüller, Melanie Waldenberger, and Liliane Pfeiffer
Subjects: 0301 basic medicine, genetics [Introns], Physiology, Pituitary-Adrenal System, lcsh:Medicine, genetics [Stress, Psychological], blood [Phospholipids], drug effects [Organ Size], 0302 clinical medicine, blood [Stress, Psychological], Medicine, Young adult, Receptor, lcsh:Science, metabolism [Receptors, Glucocorticoid], Depression (differential diagnoses), Phospholipids, Whole blood, Multidisciplinary, Brain, Organ Size, Middle Aged, Magnetic Resonance Imaging, drug effects [Brain], metabolism [Tacrolimus Binding Proteins], Female, FKBP5, Glucocorticoid, medicine.drug, Signal Transduction, Adult, drug effects [Signal Transduction], Hypothalamus, drug effects [Hypothalamus], Article, Tacrolimus Binding Proteins, 03 medical and health sciences, Young Adult, drug effects [Pituitary-Adrenal System], Receptors, Glucocorticoid, drug effects [DNA Methylation], blood [Triglycerides], physiopathology [Stress, Psychological], Humans, diagnostic imaging [Brain], Triglycerides, tacrolimus binding protein 5, business.industry, Stressor, lcsh:R, DNA Methylation, Introns, chemically induced [Stress, Psychological], genetics [Tacrolimus Binding Proteins], 030104 developmental biology, Etiology, lcsh:Q, adverse effects [Contraceptives, Oral], business, ddc:600, 030217 neurology & neurosurgery, Stress, Psychological, Contraceptives, Oral
Abstract: Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased circulating cortisol levels in those using oral contraceptives. For women taking oral contraceptives, we observed alterations in circulating phospholipid levels and elevated triglycerides and found evidence for increased glucocorticoid signalling as the transcript levels of the glucocorticoid-regulated genes DDIT4 and FKBP5 were increased in whole blood. The effects were statistically mediated by cortisol. The associations of oral contraceptives with higher FKBP5 mRNA and altered phospholipid levels were modified by rs1360780, a genetic variance implicated in psychiatric diseases. Accordingly, the methylation pattern of FKBP5 intron 7 was altered in women taking oral contraceptives depending on the rs1360780 genotype. Moreover, oral contraceptives modified the association of circulating cortisol with depressive symptoms, potentially explaining conflicting results in the literature. Finally, women taking oral contraceptives displayed smaller hippocampal volumes than non-using women. In conclusion, the integrative analyses of different types of physiological data provided converging evidence indicating that oral contraceptives may cause effects analogous to chronic psychological stressors regarding the regulation of the HPA axis.
Published: 2017

28. Domains of physical activity and brain volumes: A population-based study

Author: Hans J. Grabe, Katharina Wittfeld, Henry Völzke, Carmen Jochem, Marcus Dörr, Katrin Hegenscheid, Ulf Schminke, Stephan B. Felix, Martin Bahls, Sebastian E. Baumeister, Marcello Ricardo Paulista Markus, and Michael F. Leitzmann
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Cognitive Neuroscience, Population, methods [Image Interpretation, Computer-Assisted], Audiology, Temporal lobe, Cohort Studies, White matter, 03 medical and health sciences, 0302 clinical medicine, Image Interpretation, Computer-Assisted, medicine, Humans, ddc:610, Prospective Studies, Prefrontal cortex, education, Exercise, Anterior cingulate cortex, Aged, Aged, 80 and over, education.field_of_study, Brain, Human brain, Middle Aged, Magnetic Resonance Imaging, 030104 developmental biology, medicine.anatomical_structure, Neurology, Sample size determination, Study of Health in Pomerania, Female, Psychology, anatomy & histology [Brain], physiology [Exercise], Neuroscience, 030217 neurology & neurosurgery
Abstract: Observational studies and intervention trials suggest that physical activity (PA) is beneficial for human brain morphology, especially in older individuals. Few population-based studies examined whether domain-specific PA is associated with brain volumes. Accordingly, we studied putative associations of PA during leisure time, sports and work with volumes of the hippocampus, the prefrontal cortex, the temporal lobe, gray matter (GM), white matter (WM) and total brain (TBV) after 5.9 years by applying volumetric analysis and voxel-based morphometry (VBM) with SPM 8/VBM 8 to brain magnetic resonance imaging data of 834 participants (447 women) aged 25 to 83 years from the population-based Study of Health in Pomerania. The Baecke questionnaire was used to assess domain-specific PA (Leisure time, Sport, and Work Index) at baseline. After correcting for multiple testing, volumetric analyses did not show any significant association of domain-specific PA and volumes of the hippocampus, the prefrontal cortex, the temporal lobe, GM, WM and TBV. Multivariable-adjusted VBM analyses of the associations between PA domains with GM and WM volumes did not reveal any statistically significant results. Region of interest analyses revealed a statistically significant cluster of increased GM volume in the bilateral anterior cingulate cortex in association with PA during sports. In conclusion, the overall results contrast with the findings from previous studies that found significant associations between PA and brain volumes. In addition, it remains unclear whether a differential association exists between domains of PA and brain volumes. Thus, future studies with larger sample size and prospective design are needed to investigate potential domain-specific associations of PA with brain volumes.
Published: 2017

29. No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis

Author: Axel Krug, Maria J. Portella, Kang Sim, Bryon A. Mueller, Ian H. Gotlib, Tilo Kircher, Meng Li, Liesbeth Reneman, Elisabeth J. Leehr, Ben J. Harrison, Pedro G.P. Rosa, Hans J. Grabe, Kathryn R. Cullen, Roberto Goya-Maldonado, Andrew M. McIntosh, Geraldo Busatto Filho, Henrik Walter, Thomas Frodl, Dilara Yüksel, Quinn McLellan, Carolien G.F. de Kovel, Matthew D. Sacchet, Ivan Brack, Knut Schnell, Nils R. Winter, Sarah E. Medland, Ilya M. Veer, Angela Carballedo, Glenda MacQueen, Colm G. Connolly, David C. Glahn, Frank P. MacMaster, Clyde Francks, Igor Nenadic, Aditya Singh, Henry Völzke, Martin Walter, Anouk Schrantee, Lianne Schmaal, Sean N. Hatton, Lisa Sindermann, Steven J.A. van der Werff, Yolanda Vives-Gilabert, Danai Dima, Jim Lagopoulos, Robin Bülow, Geoffrey B. Hall, Dominik Grotegerd, Udo Dannlowski, Bernhard T. Baune, André Aleman, Melinda Westlund Schreiner, Dick J. Veltman, Neda Jahanshad, Ian B. Hickie, Tony T. Yang, Dario Zaremba, Martina Papmeyer, Oliver Gruber, Aaron Alexander-Bloch, Beata R. Godlewska, Christopher G. Davey, Lyubomir I. Aftanas, Evgeny Osipov, Mathew A. Harris, Katharina Dohm, Tiffany C. Ho, Paul M. Thompson, Bernd Kramer, Cynthia H.Y. Fu, Heather C. Whalley, Egle Simulionyte, Katharina Wittfeld, Dan J. Stein, Nynke A. Groenewold, Tracy Erwin-Grabner, Benjamin Ubani, Nic J.A. van der Wee, Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Radiology and nuclear medicine, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Personalized Medicine, Radiology and Nuclear Medicine, and APH - Mental Health
Subjects: Adult, Male, medicine.medical_specialty, CORTEX, SYMPTOMS, Databases, Factual, statistics & numerical data [Databases, Factual], BF, Neuroimaging, FRONTAL ALPHA ASYMMETRY, Audiology, Electroencephalography, Young Adult, 03 medical and health sciences, 0302 clinical medicine, ATTENUATION, AGE, Meta-Analysis as Topic, Humans, Medicine, ddc:610, Dominance, Cerebral, Temporal cortex, First episode, EEG ASYMMETRY, Depressive Disorder, Major, pathology [Depressive Disorder, Major], medicine.diagnostic_test, business.industry, Brain, Human brain, medicine.disease, Magnetic Resonance Imaging, 3. Good health, 030227 psychiatry, Psychiatry and Mental health, INDIVIDUALS, medicine.anatomical_structure, Case-Control Studies, Laterality, RC0321, Major depressive disorder, Female, Hypoactivity, business, anatomy & histology [Brain], 030217 neurology & neurosurgery, MRI
Abstract: Objective: Asymmetry is a subtle but pervasive aspect of the human brain, and it may be altered in several psychiatric conditions. MRI studies have shown subtle differences of brain anatomy between people with major depressive disorder and healthy control subjects, but few studies have specifically examined brain anatomical asymmetry in relation to this disorder, and results from those studies have remained inconclusive. At the functional level, some electroencephalography studies have indicated left fronto-cortical hypoactivity and right parietal hypoactivity in depressive disorders, so aspects of lateralized anatomy may also be affected. The authors used pooled individual-level data from data sets collected around the world to investigate differences in laterality in measures of cortical thickness, cortical surface area, and subcortical volume between individuals with major depression and healthy control subjects.Methods: The authors investigated differences in the laterality of thickness and surface area measures of 34 cerebral cortical regions in 2,256 individuals with major depression and 3,504 control subjects from 31 separate data sets, and they investigated volume asymmetries of eight subcortical structures in 2,540 individuals with major depression and 4,230 control subjects from 32 data sets. T-1-weighted MRI data were processedwith a single protocol using FreeSurfer and the Desikan-Killiany atlas. The large sample size provided 80% power to detect effects of the order of Cohen's d=0.1.Results: The largest effect size (Cohen's d) of major depression diagnosis was 0.085 for the thickness asymmetry of the superior temporal cortex, which was not significant after adjustment for multiple testing. Asymmetry measures were not significantly associated with medication use, acute compared with remitted status, first episode compared with recurrent status, or age at onset.Conclusions: Altered brain macro-anatomical asymmetry may be of little relevance to major depression etiology in most cases.
Published: 2019

30. Subcortical Shape Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group

Author: Tilo Kircher, H. VoÌˆlzke, Henrik Walter, Martin Walter, Richard Dinga, Susanne Meinert, Andreas Jansen, Ronny Redlich, Knut Schnell, Neda Jahanshad, Dan J. Stein, Dick J. Veltman, Elena Pozzi, Tiffany C. Ho, Lianne Schmaal, Igor Nenadic, Ilya M. Veer, Ian H. Gotlib, Man Li, André Aleman, Nynke A. Groenewold, Matthew D. Sacchet, Boris A. Gutman, P. G. SaÌˆmann, Bernhardt T. Baune, Hans-Jörgen Grabe, Udo Dannlowski, Paul M. Thompson, K. FoÌˆrster, Nils Opel, Dominik Grotegerd, Katharina Wittfeld, Norbert Hosten, and Axel Krug
Subjects: business.industry, Putamen, Thalamus, Subiculum, Nucleus accumbens, medicine.disease, Amygdala, 030227 psychiatry, 03 medical and health sciences, CTL, 0302 clinical medicine, medicine.anatomical_structure, nervous system, mental disorders, Medicine, Major depressive disorder, business, Neuroscience, 030217 neurology & neurosurgery, Basolateral amygdala
Abstract: Alterations in regional subcortical brain volumes have been widely investigated as part of the efforts of an international consortium, ENIGMA, to determine reliable structural brain signatures for Major Depressive Disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work to precisely map localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with MDD had lower surface area in the subiculum of the hippocampus, the basolateral amygdala, and the nucleus accumbens shell. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum of the hippocampus and the basolateral amygdala. Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala. Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.
Published: 2019
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31. Cardiorespiratory Fitness and Gray Matter Volume in the Temporal, Frontal, and Cerebellar Regions in the General Population

Author: Robin Bülow, Martin Bahls, Carmen Jochem, Ralf Ewert, Katharina Wittfeld, Stephan B. Felix, Sebastian E. Baumeister, Deborah Janowitz, Ulf Schminke, Henry Völzke, Marcello Ricardo Paulista Markus, Michael F. Leitzmann, Marcus Dörr, Sven Gläser, and Hans J. Grabe
Subjects: Cingulate cortex, Adult, Male, medicine.medical_specialty, Anaerobic Threshold, Population, 030204 cardiovascular system & hematology, computer.software_genre, White matter, 03 medical and health sciences, 0302 clinical medicine, pathology [Brain], pathology [Gray Matter], Voxel, Internal medicine, medicine, Humans, ddc:610, physiology [Cardiorespiratory Fitness], statistics & numerical data [Exercise Test], 030212 general & internal medicine, Gray Matter, education, Correlation of Data, diagnostic imaging [Brain], Aged, Aged, 80 and over, education.field_of_study, business.industry, diagnostic imaging [Gray Matter], VO2 max, Brain, Cardiorespiratory fitness, General Medicine, Voxel-based morphometry, Organ Size, Middle Aged, medicine.anatomical_structure, Cardiorespiratory Fitness, Brain size, Cardiology, Exercise Test, Female, business, computer, methods [Exercise Test]
Abstract: Objective To analyze the association between cardiorespiratory fitness (CRF) and global and local brain volumes. Participants and Methods We studied 2103 adults (21-84 years old) from 2 independent population-based cohorts (Study of Health in Pomerania, examinations from June 25, 2008, through September 30, 2012). Cardiorespiratory fitness was measured using peak oxygen uptake (VO2peak), oxygen uptake at the anaerobic threshold (VO2@AT), and maximal power output from cardiopulmonary exercise testing on a bicycle ergometer. Magnetic resonance imaging brain data were analyzed by voxel-based morphometry using regression models with adjustment for age, sex, education, smoking, body weight, systolic blood pressure, glycated hemoglobin level, and intracranial volume. Results Volumetric analyses revealed associations of CRF with gray matter (GM) volume and total brain volume. After multivariable adjustment, a 1–standard deviation increase in VO2peak was related to a 5.31 cm³ (95% CI, 3.27 to 7.35 cm³) higher GM volume. Whole-brain voxel-based morphometry analyses revealed significant positive relations between CRF and local GM volumes. The VO2peak was strongly associated with GM volume of the left middle temporal gyrus (228 voxels), the right hippocampal gyrus (146 voxels), the left orbitofrontal cortex (348 voxels), and the bilateral cingulate cortex (68 and 43 voxels). Conclusion Cardiorespiratory fitness was positively associated with GM volume, total brain volume, and specific GM and white matter clusters in brain areas not primarily involved in movement processing. These results, from a representative population sample, suggest that CRF might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.
Published: 2019

32. Effect of the interaction between childhood abuse and rs1360780 of theFKBP5gene on gray matter volume in a general population sample

Author: Norbert Hosten, Hans J. Grabe, Sandra Van der Auwera, Georg Homuth, Katharina Wittfeld, Henry Völzke, Ulrich John, Harald J. Freyberger, Katrin Hegenscheid, Mohamad Habes, Deborah Janowitz, Sven Barnow, Matthias Nauck, and Henriette E. Meyer zu Schwabedissen
Subjects: Child abuse, Cingulate cortex, education.field_of_study, medicine.medical_specialty, Radiological and Ultrasound Technology, Middle temporal gyrus, Population, Poison control, Physiology, Hippocampus, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Neurology, medicine, Radiology, Nuclear Medicine and imaging, Neurology (clinical), Anatomy, education, Psychiatry, Psychology, Insula, 030217 neurology & neurosurgery, Anterior cingulate cortex
Abstract: OBJECTIVE: The FKBP5 gene codes for a co-chaperone that regulates glucocorticoid receptor sensitivity and thereby impacts the reactivity of the hypothalamic-pituitary-adrenal (HPA)-axis. Evidence suggested that subjects exposed to childhood abuse and carrying the TT genotype of the FKBP5 gene single nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to stress-related disorders. METHOD: The hypothesis that abused TT genotype carriers show changes in gray matter (GM) volumes in affect-processing brain areas was investigated. About 1,826 Caucasian subjects (age ≤ 65 years) from the general population [Study of Health in Pomerania (SHIP)] in Germany were investigated. The interaction between rs1360780 and child abuse (Childhood Trauma Questionnaire) and its effect on GM were analyzed. RESULTS: Voxel-based whole-brain interaction analysis revealed three large clusters (FWE-corrected) of reduced GM volumes comprising the bilateral insula, the superior and middle temporal gyrus, the bilateral hippocampus, the right amygdala, and the bilateral anterior cingulate cortex in abused TT carriers. These results were not confounded by major depressive disorders. In region of interest analyses, highly significant volume reductions in the right hippocampus/parahippocampus, the bilateral anterior and middle cingulate cortex, the insula, and the amygdala were confirmed in abused TT carriers compared with abused CT/CC carriers. CONCLUSION: The results supported the hypothesis that the FKBP5 rs1360780 TT genotype predisposes subjects who have experienced childhood abuse to widespread structural brain changes in the subcortical and cortical emotion-processing brain areas. Those brain changes might contribute to an increased vulnerability of stress-related disorders in TT genotype carriers. Hum Brain Mapp, 2016. © 2016 Wiley Periodicals, Inc. Language: en
Published: 2016

33. Chronic Back Pain Is Associated With Decreased Prefrontal and Anterior Insular Gray Matter: Results From a Population-Based Cohort Study

Author: Hans-Christian Fritz, Sönke Langner, James H. McAuley, Carsten Oliver Schmidt, Katharina Wittfeld, Martin Lotze, and Katrin Hegenscheid
Subjects: Adult, Male, 0301 basic medicine, pathology [Chronic Pain], Prefrontal Cortex, pathology [Back Pain], Brain mapping, 03 medical and health sciences, 0302 clinical medicine, pathology [Gray Matter], medicine, Back pain, Humans, ddc:610, Gray Matter, Prefrontal cortex, Anterior cingulate cortex, Aged, Brain Mapping, medicine.diagnostic_test, business.industry, Chronic pain, Magnetic resonance imaging, Organ Size, Voxel-based morphometry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, pathology [Prefrontal Cortex], 030104 developmental biology, Anesthesiology and Pain Medicine, medicine.anatomical_structure, nervous system, Neurology, Back Pain, Female, Neurology (clinical), Chronic Pain, medicine.symptom, business, Insula, Neuroscience, 030217 neurology & neurosurgery
Abstract: Chronic back pain (CBP) is associated with circumscribed atrophy in gray matter (GM) predominantly localized in areas of the so-called pain matrix and the prefrontal cortex (PFC). Previous studies applying voxel-based morphometry (VBM) for identifying structural brain alterations related to CBP have reported inconsistent results, were limited to small sample sizes, and often did not control for medication. We therefore used VBM for high-resolution magnetic resonance images to investigate the association of CBP and regional GM volume in 111 individuals with CBP and 432 pain-free controls derived from the representative Study of Health in Pomerania, controlling for effects of medication. CBP was associated with decreased regional GM in the ventrolateral PFC and dorsolateral PFC, both the ventral and dorsal medial PFC, and the anterior insula. Pain intensity showed a weak negative correlation with GM volume in the left dorsolateral PFC, ventrolateral PFC, and anterior cingulate cortex. The CBP sample showed alterations in regions commonly associated with pain processing and emotional demands. To our knowledge, this is the first VBM study reporting decreased regional GM volume in the medial PFC in a CBP sample. We were unable to confirm alterations in regions other than the dorsolateral PFC and the insula. Perspective Previous studies reported inconsistent results for brain areas altered in chronic pain conditions, which may be in part attributable to small sample sizes, medication use, or emotional comorbidities. This study in a large and representative cohort helps to clarify these issues.
Published: 2016

34. High Thyrotropin Is Associated with Reduced Hippocampal Volume in a Population-Based Study from Germany

Author: Robin Bülow, Henry Völzke, Matthias Nauck, Norbert Hosten, Hans J. Grabe, Till Ittermann, and Katharina Wittfeld
Subjects: 0301 basic medicine, Adult, Male, Endocrinology, Diabetes and Metabolism, Population, Physiology, Hippocampus, Thyrotropin, Population based, Thyroid Function Tests, blood [Thyroid Diseases], 03 medical and health sciences, blood [Thyroxine], 0302 clinical medicine, Endocrinology, physiology [Organ Size], Thyroid dysfunction, Germany, Medicine, Humans, ddc:610, Gray Matter, education, Aged, diagnostic imaging [Hippocampus], education.field_of_study, business.industry, diagnostic imaging [Thyroid Diseases], diagnostic imaging [Gray Matter], Organ Size, Middle Aged, Thyroid Diseases, Population based study, Thyroxine, 030104 developmental biology, blood [Triiodothyronine], Brain size, Hippocampal volume, Triiodothyronine, Female, business, blood [Thyrotropin], 030217 neurology & neurosurgery
Abstract: Previous patient studies suggest that thyroid dysfunction affects volumes of particular regions of the brain. So far, population-based data related to this topic are lacking. The aim of this study was to investigate associations of serum levels of thyrotropin (TSH), free triiodothyronine, and free thyroxine (fT4) with total brain volume, gray matter volume, white matter volume (WMV), and hippocampal volume (HV) in a population-based study.Data on 2557 individuals were pooled from two independent population-based surveys of the Study of Health in Pomerania conducted in Northeast Germany. Brain volumes were determined from images derived from 1.5 T magnetic resonance imaging. Low and high TSH were defined using the cutoffs 0.40 and 3.29 mIU/L, respectively. Associations between thyroid hormone levels and segmented brain volumes were analyzed by linear regression models. Further, voxel-based morphometry was conducted to search for associations with thyroid hormone levels in a hypothesis-free way throughout the whole brain. All models were adjusted for confounders.Only 9/70 individuals with high TSH had low free triiodothyronine or fT4 levels. Individuals with high TSH had significantly lower total brain volume (β = -26.9 [confidence interval (CI) -49.0 to -4.8]; p = 0.017), WMV (β = -16.1 [CI -29.4 to -2.7]; p = 0.018), and HV (β = -223 [CI -395 to -50]; p = 0.011) than individuals with TSH within the reference range, while low TSH was not significantly associated with any of the brain volumes. Voxel-based morphometry analyses revealed a significant positive association with serum fT4 levels in the left middle frontal gyrus.In conclusion, the results of this study indicate that the subclinical hypothyroid state may lead to a reduced brain volume affecting particularly HV in younger subjects and WMV, which might correspond to subtle microstructural changes in white matter fiber tracts or myelination of the axones. Gray matter seems not to be affected by subclinical hypothyroid states.
Published: 2018

35. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Author: Charles DeCarli, Vilmundur Gudnason, Debra A. Fleischman, Henning Tiemeier, Rebecca F. Gottesman, William S. Kremen, Xueqiu Jian, Henry Brodaty, Maria del C. Valdés Hernández, Markus Loeffler, Reinhold Schmidt, Shahzad Ahmad, Paul A. Nyquist, Oscar L. Lopez, Anbupalam Thalamuthu, Helena Schmidt, Peter R. Schofield, Tonya White, Edith Hofer, Philip L. De Jager, David Ames, Qiong Yang, Ole A. Andreassen, Cora E. Lewis, Matthias Nauck, David S. Knopman, Anders M. Dale, Sven J. van der Lee, Jeroen van der Grond, Konstantinos Arfanakis, Margaret J. Wright, Jingyun Yang, John B.J. Kwok, Hieab H.H. Adams, Matthew S. Panizzon, Meike W. Vernooij, Yasaman Saba, David A. Bennett, Cornelia M. van Duijn, Tamara B. Harris, Pauline Maillard, Frauke Beyer, M. Arfan Ikram, Jerome I. Rotter, Ryan L. Muetzel, Tomáš Paus, Pamela J. Schreiner, Zdenka Pausova, Katharina Wittfeld, Diane M. Becker, Bruce M. Psaty, Alexander Teumer, Wei Wen, A. Veronica Witte, Karen A. Mather, Hanan El Marroun, William T. Longstreth, Perminder S. Sachdev, Mark E. Bastin, Nathan A. Gillespie, Kenneth Rice, Stella Trompet, Lisa R. Yanek, David J. Stott, Alexa S. Beiser, R. Nick Bryan, Alexander Neumann, Natalie A. Royle, Myriam Fornage, Manon Bernard, Dina Vojinovic, Najaf Amin, Ian J. Deary, Arno Villringer, Georg Homuth, Nicola J. Armstrong, Stephen Sidney, Sudha Seshadri, Joanna M. Wardlaw, Thomas H. Mosley, Hans J. Grabe, Michelle Luciano, Lenore J. Launer, J. Wouter Jukema, Robin Bülow, Markus Scholz, André G. Uitterlinden, Albert V. Smith, Shuo Li, Claudia L. Satizabal, Joshua C. Bis, Epidemiology, Radiology & Nuclear Medicine, Child and Adolescent Psychiatry / Psychology, Clinical Psychology, Internal Medicine, Psychiatry, Neurology, Faculty of Medicine (UI), Læknadeild (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands (HÍ), and University of Iceland (UI)
Subjects: 0301 basic medicine, Genetics of the nervous system, Cytoskeleton organization, General Physics and Astronomy, Genome-wide association study, Mental disorders, Genome-wide association studies, Genome, Lateral ventricles, 0302 clinical medicine, Lateral Ventricles, Ventricle (lateral), lcsh:Science, Genetics, anatomy & histology [Lateral Ventricles], education.field_of_study, Enlargement, Multidisciplinary, Brain, Organ Size, Middle Aged, Schizophrenia, ddc:500, Science, Population, Elderly people, Biology, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, medicine, Erfðafræði, Humans, Genomes, education, Aged, Genetic association, genetics [Organ Size], Genome, Human, Heilinn, Brain morphometry, Litningarannsóknir, Rannsóknir, General Chemistry, medicine.disease, 030104 developmental biology, Heritable quantitative trait, lcsh:Q, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Publisher's version (útgefin grein) Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations., The volume of the lateral ventricles (LV) increases with age and their abnormal enlargement is a key feature of several neurological and psychiatric diseases. Although lateral ventricular volume is heritable, a comprehensive investigation of its genetic determinants is lacking. In this meta-analysis of genome-wide association studies of 23,533 healthy middle-aged to elderly individuals from 26 population-based cohorts, we identify 7 genetic loci associated with LV volume. These loci map to chromosomes 3q28, 7p22.3, 10p12.31, 11q23.1, 12q23.3, 16q24.2, and 22q13.1 and implicate pathways related to tau pathology, S1P signaling, and cytoskeleton organization. We also report a significant genetic overlap between the thalamus and LV volumes (ρgenetic = −0.59, p-value = 3.14 × 10−6), suggesting that these brain structures may share a common biology. These genetic associations of LV volume provide insights into brain morphology., See Supplementary Note 2 for information on funding sources.
Published: 2018

36. Association between serum neuron-specific enolase, age, overweight, and structural MRI patterns in 901 subjects

Author: Mohamad Habes, Johanna Hoffmann, Deborah Janowitz, Henry Völzke, Matthias Nauck, Katharina Wittfeld, Jan Terock, Annemarie Goltz, Martin Bahls, Christos Davatzikos, Hans J. Grabe, Nele Friedrich, Sandra Van der Auwera, and Angela Kuhla
Subjects: Male, 0301 basic medicine, diagnostic imaging [Overweight], Overweight, Body Mass Index, 0302 clinical medicine, Medicine, Young adult, Aged, 80 and over, Sex Characteristics, education.field_of_study, Age Factors, Brain, Middle Aged, Magnetic Resonance Imaging, Psychiatry and Mental health, blood [Overweight], Female, medicine.symptom, Sex characteristics, Adult, medicine.medical_specialty, Enolase, Population, Article, lcsh:RC321-571, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, Humans, Dementia, ddc:610, blood [Phosphopyruvate Hydratase], education, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, diagnostic imaging [Brain], Biological Psychiatry, Aged, business.industry, medicine.disease, Obesity, 030104 developmental biology, Endocrinology, Phosphopyruvate Hydratase, business, Body mass index, 030217 neurology & neurosurgery
Abstract: Serum neuron-specific enolase (sNSE) is considered a marker for neuronal damage, related to gray matter structures. Previous studies indicated its potential as marker for structural and functional damage in conditions with adverse effects to the brain like obesity and dementia. In the present study, we investigated the putative association between sNSE levels, body mass index (BMI), total gray matter volume (GMV), and magnetic resonance imaging-based indices of aging as well as Alzheimer’s disease (AD)-like patterns. Subjects/Methods: sNSE was determined in 901 subjects (499 women, 22–81 years, BMI 18–48 kg/m2), participating in a population-based study (SHIP-TREND). We report age-specific patterns of sNSE levels between males and females. Females showed augmenting, males decreasing sNSE levels associated with age (males: p = 0.1052, females: p = 0.0363). sNSE levels and BMI were non-linearly associated, showing a parabolic association and decreasing sNSE levels at BMI values >25 (p = 0.0056). In contrast to our hypotheses, sNSE levels were not associated with total GMV, aging, or AD-like patterns. Pathomechanisms discussed are: sex-specific hormonal differences, neuronal damage/differentiation, or impaired cerebral glucose metabolism. We assume a sex-dependence of age-related effects to the brain. Further, we propose in accordance to previous studies an actual neuronal damage in the early stages of obesity. However, with progression of overweight, we assume more profound effects of excess body fat to the brain.
Published: 2017

37. Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group

Author: G.I. de Zubicaray, Natalie T. Mills, Henry Völzke, N. van der Wee, A Block, Margaret J. Wright, D. Schoepf, Paul M. Thompson, Miguel E. Rentería, Neda Jahanshad, Hans-Jörgen Grabe, Beata R. Godlewska, Claus Normann, Nicholas G. Martin, Ilya M. Veer, Lachlan T. Strike, Baptiste Couvy-Duchesne, Nathan A. Gillespie, T.G.M. van Erp, Katrin Hegenscheid, Ian B. Hickie, Sean N. Hatton, Katharina Wittfeld, Helen Christensen, Derrek P. Hibar, Philip J. Cowen, Lianne Schmaal, Dick J. Veltman, Katie L. McMahon, Sarah E. Medland, Elisabeth Schramm, Henrik Walter, Knut Schnell, Carsten Konrad, Bartosz Zurowski, Jim Lagopoulos, B.W.J.H. Penninx, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, and APH - Mental Health
Subjects: Male, epidemiology [Depressive Disorder, Major], Poison control, statistics & numerical data [Suicide], psychology [Depressive Disorder, Major], methods [Magnetic Resonance Imaging], 0302 clinical medicine, pathology [Brain], Risk Factors, Prevalence, Suicidal ideation, education.field_of_study, Brain, Middle Aged, Magnetic Resonance Imaging, 3. Good health, Suicide, Psychiatry and Mental health, Schizophrenia, Brain size, Major depressive disorder, Original Article, Female, medicine.symptom, methods [Neuroimaging], Psychology, Clinical psychology, Adult, medicine.medical_specialty, Population, Neuroimaging, diagnostic imaging [Depressive Disorder, Major], Suicidal Ideation, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Humans, Department Sport- und Gesundheitswissenschaften, ddc:610, education, Psychiatry, diagnostic imaging [Brain], Biological Psychiatry, Aged, Depressive Disorder, Major, psychology [Suicide], medicine.disease, 030227 psychiatry, Mood disorders, anatomy & histology [Brain], 030217 neurology & neurosurgery
Abstract: The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n = 3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N = 451) vs healthy controls (N = 1996) or MDD patients with no suicidal symptoms (N = 650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P = 4.12 × 10 - 3) or a 2.87% smaller volume compared with controls (Cohen's d = - 0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P = 0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.
Published: 2017

38. Childhood adversity impacts on brain subcortical structures relevant to depression

Author: Bartosz Zurowski, Angela Carballedo, Derrek P. Hibar, Jim Lagopoulos, Sean N. Hatton, Theo G.M. van Erp, Lianne Schmaal, Henrik Dobrowolny, Brenda W.J.H. Penninx, Hans J. Grabe, Anne Uhlmann, Leonardo Tozzi, Nic J.A. van der Wee, Thomas Frodl, Katharina Wittfeld, Dan J. Stein, Knut Schnell, Paul M. Thompson, Neda Jahanshad, Carsten Konrad, Henrik Walter, Harald Kugel, Eva Maria Frey, Volker Arolt, Elisabeth Schramm, Henry Völzke, Dominik Grotegerd, Bernhard T. Baune, Daniella Vuletic, Deborah Janowitz, Andrea Block, Samantha J. Brooks, Dick J. Veltman, Udo Dannlowski, Katrin Hegenscheid, Ian B. Hickie, Ilya M. Veer, Marie-José van Tol, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, APH - Mental Health, APH - Digital Health, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Male, drug therapy [Depressive Disorder, Major], Image Processing, Caudate, Hippocampus, Medical and Health Sciences, Computer-Assisted, POSTTRAUMATIC-STRESS-DISORDER, 0302 clinical medicine, ddc:150, Surveys and Questionnaires, Image Processing, Computer-Assisted, MALTREATMENT, Aetiology, Depression (differential diagnoses), Pediatric, Violence Research, Psychiatry, Sex Characteristics, MEDIAL PREFRONTAL CORTEX, Depression, ENIGMA, Brain, Organ Size, Middle Aged, Serious Mental Illness, Magnetic Resonance Imaging, Antidepressive Agents, Psychiatry and Mental health, Mental Health, medicine.anatomical_structure, Adult Survivors of Child Adverse Events, Major depressive disorder, drug effects [Brain], Female, social and economic factors, CA3 PYRAMIDAL NEURONS, Psychology, Sex characteristics, Clinical psychology, MRI, Adult, Department Psychologie, medicine.medical_specialty, Major Depressive Disorder, HIPPOCAMPAL VOLUME, diagnostic imaging [Depressive Disorder, Major], Amygdala, behavioral disciplines and activities, Article, 03 medical and health sciences, 2.3 Psychological, Negatively associated, Behavioral and Social Science, mental disorders, medicine, Humans, In patient, ddc:610, diagnostic imaging [Brain], METAANALYSIS, Biological Psychiatry, Psychiatric Status Rating Scales, Depressive Disorder, Major, Depressive Disorder, Psychology and Cognitive Sciences, Neurosciences, Major, MAJOR DEPRESSION, therapeutic use [Antidepressive Agents], medicine.disease, Mental health, Brain Disorders, 030227 psychiatry, AMYGDALA, SEVERITY, MORPHOLOGY, Childhood adversity, psychology [Adult Survivors of Child Adverse Events], Software, 030217 neurology & neurosurgery
Abstract: Childhood adversity plays an important role for development of major depressive disorder (MDD). There are differences in subcortical brain structures between patients with MDD and healthy controls, but the specific impact of childhood adversity on such structures in MDD remains unclear. Thus, aim of the present study was to investigate whether childhood adversity is associated with subcortical volumes and how it interacts with a diagnosis of MDD and sex. Within the ENIGMA-MDD network, nine university partner sites, which assessed childhood adversity and magnetic resonance imaging in patients with MDD and controls, took part in the current joint mega-analysis. In this largest effort world-wide to identify subcortical brain structure differences related to childhood adversity, 3036 participants were analyzed for subcortical brain volumes using FreeSurfer. A significant interaction was evident between childhood adversity, MDD diagnosis, sex, and region. Increased exposure to childhood adversity was associated with smaller caudate volumes in females independent of MDD. All subcategories of childhood adversity were negatively associated with caudate volumes in females - in particular emotional neglect and physical neglect (independently from age, ICV, imaging site and MDD diagnosis). There was no interaction effect between childhood adversity and MDD diagnosis on subcortical brain volumes. Childhood adversity is one of the contributors to brain structural abnormalities. It is associated with subcortical brain abnormalities that are relevant to psychiatric disorders such as depression. (C) 2016 Published by Elsevier Ltd.
Published: 2017

39. Novel genetic loci associated with hippocampal volume

Author: Benjamin S. Aribisala, Marjolein M.J. van Donkelaar, Randy L. Gollub, Rachel M. Brouwer, Norman Delanty, Tomas Axelsson, Oscar L. Lopez, Thomas Espeseth, Alejandro Arias-Vasquez, Kristel R. van Eijk, Tien Yin Wong, Jeroen van der Grond, Georg Homuth, James T. Becker, Sebastian Guelfi, Anton J. M. de Craen, Bruno Vellas, Christopher R.K. Ching, Charles C. DeCarli, Janita Bralten, Lars T. Westlye, Ryota Hashimoto, Sampath Arepalli, Bertram Müller-Myhsok, Loes M. Olde Loohuis, Sudha Seshadri, Simon E. Fisher, K Hegenscheid, Konstantinos Arfanakis, Zdenka Pausova, Robert C. Green, Simone Reppermund, Katie L. McMahon, Ashley Beecham, Daan van Rooij, Marcel P. Zwiers, Karen A. Mather, Randy L. Buckner, Edith Hofer, Marcella Rietschel, Fabrice Crivello, Ronald H. Zielke, G. Bruce Pike, Thomas W. Mühleisen, Myriam Fornage, Kazutaka Ohi, Gareth E. Davies, Chantal Depondt, Gabriel Cuellar-Partida, Iryna O. Fedko, Peter R. Schofield, Steven G. Potkin, Albert Hofman, Paul M. Thompson, Wiro J. Niessen, Deborah Janowitz, Nicholas G. Martin, Li Shen, Mina Ryten, Meike W. Vernooij, Michael E. Weale, Tonya White, Dennis van 't Ent, Sudheer Giddaluru, Nanda Rommelse, Wei Wen, Sven J. van der Lee, Eco J. C. de Geus, Aaron Goldman, Joanne E. Curran, Qiang Chen, Jean Shin, Wayne C. Drevets, Thomas H. Mosley, Matthias Nauck, Massimo Pandolfo, Anders M. Dale, Paul A. Nyquist, Girma Woldehawariat, Francis J. McMahon, Najaf Amin, Emma J. Rose, Norbert Hosten, David J. Stott, Sigurdur Sigursson, Andrew J. Saykin, M. Kamran Ikram, Pieter J. Hoekstra, Neda Jahanshad, Grant W. Montgomery, Michael Weiner, Aad van der Lugt, Esther Walton, Gunter Schumann, Clyde Francks, Narelle K. Hansell, Xinmin Liu, Herve Lemaitre, Cornelia M. van Duijn, Ralph L. Sacco, Clinton B. Wright, Arvin Saremi, Clifford R. Jack, Andre G. Uitterlinden, G. Donohoe, Tomáš Paus, Michael Griswold, Peter T. Fox, Alan B. Zonderman, Lukas Pirpamer, Christiane Wolf, Aiden Corvin, Shannon L. Risacher, Ian Ford, Philippe Amouyel, Henrik Walter, Beng-Choon Ho, William T. Longstreth, M. Arfan Ikram, Hieab H.H. Adams, Colin Smith, Sungeun Kim, Simon Lovestone, Stefan Ehrlich, Benno Pütz, Markus M. Nöthen, Susana Muñoz Maniega, Ian J. Deary, Elena Shumskaya, Susan H. Blanton, Jerome I. Rotter, Neeltje E.M. van Haren, Mar Matarin, I. Kloszewska, Ganesh Chauhan, Anita L. DeStefano, Barbara Franke, Lars Nyberg, Tatiana Foroud, Tianye Jia, Manon Bernard, Unn K. Haukvik, Rebecca F. Gottesman, Srdjan Djurovic, Ching-Yu Cheng, Lachlan T. Strike, Alex P. Zijdenbos, Jouke-Jan Hottenga, Vince D. Calhoun, Yuri Milaneschi, David C. Glahn, Phil Lee, Amelia A. Assareh, Adaikalavan Ramasamy, Emma Sprooten, Debra A. Fleischman, David R. McKay, J. Raphael Gibbs, Bruce M. Psaty, Kazima B. Bulayeva, Bryan J. Traynor, Vilmundur Gudnason, Jessika E. Sussmann, Alexander Teumer, Guillén Fernández, Katharina Wittfeld, Christophe Tzourio, Dennis van der Meer, Wolfgang Hoffmann, Sebastian Mohnke, David C. Liewald, Jordan W. Smoller, Theo G.M. van Erp, Marcel Van Der Brug, Dara M. Cannon, Lenore J. Launer, D. Ames, Juan C. Troncoso, Brenda W.J.H. Penninx, Dhananjay Vaidya, Thomas D. Dyer, Marie-José van Tol, Han G. Brunner, Andrew Singleton, Lavinia Athanasiu, Adam M. Brickman, Eric Westman, P. Mecocci, Sandra Barral, Dick J. Veltman, Catharina A. Hartman, Benedicto Crespo-Facorro, Alexa S. Beiser, Vincent Chouraki, Nhat Trung Doan, Marieke Klein, Jaap Oosterlaan, Natalie A. Royle, John B.J. Kwok, Saud Alhusaini, Ingrid Melle, Roberto Toro, Ravi Duggirala, Allissa Dillman, Reinhold Schmidt, Lisa R. Yanek, Anbupalam Thalamuthu, Helena Schmidt, Derrek P. Hibar, Albert V. Smith, Jean-Luc Martinot, Thomas H. Wassink, Jennifer S. Richards, Oliver Martinez, Joshua L. Roffman, Sylvane Desrivières, Hilkka Soininen, Rene L. Olvera, Ole A. Andreassen, Diana Tordesillas-Gutiérrez, Claudia L. Satizabal, Owen Carmichael, Lianne Schmaal, Bernd Kraemer, Martine Hoogman, Daniah Trabzuni, Oliver Grimm, Andrew M. McIntosh, René S. Kahn, Nazanin Karbalai, Margaret J. Wright, Harald H.H. Göring, Martina Papmeyer, Roberto Roiz-Santiañez, Luigi Ferrucci, David A. Bennett, Kwangsik Nho, Gianpiero L. Cavalleri, Andreas Meyer-Lindenberg, Masashi Ikeda, Avram J. Holmes, Greig I. de Zubicaray, Andreas Heinz, Tatjana Rundek, Maria del C. Valdés Hernández, Dalia Kasperaviciute, Dan L. Longo, Matthew J. Huentelman, Wiepke Cahn, Beverly G. Windham, Michael A. Nalls, Philipp G. Sämann, Stella Trompet, Vidar M. Steen, Marc M. Bohlken, Christopher D. Whelan, Hilleke E. Hulshoff Pol, Susanne Erk, Dorret I. Boomsma, Dirk J. Heslenfeld, Masaki Fukunaga, D. Hoehn, Stephen M. Lawrie, Mark E. Bastin, Marco P. Boks, M. Mallar Chakravarty, M. R. Cookson, C. McDonald, Magda Tsolaki, Badri N. Vardarajan, Jason L. Stein, Jan K. Buitelaar, Erik G. Jönsson, Oliver Gruber, Robert Johnson, Jingyun Yang, Joshua C. Bis, J. Wouter Jukema, Tulio Guadalupe, Nina Romanczuk-Seiferth, Kjetil Nordbø Jørgensen, Henry Brodaty, Diane M. Becker, Anouk den Braber, Allison C. Nugent, Thomas Wolfers, John Hardy, Joanna M. Wardlaw, Michelle Luciano, Christine Macare, Dena G. Hernandez, D. Morris, John Blangero, Andrew J. Schork, Daniel R. Weinberger, Johanna Hass, Andrew Simmons, Micael Andersson, Lucija Abramovic, David S. Knopman, Mark Jenkinson, Roel A. Ophoff, Sanjay M. Sisodiya, Boris A. Gutman, Asta Håberg, Stephanie Le Hellard, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Hans J. Grabe, Henry Völzke, Thomas E. Nichols, Manuel Mattheisen, Sven Cichon, Venkata S. Mattay, Ingrid Agartz, Stefan Ropele, Lorna M. Lopez, Hans van Bokhoven, Philip L. De Jager, Miguel E. Rentería, Laura Almasy, Arthur W. Toga, Michael Czisch, Florian Holsboer, Ryota Kanai, Nic J.A. van der Wee, Peter Kochunov, Perminder S. Sachdev, Andre F. Marquand, Christian Enzinger, Anderson M. Winkler, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Metacohorts Consortium, Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, sans affiliation, QIMR Berghofer Medical Research Institute, University of Washington [Seattle], Department of Psychiatry, Donders Centre for Neuroscience, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University Medical Center [Utrecht], Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Sahlgrenska University Hospital [Gothenburg], Department of Biomedical Engineering, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), Assistance Publique - Hôpitaux de Marseille (APHM), University of Oslo (UiO), Department of medical sciences, Uppsala University-Molecular Medicine-Science for Life Laboratory, John P. Hussman Institute for Human Genomics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], Université Lille Nord de France (COMUE), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Haukeland University Hospital, University of Bergen (UiB), Ames Laboratory [Ames, USA], Iowa State University (ISU)-U.S. Department of Energy [Washington] (DOE), Johns Hopkins University School of Medicine [Baltimore], Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, International Max Planck Research School for Language Sciences (IMPRS ), Laboratory of Neuro Imaging [Los Angeles] (LONI), Department of Mathematics [UCLA], Georgia Institute of Technology [Atlanta], Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany, Greifswald University Hospital, Beijing Normal University (BNU), Aalborg University [Denmark] (AAU), UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Imperial College London, Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Genomics, Life and Brain Center, University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Department of Neurology, Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Department of Neurology [Austria], Medical University Graz, Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Neurosciences [San Diego], University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [San Diego], Wuhan University [China], Plymouth University, Dpt of Psychiatry [New Haven], Yale University School of Medicine, Queensland Institute of Medical Research, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre, Depts of Radiology, Leiden University Medical Center (LUMC), University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), RCMG Ghent, Universiteit Gent = Ghent University [Belgium] (UGENT), Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), National Institutes of Health [Bethesda] (NIH), Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Université de Lille, Department of Clinical Genetics, Department of Experimental Physics, National University of Ireland Maynooth (Maynooth University), Texas Biomedical Research Institute [San Antonio, TX], The University of Texas Health Science Center at Houston (UTHealth), 849 Department of Human Genetics, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], The Mind Research Network, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Northwestern Polytechnical University [Xi'an] (NPU), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], York Structural Biology Laboratory, Department of Chemistry, University of York [York, UK], Harvard Medical School [Boston] (HMS), Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], School of Psychology, University of Queensland, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), École des hautes études en sciences sociales (EHESS), Department of Radiology, Mayo Clinic, Robertson Centre for Biostatistics, University of Glasgow, Human Genetics Center, Department of Medical and Molecular Genetics, Rensselaer Polytechnic Institute (RPI), Department of Physics, Okayama University, Okayama University, University of New Haven [Connecticut], Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., University of Science, VNU-HCM, University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Medical Genetics, HMNC Brain Health, University of Oxford [Oxford], University of Florida [Gainesville] (UF), Göteborgs Universitet (GU), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Institute of Cognitive Neuroscience, University College of London [London] (UCL), Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Psychiatry Institute, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, University of Mississippi Medical Center (UMMC), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Department of Statistics [Coventry], University of Warwick [Coventry], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Osaka University [Osaka], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Politecnico di Milano [Milan] (POLIMI), University of Applied Sciences [Munich], Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, National Institute of Aging, 3rd Department of Neurology, Aristotle University of Thessaloniki-General Hospital of Thessaloniki George Papanikolaou, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Pretoria [South Africa], University of Missouri [Columbia] (Mizzou), University of Missouri System, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of Southern California (USC), University of California (UC)-University of California (UC), Sans affiliation, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Toronto, Radboud University [Nijmegen], Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Universität Bonn = University of Bonn, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), Yale School of Medicine [New Haven, Connecticut] (YSM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Universiteit Gent = Ghent University (UGENT), Centre épigénétique et destin cellulaire (EDC), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], University of Oxford, University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, University of Eastern Finland, Universiteit Leiden, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Humboldt University Of Berlin, Radboud University [Nijmegen]-Radboud University [Nijmegen], School of Medicine / Clinical Medicine, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Other departments, Adult Psychiatry, ARD - Amsterdam Reproduction and Development, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], McGill University-McGill University, Sahlgrenska University Hospital, McGill University, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), University of Bergen (UIB), Iowa State University (ISU)-U.S. Department of Energy (DOE), Beijing Normal University, Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Gènes, Synapses et Cognition, Ghent University [Belgium] (UGENT), National University of Ireland Maynooth (NUIM), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], University of Florida [Gainesville], Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Aristotle University of Thessaloniki-G. Papanikolaou Hospital, Humboldt Universität zu Berlin, University of Missouri [Columbia], Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Internal Medicine, Neurology, Biological Psychology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Health Behaviors & Chronic Diseases, Cognitive Psychology, IBBA, APH - Personalized Medicine, Amsterdam Neuroscience - Brain Imaging, MUMC+: DA Klinische Genetica (5), Klinische Genetica, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, APH - Digital Health, Hal, GIN, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Universidad de Cantabria, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: Male, Netherlands Twin Register (NTR), Genome-wide association study, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit, Spatial memory, 0302 clinical medicine, 610 Medicine & health, Child, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Episodic memory, Aged, 80 and over, Subiculum, 220 Statistical Imaging Neuroscience, COMMON VARIANTS, ALZHEIMERS-DISEASE, ddc:500, Alzheimer's disease, genetics [Methionine Sulfoxide Reductases], Science, Locus (genetics), genetics [Protein-Serine-Threonine Kinases], Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Alzheimer Disease, ASTN2 protein, human, Humans, GENOME-WIDE ASSOCIATION, METAANALYSIS, Aged, Glycoproteins, Dentate gyrus, MEMORY, medicine.disease, R1, 030104 developmental biology, nervous system, Genetic Loci, MSRB3 protein, human, 030217 neurology & neurosurgery, 0301 basic medicine, General Physics and Astronomy, genetics [Alzheimer Disease], Hippocampal formation, Hippocampus, Genome-wide association studies, Taugasjúkdómar, Cohort Studies, DPP4 protein, human, TEMPORAL-LOBE EPILEPSY, BRAIN-REGIONS, genetics [Dipeptidyl Peptidase 4], genetics [Nerve Tissue Proteins], Genetics, Multidisciplinary, Neurodegenerative diseases, BIPOLAR DISORDER, Organ Size, Middle Aged, SUBFIELDS, Protein-Serine-Threonine Kinases, growth & development [Hippocampus], Female, genetics [Glycoproteins], Microtubule-Associated Proteins, Medical Genetics, Neuroinformatics, Adult, genetics [Microtubule-Associated Proteins], Adolescent, SUSCEPTIBILITY LOCI, Dipeptidyl Peptidase 4, genetics [Protein Serine-Threonine Kinases], Nerve Tissue Proteins, Bioinformatik och systembiologi, Protein Serine-Threonine Kinases, Biology, physiopathology [Alzheimer Disease], 150 000 MR Techniques in Brain Function, Young Adult, MAST4 protein, human, medicine, Journal Article, Erfðafræði, Genetic Predisposition to Disease, ddc:610, Medicinsk genetik, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Bioinformatics and Systems Biology, [SCCO.NEUR]Cognitive science/Neuroscience, [SCCO.NEUR] Cognitive science/Neuroscience, Rannsóknir, General Chemistry, Methionine Sulfoxide Reductases, 150 Psychology, Genome-Wide Association Study
Abstract: The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness., published version, peerReviewed
Published: 2017

40. Prediabetes is associated with lower brain gray matter volume in the general population. The Study of Health in Pomerania (SHIP)

Author: Robin Bülow, Stephan B. Felix, Wolfgang Rathmann, Nicole Werner, Hans-Jörgen Grabe, Katharina Wittfeld, Henry Völzke, Martin Bahls, S.E. Baumeister, Deborah Janowitz, Sabine Schipf, Till Ittermann, Marcello Ricardo Paulista Markus, U. Siewert-Markus, and Marcus Dörr
Subjects: Male, Blood Glucose, Glycated Hemoglobin A, endocrine system diseases, Endocrinology, Diabetes and Metabolism, epidemiology [Prediabetic State], Medicine (miscellaneous), 030204 cardiovascular system & hematology, Gastroenterology, Impaired glucose tolerance, 0302 clinical medicine, Leukoencephalopathies, Risk Factors, Germany, metabolism [Glycated Hemoglobin], Prevalence, Prediabetes, Gray Matter, Aged, 80 and over, metabolism [Blood Glucose], education.field_of_study, Glucose tolerance test, Brain Diseases, Nutrition and Dietetics, blood [Biomarkers], medicine.diagnostic_test, Fasting, Middle Aged, White Matter, Magnetic Resonance Imaging, diagnosis [Prediabetic State], Study of Health in Pomerania, diagnostic imaging [Leukoencephalopathies], Female, diagnostic imaging [Brain Diseases], Cardiology and Cardiovascular Medicine, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, metabolism [Glycated Hemoglobin A], Population, epidemiology [Germany], Risk Assessment, blood [Fasting], diagnostic imaging [White Matter], Prediabetic State, 03 medical and health sciences, Young Adult, epidemiology [Brain Diseases], Internal medicine, Diabetes mellitus, medicine, Humans, ddc:610, education, Aged, Glycated Hemoglobin, epidemiology [Leukoencephalopathies], business.industry, diagnostic imaging [Gray Matter], nutritional and metabolic diseases, Type 2 Diabetes Mellitus, blood [Prediabetic State], Glucose Tolerance Test, Impaired fasting glucose, medicine.disease, Endocrinology, Cross-Sectional Studies, Multivariate Analysis, Linear Models, hemoglobin A1c protein, human, business, 030217 neurology & neurosurgery, Biomarkers
Abstract: We investigated the associations of fasting (FG) and 2-h postload (2HG) plasma glucose from oral glucose tolerance test (OGTT) with gray (GMV) and white (WMV) matter volume.We analyzed data from 1330 subjects without known diabetes mellitus, aged 21 to 81, from the second cohort (SHIP-Trend-0) of the population-based Study of Health in Pomerania (SHIP). Following the OGTT, individuals were classified in five groups (according to the American Diabetes Association criteria): normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG and IGT (IFG + IGT) and unknown type 2 diabetes mellitus (UDM). GMV and WMV were determined by magnetic resonance imaging. FG, 2HG and OGTT groups were associated with GMV and WMV by linear regression models adjusted for confounders. FG and 2HG were inversely associated with GMV. The adjusted mean GMV, when compared with the NGT group (584 ml [95% CI: 581 to 587]), was significantly lower in the groups i-IFG (578 ml [95% CI: 573 to 582]; p = 0.035) and UDM (562 ml [95% CI: 551 to 573]; p 0.001), but not different in the i-IGT (586 ml [95% CI: 576 to 596]; p = 0.688) and IFG + IGT (579 ml [95% CI: 571 to 586]; p = 0.209) groups. There were no associations of FG, 2HG and OGTT parameters with WMV.Our findings suggest that elevated FG levels, even within the prediabetic range, might already have some harmful effects on GMV.
Published: 2017

41. Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group

Author: B.W.J.H. Penninx, Henry Völzke, Wiro J. Niessen, Nicholas G. Martin, Bernhard T. Baune, D. Schoepf, Michael Czisch, Neda Jahanshad, Jeremy Hall, Walter Heindel, Knut Schnell, Carsten Konrad, Nikolay A. Bokhan, Miguel E. Rentería, Lyubomir I. Aftanas, Christopher G. Davey, Martin Walter, Sean N. Hatton, M. A. Ikram, Joshua W. Cheung, Baptiste Couvy-Duchesne, M Selonke, Dick J. Veltman, Meng Li, Paul M. Thompson, M-J van Tol, Katharina Wittfeld, Thomas Frodl, L. S. van Velzen, Ben J. Harrison, Matthew D. Sacchet, Bartosz Zurowski, D. Hoehn, Ilya M. Veer, Nils Opel, Beata R. Godlewska, Meike W. Vernooij, Eva-Maria Frey, Henning Tiemeier, Oliver Gruber, Bernd Krämer, Angela Carballedo, Derrek P. Hibar, G.I. de Zubicaray, Ian H. Gotlib, Lianne Schmaal, Dominik Grotegerd, Thomas Nickson, Andrew M. McIntosh, Roberto Goya-Maldonado, Jim Lagopoulos, Philipp G. Sämann, Deborah Janowitz, J.E. Sussmann, Heather C. Whalley, Geoffrey B. Hall, Ivan Brack, Elisabeth Schramm, T.G.M. van Erp, Henrik Walter, Volker Arolt, Daniel Bos, Robin Bülow, Katie L. McMahon, Claus Normann, Sarah E. Medland, Lachlan T. Strike, Glenda MacQueen, Hans-Jörgen Grabe, Nathan A. Gillespie, Benson Mwangi, Bo Cao, Udo Dannlowski, Harald Kugel, Jair C. Soares, Natalie T. Mills, N.J. van der Wee, Margaret J. Wright, Ian B. Hickie, Martina Papmeyer, A. Hofman, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, Anatomy and neurosciences, APH - Digital Health, Epidemiology, Radiology & Nuclear Medicine, Neurology, Medical Informatics, and Child and Adolescent Psychiatry / Psychology
Subjects: Male, pathology [Frontal Lobe], Audiology, methods [Magnetic Resonance Imaging], 0302 clinical medicine, взрослые, pathology [Brain], pathology [Gray Matter], diagnostic imaging [Cerebral Cortex], Gray Matter, LIFE-SPAN, Cerebral Cortex, First episode, pathology [Depressive Disorder, Major], Brain, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, 3. Good health, Psychiatry and Mental health, medicine.anatomical_structure, Frontal lobe, VOXEL-BASED MORPHOMETRY, pathology [Gyrus Cinguli], Major depressive disorder, Female, Original Article, DRUG-NAIVE, methods [Neuroimaging], Psychology, psychology [Neuroimaging], Adult, medicine.medical_specialty, MOOD DISORDERS, магнитно-резонансная томография головного мозга, Adolescent, Prefrontal Cortex, Neuroimaging, 610 Medicine & health, SURFACE-AREA, diagnostic imaging [Depressive Disorder, Major], Gyrus Cinguli, behavioral disciplines and activities, 03 medical and health sciences, Cellular and Molecular Neuroscience, THICKNESS, mental disorders, medicine, Humans, ddc:610, Molecular Biology, Anterior cingulate cortex, GRAY-MATTER VOLUME, METAANALYSIS, корковые аномалии, Depressive Disorder, Major, pathology [Temporal Lobe], Voxel-based morphometry, HEALTHY-CHILDREN, medicine.disease, R1, pathology [Prefrontal Cortex], 030227 psychiatry, депрессивные расстройства, Superior frontal gyrus, ANTERIOR CINGULATE CORTEX, Posterior cingulate, pathology [Cerebral Cortex], Orbitofrontal cortex, Neuroscience, подростки, 030217 neurology & neurosurgery
Abstract: The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen's d effect sizes: -0.10 to -0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: -0.26 to -0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.
Published: 2017

42. Predicting brain structure in population-based samples with biologically informed genetic scores for schizophrenia

Author: Barbara Franke, Hans J. Grabe, Norbert Hosten, Niccolo Usberti, Katharina Wittfeld, Janita Bralten, Uwe Völker, Henry Völzke, A. Marten H. Onnink, Marcel P. Zwiers, Elena Shumskaya, Johannes Hertel, and Sandra Van der Auwera
Subjects: 0301 basic medicine, Adult, Male, Population, Population based, Biology, physiopathology [Brain], Bioinformatics, computer.software_genre, Brain mapping, 150 000 MR Techniques in Brain Function, White matter, 03 medical and health sciences, Cellular and Molecular Neuroscience, methods [Brain Mapping], 0302 clinical medicine, methods [Magnetic Resonance Imaging], Voxel, Risk Factors, mental disorders, medicine, Humans, genetics [Schizophrenia], ddc:610, education, Genetics (clinical), education.field_of_study, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], genetics [Organ Size], Healthy subjects, Brain, Voxel-based morphometry, Organ Size, Phenotype, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, medicine.anatomical_structure, Schizophrenia, Female, physiopathology [Schizophrenia], computer, anatomy & histology [Brain], 030217 neurology & neurosurgery, Forecasting
Abstract: Contains fulltext : 169790pub.pdf (Publisher’s version ) (Closed access) Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants for schizophrenia belonging to specific biological systems like synaptic function, neurodevelopment, calcium signaling, and glutamatergic neurotransmission. We hypothesized that this "biologically informed" approach would provide the missing link between genetic risk for schizophrenia and brain structural phenotypes. We applied whole-brain voxel-based morphometry (VBM) analyses in two population-based target samples and subsequent regions of interest (ROIs) analyses in an independent replication sample (total N = 2725). No consistent association between the genetic scores and brain volumes were observed in the investigated samples. These results suggest that in healthy subjects with a higher genetic risk for schizophrenia additional factors apart from common genetic variants (e.g., infection, trauma, rare genetic variants, or gene-gene interactions) are required to induce structural abnormalities of the brain. Further studies are recommended to test for possible gene-gene or gene-environment effects. (c) 2017 Wiley Periodicals, Inc.
Published: 2017

43. Novel genetic loci underlying human intracranial volume identified through genome-wide association

Author: G. Bruce Pike, Marcel P. Zwiers, Andreas Meyer-Lindenberg, Jeroen van der Grond, Randy L. Gollub, Karen A. Mather, Andrew J. Schork, Vidar M. Steen, Marc M. Bohlken, Nhat Trung Doan, Derek W. Morris, John B.J. Kwok, Emma J. Rose, Johanna Hass, Andrew Simmons, Tian Ge, Reinhold Schmidt, Micael Andersson, Ian J. Deary, Christopher Chen, Derrek P. Hibar, Simon E. Fisher, Lucija Abramovic, Marcella Rietschel, Edith Hofer, Simon Lovestone, Clyde Francks, Christopher R.K. Ching, Srdjan Djurovic, Lachlan T. Strike, Lorna M. Lopez, Rene L. Olvera, Owen Carmichael, M. Arfan Ikram, Andre F. Marquand, Christine Macare, W.T. Longstreth, Philippe Amouyel, Aaron L. Goldman, Wolfgang Hoffmann, Philip L. De Jager, David C. Liewald, Harald H H Göring, Aad van der Lugt, David Ames, Neeltje E.M. van Haren, Lars Nyberg, Nina Romanczuk-Seiferth, Lukas Pirpamer, Stefan Ehrlich, Alexa S. Beiser, Lianne Schmaal, Hilkka Soininen, Mark Jenkinson, Kazima B. Bulayeva, Anderson M. Winkler, Mike A. Nalls, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Loes M. Olde Loohuis, Andrew Singleton, Gabriel Cuellar-Partida, Randy L. Buckner, Dorret I. Boomsma, Dena G. Hernandez, Steven G. Potkin, Sudha Seshadri, Bertram Müller-Myhsok, D. Hoehn, Gareth E. Davies, Chantal Depondt, Henrik Walter, Michael E. Weale, Deborah Janowitz, Susanne Erk, Iryna O. Fedko, Daniel R. Weinberger, Nic J A van der Wee, Jean-Luc Martinot, Jessica A. Turner, Marieke Klein, Sandra Barral, Sebastian Mohnke, Albert Hofman, Ingrid Melle, Saud Alhusaini, Vincent Chouraki, Stephen M. Lawrie, Mark E. Bastin, Juan C. Troncoso, Jean Shin, Wiro J. Niessen, Diane M. Becker, Laura Almasy, Anders M. Dale, Benjamin S. Aribisala, Dennis van 't Ent, Marco P. Boks, M. Mallar Chakravarty, Paul M. Thompson, David Reese McKay, Michael Griswold, John Blangero, Narelle K. Hansell, Eco J. C. de Geus, Paul A. Nyquist, Susana Muñoz Maniega, Sampath Arepalli, Tatjana Rundek, Dan L. Longo, Anton J. M. de Craen, Rebekah McWhirter, Nazanin Mirza-Schreiber, Henning Tiemeier, Girma Woldehawariat, Sven Cichon, Irene Pappa, Amelia A. Assareh, Sudheer Giddaluru, Pieter J. Hoekstra, Hieab H.H. Adams, Hilleke E. Hulshoff Pol, Grant W. Montgomery, Roel A. Ophoff, Markus M. Nöthen, Sara Pudas, Sigurdur Sigurdsson, Arthur W. Toga, Tien Yin Wong, Massimo Pandolfo, Corina U. Greven, Esther Walton, Tianye Jia, David J. Stott, Gunter Schumann, Marie-José van Tol, Dalia Kasperaviciute, Thomas Wolfers, Henry Völzke, Ian Ford, Shannon L. Risacher, Jessika E. Sussmann, Nicholas G. Martin, Wei Wen, Daniah Trabzuni, Iwona Kłoszewska, Kwangsik Nho, Gianpiero L. Cavalleri, Adam M. Brickman, Sungeun Kim, Andreas Heinz, Ralph L. Sacco, Neda Jahanshad, Velandai Srikanth, Elena Shumskaya, Susan H. Blanton, Katharina Wittfeld, Badri N. Vardarajan, Joshua C. Bis, Joanne E. Curran, Helena Schmidt, Peter T. Fox, Clifford R. Jack, Jason L. Stein, Laura M. E. Blanken, Thomas Espeseth, Dick J. Veltman, Sebastian Guelfi, Margaret J. Wright, Norman Delanty, Michael Czisch, Martina Papmeyer, Oscar L. Lopez, Marjolein M. J. Van Donkelaar, Bruce M. Psaty, Jan K. Buitelaar, Sven J. van der Lee, David A. Bennett, Beng-Choon Ho, Oliver Martinez, Wiepke Cahn, Li Shen, J. Wouter Jukema, Janita Bralten, Peter Kochunov, Greig I. Zubicaray, Marcel P. van der Brug, Ching-Yu Cheng, Philipp G. Sämann, Stella Trompet, Roberto Roiz-Santiañez, David C. Glahn, Allissa Dillman, Venkata S. Mattay, Dara M. Cannon, Michael W. Weiner, Christopher D. Whelan, Alexander Teumer, Sylvane Desrivières, Ole A. Andreassen, Thomas E. Nichols, Manuel Mattheisen, Matthias Nauck, René S. Kahn, Albert V. Smith, Colin Smith, Vilmundur Gudnason, Denis A. Evans, Anouk den Braber, Katie L. McMahon, Han G. Brunner, Florian Holsboer, Yuri Milaneschi, Andrew J. Saykin, Jiemin Liao, Vince D. Calhoun, Neelum T. Aggarwal, Dennis van der Meer, Hans J. Grabe, Anita L. DeStefano, Claudia L. Satizabal, Alan B. Zonderman, Alex P. Zijdenbos, Tulio Guadalupe, Ingrid Agartz, Jordan W. Smoller, Allison C. Nugent, Alejandro Arias-Vasquez, Masashi Ikeda, Avram J. Holmes, Brenda W.J.H. Penninx, John Hardy, Herve Lemaitre, Charles DeCarli, Patrizia Mecocci, Catharina A. Hartman, Tomas Axelsson, Oliver Grimm, Irina Filippi, Wayne C. Drevets, Hans van Bokhoven, Miguel E. Rentería, Aiden Corvin, Ryota Kanai, Kristel R. van Eijk, Andrew M. McIntosh, Jouke-Jan Hottenga, Roberto Toro, Lavinia Athanasiu, Joanna M. Wardlaw, Thomas H. Mosley, Mina Ryten, Meike W. Vernooij, Michelle Luciano, Joshua L. Roffman, Rebecca F. Gottesman, Dhananjay Vaidya, Ryota Hashimoto, Mar Matarin, Adaikalavan Ramasamy, Jerome I. Rotter, Ryan L. Muetzel, Konstantinos Arfanakis, Theo G.M. van Erp, Ganesh Chauhan, Xinmin Liu, Tomáš Paus, Emma Sprooten, Christiane Wolf, David S. Knopman, Manon Bernard, Zdenka Pausova, Bryan J. Traynor, Maria C. Valdés Hernández, Robert C. Green, Russell Thomson, Ravi Duggirala, Lisa R. Yanek, Luigi Ferrucci, Bing Xu, Thomas D. Dyer, Thomas H. Wassink, Eric Westman, Jennifer S. Richards, Phil H. Lee, Benno Pütz, Mark R. Cookson, Benedicto Crespo-Facorro, Natalie A. Royle, Bernd Kraemer, Katrin Hegenscheid, Francis J. McMahon, Tatiana Foroud, M. Kamran Ikram, Myriam Fornage, Nanda Rommelse, Saima Hilal, Perminder S. Sachdev, Qiang Chen, Najaf Amin, Lenore J. Launer, Norbert Hosten, Guillén Fernández, Simone Reppermund, Ashley Beecham, Dirk J. Heslenfeld, Masaki Fukunaga, Cornelia M. van Duijn, Clinton B. Wright, Erik G. Jönsson, Sanjay M. Sisodiya, Oliver Gruber, Christophe Tzourio, André G. Uitterlinden, Robert Johnson, Jaap Oosterlaan, Bernard Mazoyer, H. Ronald Zielke, Stephanie Le Hellard, Jingyun Yang, Georg Homuth, Stéphanie Debette, Nicola J. Armstrong, Sarah E. Medland, Henry Brodaty, Beverly G Windham, Gary Donohoe, Rachel M. Brouwer, James T. Becker, Kumar B. Rajan, Daan van Rooij, Thomas W. Mühleisen, Kazutaka Ohi, Peter R. Schofield, Tonya White, Barbara Franke, Unn K. Haukvik, Debra A. Fleischman, J. Raphael Gibbs, Colm McDonald, Anbupalam Thalamuthu, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Keck School of Medicine [Los Angeles], University of Southern California (USC), Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Johns Hopkins University (JHU), QIMR Berghofer Medical Research Institute, Leiden University Medical Center (LUMC), Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of Miami Leonard M. Miller School of Medicine (UMMSM), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, Department of Neurology and Neurosurgery [Montreal], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Royal College of Surgeons in Ireland (RCSI), Umeå University, Illinois Institute of Technology (IIT), Rush University Medical Center [Chicago], University of Edinburgh, Lagos State University (LASU), University of New South Wales [Sydney] (UNSW), Murdoch University, University of Oslo (UiO), Uppsala University, Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Toronto, University of Washington [Seattle], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Columbia University Medical Center (CUMC), Columbia University [New York], Pennington Biomedical Research Center, Louisiana State University (LSU), McGill University = Université McGill [Montréal, Canada], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lieber Institute for Brain Development [Baltimore] (LIBD), University of California [Los Angeles] (UCLA), University of California, Vrije Universiteit Amsterdam [Amsterdam] (VU), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Massachusetts General Hospital [Boston], Neuroimagerie en psychiatrie (U1000), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of Bergen (UiB), Haukeland University Hospital, Johns Hopkins University School of Medicine [Baltimore], Universität Heidelberg [Heidelberg], University of Mississippi Medical Center (UMMC), International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], National University of Singapore (NUS), Medical University Graz, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Yale University [New Haven], University College of London [London] (UCL), Imperial College London, Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Medstar Research Institute, Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Institute of Human Genetics, University of Bonn, Department of Genomics, Life and Brain Center, Groupe d'imagerie neurofonctionnelle (GIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Dpt of Psychiatry [New Haven], Yale University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Department of Psychology [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Indiana University System, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, Respiratory Epidemiology and Public Health, Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-MRC-HPA Centre for Environment and Health, Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), INSERM, Neuroepidemiology U708, Bordeaux, France, Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), University of California-University of California, Department of Neurosciences [San Diego], Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, University of Queensland [Brisbane], Queensland Institute of Medical Research, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Genetics, King Faisal Specialist Hospital and Research Centre, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Depts of Radiology, University of Twente [Netherlands], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, National Institutes of Health [Bethesda] (NIH), General Internal Medicine, Johns Hopkins School of Medicine, Biospective [Montréal], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Southwest Foundation for Biomedical Research, Department of Psychiatry and National Ageing Research Institute, University of Melbourne, Department of Clinical Genetics, Department of Medical Parasitology and Mycology, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Siences, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, TX], 849 Department of Human Genetics, Dementia Collaborative Research Centre, Centre for Healthy Brain Ageing, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Université de Lausanne (UNIL), Department of Psychiatry [Boston], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Icahn School of Medicine at Mount Sinai [New York] (MSSM), The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Division of Molecular and Cellular Therapeutics, Metacohorts Consortium, Division of Medical Genetics, University of Basel (Unibas), Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], VU University Amsterdam, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital [Boston], Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA, Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), School of Psychology, University of Queensland, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, Molecular and Cellular Therapeutics, Department of Neurology, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB)-Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Laboratory of Neurogenetics, Department of Genomics, Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Department of Radiology, Mayo Clinic, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Department of Physics, Okayama University, Okayama University, National Institute of Aging, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Public Health Genomics Unit, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Mathematics, University of Colorado, University of Colorado [Boulder], Icelandic Heart Association, Kopavogur, Iceland., Faculty of Medicine, University of Iceland [Reykjavik], Department of Molecular Neurosciences, Institute of Neurology, UCL, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Tohoku University [Sendai], Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Centre for Allergy Research, Karolinska Institutet [Stockholm], Interuniversity Cardiology Institute Netherlands, Institute of Cognitive Neuroscience, School of Psychology, University of Sussex, Brighton BN1 9QH, UK, University of Sussex, Medical University of Łódź (MUL), Mayo Clinic [Rochester], University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), University of Maryland System, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Université de Cergy Pontoise (UCP), Université Paris-Seine, Lymphocyte Cell Biology Unit, Laboratory of Genetics, Laboratoire de Statistique Théorique et Appliquée (LSTA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Psychiatry Institute, Department of Health and Human Services, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia (UNIPG), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Medical Faculty [Mannheim], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Université de Toulon - UFR Lettres et Sciences Humaines (UTLN UFR LSH), Université de Toulon (UTLN), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Warwick Manufacturing Group [Coventry] (WMG), University of Warwick [Coventry], Department of Statistics [Warwick], Delft University of Technology (TU Delft), Rheinische Friedrich-Wilhelms-Universität Bonn, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, Group Health Research Institute, Group Health Cooperative, Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Cedars-Sinai Medical Center, Centre for Healthy Brain Ageing [Sydney], The University of Sydney, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Broad Institute [Cambridge], Harvard University [Cambridge]-Massachusetts Institute of Technology (MIT), Department of Medical Biochemistry and Microbiology, Department of Clinical and Experimental Epilepsy, Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Monash University [Melbourne], Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia, University of Tasmania [Hobart, Australia] (UTAS), Institute of Cardiovascular and Medical Sciences [Glasgow], University of Glasgow, Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Department of Epidemiology, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of York [York, UK], Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Genentech, Inc. [San Francisco], Departments of Radiology and of Epidemiology [Rotterdam], Psychiatry and Leiden Institute for Brain and Cognition, Department of Neurology [Rotterdam], Institute for Community Medicine, Berlin School of Mind and Brain [Berlin], Humboldt-Universität zu Berlin, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Centre for Population Health Sciences, Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Neurobiology, Care Sciences and Society, Research Laboratory for Archaeology & the History of Art, Singapore Eye Research Institute, Singapore National Eye Centre, School of Life Sciences, Arizona State University [Tempe] (ASU), Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, University of California [Davis] (UC Davis), Dpt of Pharmacology and Personalised Medicine [Maastricht], Maastricht University [Maastricht], University of Missouri [Columbia] (Mizzou), University of Missouri System, Göttingen Zentrum Geowissenschaften, Georg-August-University [Göttingen], Human Genetics Center, Psychiatry, EMGO - Mental health, Amsterdam Neuroscience - Complex Trait Genetics, Anatomy and neurosciences, Klinische Genetica, MUMC+: DA Klinische Genetica (5), RS: FHML non-thematic output, RS: GROW - School for Oncology and Reproduction, RS: GROW - R4 - Reproductive and Perinatal Medicine, Genetica & Celbiologie, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Universidad de Cantabria, Universiteit Leiden, Radboud University [Nijmegen], University of California (UC), Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Bonn = University of Bonn, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Yale School of Medicine [New Haven, Connecticut] (YSM), Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of California (UC)-University of California (UC), Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of California (UC)-University of California (UC)-University of California [San Diego] (UC San Diego), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), King Faisal Specialist Hospital and Research Centre (KFSH & RC), Universiteit Leiden-Universiteit Leiden, University of Twente, University of California [Irvine] (UC Irvine), Radboud University [Nijmegen]-Radboud University [Nijmegen], Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Lausanne = University of Lausanne (UNIL), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Università degli Studi di Perugia = University of Perugia (UNIPG), University Hospital Mannheim | Universitätsmedizin Mannheim, Universität Leipzig-Universität Leipzig, University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Harvard University-Massachusetts Institute of Technology (MIT), University of Eastern Finland, Humboldt University Of Berlin, Georg-August-University = Georg-August-Universität Göttingen, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Epidemiology, Child and Adolescent Psychiatry / Psychology, Ophthalmology, Radiology & Nuclear Medicine, Internal Medicine, Neurosciences, Obstetrics & Gynecology, Neurology, EMGO+ - Mental Health, Biological Psychology, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), McGill University-McGill University, National Heart, Lung, and Blood Institute [Bethesda] (NHLBI)-Boston University [Boston] (BU), McGill University, Technische Universität Dresden (TUD), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], University of Bergen (UIB), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Minnesota [Twin Cities], Karakter Child and Adolescent Psychiatry University Center Nijmegen, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Okayama University [Okayama], Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Massachusetts Institute of Technology (MIT)-Harvard University [Cambridge], University of Tasmania (UTAS), Humboldt Universität zu Berlin, Department of Physics [Kowloon], University of Missouri [Columbia], Georg-August-Universität Göttingen, and the Alzheimer's Disease Neuroimaging Initiative, EPIGEN, IMAGEN, SYS
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), Genome-wide association study, Disease, methods [Genome-Wide Association Study], Genome-wide association studies, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Cognition, PARKINSONS-DISEASE, pathology [Brain], genetics [Parkinson Disease], 610 Medicine & health, General Neuroscience, growth & development [Brain], physiology [Cognition], 220 Statistical Imaging Neuroscience, COMMON VARIANTS, Brain, Parkinson Disease, Phenotype, 17Q21.31 MICRODELETION, IGF-I, genetics [Oncogene Protein v-akt], Oncogene Protein v-akt, ALZHEIMERS-DISEASE, HEAD CIRCUMFERENCE, Brain size, genetics [Polymorphism, Single Nucleotide], Medical genetics, GROWTH, Neuroinformatics, medicine.medical_specialty, Neuroscience(all), European Continental Ancestry Group, genetics [Genetic Loci], Biology, Genetic correlation, Polymorphism, Single Nucleotide, 150 000 MR Techniques in Brain Function, Article, White People, 03 medical and health sciences, Image processing, SDG 3 - Good Health and Well-being, ddc:570, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Gene, METAANALYSIS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Neurology & Neurosurgery, Neuroscience (all), Height, [SCCO.NEUR]Cognitive science/Neuroscience, CONSORTIUM, Development of the nervous system, 1702 Cognitive Science, 030104 developmental biology, Genetic Loci, Human genome, BRAIN SIZE, 1109 Neurosciences, genetics [Phosphatidylinositol 3-Kinases], Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 165723pub.pdf (Publisher’s version ) (Closed access) Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rhogenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
Published: 2016

44. Genetic architecture of subcortical brain structures in 38,851 individuals

Author: Mar Matarin, Douglas N. Greve, Nic J.A. van der Wee, Evan Fletcher, Christiane Wolf, Arvin Saremi, Joshua W. Cheung, Randy L. Gollub, David Ames, Honghuang Lin, Nicholas G. Martin, Manon Bernard, Daniel R. Weinberger, Henry Völzke, Manuel Mattheisen, George Davey Smith, Dan J. Stein, Dorret I. Boomsma, John D. Eicher, Henrik Walter, Massimo Pandolfo, Andreas Meyer-Lindenberg, D. Hoehn, Louis N. Vinke, Wiro J. Niessen, G. Bruce Pike, Simon E. Fisher, Jerome I. Rotter, Neeltje E.M. van Haren, Neda Jahanshad, Stephen M. Lawrie, Mark E. Bastin, Sanjay M. Sisodiya, Marcella Rietschel, Jean Shin, Dirk J. Heslenfeld, Ingrid Agartz, Lars Nyberg, Nina Romanczuk-Seiferth, Clifford R. Jack, Markus Scholz, Baljeet Singh, Rachel M. Brouwer, Marco P. Boks, M. Mallar Chakravarty, Magda Tsolaki, André G. Uitterlinden, Amelia A. Assareh, Nastassja Koen, Beng-Choon Ho, Muralidharan Sargurupremraj, Perminder S. Sachdev, James T. Becker, Narelle K. Hansell, Katrin Hegenscheid, Zdenka Pausova, Irina Filippi, Hans van Bokhoven, Miguel E. Rentería, Robert C. Green, M. Kamran Ikram, Vidar M. Steen, Marc M. Bohlken, Iryna O. Fedko, Jayandra J. Himali, Hieab H.H. Adams, Erik G. Jönsson, Esther Walton, Gunter Schumann, Dennis van der Meer, Jordan W. Smoller, Ganesh Chauhan, Simon Lovestone, Kwangsik Nho, Gianpiero L. Cavalleri, Andrew Simmons, Shuo Li, Hannah J. Jones, Lavinia Athanasiu, Shahrzad Kharabian Masouleh, Micael Andersson, Andreas Heinz, Lucija Abramovic, Alexa S. Beiser, Vilmundur Gudnason, Oliver Gruber, Tianye Jia, Daan van Rooij, Philip L. De Jager, Allison Stevens, Thomas W. Mühleisen, Deborah Janowitz, Anita L. DeStefano, Gennady V. Roshchupkin, Maria C. Valdés Hernández, Nynke A. Groenewold, Vince D. Calhoun, Cornelia M. van Duijn, Roberto Toro, Wiepke Cahn, Florian Holsboer, Asta Håberg, Aaron Goldman, Lisa R. Yanek, Jingyun Yang, Matthias L. Schroeter, Patrizia Mecocci, Sven J. van der Lee, Gareth E. Davies, Elena Shumskaya, Jia Yu Koh, Thomas H. Wassink, Wei Wen, A. Veronica Witte, Anders M. Dale, Diana Tordesillas-Gutiérrez, Iwona Kłoszewska, Benedicto Crespo-Facorro, Sylvane Desrivières, Catharina A. Hartman, Saskia P. Hagenaars, Jennifer S. Richards, Martine Hoogman, Philipp G. Sämann, Andre F. Marquand, Stephanie Le Hellard, Christophe Tzourio, Sven Cichon, Tomáš Paus, Ole A. Andreassen, Pieter J. Hoekstra, Gabriel Cuellar-Partida, Joanna M. Wardlaw, Thomas H. Mosley, Bernd Kraemer, Barbara Franke, Joshua C. Bis, Katharina Wittfeld, Christopher D. Whelan, Christine Macare, Unn K. Haukvik, Lars T. Westlye, Loes M. Olde Loohuis, Sudha Seshadri, Michelle Luciano, Shannon L. Risacher, Diane M. Becker, Tamara B. Harris, Georg Homuth, Sungeun Kim, Lenore J. Launer, Debra A. Fleischman, Tulio Guadalupe, Joshua L. Roffman, Marie-José van Tol, Stéphanie Debette, Benno Pütz, Dick J. Veltman, Ching-Yu Cheng, Norman Delanty, Chantal Depondt, Jaap Oosterlaan, Nicola J. Armstrong, Myriam Fornage, Eric Westman, Anouk den Braber, Nanda Rommelse, Qiong Yang, Yasaman Saba, Tatiana Foroud, Susanne Erk, Saima Hilal, Paul M. Thompson, Eco J. C. de Geus, Paul A. Nyquist, Wolfgang Hoffmann, Alexander Teumer, Avram J. Holmes, Qiang Chen, Najaf Amin, Albert V. Smith, Tom V. Lee, Sarah E. Medland, Nazanin Mirza-Schreiber, Alejandro Arias-Vasquez, Grant W. Montgomery, Han G. Brunner, Meike W. Vernooij, Bernard Mazoyer, Guillén Fernández, Henry Brodaty, Claudia L. Satizabal, Thomas Wolfers, Herve Lemaitre, Li Shen, Greig I. de Zubicaray, Pauline Maillard, Hans J. Grabe, Ingrid Melle, Simone Reppermund, Charles DeCarli, Anbupalam Thalamuthu, Helena Schmidt, Peter R. Schofield, Marjolein M.J. van Donkelaar, Thomas Espeseth, Christopher Chen, Matthias Nauck, Norbert Hosten, Clyde Francks, Oliver Grimm, Tonya White, Andrew J. Saykin, Andrew M. McIntosh, Oscar L. Lopez, Philippe Amouyel, William T. Longstreth, Janita Bralten, Nhat Trung Doan, John B.J. Kwok, Charles C. White, Ralph Burkhardt, Jessika E. Sussmann, Michael W. Weiner, Markus M. Nöthen, Katie L. McMahon, Derrek P. Hibar, Dalia Kasperaviciute, Maria J. Knol, Hilleke E. Hulshoff Pol, Markus Loeffler, Bruno Vellas, Matthew J. Huentelman, Owen Carmichael, Jason L. Stein, Ryota Kanai, Lianne Schmaal, Hilkka Soininen, Bruce M. Psaty, Jan K. Buitelaar, Jean-Luc Martinot, Ian J. Deary, Venkata S. Mattay, Theo G.M. van Erp, Arno Villringer, Andrew D. Johnson, Srdjan Djurovic, Benjamin S. Aribisala, Lachlan T. Strike, Phil Lee, David C. Liewald, Tien Yin Wong, Tomas Axelsson, Jessica A. Turner, Marieke Klein, Kristel R. van Eijk, Saud Alhusaini, Konstantinos Arfanakis, M. Arfan Ikram, Stefan Ehrlich, Sebastian Mohnke, Marcel P. Zwiers, Karen A. Mather, Jonathan C Ipser, Joshua M. Shulman, Brenda W.J.H. Penninx, Reinhold Schmidt, Arthur W. Toga, Christopher R.K. Ching, René S. Kahn, Bertram Müller-Myhsok, Yuri Milaneschi, Margaret J. Wright, Martina Papmeyer, Fabrice Crivello, David A. Bennett, Randy L. Buckner, Edith Hofer, Roel A. Ophoff, Steven G. Potkin, Albert Hofman, Dennis van 't Ent, Sudheer Giddaluru, Roberto Roiz-Santiañez, Andrew J. Schork, Jouke-Jan Hottenga, Yanhui Hu, Kazima B. Bulayeva, Xueqiu Jian, Clinical Genetics, Epidemiology, Radiology & Nuclear Medicine, Medical Informatics, Neurology, Child and Adolescent Psychiatry / Psychology, Psychiatry, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), APH - Mental Health, Pediatric surgery, Epidemiology and Data Science, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, APH - Digital Health, General Paediatrics, ARD - Amsterdam Reproduction and Development, Psychiatrie & Neuropsychologie, Klinische Genetica, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA Klinische Genetica (5), RS: MHeNs - R2 - Mental Health, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Stochastics, Biological Psychology, APH - Methodology, Clinical Neuropsychology, IBBA, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, and Cognitive Psychology
Subjects: Netherlands Twin Register (NTR), LD SCORE REGRESSION, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Caudate nucleus, Genome-wide association study, Bio-Organic Chemistry, Language in Interaction, neuroscience, Cohort Studies, BASAL GANGLIA, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, metabolism [Drosophila melanogaster], Basal ganglia, Adult, Aged, Animals, Brain, Drosophila melanogaster, Humans, Magnetic Resonance Imaging, Middle Aged, Neurodevelopmental Disorders, Organ Size, Genetic Variation, Genome-Wide Association Study, genetics [Drosophila melanogaster], 0303 health sciences, genetics [Neurodevelopmental Disorders], Putamen, 220 Statistical Imaging Neuroscience, 3. Good health, ALZHEIMERS-DISEASE, DROSOPHILA, Globus pallidus, VINTAGE, epidemiology, Synaptic signaling, Neuroinformatics, EXPRESSION, Nucleus accumbens, Biology, 150 000 MR Techniques in Brain Function, Article, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, SDG 3 - Good Health and Well-being, ddc:570, PLASMA-PROTEIN, pathology [Neurodevelopmental Disorders], Genetics, GENOME-WIDE ASSOCIATION, HEALTHY, METAANALYSIS, 030304 developmental biology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], RISK LOCI, Genetic architecture, ALKALINE-PHOSPHATASE, nervous system, metabolism [Brain], genome-wide association studies, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, growth & development [Drosophila melanogaster], anatomy & histology [Brain], Neuroscience, 030217 neurology & neurosurgery
Abstract: Aims/hypothesis MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes. Methods Using next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic). Results We identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3–5 (vs 2.4% in controls; p = 0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls; p = 1.6 × 10−5). HNF1A showed the strongest enrichment of class 3–5 variants, with 3.9% among antibody-negative patients (vs 0.4% in controls; p = 0.0002). Antibody-negative carriers of variants in class 3 had a similar phenotype to those carrying variants in classes 4 and 5. Conclusions/interpretation This is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important for treatment and genetic counselling, molecular screening of all antibody-negative children should be considered in routine diagnostics.
Published: 2019

45. Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

Author: Svante Pääbo, Philipp Gunz, Han G. Brunner, Katharina Wittfeld, Uwe Völker, Simon E. Fisher, Beate St Pourcain, Janet Kelso, Barbara Franke, Fabio Macciardi, Tulio Guadalupe, Amanda K. Tilot, Fabio Di Vincenzo, Chin Yang Shapland, Giorgio Manzi, Antonio Profico, Guillén Fernández, Hans J. Grabe, Jean-Jacques Hublin, Norbert Hosten, Theo G.M. van Erp, James H. Fallon, Benjamin Vernot, Wolfgang Enard, Michael Dannemann, Alexander Teumer, Simon Neubauer, MUMC+: DA Klinische Genetica (5), Klinische Genetica, and RS: GROW - R4 - Reproductive and Perinatal Medicine
Subjects: brain shape, Male, 0301 basic medicine, genetic association, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Brain tissue, Language in Interaction, BASAL GANGLIA, 0302 clinical medicine, SCHIZOPHRENIA, magnetic resonance imaging, anatomy & histology [Skull], Neanderthals, Netherlands, Aged, 80 and over, 0303 health sciences, Fossils, Brain, myelination, Hominidae, ASSOCIATION, Middle Aged, Biological Evolution, GENOME, Phenotype, medicine.anatomical_structure, basal ganglia, Female, General Agricultural and Biological Sciences, cerebellum, evolution, gene expression, homo sapiens, Neandertal, Neuroinformatics, Adult, HOMO, Adolescent, Introgression, Genomics, Biology, SEQUENCE, Article, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Globular shape, ddc:570, Endocranium, medicine, Animals, Humans, PHLPP, 030304 developmental biology, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], AKT, Skull, EVOLUTION, anatomy & histology [Neanderthals], 030104 developmental biology, Homo sapiens, Evolutionary biology, Hybridization, Genetic, MYELINATION, 030217 neurology & neurosurgery, Endocast
Abstract: SUMMARY One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1–4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape., In Brief Gunz, Tilot et al. combine paleoanthropology, archaic genomics, neuroimaging, and gene expression to study biological foundations of the characteristic modern human endocranial shape. They find introgressed Neandertal alleles that associate with reduced endocranial globularity and affect expression of genes linked to neurogenesis and myelination.
Published: 2019

46. Advanced brain aging: relationship with epidemiologic and genetic risk factors, and overlap with Alzheimer disease atrophy patterns

Author: Hans-Jörgen Grabe, Wolfgang Hoffmann, Reiner Biffar, S. Van der Auwera, Mohamad Habes, Norbert Hosten, Henry Völzke, Georg Homuth, Deborah Janowitz, K Hegenscheid, Susan M. Resnick, Christos Davatzikos, Jon B. Toledo, Guray Erus, Katharina Wittfeld, and Jimit Doshi
Subjects: 0301 basic medicine, Male, Aging, Pathology, epidemiology [Alzheimer Disease], Physiology, genetics [Alzheimer Disease], Brain mapping, Cohort Studies, pathology [Alzheimer Disease], methods [Brain Mapping], 0302 clinical medicine, pathology [Aging], methods [Magnetic Resonance Imaging], pathology [Brain], Risk Factors, Prevalence, Aged, 80 and over, Brain Mapping, Brain, Middle Aged, Magnetic Resonance Imaging, Psychiatry and Mental health, Study of Health in Pomerania, genetics [Aging], Cohort, Original Article, Female, Alzheimer's disease, Abnormality, Psychology, Adult, medicine.medical_specialty, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Atrophy, Alzheimer Disease, medicine, Dementia, Humans, ddc:610, Sex Distribution, diagnostic imaging [Brain], Biological Psychiatry, Aged, medicine.disease, 030104 developmental biology, Behavioral medicine, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: We systematically compared structural imaging patterns of advanced brain aging (ABA) in the general-population, herein defined as significant deviation from typical BA to those found in Alzheimer disease (AD). The hypothesis that ABA would show different patterns of structural change compared with those found in AD was tested via advanced pattern analysis methods. In particular, magnetic resonance images of 2705 participants from the Study of Health in Pomerania (aged 20–90 years) were analyzed using an index that captures aging atrophy patterns (Spatial Pattern of Atrophy for Recognition of BA (SPARE-BA)), and an index previously shown to capture atrophy patterns found in clinical AD (Spatial Patterns of Abnormality for Recognition of Early Alzheimer’s Disease (SPARE-AD)). We studied the association between these indices and risk factors, including an AD polygenic risk score. Finally, we compared the ABA-associated atrophy with typical AD-like patterns. We observed that SPARE-BA had significant association with: smoking (P<0.05), anti-hypertensive (P<0.05), anti-diabetic drug use (men P<0.05, women P=0.06) and waist circumference for the male cohort (P<0.05), after adjusting for age. Subjects with ABA had spatially extensive gray matter loss in the frontal, parietal and temporal lobes (false-discovery-rate-corrected q
Published: 2016

47. Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Author: Derek W. Morris, Carles Soriano-Mas, Tomáš Paus, Henrik Walter, Dick J. Veltman, Yuqi Cheng, Benjamin S. Aribisala, Anna Cattrell, Hilleke E. Hulshoff Pol, Vatche G. Baboyan, Simon E. Fisher, Michael N. Smolka, Saskia P. Hagenaars, Sarah Jurk, Roberto Roiz-Santiañez, Nicholas G. Martin, Lars T. Westlye, Odile A. van den Heuvel, Lucija Abramovic, Jan Egil Nordvik, Guillén Fernández, Jürgen Gallinat, Je Yeon Yun, Benson Mwangi, Ignacio Martínez-Zalacaín, Bernd Kraemer, Gareth J. Barker, José M. Menchón, Marie-Laure Paillère Martinot, Zhen Wang, Jan K. Buitelaar, Jean-Luc Martinot, Herve Lemaitre, Aiden Corvin, Henry Brodaty, Thomas Wolfers, Silvia Brem, Christine Lochner, Derrek P. Hibar, Susanne Walitza, Susana Muñoz Maniega, Premika S.W. Boedhoe, Nathalie Tzourio-Mazoyer, Uli Bromberg, Sonja M C de Zwarte, Dan J. Stein, Mark E. Bastin, Clyde Francks, Tobias U. Hauser, Sinead Kelly, Hugh Garavan, Omar Mothersill, Gary Donohoe, Neda Jahanshad, Greig I. de Zubicaray, Yoshinari Abe, Roel A. Ophoff, Christian Büchel, Esther Walton, Pieter J. Hoekstra, Nils Opel, Gunter Schumann, Jian Xu, Dara M. Cannon, Elena Shumskaya, Ingrid Agartz, Bernhard T. Baune, A. Marten H. Onnink, Tomohiro Nakao, Rosa Ayesa-Arriola, David Mataix-Cols, Sylvane Desrivières, Klaus-Peter Lesch, Paul Pauli, Wei Wen, Nora C. Vetter, Martine Hoogman, Ganesan Venkatasubramanian, Miguel E. Rentería, Ole A. Andreassen, Penny A. Gowland, Ian J. Deary, Patricia J. Conrod, Nicola J. Armstrong, Masaki Fukunaga, Vince D. Calhoun, Volker Arolt, Dimitri Papadopoulos Orfanos, Benedicto Crespo-Facorro, Lachlan T. Strike, Natalie A. Royle, Joanna M. Wardlaw, Sarah E. Medland, Annette Conzelmann, Andrea Gonzalez Suarez, Arun L.W. Bokde, Ryota Hashimoto, Robert Whelan, Michelle Luciano, Pascual Sánchez-Juan, Neeltje E.M. van Haren, Hao Hu, Luise Poustka, Jun Soo Kwon, Hans J. Grabe, Andreas Heinz, Katharina Wittfeld, Michael Gill, Erik G. Jönsson, Frauke Nees, Perminder S. Sachdev, Oliver Gruber, David C. Glahn, Chaim Huyser, Anushree Bose, Herta Flor, Janardhan Y. C. Reddy, Bernd Ittermann, John Blangero, Dennis van der Meer, Andre F. Marquand, Xiufeng Xu, Tulio Guadalupe, Dominik Grotegerd, Jessica A. Turner, Annerine Roos, Tobias Banaschewski, Theo G.M. vanErp, Jean-Paul Fouche, Paul M. Thompson, Alejandro Arias-Vasquez, Christopher D. Whelan, Maria del C. Valdés Hernández, Eric Artiges, Janardhanan C. Narayanaswaamy, Thomas Espeseth, Bernard Mazoyer, Katie L. McMahon, Erlend S. Dørum, Samantha J. Brooks, Samuel R. Mathias, Vincent Frouin, Fleur M. Howells, Barbara Franke, Colm McDonald, Jingjing Zhao, Daniella Vuletic, Nhat Trung Doan, Harald Kugel, Lianne Schmaal, Marcel P. Zwiers, Fabrice Crivello, Anne Uhlmann, Karen A. Mather, René S. Kahn, Roberto Toro, Stefan Ehrlich, Udo Dannlowski, Jair C. Soares, Takashi Nakamae, Margaret J. Wright, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Brain Imaging, Child Psychiatry, Other departments, ANS - Complex Trait Genetics, International Max Planck Research School for Language Sciences (IMPRS ), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Language and Genetics Department [Nijmegen], Yale University [New Haven], Department of Psychiatry and Human Behavior, University of California [Irvine] (UCI), University of California-University of California, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Department of Psychiatry, Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan, University Medical Center [Utrecht], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], University of Oslo (UiO), Department of Human Genetics, Radboud University Medical Center [Nijmegen], Department of Psychiatry, Donders Centre for Neuroscience, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Mental Health Sciences Unit, University College of London [London] (UCL), Adolescent psychopathology and Medicine, CHU Cochin [AP-HP], Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Hospital Sant Joan de Déu [Barcelona], Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Southern California (USC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg], Centre for Neuroimaging Sciences, Institute of Psychiatry, King‘s College London, University of Adelaide, The University of Texas Health Science Center at Houston (UTHealth), Texas Biomedical Research Institute [San Antonio, Texas], Discipline of Psychiatry [Dublin], School of Medicine [Dublin], Trinity College Dublin-Trinity College Dublin, VU University Medical Center [Amsterdam], National Institute of Mental Health and Neurosciences [Bagalore, India], Hospital of the University of Pennsylvania, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Dementia Collaborative Research Centre, University of New South Wales [Sydney] (UNSW), Centre for Healthy Brain Ageing, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), The University of New Mexico [Albuquerque], Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Institute of Psychiatry, Psychology & Neuroscience, King's College London, Center for disease control, China (Chinese CDC), Center for Disease Control, China, Department of Psychology (Biological Psychology, Clinical Psychology, and Psychotherapy), University of Würzburg, Germany, Tübingen, Würzburg, Germany, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Trinity College Dublin-St. James's Hospital, Groupe d'imagerie neurofonctionnelle (GIN), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), School of Psychology, University of Queensland, University of Queensland [Brisbane], MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), sans affiliation, Universität Mannheim [Mannheim], Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Division of Cerebral Integration National Institute for Physiological Sciences Okazaki Japan, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, University of Calgary, Sir Peter Mansfield Magnetic Resonance Centre [Nottingham], University of Nottingham, UK (UON), Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], University Clinic for Child and Adolescent Psychiatry (UCCAP), University of Zürich [Zürich] (UZH), University Medical Center Groningen [Groningen] (UMCG), Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Brain Centre Rudolf Magnus [Utrecht], MetaCase [Jyväskylä], Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Department of Psychiatry & Behavioral Science Seoul National University College of Medicine Seoul Republic of Korea, Université de Cergy Pontoise (UCP), Université Paris-Seine, Institute of Human Genetics, Rheinische Friedrich-Wilhelms-Universität Bonn, Medstar Research Institute, Neuroimagerie en psychiatrie (U1000), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), IFR de Neuroimagerie Fonctionnelle (IFR 49), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Life Sciences, Imperial College London, Centre for Advanced Imaging, Queensland Institute of Medical Research, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Universitat de Barcelona (UB), National University of Ireland [Galway] (NUI Galway), Climate Change Unit [Ispra], JRC Institute for Environment and Sustainability (IES), European Commission - Joint Research Centre [Ispra] (JRC)-European Commission - Joint Research Centre [Ispra] (JRC), Sunnaas Rehabilitation Hospital HT Nesodden Norway, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University-McGill University, Texas A&M University [College Station], QIMR Berghofer Medical Research Institute, Universiteit van Amsterdam (UvA), Centre for Healthy Brain Ageing [Sydney], The University of Sydney, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Göttingen Zentrum Geowissenschaften, Georg-August-Universität Göttingen, Technische Universität Dresden (TUD), Instituto de Geociências, Universidade de Brasília, Magnetic Resonance Imaging, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa, Centre for Advanced Imaging, University of Queensland, Brisbane 4072, Australia, School of Psychology, University of Queensland, Brisbane 4072, Australia, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], University of York [York, UK], Centre for Cognitive Ageing & Cognitive Epidemiology, Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands, University of Twente [Netherlands], Berlin School of Mind and Brain [Berlin], Humboldt Universität zu Berlin, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Computational and Applied Mathematics [Houston], Rice University [Houston], Department of Physics [Kowloon], Hong Kong University of Science and Technology (HKUST), University College Dublin [Dublin] (UCD), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University of Missouri [Columbia], University of Missouri System, Mechanics surfaces and materials processing (MSMP), École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), Department of Genetics, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Dpt of Psychiatry [New Haven], Yale University School of Medicine, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Radboud University [Nijmegen], Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Universität Heidelberg [Heidelberg] = Heidelberg University, Texas Biomedical Research Institute [San Antonio, TX], University of Pennsylvania-University of Pennsylvania, Radboud University [Nijmegen]-Radboud University [Nijmegen], [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Sans affiliation, Universität Mannheim, Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Universität Zürich [Zürich] = University of Zurich (UZH), Seoul National University [Seoul] (SNU), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Georg-August-University = Georg-August-Universität Göttingen, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Twente, Humboldt University Of Berlin, Centre épigénétique et destin cellulaire (EDC), Department of Physics [Hong Kong University of Science and Technology], University of Missouri [Columbia] (Mizzou), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Yale School of Medicine [New Haven, Connecticut] (YSM), Hal, GIN, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Georg-August-University [Göttingen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Humboldt-Universität zu Berlin, International Max Planck Research School for Language Sciences ( IMPRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, Department of Psychiatry Yale School of Medicine New Haven USA, University of California [Irvine] ( UCI ), Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), University College of London [London] ( UCL ), Centro de Investigación Biomédica en Red de Salud Mental ( CIBERSAM ), Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, University of Southern California, Marina del Rey, CA, USA, The University of Adelaide, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India, Hospital of the University of Pennsylvania, University of New South Wales [Sydney] ( UNSW ), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] ( UKE ), The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), King's College, Center for disease control, China ( Chinese CDC ), GIN - IMN UMR 5293 CNRS CEA Université de Bordeaux, Institut des Maladies Neurodégénératives [Bordeaux] ( IMN ), Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Institut national de la recherche agronomique [Jouy en Josas] ( INRA Jouy en Josas ), Department of Psychology, University of Oslo, Oslo 0373, Norway, Service NEUROSPIN ( NEUROSPIN ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Charite-Universitatsmedizin Berlin [Berlin], University of Nottingham, UK ( UON ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, (UCCAP) University of Zurich Zurich Switzerland, University Medical Center Groningen, University of Groningen, Karolinska University Hospital (Solna), Université de Cergy Pontoise ( UCP ), Bonn Universität [Bonn], Institut de Physique Nucléaire d'Orsay ( IPNO ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR de Neuroimagerie Fonctionnelle ( IFR 49 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] ( IDIBELL ), Universitat de Barcelona ( UB ), National University of Ireland [Galway] ( NUI Galway ), JRC Institute for Environment and Sustainability ( IES ), European Commission - Joint Research Centre [Ispra] ( JRC ) -European Commission - Joint Research Centre [Ispra] ( JRC ), University Medical Center Utrecht-Brain Center Rudolf Magnus, McConnell Brain Imaging Centre ( MNI ), Montreal Neurological Institute [Montréal], Universiteit van Amsterdam ( UvA ), The University of Sydney [Sydney], Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Technische Universität Dresden ( TUD ), Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Hong Kong University of Science and Technology ( HKUST ), University College Dublin [Dublin] ( UCD ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, University of Missouri-Columbia, Mechanics surfaces and materials processing ( MSMP ), North Carolina State University [Raleigh] ( NCSU ), and Yale School of Medicine
Subjects: Male, Aging, Planum temporale, Caudate nucleus, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Subcortical brain asymmetry, Functional Laterality, Behavioral Neuroscience, 0302 clinical medicine, pathology [Aging], ddc:150, 130 000 Cognitive Neurology & Memory, Basal ganglia, YOUNG-ADULTS, Brain asymmetry, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Handedness, Original Research, Sex Characteristics, Age, Enigma, Heritability, Meta-analysis, Sex, Putamen, 05 social sciences, Brain, Human brain, Organ Size, Middle Aged, Magnetic Resonance Imaging, AMYGDALA VOLUME, Psychiatry and Mental health, genetics [Functional Laterality], Globus pallidus, medicine.anatomical_structure, Neurology, BASAL GANGLIA VOLUMES, Radiology Nuclear Medicine and imaging, genetics [Aging], [ SCCO.NEUR ] Cognitive science/Neuroscience, CAUDATE-NUCLEUS, Female, Psychology, Sex characteristics, MRI, Neuroinformatics, Adult, Adolescent, Cognitive Neuroscience, Clinical Neurology, BF, HAND PREFERENCE, 050105 experimental psychology, 150 000 MR Techniques in Brain Function, 03 medical and health sciences, Cellular and Molecular Neuroscience, Young Adult, Quantitative Trait, Heritable, Meta-Analysis as Topic, medicine, Journal Article, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, diagnostic imaging [Brain], Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SCCO.NEUR]Cognitive science/Neuroscience, TOURETTE-SYNDROME, [SCCO.NEUR] Cognitive science/Neuroscience, PLANUM TEMPORALE, NORMAL INDIVIDUALS, HEMISPHERIC-DIFFERENCES, nervous system, RC0321, Neurology (clinical), Neuroscience, anatomy & histology [Brain], 030217 neurology & neurosurgery
Abstract: The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders. Electronic supplementary material The online version of this article (doi:10.1007/s11682-016-9629-z) contains supplementary material, which is available to authorized users.
Published: 2016

48. Alexithymia Is Associated with Altered Cortical Thickness Networks in the General Population

Author: Stefan Frenzel, Henry Völzke, Katharina Wittfeld, Norbert Hosten, Robin Bülow, Johanna Klinger-König, Hans J. Grabe, Jan Terock, and Deborah Janowitz
Subjects: Adult, Male, epidemiology [Affective Symptoms], media_common.quotation_subject, Population, pathology [Nerve Net], epidemiology [Germany], physiopathology [Affective Symptoms], 03 medical and health sciences, Toronto Alexithymia Scale, 0302 clinical medicine, Alexithymia, Neuroimaging, physiology [Personality], Germany, diagnostic imaging [Cerebral Cortex], Medicine, Personality, Humans, Affective Symptoms, ddc:610, education, Paracentral lobule, Biological Psychiatry, media_common, Aged, Cerebral Cortex, diagnostic imaging [Affective Symptoms], education.field_of_study, medicine.diagnostic_test, business.industry, diagnostic imaging [Nerve Net], Chronic pain, pathology [Affective Symptoms], Middle Aged, medicine.disease, Health Surveys, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Study of Health in Pomerania, pathology [Cerebral Cortex], Female, Nerve Net, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background: Alexithymia is a personality trait characterized by difficulties in identifying and describing emotions and associated with various psychiatric disorders. Neuroimaging studies found evidence for morphological and functional brain alterations in alexithymic subjects. However, the neurobiological mechanisms underlying alexithymia remain incompletely understood. Methods: We study the association of alexithymia with cortical correlation networks in a large community-dwelling sample of the Study of Health in Pomerania. Our analysis includes data of n = 2,199 individuals (49.4% females, age = 52.1 ± 13.6 years) which were divided into a low and high alexithymic group by a median split of the Toronto Alexithymia Scale. Cortical correlation networks were constructed based on the mean thicknesses of 68 regions, and differences in centralities were investigated. Results: We found a significantly increased centrality of the right paracentral lobule in the high alexithymia network after correction for multiple testing. Several other regions with motoric and sensory functions showed altered centrality on a nominally significant level. Conclusions: Finding increased centrality of the paracentral lobule, a brain area with sensory as well as motoric features and involvement in bowel and bladder voiding, may contribute to explain the association of alexithymia with functional somatic disorders and chronic pain syndromes.
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