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333 results on '"Donders Centre for Cognitive Neuroimaging"'

1. Slow-SPEED-NL: Slowing Parkinson's Early Through Exercise Dosage-Netherlands (Slow-SPEED-NL)

Author

Stichting ParkinsonNL, ZonMw: The Netherlands Organisation for Health Research and Development, Michael J. Fox Foundation for Parkinson's Research, PARKINSONS UK, Cure Parkinsons, Edmond J. Safra Foundation, Davis Phinney Foundation, Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, Anne Wojcicki Foundation, Sleep Medicine Centre Kempenhaeghe, Sleep Medicine Centre SEIN, Queen Mary University of London, 23andMe, Inc., Parkinsons Progression Markers Initiative (PPMI), Massachusetts General Hospital, Harvard School of Public Health (HSPH), IJsfontein B.V., Netherlands, Hoffmann-La Roche, Erasmus Medical Center, University of Illinois at Chicago, University of Rochester, University of Bristol, University of Plymouth, University of Luebeck, McGill University, and University of Pittsburgh

Published
2024

3. Dopamine and Cognition

Author

Dr. Hanneke den Ouden, Donders Centre for Cognition, Radboud University, Dr. Rebecca Calcott, Donders Centre for Cognitive Neuroimaging, Radboud University, Prof. Dr. Robbert-Jan Verkes, Radboud University Medical Centre Department of Psychiatry, Floortje Spronkers, Donders Centre for Cognition, Radboud University, Funding: NWO + KNAW, and Roshan Cools, Prof. Dr.

Published
2023

4. LSD to Improve Cluster Headache Impact Trial (LICIT)

Author

ZonMw: The Netherlands Organisation for Health Research and Development, Canisius-Wilhelmina Hospital, Leiden University Medical Center, and Donders Centre for Cognitive Neuroimaging

Published
2023

6. Diffusion imaging of the brain: technical considerations and practical applications

Author

FC Donders Centre for Cognitive Neuroimaging, Universität Leipzig, Norris, David G., FC Donders Centre for Cognitive Neuroimaging, Universität Leipzig, and Norris, David G.

Abstract

This chapter presents a brief introduction to the application of diffusion-weighted magnetic resonance imaging (MRI) to in vivo studies. Diffusion-weighted MRI has found application both in the clinic, and in basic neuroscience. In the former situation it is primarily used for the detection of brain lesions, in particular infarcted regions. The ability to follow fibre tracts in white matter via diffusion tensor imaging has also made this methodology of interest to the neurosurgeon wishing to avoid severance of essential fibre tracts, but also of interest to the cognitive neuroscientist exploring anatomical connectivity in the brain. The chapter starts with a brief recap of the theory of diffusionweighted MRI and moves on to examine the two major experimental confounds, eddy currents and bulk motion. Current correction schemes for these problems are touched upon. Diffusion anisotropy is introduced as a potential source of artefacts for lesion detection in white matter, and the diffusion tensor model presented. The chapter concludes with a short introduction to fibre tracking.

Published
2016

7. The Link Between Autism and Sex-Related Neuroanatomy, and Associated Cognition and Gene Expression

Author

Dorothea L, Floris, Han, Peng, Varun, Warrier, Michael V, Lombardo, Charlotte M, Pretzsch, Clara, Moreau, Alex, Tsompanidis, Weikang, Gong, Maarten, Mennes, Alberto, Llera, Daan, van Rooij, Marianne, Oldehinkel, Natalie J, Forde, Tony, Charman, Julian, Tillmann, Tobias, Banaschewski, Carolin, Moessnang, Sarah, Durston, Rosemary J, Holt, Christine, Ecker, Flavio, Dell'Acqua, Eva, Loth, Thomas, Bourgeron, Declan G M, Murphy, Andre F, Marquand, Meng-Chuan, Lai, Jan K, Buitelaar, Simon, Baron-Cohen, Christian F, Beckmann, Universität Zürich [Zürich] = University of Zurich (UZH), Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre, 6525 EN Nijmegen., Wellcome Trust Centre for Integrative Neuroimaging (WIN - FMRIB), University of Oxford, University of Cambridge [UK] (CAM), Autism Research Centre [Cambridge, Royaume-Uni], University of Trento [Trento], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, 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), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], Radboud University Medical Center [Nijmegen], Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Monash University [Melbourne], Roche Pharma Research and Early Development [Basel] (pRED), F. Hoffmann-La Roche [Basel], University Hospital Mannheim | Universitätsmedizin Mannheim, Heidelberg University, University Medical Center [Utrecht], Curtin University [Perth], Planning and Transport Research Centre (PATREC), and Sackler Institute of Translational Neurodevelopment [London]

Subjects
Machine Learning, Psychiatry and Mental health, Gender Differences, Neuroanatomy, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Autism Spectrum Disorder, Neurodevelopmental Disorders, 130 000 Cognitive Neurology & Memory, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], 220 Statistical Imaging Neuroscience, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Brain Imaging Techniques
Abstract

Item does not contain fulltext OBJECTIVE: The male preponderance in prevalence of autism is among the most pronounced sex ratios across neurodevelopmental conditions. The authors sought to elucidate the relationship between autism and typical sex-differential neuroanatomy, cognition, and related gene expression. METHODS: Using a novel deep learning framework trained to predict biological sex based on T(1)-weighted structural brain images, the authors compared sex prediction model performance across neurotypical and autistic males and females. Multiple large-scale data sets comprising T(1)-weighted MRI data were employed at four stages of the analysis pipeline: 1) pretraining, with the UK Biobank sample (>10,000 individuals); 2) transfer learning and validation, with the ABIDE data sets (1,412 individuals, 5-56 years of age); 3) test and discovery, with the EU-AIMS/AIMS-2-TRIALS LEAP data set (681 individuals, 6-30 years of age); and 4) specificity, with the NeuroIMAGE and ADHD200 data sets (887 individuals, 7-26 years of age). RESULTS: Across both ABIDE and LEAP, features positively predictive of neurotypical males were on average significantly more predictive of autistic males (ABIDE: Cohen's d=0.48; LEAP: Cohen's d=1.34). Features positively predictive of neurotypical females were on average significantly less predictive of autistic females (ABIDE: Cohen's d=1.25; LEAP: Cohen's d=1.29). These differences in sex prediction accuracy in autism were not observed in individuals with ADHD. In autistic females, the male-shifted neurophenotype was further associated with poorer social sensitivity and emotional face processing while also associated with gene expression patterns of midgestational cell types. CONCLUSIONS: The results demonstrate an increased resemblance in both autistic male and female individuals' neuroanatomy with male-characteristic patterns associated with typically sex-differential social cognitive features and related gene expression patterns. The findings hold promise for future research aimed at refining the quest for biological mechanisms underpinning the etiology of autism.

Published
2023

8. Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Author

Zhiqiang Sha, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Boris Bernhardt, Sven Bolte, Geraldo F. Busatto, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Meiyu Duan, Fabio Luis Souza Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Jacqueline Fitzgerald, Dorothea L. Floris, Barbara Franke, Christine M. Freitag, Louise Gallagher, David C. Glahn, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Luisa Lazaro, Beatriz Luna, Jane McGrath, Sarah E. Medland, Filippo Muratori, Declan G. M. Murphy, Janina Neufeld, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Jose C. Pariente, Merel C. Postema, Karl Lundin Remnelius, Alessandra Retico, Pedro Gomes Penteado Rosa, Katya Rubia, Devon Shook, Kristiina Tammimies, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of Toronto, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Stockholm Health Care Services (SLSO), Curtin University [Perth], Planning and Transport Research Centre (PATREC), Universidade de São Paulo = University of São Paulo (USP), University of Pisa - Università di Pisa, Department of Child and Adolescent Psychiatry and Psychology, Centro de Investigación Biomédica en Red de Salut Mental (CIBER-SAM Network), Hospital Clinic Barcelona, King‘s College London, University Medical Center [Utrecht], Goethe-Universität Frankfurt am Main, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oregon Health and Science University [Portland] (OHSU), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, and McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada]

Subjects
Neuroinformatics, Biochemistry & Molecular Biology, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], CHILDREN, ORGANIZATION, ACTIVATION, Cellular and Molecular Neuroscience, CONNECTIVITY, 130 000 Cognitive Neurology & Memory, CEREBRAL-CORTEX, Neural Pathways, Humans, HETEROGENEITY, Molecular Biology, 11 Medical and Health Sciences, Psychiatry, Cerebral Cortex, Brain Mapping, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, LANGUAGE LATERALIZATION, Neurosciences, Brain, 06 Biological Sciences, Magnetic Resonance Imaging, 17 Psychology and Cognitive Sciences, Psychiatry and Mental health, INDIVIDUALS, MORPHOMETRY, Neurosciences & Neurology, Life Sciences & Biomedicine, CORTICAL THICKNESS
Abstract

Contains fulltext : 251394.pdf (Publisher’s version ) (Open Access) Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Published
2022

9. Author Correction: Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Author

Merel C. Postema, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Geraldo Busatto Filho, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Adriana Di Martino, Ilan Dinstein, Fabio Luis S. Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Xin Feng, Jackie Fitzgerald, Dorothea L. Floris, Christine M. Freitag, Louise Gallagher, David C. Glahn, Ilaria Gori, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Xiang Zhen Kong, Luisa Lazaro, Jason P. Lerch, Beatriz Luna, Mauricio M. Martinho, Jane McGrath, Sarah E. Medland, Filippo Muratori, Clodagh M. Murphy, Declan G. M. Murphy, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Olga Puig, Alessandra Retico, Pedro Rosa, Katya Rubia, Devon Shook, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Holland Bloorview Kids Rehabilitation Hospital [Toronto, ON, Canada], University of Toronto, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of Pisa - Università di Pisa, Department of Child and Adolescent Psychiatry and Psychology, Centro de Investigación Biomédica en Red de Salut Mental (CIBER-SAM Network), Hospital Clinic Barcelona, King‘s College London, NYU Langone Medical Center, Utrecht University [Utrecht], MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Oregon Health and Science University [Portland] (OHSU), School of Management, Fujian Agriculture and Forestry University (FAFU), and Goethe-University Frankfurt am Main

Subjects
Adult, Male, Adolescent, Autism Spectrum Disorder, Science, [SDV]Life Sciences [q-bio], Prefrontal Cortex, General Physics and Astronomy, Gyrus Cinguli, General Biochemistry, Genetics and Molecular Biology, Young Adult, Humans, Author Correction, Child, Cerebral Cortex, Multidisciplinary, Brain, Organ Size, General Chemistry, Autism spectrum disorders, Middle Aged, Magnetic Resonance Imaging, Temporal Lobe, Frontal Lobe, Case-Control Studies, Female, Neuroscience
Abstract

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Published
2021

10. Bat Biology, Genomes, and the Bat1K Project: To Generate Chromosome-Level Genomes for All Living Bat Species

Author

Lucy Burkitt-Gray, Liliana Davalos, Tamily Carvalho Melo dos Santos, Graham Hughes, Emma Teeling, David Ray, Alexander Graphodatsky, Germán Botto Nuñez, Ella Lattenkamp, Serena Dool, Marcus Gilbert, Zixia Huang, Luisa Rodrigues, Gerson Paulino Lopes, University College Dublin [Dublin] (UCD), Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen], Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Texas Tech University [Lubbock] (TTU), University of Copenhagen = Københavns Universitet (KU), Natural History Museum of Denmark, Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), NTNU University Museum [Trondheim], Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Universität Greifswald - University of Greifswald, Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche pour le développement [IRD] : UR226

Subjects
0301 basic medicine, Pollination, media_common.quotation_subject, Endangered species, Human echolocation, Biology, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Genome, Ecosystem services, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chiroptera, Genetics, Animals, ComputingMilieux_MISCELLANEOUS, media_common, Genetic diversity, General Veterinary, Ecology, Longevity, High-Throughput Nucleotide Sequencing, 15. Life on land, Adaptation, Physiological, Biological Evolution, 030104 developmental biology, Research Design, Threatened species, Animal Science and Zoology, Biotechnology
Abstract

Bats are unique among mammals, possessing some of the rarest mammalian adaptations, including true self-powered flight, laryngeal echolocation, exceptional longevity, unique immunity, contracted genomes, and vocal learning. They provide key ecosystem services, pollinating tropical plants, dispersing seeds, and controlling insect pest populations, thus driving healthy ecosystems. They account for more than 20% of all living mammalian diversity, and their crown-group evolutionary history dates back to the Eocene. Despite their great numbers and diversity, many species are threatened and endangered. Here we announce Bat1K, an initiative to sequence the genomes of all living bat species (n∼1,300) to chromosome-level assembly. The Bat1K genome consortium unites bat biologists (>148 members as of writing), computational scientists, conservation organizations, genome technologists, and any interested individuals committed to a better understanding of the genetic and evolutionary mechanisms that underlie the unique adaptations of bats. Our aim is to catalog the unique genetic diversity present in all living bats to better understand the molecular basis of their unique adaptations; uncover their evolutionary history; link genotype with phenotype; and ultimately better understand, promote, and conserve bats. Here we review the unique adaptations of bats and highlight how chromosome-level genome assemblies can uncover the molecular basis of these traits. We present a novel sequencing and assembly strategy and review the striking societal and scientific benefits that will result from the Bat1K initiative.

Published
2017

11. Cortical and subcortical brain morphometry differences between patients with autism spectrum disorders (ASD) and healthy individuals across the lifespan:results from the ENIGMA-ASD working group

Author

Sarah Durston, Ilan Dinstein, Paul M. Thompson, Mara Parellada, Clodagh M. Murphy, Ilaria Gori, Mauricio Moller Martinho, Shlomi Haar, Louise Gallagher, Fengfeng Zhou, Devon Shook, Neda Jahanshad, Jackie Fitzgerald, Geraldo F. Busatto, Kirsten O'Hearn, Declan Murphy, Christine Ecker, Adriana Di Martino, Jane McGrath, Gregory L. Wallace, Evdokia Anagnostou, Celso Arango, Christine Deruelle, Eileen Daly, Katya Rubia, Christine M. Freitag, Pedro G.P. Rosa, Michela Tosetti, Jan K. Buitelaar, Bob Oranje, Margot J. Taylor, Marlene Behrmann, Maria Jalbrzikowski, Damien A. Fair, Daan van Rooij, Jennifer Fedor, Filippo Muratori, Beatriz Luna, Guillaume Auzias, Joost Janssen, Alessandra Retico, Liesbeth Hoekstra, Jason Lerch, Sara Calderoni, Fabio Luis Souza Duran, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], Human Genetics Center, The University of Texas Health Science Center at Houston (UTHealth), Psychiatry Department, Adolescent Unit, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), University of São Paulo (USP), NYU Langone Medical Center, University Medical Center [Utrecht], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Oregon Health and Science University [Portland] (OHSU), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, The Hospital for sick children [Toronto] (SickKids), Instituto de Fisica (IF), Universidad Autonoma de San Luis Potosi [México] (UASLP), IRCCS Fondazione Stella Maris [Pisa], Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of psychiatry-King‘s College London, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Instituto Superior Técnico, Universidade Técnica de Lisboa, Child Psychiatry, Laboratory of Neuro Imaging [Los Angeles] (LONI), Stella Maris, IRCCS, Department of Chemistry, University of Western Ontario, Western University, Department of Psychiatry, Radboud University Medical Center [Nijmegen], Radboud University [Nijmegen]-Radboud University [Nijmegen], Universidade de São Paulo = University of São Paulo (USP), and University of California (UC)-University of California (UC)

Subjects
Male, 0301 basic medicine, Autism Spectrum Disorder, Autism, [SDV]Life Sciences [q-bio], Audiology, 0302 clinical medicine, Reference Values, Child, ComputingMilieux_MISCELLANEOUS, Cerebral Cortex, Lifespan, Age Factors, ENIGMA, Healthy subjects, Brain, Middle Aged, Magnetic Resonance Imaging, Psychiatry and Mental health, Autism spectrum disorder, Child, Preschool, Healthy individuals, Female, Psychology, Adult, medicine.medical_specialty, Adolescent, behavioral disciplines and activities, Article, 150 000 MR Techniques in Brain Function, Young Adult, 03 medical and health sciences, Neuroimaging, Neuroimaging genetics, AUTISMO, Image Interpretation, Computer-Assisted, Healthy control, mental disorders, medicine, Humans, Brain Morphology, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Brain morphometry, medicine.disease, 030104 developmental biology, Case-Control Studies, Neuroscience, 030217 neurology & neurosurgery
Abstract

Objective:Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group.Method:The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2–64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach.Results:The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen’s d], 0.13 to –0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, −0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions.Conclusions:The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Published
2017

12. 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

13. ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide

Author

Thompson, Paul M., Dennis, Emily L., Gutman, Boris A., Hibar, Derrek P., Jahanshad, Neda, Kelly, Sinead, Stein, Jason L., Whelan, Christopher D., Andreassen, Ole A., Arias-Vasquez, Alejandro, Bearden, Carrie E., Boedhoe, Premika S., van den Heuvel, Odile L., Veltman, Dick J., Brouwer, Rachel M., de Reus, Marcel A., Pol, Hilleke E.Hulshoff, van den Heuvel, Martijn P., Buckner, Randy L., Buitelaar, Jan K., Fisher, Simon E., Francks, Clyde, Franke, Barbara, Hoogman, Martine, van Rooij, Daan, Bulayeva, Kazima B., Cannon, Dara M., McDonald, Colm, Cohen, Ronald A., Conrod, Patricia J., Dale, Anders M., Holland, Dominic, Deary, Ian J., Wardlaw, Joanna M., Desrivieres, Sylvane, Schumann, Gunter, Dima, Danai, Frangou, Sophia, Donohoe, Gary, Guadalupe, Tulio, Fouche, Jean Paul, Stein, Dan J., Ganjgahi, Habib, Garavan, Hugh, Glahn, David C., Grabe, Hans J., Hashimoto, Ryota, Hosten, Norbert, Kochunov, Peter, Kremen, William S., Lee, Phil H., Mackey, Scott, Mazoyer, Bernard, Martin, Nicholas G., Medland, Sarah E., Morey, Rajendra A., Nichols, Thomas E., Paus, Tomas, Pausova, Zdenka, Shen, Li, Sisodiya, Sanjay M., Smit, Dirk J.A., Smoller, Jordan W., Toro, Roberto, Turner, Jessica A., Schmaal, Lianne, van Erp, Theo G.M., Walter, Henrik, Wang, Yalin, Wright, Margaret J., Ye, Jieping, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, University of Southern California (USC), Division of Mental Health and Addiction, Oslo University Hospital [Oslo], KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], 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], Department of Anatomy & Neurosciences, VU University Medical Center, Amsterdam, The Netherlands, Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [Nijmegen], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), University of Florida [Gainesville], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, University of California [San Diego] (UC San Diego), University of California, University of Edinburgh, Department of Hematology, 'Ion Chiricuta' Cancer Institute, Trinity College Dublin-St. James's Hospital, Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Shahid Beheshti Medical University, University of Vermont [Burlington], Dpt of Psychiatry [New Haven], Yale University School of Medicine, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, International Max Planck Research School for Language Sciences (IMPRS ), Department of Mathematics [UCLA], University of California [Los Angeles] (UCLA), University of California-University of California, Laboratory of Neuro Imaging [Los Angeles] (LONI), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University [Osaka], David Geffen School of Medicine [Los Angeles], University Medical Center [Utrecht], Greifswald University Hospital, MetaCase [Jyväskylä], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, University of Maryland System, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Vermont, Burlington 05401, VT, USA, Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-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-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, Department of Life Sciences, Imperial College London, Queensland Institute of Medical Research, Duke University [Durham], Warwick Manufacturing Group [Coventry] (WMG), University of Warwick [Coventry], Department of Statistics [Warwick], McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University-McGill University, Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, VU University Medical Center [Amsterdam], Göttingen Zentrum Geowissenschaften, Georg-August-Universität Göttingen, Indiana University School of Medicine, Indiana University System, Department of Clinical and Experimental Epilepsy, University College of London [London] (UCL), Shell (Netherlands), 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), University of York [York, UK], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Berlin School of Mind and Brain [Berlin], Humboldt Universität zu Berlin, Arizona State University [Tempe] (ASU), Queensland Brain Institute, University of Queensland, Brisbane 4072, Australia, Chinese Center for Disease Control and Prevention, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], University of Florida [Gainesville] (UF), McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Georg-August-University [Göttingen], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Humboldt-Universität zu Berlin, University of Maryland School of Medicine, University of Maryland System-University of Maryland System-University of Maryland [Baltimore County] (UMBC), Amsterdam Neuroscience - Brain Imaging, Biological Psychology, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Radboud University [Nijmegen]-Radboud University [Nijmegen], University of California (UC), Radboud University [Nijmegen], Yale School of Medicine [New Haven, Connecticut] (YSM), University of California (UC)-University of California (UC), Service NEUROSPIN (NEUROSPIN), 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)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Georg-August-University = Georg-August-Universität Göttingen, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), Humboldt University Of Berlin, and Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie

Subjects
0301 basic medicine, Neuroinformatics, Candidate gene, endocrine system, Cognitive Neuroscience, Brain Structure and Function, BF, Genome-wide association study, Disease, Affect (psychology), Article, 150 000 MR Techniques in Brain Function, 03 medical and health sciences, 0302 clinical medicine, SDG 17 - Partnerships for the Goals, Neuroimaging, cortical surface-area, medicine, Journal Article, Humans, Multicenter Studies as Topic, alzheimers-disease, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Depression (differential diagnoses), Brain Diseases, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], white-matter, Mental Disorders, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, heritability analysis, susceptibility loci, 3. Good health, 030104 developmental biology, Neurology, Evolutionary biology, Schizophrenia, 22q11.2 deletion syndrome, Research Programm of Donders Centre for Neuroscience, genome-wide association, chronic-schizophrenia, genetic associations, Psychology, candidate genes, Neuroscience, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Contains fulltext : 165964pub.pdf (Publisher’s version ) (Open Access) In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) – a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date – of schizophrenia and major depression – ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others11 Abbreviations: ADNI, Alzheimer's Disease Neuroimaging Initiative (http://www.adni-info.org); CHARGE, the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (http://www.chargeconsortium.com); IMAGEN, IMAging GENetics Consortium (http://www.imagen-europe.com). , ENIGMA's genomic screens – now numbering over 30,000 MRI scans – have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants – and genetic variants in general – may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures – from tens of thousands of people – that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

Published
2017

14. 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

15. 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

16. Common genetic variants influence human subcortical brain structures

Author

Hibar, Derrek P, Stein, Jason L, Aribisala, Benjamin S, de Zubicaray, Greig I, Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D, Erk, Susanne, Fedko, Iryna O, Ferrucci, Luigi, Foroud, Tatiana M, Fox, Peter T, Fukunaga, Masaki, Armstrong, Nicola J, Gibbs, J Raphael, Göring, Harald H H, Green, Robert C, Guelfi, Sebastian, Hansell, Narelle K, Hartman, Catharina A, Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G, Heslenfeld, Dirk J, Bernard, Manon, Hoekstra, Pieter J, Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R, Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Bohlken, Marc M, Kent, Jack W, Kochunov, Peter, Kwok, John B, Lawrie, Stephen M, Liu, Xinmin, Longo, Dan L, McMahon, Katie L, Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Boks, Marco P, Montgomery, Grant W, Mostert, Jeanette C, Mühleisen, Thomas W, Nalls, Michael A, Nichols, Thomas E, Nilsson, Lars G, Nöthen, Markus M, Ohi, Kazutaka, Olvera, Rene L, Perez-Iglesias, Rocio, Bralten, Janita, Pike, G Bruce, Potkin, Steven G, Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D, Rujescu, Dan, Schnell, Knut, Schofield, Peter R, Brown, Andrew A, Smith, Colin, Steen, Vidar M, Sussmann, Jessika E, Thalamuthu, Anbupalam, Toga, Arthur W, Traynor, Bryan J, Troncoso, Juan, Turner, Jessica A, Valdés Hernández, Maria C, van 't Ent, Dennis, Chakravarty, M Mallar, van der Brug, Marcel, van der Wee, Nic J A, van Tol, Marie-Jose, Veltman, Dick J, Wassink, Thomas H, Westman, Eric, Zielke, Ronald H, Zonderman, Alan B, Ashbrook, David G, Hager, Reinmar, Chen, Qiang, Lu, Lu, McMahon, Francis J, Morris, Derek W, Williams, Robert W, Brunner, Han G, Buckner, Randy L, Buitelaar, Jan K, Cahn, Wiepke, Calhoun, Vince D, Cavalleri, Gianpiero L, Ching, Christopher R K, Crespo-Facorro, Benedicto, Dale, Anders M, Davies, Gareth E, Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C, Espeseth, Thomas, Gollub, Randy L, Ho, Beng-Choon, Renteria, Miguel E, Cuellar-Partida, Gabriel, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S, Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W J H, den Braber, Anouk, Roffman, Joshua L, Sisodiya, Sanjay M, Smoller, Jordan W, van Bokhoven, Hans, van Haren, Neeltje E M, Völzke, Henry, Walter, Henrik, Weiner, Michael W, Wen, Wei, White, Tonya, Giddaluru, Sudheer, Agartz, Ingrid, Andreassen, Ole A, Blangero, John, Boomsma, Dorret I, Brouwer, Rachel M, Cannon, Dara M, Cookson, Mark R, de Geus, Eco J C, Deary, Ian J, Donohoe, Gary, Goldman, Aaron L, Fernández, Guillén, Fisher, Simon E, Francks, Clyde, Glahn, David C, Grabe, Hans J, Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E, Jönsson, Erik G, Grimm, Oliver, Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S, Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M, Ophoff, Roel A, Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Guadalupe, Tulio, Sachdev, Perminder S, Saykin, Andrew J, Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M, Weale, Michael E, Weinberger, Daniel R, Adams, Hieab H H, Launer, Lenore J, Hass, Johanna, Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L, Becker, James T, Yanek, Lisa, van der Lee, Sven J, Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Woldehawariat, Girma, Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N, van Duijn, Cornelia M, Xue, Luting, Mazoyer, Bernard, Bis, Joshua C, Gudnason, Vilmundur, Seshadri, Sudha, Holmes, Avram J, Ikram, M Arfan, Initiative, Alzheimer’s Disease Neuroimaging, Consortium, CHARGE, EPIGEN, IMAGEN, SYS, Martin, Nicholas G, Wright, Margaret J, Schumann, Gunter, Franke, Barbara, Hoogman, Martine, Thompson, Paul M, Medland, Sarah E, Weiner, Michael, Aisen, Paul, Petersen, Ronald, Jagust, William, Trojanowki, John Q, Beckett, Laurel, Arias-Vasquez, Alejandro, Janowitz, Deborah, Morris, John, Shaw, Leslie M, Khachaturian, Zaven, Sorensen, Greg, Carrillo, Maria, Kuller, Lew, Raichle, Marc, Paul, Steven, Jia, Tianye, Davies, Peter, Fillit, Howard, Hefti, Franz, Holtzman, Davie, Mesulman, M Marcel, Potter, William, Snyder, Peter, Schwartz, Adam, Montine, Tom, Kim, Sungeun, Thomas, Ronald G, Donohue, Michael, Walter, Sarah, Gessert, Devon, Sather, Tamie, Jiminez, Gus, Harvey, Danielle, Klein, Marieke, Bernstein, Matthew, Fox, Nick, Thompson, Paul, Schuff, Norbert, DeCarli, Charles, Borowski, Bret, Gunter, Jeff, Senjem, Matt, Kraemer, Bernd, Vemuri, Prashanthi, Jones, David, Kantarci, Kejal, Ward, Chad, Koeppe, Robert A, Foster, Norm, Reiman, Eric M, Chen, Kewei, Mathis, Chet, Lee, Phil H, Landau, Susan, Cairns, Nigel J, Householder, Erin, Taylor-Reinwald, Lisa, Trojanowki, J. Q., Shaw, Les, Lee, Virginia M Y, Korecka, Magdalena, Figurski, Michal, Olde Loohuis, Loes M, Crawford, Karen, Neu, Scott, Potkin, Steven, Shen, Li, Faber, Kelley, Nho, Kwangsik, Luciano, Michelle, Thal, Leon, Frank, Richard, Snyder, Peter J, Buckholtz, Neil, Macare, Christine, Albert, Marilyn, Hsiao, John, Kaye, Jeffrey, Quinn, Joseph, Lind, Betty, Carter, Raina, Dolen, Sara, Gutman, Boris A, Schneider, Lon S, Mather, Karen A, Pawluczyk, Sonia, Beccera, Mauricio, Teodoro, Liberty, Spann, Bryan M, Brewer, James, Vanderswag, Helen, Fleisher, Adam, Heidebrink, Judith L, Lord, Joanne L, Desrivières, Sylvane, Mattheisen, Manuel, Mason, Sara S, Albers, Colleen S, Knopman, David, Johnson, Kris, Doody, Rachelle S, Villanueva-Meyer, Javier, Chowdhury, Munir, Rountree, Susan, Dang, Mimi, Stern, Yaakov, Milaneschi, Yuri, Honig, Lawrence S, Bell, Karen L, Ances, Beau, Morris, John C, Carroll, Maria, Leon, Sue, Mintun, Mark A, Schneider, Stacy, Oliver, Angela, Marson, Daniel, Griffith, Randall, Clark, David, Geldmacher, David, Brockington, John, Roberson, Erik, Grossman, Hillel, Mitsis, Effie, deToledo-Morrell, Leyla, Shah, Raj C, Papmeyer, Martina, Duara, Ranjan, Varon, Daniel, Greig, Maria T, Roberts, Peggy, Onyike, Chiadi, D'Agostino, Daniel, Kielb, Stephanie, Galvin, James E, Pogorelec, Dana M, Ramasamy, Adaikalavan, Cerbone, Brittany, Michel, Christina A, Rusinek, Henry, de Leon, Mony J, Glodzik, Lidia, De Santi, Susan, Doraiswamy, P Murali, Petrella, Jeffrey R, Wong, Terence Z, Arnold, Steven E, Risacher, Shannon L, Karlawish, Jason H, Wolk, David, Smith, Charles D, Jicha, Greg, Hardy, Peter, Sinha, Partha, Oates, Elizabeth, Conrad, Gary, Lopez, Oscar L, Oakley, MaryAnn, Roiz-Santiañez, Roberto, Simpson, Donna M, Porsteinsson, Anton P, Goldstein, Bonnie S, Martin, Kim, Makino, Kelly M, Ismail, M Saleem, Brand, Connie, Mulnard, Ruth A, Thai, Gaby, Mc-Adams-Ortiz, Catherine, Rose, Emma J, Womack, Kyle, Mathews, Dana, Quiceno, Mary, Diaz-Arrastia, Ramon, King, Richard, Weiner, Myron, Martin-Cook, Kristen, DeVous, Michael, Levey, Allan I, Lah, James J, Salami, Alireza, Cellar, Janet S, Burns, Jeffrey M, Anderson, Heather S, Swerdlow, Russell H, Apostolova, Liana, Tingus, Kathleen, Woo, Ellen, Silverman, Daniel H S, Lu, Po H, Bartzokis, George, Sämann, Philipp G, Graff-Radford, Neill R, Parfitt, Francine, Kendall, Tracy, Johnson, Heather, Farlow, Martin R, Hake, Ann Marie, Matthews, Brandy R, Herring, Scott, Hunt, Cynthia, van Dyck, Christopher H, Jahanshad, Neda, Schmaal, Lianne, Carson, Richard E, MacAvoy, Martha G, Chertkow, Howard, Bergman, Howard, Hosein, Chris, Black, Sandra, Stefanovic, Bojana, Caldwell, Curtis, Hsiung, Yuek Robin, Feldman, Howard, Schork, Andrew J, Mudge, Benita, Assaly, Michele, Kertesz, Andrew, Rogers, John, Trost, Dick, Bernick, Charles, Munic, Donna, Kerwin, Diana, Mesulam, Marek-Marsel, Lipowski, Kristine, Shin, Jean, Wu, Chuang-Kuo, Johnson, Nancy, Sadowsky, Carl, Martinez, Walter, Villena, Teresa, Turner, Raymond Scott, Johnson, Kathleen, Reynolds, Brigid, Sperling, Reisa A, Johnson, Keith A, Strike, Lachlan T, Marshall, Gad, Frey, Meghan, Yesavage, Jerome, Taylor, Joy L, Lane, Barton, Rosen, Allyson, Tinklenberg, Jared, Sabbagh, Marwan N, Belden, Christine M, Jacobson, Sandra A, Teumer, Alexander, Sirrel, Sherye A, Kowall, Neil, Killiany, Ronald, Budson, Andrew E, Norbash, Alexander, Johnson, Patricia Lynn, Obisesan, Thomas O, Wolday, Saba, Allard, Joanne, Lerner, Alan, van Donkelaar, Marjolein M J, Ogrocki, Paula, Hudson, Leon, Fletcher, Evan, Carmichael, Owen, Olichney, John, Kittur, Smita, Borrie, Michael, Lee, T-Y, Bartha, Rob, van Eijk, Kristel R, Johnson, Sterling, Asthana, Sanjay, Carlsson, Cynthia M, Preda, Adrian, Nguyen, Dana, Tariot, Pierre, Reeder, Stephanie, Bates, Vernice, Walters, Raymond K, Capote, Horacio, Rainka, Michelle, Scharre, Douglas W, Kataki, Maria, Adeli, Anahita, Zimmerman, Earl A, Celmins, Dzintra, Brown, Alice D, Pearlson, Godfrey D, Blank, Karen, Westlye, Lars T, Anderson, Karen, Santulli, Robert B, Kitzmiller, Tamar J, Schwartz, Eben S, Sink, Kaycee M, Williamson, Jeff D, Garg, Pradeep, Watkins, Franklin, Ott, Brian R, Querfurth, Henry, Whelan, Christopher D, Tremont, Geoffrey, Salloway, Stephen, Malloy, Paul, Correia, Stephen, Rosen, Howard J, Miller, Bruce L, Mintzer, Jacobo, Spicer, Kenneth, Bachman, David, Finger, Elizabether, Toro, Roberto, Winkler, Anderson M, Pasternak, Stephen, Rachinsky, Irina, Drost, Dick, Pomara, Nunzio, Hernando, Raymundo, Sarrael, Antero, Schultz, Susan K, Ponto, Laura L Boles, Zwiers, Marcel P, Shim, Hyungsub, Smith, Karen Elizabeth, Relkin, Norman, Chaing, Gloria, Raudin, Lisa, Smith, Amanda, Fargher, Kristin, Raj, Balebail Ashok, Amin, Najaf, Becker, Diane, Alhusaini, Saud, Beiser, Alexa, Debette, Stéphanie, DeStefano, Anita, Hofer, Edith, Hofman, Albert, Niessen, Wiro J, Smith, Albert, Tzourio, Christophe, Vaidya, Dhananjay, Athanasiu, Lavinia, Vernooij, Meike W, Goldstein, David B, Heinzen, Erin L, Shianna, Kevin, Radtke, Rodney, Ottmann, Ruth, Albrecht, Lisa, Andrew, Chris, Arroyo, Mercedes, Artiges, Eric, Ehrlich, Stefan, Aydin, Semiha, Bach, Christine, Banaschewski, Tobias, Barbot, Alexis, Barker, Gareth, Boddaert, Nathalie, Bokde, Arun, Bricaud, Zuleima, Bromberg, Uli, Bruehl, Ruediger, Hakobjan, Marina M H, Büchel, Christian, Cachia, Arnaud, Cattrell, Anna, Conrod, Patricia, Constant, Patrick, Crombag, Hans, Czech, Katharina, Dalley, Jeffrey, Decideur, Benjamin, Desrivieres, Sylvane, Hartberg, Cecilie B, Fadai, Tahmine, Flor, Herta, Frouin, Vincent, Fuchs, Birgit, Gallinat, Jürgen, Garavan, Hugh, Briand, Fanny Gollier, Gowland, Penny, Head, Kay, Heinrichs, Bert, Haukvik, Unn K, Heym, Nadja, Hübner, Thomas, Ihlenfeld, Albrecht, Ireland, James, Ittermann, Bernd, Ivanov, Nikolay, Jones, Jennifer, Klaassen, Arno, Heister, Angelien J G A M, Lalanne, Christophe, Lathrop, Mark, Lanzerath, Dirk, Lemaitre, Hervé, Lüdemann, Katharina, Mallik, Catherine, Mangin, Jean-François, Mann, Karl, Mar, Adam, Hoehn, David, Martinot, Jean-Luc, Massicotte, Jessica, Mennigen, Eva, Mesquita de Carvahlo, Fabiana, Mignon, Xavier, Miranda, Ruben, Müller, Kathrin, Nees, Frauke, Nymberg, Charlotte, Paillere, Marie-Laure, Wittfeld, Katharina, Kasperaviciute, Dalia, Pena-Oliver, Yolanda, Poline, Jean-Baptiste, Poustka, Luise, Rapp, Michael, Reed, Laurence, Robert, Gabriel, Reuter, Jan, Liewald, David C M, Ripke, Stephan, Ripley, Tamzin, Robbins, Trevor, Rodehacke, Sarah, Romanowski, Alexander, Ruggeri, Barbara, Schilling, Christina, Schmäl, Christine, Schmidt, Dirk, Lopez, Lorna M, Schneider, Sophia, Schroeder, Markus, Schubert, Florian, Schwartz, Yannick, Smolka, Michael, Sommer, Wolfgang, Spanagel, Rainer, Speiser, Claudia, Spranger, Tade, Stedman, Alicia, Makkinje, Remco R R, Steiner, Sabina, Stephens, Dai, Strache, Nicole, Ströhle, Andreas, Struve, Maren, Subramaniam, Naresh, Theobald, David, Topper, Lauren, Vollstaedt-Klein, Sabine, Walaszek, Bernadeta, Matarin, Mar, Weiß, Katharina, Werts, Helen, Whelan, Robert, Williams, Steve, Yacubian, Juliana, Ziesch, Veronika, Zilbovicius, Monica, Wong, C Peng, Lubbe, Steven, Naber, Marlies A M, Martinez-Medina, Lourdes, Kepa, Agnes, Fernandes, Alinda, Tahmasebi, Amir, Abrahamowicz, Michal, Gaudet, Daniel, Leonard, Gabriel, Perron, Michel, Richer, Louis, Seguin, Jean, McKay, D Reese, Veillette, Suzanne, Needham, Margaret, Nugent, Allison C, Pütz, Benno, Abramovic, Lucija, Royle, Natalie A, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S L, van Hulzen, Kimm J E, Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Andersson, Micael, Arepalli, Sampath, Assareh, Amelia A, Bastin, Mark E, Brodaty, Henry, Bulayeva, Kazima B, Carless, Melanie A, Cichon, Sven, Corvin, Aiden, Curran, Joanne E, Czisch, Michael, MUMC+: DA Klinische Genetica (5), RS: GROW - Developmental Biology, RS: GROW - R4 - Reproductive and Perinatal Medicine, Université de Montréal. Faculté de médecine. Département de psychiatrie et d'addictologie, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Department of Psychiatry, Donders Centre for Neuroscience, Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud University [Nijmegen]-Radboud University Medical Center [Nijmegen], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, PRES Sorbonne Paris Cité, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Greifswald University Hospital, University Medical Center [Utrecht], European Commission, University of Edinburgh, Lagos State University (LASU), Heriot-Watt University [Edinburgh] (HWU), Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA), Donders Institute for Brain, Cognition and Behaviour, Radboud University [Nijmegen], University of Oslo (UiO), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], School of Technical Physics, Xidian University, Dept. of Mechanical Engineering, McMaster University [Hamilton, Ontario], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, Haukeland University Hospital, University of Bergen (UiB), Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 (PC2A), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg] = Heidelberg University, 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 ), Georgia Institute of Technology [Atlanta], National Institutes of Health [Bethesda] (NIH), Yale University [New Haven], Massachusetts General Hospital [Boston], Mental Health Sciences Unit, University College of London [London] (UCL), Beijing Normal University (BNU), Indiana University School of Medicine, Indiana University System, Indiana Alzheimer Disease Center, Indiana University System-Indiana University System, Center for Translational Research in Systems Neuroscience and Psychiatry, Department of Psychiatry and Psychotherapy, University Medical Center, Goettingen 37075, Germany, Scottish Fish Immunology Research Centre, School of Biological Sciences, University of Aberdeen, University of California (UC), Medstar Research Institute, 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, Universität Bonn = University of Bonn, Institute of Human Genetics, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], VU University Medical Center [Amsterdam], 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), 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), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Department of Neurosciences [Univ California San Diego] (Neuro - UC San Diego), School of Medicine [Univ California San Diego] (UC San Diego), University of 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), The Hospital for sick children [Toronto] (SickKids), 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, Department of Genomics of Common Disease, Imperial College London, Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Deutsche Bundesbank, Department of Neurology and Neurosurgery [Montreal], McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), MetaGenoPolis, Department of Psychiatric Research and Development, Diakonhjemmet Hospital, Oslo 0319, Norway, UCL Institute of Neurology and Epilepsy Society, Department of Medicine, Clinical And Experimental Epilepsy, Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Hartford Hospital, Neuropsychiatric Genetics Research Group and Department of Psychiatry, Trinity College Institute of Psychiatry, Trinity College Dublin, Dublin 2, Ireland, Institute of Food & Health, University College Dublin, University College Dublin [Dublin] (UCD), Statistical Genetics Group, State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL, Institute of Neurology [London], Department of Genetics, King Faisal Specialist Hospital and Research Centre (KFSH & RC), Centre épigénétique et destin cellulaire (EDC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Dundee Technopole, CXR Biosciences Ltd, Ninewells Hospital and Medical School, Biomedical Research Centre, University of Dundee, 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, Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Dementia Collaborative Research Centre, N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Texas Biomedical Research Institute [San Antonio, TX], Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Division of Medical Genetics, University of Basel (Unibas), Trinity College Dublin-St. James's Hospital, Neuropsychiatric Genetics Research Group, Trinity College Dublin, Department of Materials Science & Metallurgy, University of Cambridge [UK] (CAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], School of Psychology, University of Queensland, Laboratory of Neurogenetics, The University of Texas Health Science Center at Houston (UTHealth), Department of Genomics, Department of Medical and Molecular Genetics, South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, Biofunctional Imaging, Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan, Public Health Genomics Unit, Department of Biomolecular Engineering, Rheinische Friedrich-Wilhelms-Universität Bonn, Estación Experimental de Pastos y Forrajes 'Indio Hatuey', University Medical Center Groningen [Groningen] (UMCG), Neuronal Plasticity / Mouse Behaviour, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Department of Psychiatry, Fujita Health University School of Medicine, Toyoake 470-1192, Japan, Department of Radiology, Mayo Clinic, Department of Clinical Neurology [Oxford], University of Oxford-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], University of Maryland School of Medicine, University of Maryland System, University of Sussex, Institute of Cognitive Neuroscience, United Kingdom Met Office [Exeter], University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, Department of Civil and Structural Engineering, The Hong Kong Polytechnic University [Hong Kong] (POLYU)-The Hong Kong Polytechnic University [Hong Kong] (POLYU), Columbia University Irving Medical Center (CUIMC), Lymphocyte Cell Biology Unit, Laboratory of Genetics, Centre for Advanced Imaging, Psychiatry and Psychotherapy, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Division of Mental Health and Addiction, Oslo University Hospital [Oslo], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Genetic Epidemiology Unit, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Statistics [Warwick], University of Warwick [Coventry], Osaka University [Osaka], Institute of Psychiatry, King’s College London, London SE5 8AF, UK, University of Calgary, Psychiatry and Human Behavior, University of California, Irvine, California 92617, USA, University of California [Irvine] (UC Irvine), Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], University Hospital Mannheim | Universitätsmedizin Mannheim-University Hospital Mannheim | Universitätsmedizin Mannheim, Space and Naval Warfare Systems Center, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Department of Psychiatry, Division of Medical Psychology, Genetics of Mental Illness and Brain Function, Neuroscience Research Australia, Développement et amélioration des plantes (UMR DAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Laboratory of Neuro Imaging [Los Angeles] (LONI), Departamento de Física Aplicada, Universidade de Vigo, Georgia State University, University System of Georgia (USG), Genentech, Inc. [San Francisco], Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Department of Neurobiology, Care Sciences and Society, Karolinska Institutet [Stockholm], University of Manchester [Manchester], The University of Tennessee Health Science Center [Memphis] (UTHSC), iangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Medical College of Nantong University, Nantong 226001, China, Centre for Ultrahigh Bandwidth Devices for Optical Systems (CUDOS), Macquarie University, Cognitive Neuroscience Laboratory (CNL), Harvard University, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], 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], Division of Molecular and Cellular Therapeutics, Scottish Association for Marine Science (SAMS), Structural Biology Laboratory, Department of Chemistry, University of York, Neurology Division, Beaumont Hospital, Dublin 9, Ireland, Beaumont Hospital, 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), Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Institute for Community Medicine, Department Epidemiology of Health Care and Community Health, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Institute of Clinical Chemistry and Laboratory Medicine, Department of Health Science, Division of Health and Rehabilitation, Luleå University of Technology (LUT), Stanley Center for Psychiatric Research, 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], Psychiatric and Neurodevelopmental Genetics Unit, 849 Department of Human Genetics, Institute for Community Medicine, Institute for Energy Systems and Thermodynamics, Renyi Institute, Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, NSW, Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam 3000 CB, The Netherlands, Department of Radiology, Erasmus University Medical Centre, Rotterdam 3015 CN, The Netherlands, Vrije Universiteit Amsterdam [Amsterdam] (VU), Cell Biology and Gene Expression Section, National Institute of Health, Bethesda, Dept of Psychology, Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations (ISEOR), Institut de socio-économie des entreprises et des organisations, Department of Psychiatry and Psychotherapy, HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Laboratoire d'Informatique de Grenoble (LIG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Centre for Allergy Research, Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital [Stockholm], Medical University of Łódź (MUL), Psychiatry Institute, Department of Health and Human Services, Institute of Gerontology and Geriatrics, Università degli Studi di Perugia = University of Perugia (UNIPG), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Australian Centre for Research into Injury in Sport and its Prevention, Monash University [Clayton], University Medical Center [Utrecht]-Brain Center Rudolf Magnus, School of Psychology [Nottingham], University of Nottingham, UK (UON), McConnell Brain Imaging Centre (MNI), SickKids - The Hospital for sick children, European Centre for Medium-Range Weather Forecasts (ECMWF), University of Eastern Finland, Centre for Population Health Sciences, Lieber Institute for Brain Development [Baltimore] (LIBD), Johns Hopkins University (JHU), Institut Gilbert-Laustriat : Biomolécules, Biotechnologie, Innovation Thérapeutique, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz 8010, Austria, Austrian Institute of Technology [Vienna] (AIT), INSERM Research Center for Epidemiology and Biostatistics (U897) Team Neuroepidemiology, Bordeaux, France College of Health Sciences, University of Bordeaux, Bordeaux, France, INSERM, Neuroepidemiology U708, Bordeaux, France, Karlsruhe Institute of Technology (KIT), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Harvard Medical School [Boston] (HMS), Computer Science and Artificial Intelligence Laboratory [Cambridge] (CSAIL), Massachusetts Institute of Technology (MIT), University of Washington [Seattle], Department of Physics [Stockholm], Stockholm University, Center for Medical Systems Biology, Netherlands Genomics Initiative, Leiden University Medical Center, Leiden, The Netherlands, Netherlands Consortium for Healthy Ageing, Leiden, The Netherlands, Boston University [Boston] (BU), Groupe d'Imagerie Neurofonctionnelle (GIN - UMR 5296), Service NEUROSPIN (NEUROSPIN), 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)-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)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Faculty of Medicine, University of Iceland [Reykjavik], Icelandic Heart Association, Kopavogur, Iceland., Boston University School of Medicine (BUSM), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], University of California-University of California, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), UE 1354 Unité d'expérimentation sur les Ruminants de Theix, Institut National de la Recherche Agronomique (INRA)-Physiologie Animale et Systèmes d'Elevage (PHASE), Institut National de la Recherche Agronomique (INRA)-Unité d'expérimentation sur les Ruminants de Theix (UE RT), Radboud university [Nijmegen], McGill University, University of Bergen (UIB), Universität Heidelberg [Heidelberg], Beijing Normal University, University of California, University of Bonn, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Neurosciences [San Diego], Department of Cognitive Sciences [San Diego], The Hospital for Sick Children, University of Toronto, Toronto M5G 1X8, Canada, McGill University-McGill University, US 1367 MetaGénoPolis, Institut National de la Recherche Agronomique (INRA)-Département Microbiologie et Chaîne Alimentaire (MICA), Institut National de la Recherche Agronomique (INRA)-MetaGénoPolis (MGP), Yale University School of Medicine, King Faisal Specialist Hospital and Research Centre, Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Texas Biomedical Research Institute [San Antonio, Texas], Bijvoet Center of Biomolecular Research, Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne 3101, Australia, Department of Genomics, Life & Brain Center, University of Bonn, Bonn D-53127, Germany, University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], School of Psychology, University of Sussex, Brighton BN1 9QH, UK, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Neurology [University of Calgary], Department of Clinical Neuroscience [University of Calgary], University of California [Irvine] (UCI), Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Recherche Agronomique (INRA)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Universidate de Vigo, Harvard University [Cambridge], Radboud university [Nijmegen]-Radboud university [Nijmegen], Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Università degli Studi di Perugia (UNIPG), 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, Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-Service NEUROSPIN (NEUROSPIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), The Alzheimer’s Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF), 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, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, Neurology, Psychiatry, Anatomy and neurosciences, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Biological Psychology, Cognitive Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, EMGO+ - Mental Health, Child and Adolescent Psychiatry / Psychology, Epidemiology, Radiology & Nuclear Medicine, Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California, Los Angeles, California, USA, Donders Centre for Neuroscience, Radboud University Nijmegen Medical Centre, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Greifswald 17487, Germany, Department of Psychiatry, University Medicine Greifswald, Greifswald 17489, Germany, Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, 3584 CX, The Netherlands, Brain Research Imaging Centre, University of Edinburgh, Edinburgh EH4 2XU, UK, Department of Computer Science, Lagos State University, Lagos, Nigeria, Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Heriot-Watt University [Edinburgh] ( HWU ), Institut National de la Recherche Agronomique ( INRA ) -Physiologie Animale et Systèmes d'Elevage ( PHASE ) -Unité d'expérimentation sur les Ruminants de Theix ( UE RT ), Department of Human Genetics, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, Department of Cognitive Neuroscience, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, NORMENT - KG Jebsen Centre, Institute of Clinical Medicine, University of Oslo, Oslo N-0316, Norway, NORMENT - KG Jebsen Centre, Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0424, Norway, Montreal Neurological Institute [Montréal], NORMENT - KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, 5021 Bergen, Norway, Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen 5021, Norway, Physicochimie des Processus de Combustion et de l’Atmosphère - UMR 8522 ( PC2A ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen 6525 XD, The Netherlands, International Max Planck Research School for Language Sciences, Nijmegen 6525 XD, The Netherlands, Human Genetics Branch and Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health Intramural Research Program, Bethesda, Maryland 20892, USA, Department of Psychology, Yale University, New Haven, Connecticut 06511, USA, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts 02115, USA, University College of London [London] ( UCL ), Center for Neuroimaging, Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Center for Neurobehavioral Genetics, University of California, Los Angeles, California 90095, USA, Université de Bonn, Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam 1081 HL, The Netherlands, Division of Psychiatry, Royal Edinburgh Hospital, University of Edinburgh, Edinburgh EH10 5HF, UK, Imperial College London-School of public health-MRC-HPA Centre for Environment and Health, Cibersam (Centro Investigación Biomédica en Red Salud Mental), Madrid 28029, Spain, Institut Parisien de Chimie Moléculaire ( IPCM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Aging Research Center [Karolinska Institutet] ( ARC ), Max Planck Institute of Psychiatry, Munich 80804, Germany, Multimodal Imaging Laboratory, Department of Neurosciences, University of California, San Diego, California 92093, USA, Department of Cognitive Sciences, University of California, San Diego, California 92161, USA, Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia, Department of Psychology, University of Oslo, Oslo 0373, Norway, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada, Molecular and Cellular Therapeutics, The Royal College of Surgeons, Dublin 2, Ireland, Institut National de la Recherche Agronomique ( INRA ) -MetaGénoPolis ( MGP ) -Microbiologie et Chaîne Alimentaire ( MICA ), UCL Institute of Neurology, London, United Kingdom and Epilepsy Society, London WC1N 3BG, UK, Department of Medicine, Imperial College London, London W12 0NN, UK, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK, Yale School of Medicine, Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, Connecticut 06106, USA, University College Dublin [Dublin] ( UCD ), Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK, Department of Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia, Centre épigénétique et destin cellulaire ( EDC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), School of public health-Tehran University of Medical Siences, University of New South Wales [Sydney] ( UNSW ), Texas Biomedical Research Institute, San Antonio, Texas 78245, USA, Institute of Neuroscience and Medicine ( INM-1 ), University of Basel ( Unibas ), Cambridge University, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA, University of Texas Health Science Center, San Antonio, Texas 78229, USA, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland 20892, USA, Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald 17475, Germany, University Medical Center Groningen, University of Groningen, University of Greifswald, Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA, NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland Medical School, Baltimore, Maryland 21201, USA, nstitute of Cognitive Neuroscience, University College London, London WC1N 3AR, UK, Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland, Baltimore, Maryland 21201, USA, Department of Pathology and Cell Biology, Columbia University Medical Center, New York 10032, USA, Lymphocyte Cell Biology Unit, Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA, University of Oslo ( UiO ) -Institute of Clinical Medicine-Oslo University Hospital, Oslo University Hospital, Institute of Clinical Medicine, University of Oslo ( UiO ) -European Network of Bipolar Research Expert Centers (ENBREC) Group, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, CCM, Berlin 10117, Germany, Erasmus MC, Laboratory of Neurogenetics, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIH), Bethesda, Maryland, USA, Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA, Central Institute of Mental Health, UMR 1098 Développement et Amélioration des Plantes, Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -MontpellierSupAgro ( MontpellierSupAgro ) -Génétique et amélioration des plantes ( G.A.P. ) -Développement et Amélioration des Plantes ( DAP ), Laboratory of Neuro Imaging [Los Angeles] ( LONI ), University of California at Los Angeles [Los Angeles] ( UCLA ), Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH4 2XU, UK, Genentech, South San Francisco, California 94080, USA, Psychiatry and Leiden Institute for Brain and Cognition, Leiden University Medical Center, Leiden 2333 ZA, The Netherlands, LUMC, Carver College of Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm SE-141 83, Sweden, Behavioral Epidemiology Section, National Institute on Aging Intramural Research Program, Baltimore, Maryland 20892, USA, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK, Center for Integrative and Translational Genomics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA, Centre Interlangues - Texte, Image, Langage ( TIL ), Université de Bourgogne ( UB ), Centre for Ultrahigh Bandwidth Devices for Optical Systems ( CUDOS ), Icahn School of Medicine at Mount Sinai [New York], The Mind Research Network & LBERI, Albuquerque, New Mexico 87106, USA, Department of ECE, University of New Mexico, Albuquerque, New Mexico 87131, USA, Scottish Association for Marine Science ( SAMS ), Department of Neurology, Hopital Erasme, Universite Libre de Bruxelles, Brussels 1070, Belgium, National Institutes of Health ( NIH ) -National Institute of Mental Health (NIMH), Harvard Medical School [Boston] ( HMS ) -Massachusetts General Hospital [Boston], Department of Psychiatry, University of Iowa, Iowa City, Iowa 52242, USA, Luleå University of Technology ( LUT ), Broad Institute of MIT and Harvard, Massachusetts General Hospital, Vrije Universiteit Amsterdam [Amsterdam] ( VU ), Université Jean Moulin - Lyon III-Institut d'Administration des Entreprises (IAE) - Lyon, Institut de Socio-économie des Entreprises et des ORganisations ( ISEOR ), University Medicine Greifswald,-HELIOS Hospital Stralsund, Laboratoire d'Informatique de Grenoble ( LIG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Molecular Research Center for Children’s Mental Development, United Graduate School of Child Development, Osaka University, Osaka 565-0871, Japan, Karolinska University Hospital (Solna), Medical University of Łódź ( MUL ), National Institutes of Health ( NIH ), University of Perugia, Commonwealth Scientific and Industrial Research Organisation, University Medical Center Utrecht-Brain Center Rudolf Magnus, University of Nottingham, UK ( UON ), McConnell Brain Imaging Centre ( MNI ), The Hospital for sick children [Toronto] ( SickKids ), Department of Medical and Molecular Genetics, King’s College London, London SE1 9RT, UK, European Centre for Medium-Range Weather Forecasts ( ECMWF ), Lieber Institute for Brain Development, Baltimore, Maryland 21205, USA, Departments of Psychiatry, Neurology, Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique ( CNRS ), Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands, Austrian Institute of Technology [Vienna] ( AIT ), Karlsruhe Institute of Technology ( KIT ), General Internal Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA, Department of Radiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA, Computer Science and Artificial Intelligence Laboratory [Cambridge] ( CSAIL ), Massachusetts Institute of Technology ( MIT ), Department of Epidemiology, University of Washington, Seattle, Washington, USA, Department of Neurology, University of Washington, Seattle, Washington, USA, Department of Physics, Stockholm University ( Department of Physics, Stockholm University ), Université de Lille, Sciences Humaines et Sociales, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA, Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA, Groupe d'Imagerie Neurofonctionnelle ( GIN - UMR 5296 ), 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-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-Centre National de la Recherche Scientifique ( CNRS ) -Université de Bordeaux ( UB ), Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA, Faculty of Medicine, University of Iceland, Reykjavik, Iceland, Department of Neurology, Boston University School of Medicine, Framingham Heart Study, Boston, MA, Department of Neurology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands, Laboratoire d'Ingénierie des Matériaux de Bretagne ( LIMATB ), Université de Bretagne Sud ( UBS ) -Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université de Brest ( UBO ) -Université de Brest ( UBO ), King's College, Department of Psychiatry, Radboud university medical center, Nijmegen 6500 HB, The Netherlands, and Broad Institute of © 2012 Nature America, Inc. All rights reserved. Nature Ge N etics aDV a NCE ONLINE PUBLIC a TION 7 l e t t e r s Harvard and MIT, Cambridge, Massachusetts, US

Subjects
CHROMATIN, Male, Netherlands Twin Register (NTR), Aging, Identification, nervous-system, human geography, SEGMENTATION, Caudate nucleus, Apoptosis, Expression, Genome-wide association study, Striatum, Hippocampal formation, Hippocampus, BASAL GANGLIA, 130 000 Cognitive Neurology & Memory, Basal ganglia, genetics [Gene Expression Regulation, Developmental], Hippocampal, Child, anatomy & histology [Skull], Aged, 80 and over, Genetics, Sex Characteristics, KINECTIN, Genome-wide association, Multidisciplinary, Putamen, Brain, Gene Expression Regulation, Developmental, blood, brain, disease incidence, genetic variation, neurology, Organ Size, Human brain, Middle Aged, organization, Magnetic Resonance Imaging, genetics [Genetic Variation], Chromatin, Dynamics, genetics [Membrane Proteins], medicine.anatomical_structure, genetics [Aging], Anatomy & histology, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, ddc:500, anatomy & histology [Caudate Nucleus], Neuroinformatics, EXPRESSION, Adult, Adolescent, Evolution, anatomy & histology [Hippocampus], ORGANIZATION, genetics [Genetic Loci], Biology, Article, Young Adult, SDG 3 - Good Health and Well-being, Journal Article, medicine, Humans, GENOME-WIDE ASSOCIATION, General, genetics [Apoptosis], Kinectin, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], HIPPOCAMPAL, IDENTIFICATION, genetics [Organ Size], [SCCO.NEUR]Cognitive science/Neuroscience, Skull, segmentation, Genetic Variation, Membrane Proteins, NERVOUS-SYSTEM, anatomy & histology [Putamen], Genetic Loci, KTN1 protein, human, Caudate Nucleus, anatomy & histology [Brain], Neuroscience, Genome-Wide Association Study
Abstract

Contains fulltext : 144426.pdf (Publisher’s version ) (Closed access) Contains fulltext : 144426pre.pdf (Author’s version preprint ) (Open Access) The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 x 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. 6 p.

Published
2015

17. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs

Author

Laura J. Scott, Bernie Devlin, Steven A. McCarroll, James S. Sutcliffe, Stefan Herms, Yunjung Kim, Richard O. Day, Thomas F. Wienker, Frank Dudbridge, I. Nicol Ferrier, Bettina Konte, Marta Ribasés, C. Robert Cloninger, Brenda W.J.H. Penninx, Detelina Grozeva, Herbert Roeyers, Peter Holmans, Colm O'Dushlaine, Scott D. Gordon, Sarah E. Bergen, Fan Meng, Morten Mattingsdal, Hugh Gurling, Ina Giegling, Gerard van Grootheest, Ania Korszun, Markus J. Schwarz, George Kirov, Sebastian Zöllner, Kenneth S. Kendler, Nicholas G. Martin, Michael Conlon O'Donovan, Michael C. Neale, Jim van Os, Aravinda Chakravarti, Timothy W. Yu, Mikael Landén, Inez Myin-Germeys, Markus M. Nöthen, Kathryn Roeder, James B. Potash, Alan W. McLean, Louise Gallagher, Anna K. Kähler, Thomas Bettecken, Nigel Williams, Frank Bellivier, Joseph D. Buxbaum, Derek W. Morris, Susan L. Smalley, Jung-Ying Tzeng, Martin Schalling, Douglas M. Ruderfer, Caroline M. Nievergelt, T. Scott Stroup, David H. Ledbetter, Jennifer Crosbie, Anita Thapar, Barbara Franke, Jeffrey A. Lieberman, Huda Akil, Miguel Casas, Daniel H. Geschwind, Paul Cormican, Bertram Müller-Myhsok, Lyudmila Georgieva, Robert Krasucki, Martin Hautzinger, Alysa E. Doyle, Cinnamon S. Bloss, Gerard D. Schellenberg, Todd Lencz, Melvin G. McInnis, Catalina Betancur, Josep Antoni Ramos-Quiroga, Stephen Sanders, Eftichia Duketis, Don H. Linszen, Matthew W. State, Richard M. Myers, Soumya Raychaudhuri, Lizzy Rossin, Howard J. Edenberg, Michael E. Goddard, S. Hong Lee, Elisabeth B. Binder, Pablo V. Gejman, William A. Scheftner, Wolfgang Maier, Judith A. Badner, Christel M. Middeldorp, Maria Helena Pinto de Azevedo, Johannes H. Smit, Willem A. Nolen, Lieuwe de Haan, Gonneke Willemsen, Keith Matthews, Ellen M. Wijsman, Jennifer K. Lowe, Rebecca McKinney, Magdalena Gross, Dorothy E. Grice, James A. Knowles, Andrew C. Heath, Jana Strohmaier, Vishwajit L. Nimgaonkar, William Byerley, William E. Bunney, Dan E. Arking, Andrew McQuillin, William M. McMahon, Manuel Mattheisen, Hans-Christoph Steinhausen, Joseph Biederman, Guy A. Rouleau, James J. McGough, Sian Caesar, Edward M. Scolnick, Lefkos T. Middleton, Jack D. Barchas, Ian B. Hickie, Danyu Lin, Patrik K. E. Magnusson, Douglas Blackwood, Francis J. McMahon, Ingrid Agartz, Elena Maestrini, Marian L. Hamshere, Lindsey Kent, Walter J. Muir, Stephan Ripke, Lydia Krabbendam, Christine Fraser, Maria Hipolito, Louise Frisén, Eric Fombonne, Emma M. Quinn, Michael Bauer, Richard P. Ebstein, Michael Steffens, Jordan W. Smoller, Stanley J. Watson, Michael Boehnke, Philip Asherson, Agatino Battaglia, Elliot S. Gershon, Russell Schachar, Marcus Ising, Peng Zhang, Margaret A. Pericak-Vance, Joachim Hallmayer, Sean Ennis, Radhika Kandaswamy, René S. Kahn, Susanne Hoefels, Thomas W. Mühleisen, Pamela Sklar, Paul Lichtenstein, Verneri Anttila, Michael L. Cuccaro, Florian Holsboer, René Breuer, Eric M. Morrow, Vinay Puri, Naomi R. Wray, Szabocls Szelinger, Sabine M. Klauck, John B. Vincent, Shrikant Mane, Aribert Rothenberger, Marion Friedl, Ian Jones, Khalid Choudhury, Michael R. Barnes, Adebayo Anjorin, Edwin H. Cook, William Lawson, Allan H. Young, Lambertus Klei, Bryan J. Mowry, Johannes Schumacher, Michael Gill, James L. Kennedy, Marcella Rietschel, Aiden Corvin, Henrik B. Rasmussen, Susmita Datta, Kimberly Chambert, Daniel Moreno-De-Luca, Benjamin S. Pickard, Stan F. Nelson, Veronica J. Vieland, Stephen W. Scherer, Peter M. Visscher, John Strauss, Andreas Reif, Andrew D. Paterson, Ann Olincy, Phoenix Kwan, Anthony J. Bailey, Patrick F. Sullivan, Pierandrea Muglia, Gunnar Morken, Susanne Lucae, Ayman H. Fanous, Jacob Lawrence, Donald J. MacIntyre, Nancy G. Buccola, Rita M. Cantor, Christina M. Hultman, Weihua Guan, Anthony P. Monaco, Jouke-Jan Hottenga, Elaine Kenny, Jianxin Shi, Dale R. Nyholt, Kevin A. McGhee, Falk W. Lohoff, Jonna Kuntsi, Niklas Långström, John I. Nurnberger, Nelson B. Freimer, Erin N. Smith, John P. Rice, Michael T. Murtha, Thomas H. Wassink, Alexandre A. Todorov, Edmund J.S. Sonuga-Barke, Dan Rujescu, Roy H. Perlis, John S. Witte, Christopher A. Walsh, Matthew C. Keller, Pamela B. Mahon, Patrick J. McGrath, Susan L. Santangelo, Annette M. Hartmann, Ole A. Andreassen, Tatiana Foroud, Shaun Purcell, Josef Frank, Douglas F. Levinson, William Coryell, Ana Miranda, Alan F. Schatzberg, Peter Szatmari, Jun Li, Gerome Breen, Stephen V. Faraone, Anil K. Malhotra, Helena Medeiros, Martin A. Kohli, Nicholas Bass, Catherine Lord, Peter Propping, Wei Xu, Federica Tozzi, Ivan Nikolov, Jan K. Buitelaar, Thomas G. Schulze, Katherine Gordon-Smith, Michele L. Pergadia, Fritz Poustka, Valentina Moskvina, David Curtis, Tobias Banaschewski, Devin Absher, Danielle Posthuma, Stanley Zammit, Gary Donohoe, Ingrid Melle, Karola Rehnström, Thomas Hansen, Myrna M. Weissman, Stanley I. Shyn, Hakon Hakonarson, Christa Lese Martin, Digby Quested, Darina Czamara, Jeremy R. Parr, Pamela A. F. Madden, Jens Treutlein, Aarno Palotie, Robert Freedman, Sandra Meier, Bru Cormand, Nicholas J. Schork, Michele T. Pato, John R. Kelsoe, Vanessa Hus, Frans G. Zitman, Josephine Elia, David St Clair, Roel A. Ophoff, Peter McGuffin, Jonathan Pimm, Jonathan L. Haines, Wiepke Cahn, Matthew Flickinger, Steven P. Hamilton, Michael John Owen, Paul D. Shilling, Jeremy M. Silverman, David Craig, Mark J. Daly, Sarah E. Medland, Robert D. Oades, Marion Leboyer, Alan R. Sanders, Vihra Milanova, Chunyu Liu, Jobst Meyer, Dorret I. Boomsma, Evaristus A. Nwulia, Thomas B. Barrett, Jennifer L. Moran, Donald W. Black, Mònica Bayés, Witte J.G. Hoogendijk, Franziska Degenhardt, Benjamin M. Neale, Daniel L. Koller, Carlos N. Pato, Nicholas John Craddock, Richard Bruggeman, Enda M. Byrne, Edward G. Jones, Eco J. C. de Geus, Stéphane Jamain, Jubao Duan, Anne Farmer, Astrid M. Vicente, Grant W. Montgomery, Thomas Werge, Cathryn M. Lewis, Srdjan Djurovic, Phil Lee, Richard Anney, Elaine K. Green, Wade H. Berrettini, Peter P. Zandi, Susan L. Slager, Stephanie H. Witt, Ian W. Craig, Lisa Jones, Sven Cichon, Bruno Etain, Mark Lathrop, Hilary Coon, Robert C. Thompson, Lena Backlund, A. Jeremy Willsey, Andres Ingason, Christine M. Freitag, Sandra K. Loo, Guiomar Oliveira, Line Olsen, Edwin J. C. G. van den Oord, Geraldine Dawson, Joseph A. Sergeant, David A. Collier, Farooq Amin, Srinivasa Thirumalai, Manfred Uhr, Joseph Piven, Andrew M. McIntosh, Anjali K. Henders, Urban Ösby, Klaus-Peter Lesch, Tiffany A. Greenwood, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Lee, S Hong, Ripke, Stephan, Neale, Benjamin M, Faraone, Stephen V, Wray, Naomi R, Cross-Disorder Group of the Psychiatric Genomics Consortium, International Inflammatory Bowel Disease Genetics Consortium (IIBDGC), Queensland Brain Institute, University of Queensland [Brisbane], Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], SUNY Upstate Medical University, State University of New York (SUNY), Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Psychiatric and Neurodevelopmental Genetics Unit, Queensland Centre for Mental Health Research, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council (MRC)-School of Medicine [Cardiff], Cardiff University-Institute of Medical Genetics [Cardiff]-Cardiff University-Institute of Medical Genetics [Cardiff], New South Wales Department of Primary Industries (NSW DPI), Faculty of Land and Food Resources, University of Melbourne, HudsonAlpha Institute for Biotechnology [Huntsville, AL], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Diakonhjemmet Hospital, University of Michigan [Ann Arbor], University of Michigan System, Molecular and Behavioral Neuroscience Institute (MBNI), University of Michigan System-University of Michigan System, Emory University [Atlanta, GA], Oslo University Hospital [Oslo], University College of London [London] (UCL), Trinity College Dublin, Johns Hopkins University School of Medicine [Baltimore], MRC Social Genetic Developmental and Psychiatry Centre, Institute of Psychiatry, King's College London, University of Coimbra [Portugal] (UC), Karolinska Institutet [Stockholm], University of Chicago, University of British Columbia (UBC), Department of Child and Adolescent Psychiatry and Psychotherapy [Mannheim], Universität Heidelberg [Heidelberg] = Heidelberg University, Weill Medical College of Cornell University [New York], GlaxoSmithKline, Glaxo Smith Kline, Portland Veterans Administration Medical Center, Windeyer Institute for Medical Sciences, IRCCS Fondazione Stella Maris [Pisa], University Hospital Carl Gustav Carus [Dresden, Germany], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), European Network of Bipolar Research Expert Centres (ENBREC), ENBREC, Department of Psychiatry [Philadelphia], University of Pennsylvania, Physiopathologie des Maladies du Système Nerveux Central, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche Phytopharmacie et Médiateurs Chimiques (UPMC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Massachusetts General Hospital [Boston, MA, USA], University of Iowa [Iowa City], University of Edinburgh, Royal Hospital for Sick Children [Edinburgh], The Scripps Research Institute [La Jolla, San Diego], MRC Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London-The Institute of Psychiatry, Institute of Medical Sciences, University of Aberdeen, Social, Genetic and Developmental Psychiatry Centre (SGDP), King‘s College London, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, Department of Psychiatry, University of Groningen [Groningen]-University Medical Center Groningen [Groningen] (UMCG), Trinity College Dublin-St. James's Hospital, School of Nursing, Louisiana State University (LSU), Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud University [Nijmegen]-Radboud University [Nijmegen], Department of Psychiatry and Human Behavior, University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Friedman Brain Institute, Mount Sinai, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Seaver Autism Center for Research and Treatment, Department of Neuroscience, Departments of Psychiatry, Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Seaver Autism Center-, The Mindich Child Health & Development Institute, Friedman Brain Institute, The Mindich Child Health and Development Institute, University of California [San Francisco] (UC San Francisco), Department of Psychiatry, School of Clinical and Experimental Medicine, University of Alabama at Birmingham [ Birmingham] (UAB), Department of Human Genetics, Los Angeles, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Stanley Center for Psychiatric Research, 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], Mental Health Sciences Unit, Department of Genomics, Life and Brain Center, Universität Bonn = University of Bonn, Institute of Human Genetics, Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Academic Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Department of Disability and Human Development, University of Illinois [Chicago] (UIC), University of Illinois System-University of Illinois System, Department of Developmental Neuroscience, Neuropsychiatric Genetics Research Group, University of California [San Diego] (UC San Diego), John P. Hussman Institute for Human Genomics, University of Miami [Coral Gables], East London NHS Foundation Trust, Queen Mary University of London (QMUL), Max-Planck-Institut für Psychiatrie, Genetics Institute, Autism Speaks and the Department of Psychiatry, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), School of Neurology, Neurobiology and Psychiatry, Royal Victoria Infirmary, Medstar Research Institute, KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Deparment of Medical Genetics, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Department of Psychiatry and Behavioral Sciences, University of Chicago-NorthShore University Health System, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine (LSHTM), Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Goethe-Universität Frankfurt am Main, Psychology Department, National University of Singapore (NUS), Department of Biochemistry and Molecular Biology, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de psychiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University (VCU), University of Dundee School of Medicine, University of Dundee, Department of Biostatistics and Center for Statistical Genetics, University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Child Psychiatry, McGill University = Université McGill [Montréal, Canada]-Montreal Children's Hospital, McGill University Health Center [Montreal] (MUHC)-McGill University Health Center [Montreal] (MUHC), Howard University College of Medicine, University of Colorado [Denver], Center for Neurobehavioral Genetics, Department of Genomics, Department of Molecular Medicine, Department of Neurology, University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Medical Research Council-Cardiff University, Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Fisico-Quimica Biologica, Universidade Federal do Rio de Janeiro (UFRJ), Vanderbilt Brain Institute, Vanderbilt University School of Medicine [Nashville], Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania-University of Pennsylvania-Children’s Hospital of Philadelphia (CHOP ), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Institute for Human Genetics, Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Research and Development, Center for Genomic Medicine, Copenhagen University Hospital-Rigshospitalet [Copenhagen], Copenhagen University Hospital, Department of Clinical and Developmental Psychology, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Functional Genomics, Neuronal Plasticity / Mouse Behaviour, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Medical Epidemiology and Biostatistics (MEB), Autism and Communicative Disorders Centre, Center for Human Genetic Research, Center for neuroscience-University of California [Davis] (UC Davis), Bioinformatics Research Center, North Carolina State University [Raleigh] (NC State), Norwegian University of Science and Technology [Trondheim] (NTNU), Norwegian University of Science and Technology (NTNU)-Norwegian University of Science and Technology (NTNU), Emory University [Atlanta, GA]-Atlanta Veterans Affairs Medical Center, Psychiatric Neurogenetics Section, Centre for Addiction and Mental Health, School of Medicine, University of St Andrews [Scotland], Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Division of Molecular Genome Analysis, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Ecology and Evolutionary Biology, Insitute of Neuroscience and Physiology, University of Gothenburg (GU), Institut de Génomique d'Evry (IG), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), 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)-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), Developmental Brain and Behaviour Unit, University of Southampton, Division of Psychiatric Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Statistical Genetics Group, Department of Human Genetics, Department of Pharmacy and Biotechnology, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Department of Psychiatry and Psychotherapy, Department of Mental Health, Johns Hopkins University and Hospital, W.M. Keck Biotechnology Resource Laboratory, Yale University [New Haven], Institutes of Neuroscience and Health and Society, Newcastle University [Newcastle], Genetic Epidemiology Unit, Queensland Institute of Medical Research, Department of Biomedicine and the Centre for Integrative Sequencing, Aarhus University [Aarhus], Sorlandet Hospital HF, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Medical Genetics Section, University of Edinburgh-Western General Hospital, Unit on the Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health [Bethesda] (NIH), Unidade de Neurodesenvolvimento e Autismo (UNDA), Hospital Pediatrico de Coimbra, Division of Mental Health and Addiction, Molecular Psychiatry Laboratory, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Research and Development, First Psychiatric Clinic-Alexander University Hospital, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, St. Olav's Hospital, Brown University, Department of Molecular Biology, Cell Biology and Biochemistry, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig-Universität Leipzig, Human Genetics Department, University of Pittsburgh (PITT), Institute for Biomedical Imaging and Life Science, University Medical Center [Utrecht]-Brain Center Rudolf Magnus, Head of Medical Sequencing, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Carolina Institute for Developmental Disabilities, Analytic and Translational Genetics Unit, Rush University Medical Center [Chicago], Julius-Maximilians-Universität Würzburg (JMU), Washington University in Saint Louis (WUSTL), Department of Statistics, Carnegie Mellon University [Pittsburgh] (CMU), Department of Experimental Clinical and Health Psychology, Universiteit Gent = Ghent University (UGENT), Department of Child and Adolescent Psychiatry, Georg-August-University = Georg-August-Universität Göttingen, Department of Medicine, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM)-Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Departments of Psychiatry and Genetics, Yale School of Medicine [New Haven, Connecticut] (YSM), Maine Medical Center, Free University of Amsterdam, Department of Psychiatry and Behavioral Sciences [Stanford], Pathology and Laboratory Medicine, The Scripps Translational Science Institute and The Scripps Research Institute, Psychiatric Center Nordbaden, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), The Scripps Translational Science Institute and Scripps Health, Child and Adolescent Psychiatry, Aarhus University Hospital, Molecular Neuropsychiatry and Development Laboratory, Department of Molecular Physiology & Biophysics and Psychiatry, Vanderbilt University [Nashville]-Centers for Human Genetics Research and Molecular Neuroscience, Department of Psychiatry and Behavioural Neurosciences, McMaster University [Hamilton, Ontario]-Offord Centre for Child Studies, The Translational Genomics Research Institute (TGen), Oxford Health NHS Foundation Trust, Marlborough House Secure Unit, Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal] (INSA), BioFIG, Center for Biodiversity, Functional and Integrative Genomics, Battelle Center for Mathematical Medicine, Ohio State University [Columbus] (OSU)-Nationwide Children's Hospital, University of Toronto, Diamantina Institute, Carver College of Medicine [Iowa City], University of Iowa [Iowa City]-University of Iowa [Iowa City], Departments of Biostatistics and Medicine, University of Washington [Seattle], ArcelorMittal Maizières Research SA, ArcelorMittal, Institute of Mental Health, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Psychiatrie & Neuropsychologie, Farmacologie en Toxicologie, RS: CARIM School for Cardiovascular Diseases, RS: MHeNs School for Mental Health and Neuroscience, Biological Psychology, Educational Neuroscience, Clinical Neuropsychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, LEARN! - Social cognition and learning, Biophotonics and Medical Imaging, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, LEARN! - Brain, learning and development, EMGO+ - Mental Health, LEARN!, Neuroscience Campus Amsterdam - Brain Imaging Technology, LaserLaB - Biophotonics and Microscopy, State University of New York (SUNY)-State University of New York (SUNY), Department of Neuroscience and Physiology, Faculty of Land and Environment, Biosciences Research Division, Department of Environment and Primary Industries Victoria, Department of Epidemiology and Biostatistics, University of California [San Francisco] (UCSF), University of California-University of California, Universität Heidelberg [Heidelberg], Cornell University [New York]-Weill Medical College of Cornell University [New York], Bioinformatics, Internal Medicine, Portland Va Medical Center : Ganzini Linda MD, Technische Universität Dresden = Dresden University of Technology (TU Dresden)-University Hospital Carl Gustav Carus, Centro Nacional de Análisis Genómico (CNAG), Parc Científic de Barcelona (PCB), University of Pennsylvania [Philadelphia], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Clinical and Research Programs in Pediatric Psychopharmacology and Adult ADHD, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Radboud university [Nijmegen]-Radboud university [Nijmegen], University of California [Irvine] (UCI), University of California-University of California-University of California [Los Angeles] (UCLA), University of Bonn, University of California-University of California-David Geffen School of Medicine [Los Angeles], Cardiff University-Medical Research Council, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Oxford [Oxford], Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Universiteit Gent = Ghent University [Belgium] (UGENT), University of Göttingen - Georg-August-Universität Göttingen, Yale University School of Medicine, Georg-August-University [Göttingen], ANS - Amsterdam Neuroscience, Adult Psychiatry, Child Psychiatry, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, Perlis RH, Mowry BJ, Thapar A, Goddard ME, Witte JS, Absher D, Agartz I, Akil H, Amin F, Andreassen OA, Anjorin A, Anney R, Anttila V, Arking DE, Asherson P, Azevedo MH, Backlund L, Badner JA, Bailey AJ, Banaschewski T, Barchas JD, Barnes MR, Barrett TB, Bass N, Battaglia A, Bauer M, Bayés M, Bellivier F, Bergen SE, Berrettini W, Betancur C, Bettecken T, Biederman J, Binder EB, Black DW, Blackwood DH, Bloss CS, Boehnke M, Boomsma DI, Breen G, Breuer R, Bruggeman R, Cormican P, Buccola NG, Buitelaar JK, Bunney WE, Buxbaum JD, Byerley WF, Byrne EM, Caesar S, Cahn W, Cantor RM, Casas M, Chakravarti A, Chambert K, Choudhury K, Cichon S, Cloninger CR, Collier DA, Cook EH, Coon H, Cormand B, Corvin A, Coryell WH, Craig DW, Craig IW, Crosbie J, Cuccaro ML, Curtis D, Czamara D, Datta S, Dawson G, Day R, De Geus EJ, Degenhardt F, Djurovic S, Donohoe GJ, Doyle AE, Duan J, Dudbridge F, Duketis E, Ebstein RP, Edenberg HJ, Elia J, Ennis S, Etain B, Fanous A, Farmer AE, Ferrier IN, Flickinger M, Fombonne E, Foroud T, Frank J, Franke B, Fraser C, Freedman R, Freimer NB, Freitag CM, Friedl M, Frisén L, Gallagher L, Gejman PV, Georgieva L, Gershon ES, Geschwind DH, Giegling I, Gill M, Gordon SD, Gordon-Smith K, Green EK, Greenwood TA, Grice DE, Gross M, Grozeva D, Guan W, Gurling H, De Haan L, Haines JL, Hakonarson H, Hallmayer J, Hamilton SP, Hamshere ML, Hansen TF, Hartmann AM, Hautzinger M, Heath AC, Henders AK, Herms S, Hickie IB, Hipolito M, Hoefels S, Holmans PA, Holsboer F, Hoogendijk WJ, Hottenga JJ, Hultman CM, Hus V, Ingason A, Ising M, Jamain S, Jones EG, Jones I, Jones L, Tzeng JY, Kähler AK, Kahn RS, Kandaswamy R, Keller MC, Kennedy JL, Kenny E, Kent L, Kim Y, Kirov GK, Klauck SM, Klei L, Knowles JA, Kohli MA, Koller DL, Konte B, Korszun A, Krabbendam L, Krasucki R, Kuntsi J, Kwan P, Landén M, Långström N, Lathrop M, Lawrence J, Lawson WB, Leboyer M, Ledbetter DH, Lee PH, Lencz T, Lesch KP, Levinson DF, Lewis CM, Li J, Lichtenstein P, Lieberman JA, Lin DY, Linszen DH, Liu C, Lohoff FW, Loo SK, Lord C, Lowe JK, Lucae S, MacIntyre DJ, Madden PA, Maestrini E, Magnusson PK, Mahon PB, Maier W, Malhotra AK, Mane SM, Martin CL, Martin NG, Mattheisen M, Matthews K, Mattingsdal M, McCarroll SA, McGhee KA, McGough JJ, McGrath PJ, McGuffin P, McInnis MG, McIntosh A, McKinney R, McLean AW, McMahon FJ, McMahon WM, McQuillin A, Medeiros H, Medland SE, Meier S, Melle I, Meng F, Meyer J, Middeldorp CM, Middleton L, Milanova V, Miranda A, Monaco AP, Montgomery GW, Moran JL, Moreno-De-Luca D, Morken G, Morris DW, Morrow EM, Moskvina V, Muglia P, Mühleisen TW, Muir WJ, Müller-Myhsok B, Murtha M, Myers RM, Myin-Germeys I, Neale MC, Nelson SF, Nievergelt CM, Nikolov I, Nimgaonkar V, Nolen WA, Nöthen MM, Nurnberger JI, Nwulia EA, Nyholt DR, O'Dushlaine C, Oades RD, Olincy A, Oliveira G, Olsen L, Ophoff RA, Osby U, Owen MJ, Palotie A, Parr JR, Paterson AD, Pato CN, Pato MT, Penninx BW, Pergadia ML, Pericak-Vance MA, Pickard BS, Pimm J, Piven J, Posthuma D, Potash JB, Poustka F, Propping P, Puri V, Quested DJ, Quinn EM, Ramos-Quiroga JA, Rasmussen HB, Raychaudhuri S, Rehnström K, Reif A, Ribasés M, Rice JP, Rietschel M, Roeder K, Roeyers H, Rossin L, Rothenberger A, Rouleau G, Ruderfer D, Rujescu D, Sanders AR, Sanders SJ, Santangelo SL, Sergeant JA, Schachar R, Schalling M, Schatzberg AF, Scheftner WA, Schellenberg GD, Scherer SW, Schork NJ, Schulze TG, Schumacher J, Schwarz M, Scolnick E, Scott LJ, Shi J, Shilling PD, Shyn SI, Silverman JM, Slager SL, Smalley SL, Smit JH, Smith EN, Sonuga-Barke EJ, St Clair D, State M, Steffens M, Steinhausen HC, Strauss JS, Strohmaier J, Stroup TS, Sutcliffe JS, Szatmari P, Szelinger S, Thirumalai S, Thompson RC, Todorov AA, Tozzi F, Treutlein J, Uhr M, van den Oord EJ, Van Grootheest G, Van Os J, Vicente AM, Vieland VJ, Vincent JB, Visscher PM, Walsh CA, Wassink TH, Watson SJ, Weissman MM, Werge T, Wienker TF, Wijsman EM, Willemsen G, Williams N, Willsey AJ, Witt SH, Xu W, Young AH, Yu TW, Zammit S, Zandi PP, Zhang P, Zitman FG, Zöllner S, Devlin B, Kelsoe JR, Sklar P, Daly MJ, O'Donovan MC, Craddock N, Sullivan PF, Smoller JW, Kendler KS, Wray NR, Cardiff University-Medical Research Council (MRC), HudsonAlpha Institute for Biotechnology, The Institute of Psychiatry-King‘s College London, Cornell University-Weill Medical College of Cornell University [New York], Stanford University Medical School, Technische Universität Dresden (TUD)-University Hospital Carl Gustav Carus, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, McGill University-Montreal Children's Hospital, Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Stanford University School of Medicine [Stanford], Stanford University [Stanford], Eberhard Karls Universität Tübingen, Friedrich Alexander University [Erlangen-Nürnberg], Università di Bologna [Bologna] (UNIBO), University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Washington University School of Medicine, Ghent University [Belgium] (UGENT), University of Goettingen, CHUM Research Center, Psychiatry and Behavioral Science, Stanford University School of Medicine [CA, USA], Aalborg Psychiatric Hospital, Aarhus University Hospital, Washington University in St Louis, Instituto Nacional de Saude Dr Ricardo Jorge, Oades, Robert D., Guellaen, Georges, Medical Oncology, Epidemiology, Child and Adolescent Psychiatry / Psychology, and Hematology

Subjects
Netherlands Twin Register (NTR), Medizin, Inheritance Patterns, Social Sciences, AUTISM SPECTRUM DISORDERS, nosology, heritability, COMMON SNPS, 0302 clinical medicine, Crohn Disease, SCHIZOPHRENIA, Child, Psychiatric genetics, Genetics & Heredity, MAJOR DEPRESSIVE DISORDER, RISK, 0303 health sciences, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, 120 000 Neuronal Coherence, Mental Disorders, Variants, BIPOLAR DISORDER, ASSOCIATION, Genomic disorders and inherited multi-system disorders [DCN PAC - Perception action and control IGMD 3], Psychiatric Disorders, CROHNS-DISEASE, 3. Good health, Schizophrenia, genetic association study, Medical genetics, Major depressive disorder, SNPs, Adult, medicine.medical_specialty, genetic etiology, medical genetics, DEFICIT HYPERACTIVITY DISORDER, Biology, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, Genomic disorders and inherited multi-system disorders DCN MP - Plasticity and memory [IGMD 3], Heritability, Genetic Heterogeneity, 03 medical and health sciences, Prevalence of mental disorders, mental disorders, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Genetics, medicine, ddc:61, Humans, Attention deficit hyperactivity disorder, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, DCN PAC - Perception action and control NCEBP 9 - Mental health, ddc:610, Medizinische Fakultät » Universitätsklinikum Essen » LVR-Klinikum Essen » Klinik für Psychiatrie, Psychosomatik und Psychotherapie des Kindes- und Jugendalters, Bipolar disorder, Psychiatry, 030304 developmental biology, Depressive Disorder, Major, Genome, Human, Genetic heterogeneity, medicine.disease, schizophrenia, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, Perturbações do Desenvolvimento Infantil e Saúde Mental, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

AM Vicente - Cross-Disorder Group of the Psychiatric Genomics Consortium Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Published
2013

18. Diffusion imaging of the brain: technical considerations and practical applications

Author

Norris, David G., FC Donders Centre for Cognitive Neuroimaging, and Universität Leipzig

Subjects
diffusion, transport, ddc:530
Abstract

This chapter presents a brief introduction to the application of diffusion-weighted magnetic resonance imaging (MRI) to in vivo studies. Diffusion-weighted MRI has found application both in the clinic, and in basic neuroscience. In the former situation it is primarily used for the detection of brain lesions, in particular infarcted regions. The ability to follow fibre tracts in white matter via diffusion tensor imaging has also made this methodology of interest to the neurosurgeon wishing to avoid severance of essential fibre tracts, but also of interest to the cognitive neuroscientist exploring anatomical connectivity in the brain. The chapter starts with a brief recap of the theory of diffusionweighted MRI and moves on to examine the two major experimental confounds, eddy currents and bulk motion. Current correction schemes for these problems are touched upon. Diffusion anisotropy is introduced as a potential source of artefacts for lesion detection in white matter, and the diffusion tensor model presented. The chapter concludes with a short introduction to fibre tracking.

Published
2005

19. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author

Pm, Thompson, Jl, Stein, Se, Medland, Dp, Hibar, Aa, Vasquez, Me, Renteria, Toro R, Jahanshad N, Schumann G, Franke B, Mj, Wright, Ng, Martin, Agartz I, Alda M, Alhusaini S, Almasy L, Almeida J, Alpert K, Nc, Andreasen, Oa, Andreassen, Lg, Apostolova, Appel K, Nj, Armstrong, Aribisala B, Me, Bastin, Bauer M, Ce, Bearden, Bergmann O, Eb, Binder, Blangero J, Hj, Bockholt, Bøen E, Bois C, Di, Boomsma, Booth T, Ij, Bowman, Bralten J, Rm, Brouwer, Hg, Brunner, Dg, Brohawn, Rl, Buckner, Buitelaar J, Bulayeva K, Jr, Bustillo, Vd, Calhoun, Dm, Cannon, Rm, Cantor, Ma, Carless, Caseras X, Gl, Cavalleri, Mm, Chakravarty, Kd, Chang, Cr, Ching, Christoforou A, Cichon S, Vp, Clark, Conrod P, Coppola G, Crespo-Facorro B, Je, Curran, Czisch M, Ij, Deary, Ej, Geus, den Braber A, Delvecchio G, Depondt C, de Haan L, Gi, Zubicaray, Dima D, Dimitrova R, Djurovic S, Dong H, Donohoe G, Duggirala R, Td, Dyer, Ehrlich S, Cj, Ekman, Elvsåshagen T, Emsell L, Erk S, Espeseth T, Fagerness J, Fears S, Fedko I, Fernández G, Se, Fisher, Foroud T, Pt, Fox, Francks C, Frangou S, Em, Frey, Frodl T, Frouin V, Garavan H, Giddaluru S, Dc, Glahn, Godlewska B, Rz, Goldstein, Rl, Gollub, Hj, Grabe, Grimm O, Gruber O, Guadalupe T, Re, Gur, Rc, Gur, Hh, Göring, Hagenaars S, Hajek T, Gb, Hall, Hall J, Hardy J, Ca, Hartman, Hass J, Sn, Hatton, Uk, Haukvik, Hegenscheid K, Heinz A, Ib, Hickie, Bc, Ho, Hoehn D, Pj, Hoekstra, Hollinshead M, Aj, Holmes, Homuth G, Martine Hoogman, Le, Hong, Hosten N, Jj, Hottenga, He, Hulshoff Pol, Ks, Hwang, Cr, Jack Jr, Jenkinson M, Johnston C, Eg, Jönsson, Rs, Kahn, Kasperaviciute D, Kelly S, Kim S, Kochunov P, Koenders L, Krämer B, Jb, Kwok, Lagopoulos J, Laje G, Landen M, Ba, Landman, Lauriello J, Sm, Lawrie, Ph, Lee, Le Hellard S, Lemaître H, Cd, Leonardo, Cs, Li, Liberg B, Dc, Liewald, Liu X, Lm, Lopez, Loth E, Lourdusamy A, Luciano M, Macciardi F, Mw, Machielsen, Gm, Macqueen, Uf, Malt, Mandl R, Ds, Manoach, Jl, Martinot, Matarin M, Ka, Mather, Mattheisen M, Mattingsdal M, Meyer-Lindenberg A, McDonald C, Am, Mcintosh, Fj, Mcmahon, Kl, Mcmahon, Meisenzahl E, Melle I, Milaneschi Y, Mohnke S, Gw, Montgomery, Dw, Morris, Ek, Moses, Ba, Mueller, Muñoz Maniega S, Tw, Mühleisen, Müller-Myhsok B, Mwangi B, Nauck M, Nho K, Te, Nichols, Lg, Nilsson, Ac, Nugent, Nyberg L, Rl, Olvera, Oosterlaan J, Ra, Ophoff, Pandolfo M, Papalampropoulou-Tsiridou M, Papmeyer M, Paus T, Pausova Z, Gd, Pearlson, Bw, Penninx, Cp, Peterson, Pfennig A, Phillips M, Gb, Pike, Jb, Poline, Sg, Potkin, Pütz B, Ramasamy A, Rasmussen J, Rietschel M, Rijpkema M, Sl, Risacher, Jl, Roffman, Roiz-Santiañez R, Romanczuk-Seiferth N, Ej, Rose, Na, Royle, Rujescu D, Ryten M, Ps, Sachdev, Salami A, Td, Satterthwaite, Savitz J, Aj, Saykin, Scanlon C, Schmaal L, Hg, Schnack, Aj, Schork, Sc, Schulz, Schür R, Seidman L, Shen L, Jm, Shoemaker, Simmons A, Sm, Sisodiya, Smith C, Jw, Smoller, Jc, Soares, Sr, Sponheim, Sprooten E, Jm, Starr, Vm, Steen, Strakowski S, Strike L, Sussmann J, Pg, Sämann, Teumer A, Aw, Toga, Tordesillas-Gutierrez D, Trabzuni D, Trost S, Turner J, Van den Heuvel M, Nj, Wee, van Eijk K, Tg, Erp, Ne, Haren, van 't Ent D, Mj, Tol, Mc, Valdés Hernández, Dj, Veltman, Versace A, Völzke H, Walker R, Walter H, Wang L, Jm, Wardlaw, Me, Weale, Mw, Weiner, Wen W, Lt, Westlye, Hc, Whalley, Cd, Whelan, White T, Am, Winkler, Wittfeld K, Woldehawariat G, Wolf C, Zilles D, Mp, Zwiers, Thalamuthu A, Pr, Schofield, Nb, Freimer, Ns, Lawrence, Drevets W, The Alzheimer’s Disease Neuroimaging Initiative, Epigen Consortium, Laboratory of Neuro Imaging [Los Angeles] (LONI), University of California [Los Angeles] (UCLA), University of California-University of California, David Geffen School of Medicine [Los Angeles], Medstar Research Institute, Keck School of Medicine [Los Angeles], University of Southern California (USC), Génétique Humaine et Fonctions Cognitives, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Department of Psychiatry, Donders Centre for Neuroscience, Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen], Genetic Epidemiology Lab [Brisbane], Queensland Institute of Medical Research, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), KG Jebsen Centre for Psychosis Research, University of Oslo (UiO)-Institute of Clinical Medicine-Oslo University Hospital [Oslo], Dalhousie University [Halifax], Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland (RCSI), Department of Genetics, Southwest Foundation for Biomedical Research, Departamento de Matemática Pura, Faculdade de Ciências (UNIVERSIDADE DO PORTO), Universidade do Porto = University of Porto, Department of Psychiatry and Psychotherapy, University of Edinburgh, Center for Sepsis Control & Care, Jena University Hospital, Division Genetic Epidemiology in Psychiatry, Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim]-Medical Faculty [Mannheim], Texas Biomedical Research Institute [San Antonio, TX], Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], Brain Center Rudolf Magnus, Department of Psychiatry, UMC Utrecht, Utrecht 3584 CX, The Netherlands, Radboud University Medical Center [Nijmegen], Department of Psychiatry [Boston], Massachusetts General Hospital [Boston], Karakter Child and Adolescent Psychiatry University Centre [Nijmegen], N.I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119333, Russia, Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Department of Genomics, Douglas Mental Health University Institute, McGill University = Université McGill [Montréal, Canada], sans affiliation, Università degli Studi di Salermo, Università degli Studi di Salerno (UNISA), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Bijvoet Center of Biomolecular Research [Utrecht], Utrecht University [Utrecht], Biological Psychology, Neuroscience Campus Amsterdam & EMGO Institute for Health and Care Research, VU University & VU Medical Center, Amsterdam 1081 BT, The Netherlands, 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), Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), School of Psychology, University of Queensland, University of Queensland [Brisbane], Department of Hematology, 'Ion Chiricuta' Cancer Institute, University of Oslo (UiO), The University of Texas Health Science Center at Houston (UTHealth), MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Department of Psychiatry, Division of Medical Psychology, Champalimaud Neuroscience Programme, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indiana University System-Indiana University System, Language and Genetics Department [Nijmegen], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Division of Hemato-Oncology, Saint Anna Children's Hospital [Vienne] = St Anna Kinderspital (St. Anna Children's Hospital), Psychiatry and Psychotherapy, Service NEUROSPIN (NEUROSPIN), 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), University of Vermont [Burlington], Haukeland University Hospital, University of Bergen (UiB), Dpt of Psychiatry [New Haven], Yale School of Medicine [New Haven, Connecticut] (YSM), Laboratory of Molecular Neuropsychiatry, Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], HELIOS Klinikum Stralsund Hanseatic-Greifswald University Hospital, Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Universität Heidelberg [Heidelberg], International Max Planck Research School for Language Sciences (IMPRS ), Lancaster University, Georgia Institute of Technology [Atlanta], Greifswald University Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Clinical Research Unit, Brain & Mind Research Institute-The University of Sydney, Department of Psychiatry, University of Iowa, University of Iowa [Iowa City], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, University Medical Center Groningen [Groningen] (UMCG), Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Mental Health Sciences Unit, University College of London [London] (UCL), University Medical Center [Utrecht], Department of Radiology [Rochester], Mayo Clinic [Rochester], Department of Clinical Neurology [Oxford], University of Oxford [Oxford]-FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital], Centre for the Cellular Basis of Behavior, Bureau d'Économie Théorique et Appliquée (BETA), Institut National de la Recherche Agronomique (INRA)-Université de Strasbourg (UNISTRA)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Department of Medicine, Imperial College London, MetaCase [Jyväskylä], Structure et Réactivité des Systèmes Moléculaires Complexes (SRSMC), Institut de Chimie du CNRS (INC)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), University of Maryland [Baltimore County] (UMBC), University of Maryland System-University of Maryland System-University of Maryland School of Medicine, University of Maryland System, Sahlgrenska Academy at University of Gothenburg [Göteborg], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Université de Cergy Pontoise (UCP), Université Paris-Seine, National Institutes of Health [Bethesda] (NIH), Department of Forensic and Neurodevelopmental Sciences, University of California [Irvine] (UCI), University of California, 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), Clinical And Experimental Epilepsy, Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia, Department of Life Sciences, Mathematical Sciences Institute (MSI), Australian National University (ANU), Centre for Advanced Imaging, Division of Mental Health and Addiction, Oslo University Hospital [Oslo], VU University Medical Center [Amsterdam], Metacohorts Consortium, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Institute of Clinical Chemistry and Laboratory Medicine, Indiana Alzheimer Disease Center, Department of Statistics [Warwick], University of Warwick [Coventry], 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), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Modelling brain structure, function and variability based on high-field MRI data (PARIETAL), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), 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, Donders Center for Cognitive Neuroimaging, Donders Centre for Cognitive Neuroimaging, Radboud university [Nijmegen]-Radboud university [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), Centre for Healthy Brain Ageing, University of New South Wales [Sydney] (UNSW), Umeå Centre for Functional Brain Imaging (UFBI), Umeå University, Umeå 901 87, Sweden, University of Pennsylvania [Philadelphia], Department of Cognitive Sciences [San Diego], University of California [San Diego] (UC San Diego), Indiana University System, Natbrainlab, Department of Forensic and Neurodevelopmental Sciences, Institute of psychiatry-King‘s College London, Institute of Neurology [London], Laboratoire des symbioses tropicales et méditerranéennes (UMR LSTM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Stanley Center for Psychiatric Research, 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], King Faisal Specialist Hospital and Research Centre, Georgia State University, University System of Georgia (USG), Department of Psychiatry and Human Behavior [Irvine], Leiden University Medical Center (LUMC), Institute for Community Medicine, School of Music and Music Education (UNSW), Science & Technology Information Institute, Shandong Academy of Agricultural Science, University of California [San Francisco] (UCSF), Department of Physics [Hong Kong University of Science and Technology], Hong Kong University of Science and Technology (HKUST), Department of Psychology [Oslo], Faculty of Social Sciences [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Research Laboratory for Archaeology & the History of Art, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Dundee Technopole, CXR Biosciences Ltd, Georg-August-University [Göttingen], Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney 2052, Australia, Prince of Wales Medical Research Institute, Center for Neurobehavioral Genetics, Wales Institute of Cognitive Neuroscience, Cardiff University, Complutense University of Madrid (UCM), Universidade do Porto [Porto], Texas Biomedical Research Institute [San Antonio, Texas], Karakter Child and Adolescent Psychiatry University Centre, McGill University, Bijvoet Center of Biomolecular Research, Université Libre de Bruxelles [Bruxelles] (ULB)-Hôpital Erasme (Bruxelles), St. Anna Children's Hospital, 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, University of Bergen (UIB), Yale University School of Medicine, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), 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), McGill University-McGill University, Technische Universität Dresden (TUD), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Inria Saclay - Ile de France, Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Physics [Kowloon], University of California (UC)-University of California (UC), QIMR Berghofer Medical Research Institute, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Department of Clinical Neurosciences, Neurology Division, Karolinska Institutet, Karolinska University Hospital [Stockholm], Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University [Chicago, Ill. USA], Norwegian Centre for Mental Disorders Research [Oslo] (NORMENT), University of Oslo (UiO)-Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB)-Oslo University Hospital [Oslo], Ernst-Moritz-Arndt-Universität Greifswald, School of Mathematics and Statistics, Brain Research Imaging Centre, Imaging Sciences, University Hospital Carl Gustav Carus [Dresden, Germany], Semel Institute for Neuroscience and Human Behavior [Los Angeles, Ca], Institute of Clinical Medicine [Oslo], Faculty of Medicine [Oslo], Royal Hospital for Sick Children [Edinburgh], Department of General Practice/EMGO Institute, Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), University of Edinburgh-Medical Research Council (MRC), Radboud University [Nijmegen], Brain Centre Rudolf Magnus [Utrecht], Department of Human Genetics [Nijmegen], Psychiatric and Neurodevelopmental Genetics Unit, Harvard University, Russian Academy of Sciences [Moscow] (RAS), The University of New Mexico [Albuquerque], The Mind Research Network, Department of Electrical and Computer Engineering [Albuquerque] (ECE Department), National University of Ireland [Galway] (NUI Galway), University of California (UC), Institute of Psychological Medicine and Clinical Neurosciences, Centre for Addiction and Mental Health [Toronto] (CAMH), Institute of Biomaterials and Biomedical Engineering [Toronto, ON, Canada] (IBBME), University of Toronto, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Universität Bonn = University of Bonn, Jülich Research Centre, University of Basel (Unibas), Centre de recherche du CHU Sainte-Justine / Research Center of the Sainte-Justine University Hospital [Montreal, Canada], Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Fundación Marqués de Valdecilla-Instituto de Formación e Investigación Marqués de Valdecilla (IFIMAV), Centre for Cognitive Ageing and Cognitive Epidemiology, Trinity College Dublin, Department of Psychiatry Massachusetts General Hospital (MGH), South Texas Veterans Health Care System, San Antonio, Texas 78229, USA, University Hospital Regensburg, Hartford Hospital, University of Oxford, HELIOS Klinikum Stralsund Hanseatic, University of Heidelberg, Medical Faculty, Georg-August-University = Georg-August-Universität Göttingen, University of Pennsylvania, McMaster University [Hamilton, Ontario], UCL, Institute of Neurology [London], Brain and Mind Research Institute, University of Technology Sydney (UTS), Diakonhjemmet Hospital, University of Maryland School of Medicine, Oakland University, University of Rochester School of Medicine, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), South London and Maudsley NHS Foundation Trust, Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Maryland [Baltimore], Neuroscience Research Australia (NeuRA), University of Gothenburg (GU), Karolinska Institutet [Stockholm], Vanderbilt University [Nashville], University of Missouri [Columbia] (Mizzou), University of Missouri System, Service Hospitalier Frédéric Joliot (SHFJ), 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), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neuroscience, Yale University School of Medicine, Columbia University Medical Center (CUMC), Columbia University [New York], University of Nottingham, UK (UON), University of California [Irvine] (UC Irvine), Università degli Studi di Milano = University of Milan (UNIMI), Hotchkiss Brain Institute, University of Calgary, Oslo and Akershus University College of Applied Sciences [Oslo] (HiOA), Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, University of New South Wales, Sydney, Aarhus University [Aarhus], Sorlandet Hospital HF, University Hospital Mannheim | Universitätsmedizin Mannheim, Centre for Advanced Imaging [Brisbane] (CAI), Ludwig Maximilian University [Munich] (LMU), Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, The University of Western Australia (UWA), University of Minnesota [Morris], University of Minnesota System, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), The University of Texas Medical School at Houston, Indiana State University, Stockholm Brain Institute [Stockholm, Sweden], Stockholm University, Umeå University, University of Texas Health Science Center, Department of Clinical Neuropsychology, University of Amsterdam [Amsterdam] (UvA), Rotman Research Institute at the Baycrest Centre (RRI), The Hospital for sick children [Toronto] (SickKids), University of Pittsburgh (PITT), University of California [Berkeley] (UC Berkeley), King's College, Reta Lila Weston Institute, UCL Institute of Neurology, Department of Molecular Neuroscience, University College of London [London] (UCL)-Institute of Neurology, University of Cantabria, Santander, Research Triangle Institute International (RTI International), Martin-Luther-Universität Halle Wittenberg (MLU), Prince of Wales Hospital, Karolinska Institute, Laureate institute for brain research, Tulsa, University of Tulsa, Department of Cognitive Sciences [Univ California San Diego] (CogSci - UC San Diego), University of Minnesota Medical School, Beth Israel Deaconess Medical Center [Boston] (BIDMC), Harvard Medical School [Boston] (HMS), Maudsley NHS Foundation Trust and Institute of Psychiatry, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Edinburgh Dementia Prevention & Centre for Clinical Brain Sciences, Center for Human Genetic Research, VA NY Harbor Health Care System, Alzheimer Scotland Dementia Research Centre, Department of Psychiatry and Behavioral Neuroscience [UC, Cincinnati], University of Cincinnati (UC), University of Cincinnati College of Medicine, Marqués de Valdecilla University Hospital [Santander], King Faisal Specialist Hospital and Resarch Centre [Riyadh, Saudi Arabia] (KFSHRC), Psychiatry and Leiden Institute for Brain and Cognition, Universiteit Leiden-Universiteit Leiden, Universiteit Leiden, Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), The Centre for Regenerative Medicine, Berlin School of Mind and Brain [Berlin], Humboldt University Of Berlin, University of California [San Francisco] (UC San Francisco), School of Chemistry, University of Edinburgh, Department of Public Health, Erasmus University Medical Centre, Rotterdam, Erasmus University Medical Centre, Rotterdam, Department of Psychiatry and Biobehavioral Sciences, University of Exeter, Janssen Research & Development, A complete listing of ADNI investigators is available at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf The work reviewed here was funded by a large number of federal and private agencies worldwide, listed in Stein et al. (2012), the funding for listed consortia is also itemized in Stein et al. (2012)., Medical Oncology, Epidemiology, Clinical Chemistry, Cardiology, Neurosciences, Child and Adolescent Psychiatry / Psychology, Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen]-Radboud University Medical Center [Nijmegen]-Radboud university [Nijmegen], Universidade do Porto, FMRIB Centre- John Radcliffe Hospital [Oxford University Hospital]-University of Oxford [Oxford], Université de Lorraine (UL)-Université de Strasbourg (UNISTRA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), 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), Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Service NEUROSPIN (NEUROSPIN), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Smoller, Jordan, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ANS - Amsterdam Neuroscience, Adult Psychiatry, Other departments, University of Oxford [Oxford]- John Radcliffe Hospital [Oxford University Hospital]-FMRIB Centre, and 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)

Subjects
endocrine system, Multi-site, Cognitive Neuroscience, [SDV]Life Sciences [q-bio], body-mass index, Clinical Neurology, multivariate parallel ica, Neuroimaging, methods [Genome-Wide Association Study], human brain structure, methods [Brain Mapping], Behavioral Neuroscience, Cellular and Molecular Neuroscience, ddc:150, Meta-Analysis as Topic, cortical surface-area, Genetics, voxel-based morphometry, GWAS, Humans, Cooperative Behavior, disease risk variant, Brain Mapping, MRI, Consortium, Meta-analysis, white-matter microstructure, SI: Genetic Neuroimaging in Aging and Age-Related Diseases, Psychiatry and Mental health, Neurology, Radiology Nuclear Medicine and imaging, quantitative trait loci, RC0321, genome-wide association, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tensor-based morphometry, methods [Neuroimaging], Genome-Wide Association Study
Abstract

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA’s first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

20. Stimulant medication and symptom interrelations in children, adolescents and adults with attention-deficit/hyperactivity disorder.

Author

van der Pal Z, Geurts HM, Haslbeck JMB, van Keeken A, Bruijn AM, Douw L, van Rooij D, Franke B, Buitelaar J, Lambregts-Rommelse N, Hartman C, Oosterlaan J, Luman M, Reneman L, Hoekstra PJ, Blanken TF, and Schrantee A

Abstract

Stimulant medication is effective in alleviating overall symptom severity of attention-deficit/hyperactivity disorder (ADHD), yet interindividual variability in treatment response and tolerability still exists. While network analysis has identified differences in ADHD symptom relations, the impact of stimulant medication remains unexplored. Increased understanding of this association could provide valuable insights for optimizing treatment approaches for individuals with ADHD. In this study, we compared and characterized ADHD symptom networks (including 18 ADHD symptoms) between stimulant-treated (n = 348) and untreated (n = 70) individuals with ADHD and non-ADHD controls (NACs; n = 444). Moreover, we compared symptom networks between subgroups defined by their stimulant treatment trajectory (early-and-intense use, late-and-moderate use). Stimulant-treated individuals with ADHD showed stronger associations between symptoms, compared with untreated individuals with ADHD and NACs. We found no differences in symptom networks between the stimulant treatment trajectory subgroups. Prospective longitudinal studies are needed to disentangle whether the identified differences stem from treatment or pre-existing factors., Competing Interests: Declarations Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the medical ethical committees of the VU University Medical Centre and Radboud University Medical Centre (NL23894.091.08). Informed consent We obtained written informed consent from all participants aged 12 years and older, and from parents for participants under 18, for participation in the NeuroIMAGE study and use of their de-identified data in analysis and publications. Competing interests JB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Medice, Angelini, Boehringer-Ingelheim, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, and royalties. All other authors have no competing interest or industry support to report., (© 2024. The Author(s).)

Published
2024
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21. Emotion regulation flexibility: EEG/EMG predictors and consequences of switching between reappraisal and distraction strategies.

Author

Adamczyk AK, Koch SBJ, Wyczesany M, Roelofs K, and van Peer JM

Subjects
Humans, Female, Young Adult, Adult, Facial Muscles physiology, Attention physiology, Male, Electroencephalography, Electromyography, Emotional Regulation physiology, Evoked Potentials physiology
Abstract

Flexible use of emotion regulation (ER) strategies is central to mental health. To advance our understanding of what drives adaptive strategy-switching decisions, in this preregistered study, we used event-related potentials (late positive potential, LPP and stimulus preceding negativity, SPN) and facial electromyography (EMG corrugator activity) to test the antecedents and consequences of switching to an alternative ER strategy. Participants (N = 63, M age  = 24.8 years, all female) passively watched and then implemented an instructed ER strategy (reappraisal or distraction) in response to high-intensity negative pictures that were either easy or difficult to reinterpret (high or low reappraisal affordance, respectively). Next, they decided to "switch from" or "maintain" the instructed strategy and subsequently implemented the chosen strategy. Reappraisal affordance manipulations successfully induced switching. Regarding antecedents, switching was predicted by the reduced ER efficacy of the current strategy (corrugator, but not LPP). Switching to distraction was additionally predicted by increased responses to the stimulus during passive viewing (corrugator and LPP) and increased anticipatory effort in implementing reappraisal (SPN). Concerning consequences, switching to distraction improved, whereas switching to reappraisal impaired post-choice ER effects (LPP). However, starting with reappraisal was overall more effective than starting with distraction, irrespective of the subsequent decision (corrugator). Our results suggest that switching between ER strategies occurs in accordance with situational demands (stimulus affordances) and is predicted by reduced peripheral physiological ER efficacy. However, only switching to distraction leads to improved regulatory effects. These insights provide neurocognitively grounded starting points for developing interventions targeting ER flexibility., (© 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Published
2024
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22. The structure and statistics of language jointly shape cross-frequency neural dynamics during spoken language comprehension.

Author

Weissbart H and Martin AE

Subjects
Humans, Male, Female, Adult, Young Adult, Speech physiology, Magnetoencephalography, Comprehension physiology, Language, Speech Perception physiology, Brain physiology
Abstract

Humans excel at extracting structurally-determined meaning from speech despite inherent physical variability. This study explores the brain's ability to predict and understand spoken language robustly. It investigates the relationship between structural and statistical language knowledge in brain dynamics, focusing on phase and amplitude modulation. Using syntactic features from constituent hierarchies and surface statistics from a transformer model as predictors of forward encoding models, we reconstructed cross-frequency neural dynamics from MEG data during audiobook listening. Our findings challenge a strict separation of linguistic structure and statistics in the brain, with both aiding neural signal reconstruction. Syntactic features have a more temporally spread impact, and both word entropy and the number of closing syntactic constituents are linked to the phase-amplitude coupling of neural dynamics, implying a role in temporal prediction and cortical oscillation alignment during speech processing. Our results indicate that structured and statistical information jointly shape neural dynamics during spoken language comprehension and suggest an integration process via a cross-frequency coupling mechanism., (© 2024. The Author(s).)

Published
2024
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23. How distributed subcortical integration of reward and threat may inform subsequent approach-avoidance decisions.

Author

Hulsman AM, Klaassen FH, de Voogd LD, Roelofs K, and Klumpers F

Abstract

Healthy and successful living involves carefully navigating rewarding and threatening situations by balancing approach and avoidance behaviours. Excessive avoidance to evade potential threats often leads to forfeiting potential rewards. However, little is known about how reward and threat information is integrated neurally to inform approach or avoidance decisions. In this preregistered study, participants (N behaviour =31, 17F; N MRI =28, 15F) made approach-avoidance decisions under varying reward (monetary gains) and threat (electrical stimulations) prospects during functional MRI scanning. In contrast to theorized parallel subcortical processing of reward and threat information before cortical integration, Bayesian Multivariate Multilevel analyses revealed subcortical reward and threat integration prior to indicating approach-avoidance decisions. This integration occurred in the ventral striatum, thalamus, and bed nucleus of the stria terminalis (BNST). When reward was low, risk-diminishing avoidance decisions dominated, which was linked to more positive tracking of threat magnitude prior to indicating avoidance than approach decisions across these regions. In contrast, the amygdala exhibited dual sensitivity to reward and threat. While anticipating outcomes of risky approach decisions, we observed positive tracking of threat magnitude within the salience network (dorsal anterior cingulate cortex, thalamus, periaqueductal gray, BNST). Conversely, after risk-diminishing avoidance, characterized by reduced reward prospects, we observed more negative tracking of reward magnitude in the ventromedial prefrontal cortex and ventral striatum. These findings shed light on the temporal dynamics of approach-avoidance decision-making. Importantly, they demonstrate the role of subcortical integration of reward and threat information in balancing approach and avoidance, challenging theories positing predominantly separate subcortical processing prior to cortical integration. Significance statement When deciding whether to approach or avoid situations, our decision-making involves balancing potential rewards and threats. Widespread theories of decision-making in humans propose parallel processing of reward and threat information in subcortical regions, followed by cortical integration. Challenging these notions, we found evidence for dual and integrated processing of reward and threat in subcortical regions during decision-making. In contrast, after decision-making, we observed the expected parallel processing while anticipating decision outcomes. These findings advance our understanding of approach-avoidance decision-making processes, opposing traditional views that segregate brain regions as predominantly reward-sensitive or threat-sensitive, thereby paving the way for a more nuanced perspective that takes into account the stage of decision-making., (Copyright © 2024 the authors.)

Published
2024
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24. Personalizing progressive changes to brain structure in Alzheimer's disease using normative modeling.

Author

Verdi S, Rutherford S, Fraza C, Tosun D, Altmann A, Raket LL, Schott JM, Marquand AF, and Cole JH

Subjects
Humans, Female, Male, Aged, Alzheimer Disease pathology, Alzheimer Disease diagnostic imaging, Magnetic Resonance Imaging, Disease Progression, Cognitive Dysfunction pathology, Cognitive Dysfunction diagnostic imaging, Brain pathology, Brain diagnostic imaging, Atrophy pathology
Abstract

Introduction: Neuroanatomical normative modeling captures individual variability in Alzheimer's disease (AD). Here we used normative modeling to track individuals' disease progression in people with mild cognitive impairment (MCI) and patients with AD., Methods: Cortical and subcortical normative models were generated using healthy controls (n ≈ 58k). These models were used to calculate regional z scores in 3233 T1-weighted magnetic resonance imaging time-series scans from 1181 participants. Regions with z scores < -1.96 were classified as outliers mapped on the brain and summarized by total outlier count (tOC)., Results: tOC increased in AD and in people with MCI who converted to AD and also correlated with multiple non-imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of progression from MCI to AD. Brain outlier maps identified the hippocampus as having the highest rate of change., Discussion: Individual patients' atrophy rates can be tracked by using regional outlier maps and tOC., Highlights: Neuroanatomical normative modeling was applied to serial Alzheimer's disease (AD) magnetic resonance imaging (MRI) data for the first time. Deviation from the norm (outliers) of cortical thickness or brain volume was computed in 3233 scans. The number of brain-structure outliers increased over time in people with AD. Patterns of change in outliers varied markedly between individual patients with AD. People with mild cognitive impairment whose outliers increased over time had a higher risk of progression from AD., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Published
2024
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25. Domain-general cognitive control processes in bilingual switching: Evidence from midfrontal theta oscillations.

Author

Cui N, Piai V, and Zheng XY

Subjects
Humans, Male, Female, Adult, Cognition physiology, Frontal Lobe physiology, Young Adult, Executive Function physiology, Speech physiology, Electroencephalography methods, Multilingualism, Theta Rhythm physiology
Abstract

Language control in bilingual speakers is thought to be implicated in effectively switching between languages, inhibiting the non-intended language, and continuously monitoring what to say and what has been said. It has been a matter of controversy concerning whether language control operates in a comparable manner to cognitive control processes in non-linguistic domains (domain-general) or if it is exclusive to language processing (domain-specific). As midfrontal theta oscillations have been considered as an index of cognitive control, examining whether a midfrontal theta effect is evident in tasks requiring bilingual control could bring new insights to the ongoing debate. To this end, we reanalysed the EEG data from two previous bilingual production studies where Dutch-English bilinguals named pictures based on colour cues. Specifically, we focused on three fundamental control processes in bilingual production: switching between languages, inhibition of the nontarget language, and monitoring of speech errors. Theta power increase was observed in switch trials compared to repeat trials, with a midfrontal scalp distribution. However, no theta power difference was observed in switch trials following a shorter sequence of same-language trials compared to a longer sequence, suggesting a missing modulation of inhibitory control. Similarly, increased midfrontal theta power was observed when participants failed to switch to the intended language compared to correct responses. Altogether, these findings tentatively support the involvement of domain-general cognitive control mechanisms in bilingual switching., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Published
2024
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26. The association between liking, learning and creativity in music.

Author

Zioga I, Harrison PMC, Pearce M, Bhattacharya J, and Di Bernardi Luft C

Subjects
Humans, Male, Female, Adult, Young Adult, Brain physiology, Acoustic Stimulation, Music psychology, Creativity, Learning physiology, Auditory Perception physiology, Electroencephalography
Abstract

Aesthetic preference is intricately linked to learning and creativity. Previous studies have largely examined the perception of novelty in terms of pleasantness and the generation of novelty via creativity separately. The current study examines the connection between perception and generation of novelty in music; specifically, we investigated how pleasantness judgements and brain responses to musical notes of varying probability (estimated by a computational model of auditory expectation) are linked to learning and creativity. To facilitate learning de novo, 40 non-musicians were trained on an unfamiliar artificial music grammar. After learning, participants evaluated the pleasantness of the final notes of melodies, which varied in probability, while their EEG was recorded. They also composed their own musical pieces using the learned grammar which were subsequently assessed by experts. As expected, there was an inverted U-shaped relationship between liking and probability: participants were more likely to rate the notes with intermediate probabilities as pleasant. Further, intermediate probability notes elicited larger N100 and P200 at posterior and frontal sites, respectively, associated with prediction error processing. Crucially, individuals who produced less creative compositions preferred higher probability notes, whereas individuals who composed more creative pieces preferred notes with intermediate probability. Finally, evoked brain responses to note probability were relatively independent of learning and creativity, suggesting that these higher-level processes are not mediated by brain responses related to performance monitoring. Overall, our findings shed light on the relationship between perception and generation of novelty, offering new insights into aesthetic preference and its neural correlates., (© 2024. The Author(s).)

Published
2024
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27. Multiscale heterogeneity of white matter morphometry in psychiatric disorders.

Author

Segal A, Smith RE, Chopra S, Oldham S, Parkes L, Aquino K, Kia SM, Wolfers T, Franke B, Hoogman M, Beckmann CF, Westlye LT, Andreassen OA, Zalesky A, Harrison BJ, Davey CG, Soriano-Mas C, Cardoner N, Tiego J, Yücel M, Braganza L, Suo C, Berk M, Cotton S, Bellgrove MA, Marquand AF, and Fornito A

Abstract

Background: Inter-individual variability in neurobiological and clinical characteristics in mental illness is often overlooked by classical group-mean case-control studies. Studies using normative modelling to infer person-specific deviations of grey matter volume have indicated that group means are not representative of most individuals. The extent to which this variability is present in white matter morphometry, which is integral to brain function, remains unclear., Methods: We applied Warped Bayesian Linear Regression normative models to T1-weighted magnetic resonance imaging data and mapped inter-individual variability in person-specific white matter volume deviations in 1,294 cases (58% male) diagnosed with one of six disorders (attention-deficit/hyperactivity, autism, bipolar, major depressive, obsessive-compulsive and schizophrenia) and 1,465 matched controls (54% male) recruited across 25 scan sites. We developed a framework to characterize deviation heterogeneity at multiple spatial scales, from individual voxels, through inter-regional connections, specific brain regions, and spatially extended brain networks., Results: The specific locations of white matter volume deviations were highly heterogeneous across participants, affecting the same voxel in fewer than 8% of individuals with the same diagnosis. For autism and schizophrenia, negative deviations (i.e., areas where volume is lower than normative expectations) aggregated into common tracts, regions and large-scale networks in up to 35% of individuals., Conclusions: The prevalence of white matter volume deviations was lower than previously observed in grey matter, and the specific location of these deviations was highly heterogeneous when considering voxel-wise spatial resolution. Evidence of aggregation within common pathways and networks was apparent in schizophrenia and autism but not other disorders., Competing Interests: Disclosures This manuscript has been submitted on bioRxiv. KMA is a scientific advisor to and shareholder in BrainKey Inc., a medical image analysis software company. BF has received educational speaking fees from Medice GmbH. CFB is a director and shareholder of SBGNeuro Ltd. OAA is a consultant to Cortechs.ai and received speaker’s honorarium from Lundbeck, Janssen, Otsuka and Sunovion. NC participed in advisory boards and received speaker’s honoraria from Angelini, Esteve, Janssen, Lundbeck, Novartis, Pfizer, and Viatris. Furthermore, they have been awarded research grants from the Ministry of Health, Ministry of Science and Innovation (CIBERSAM), and the Strategic Plan for Research and Innovation in Health (PERIS) for the period 2016–2020, as well as from Recercaixa and Marato TV3. MY received philanthropic donations from the David Winston Turner Endowment Fund, Wilson Foundation. He has also received funding to conduct sponsored Investigator-Initiated trials (including Incannex Healthcare Ltd). These funding sources had no role in the design, management, data analysis, presentation, or interpretation and write-up of the data. MY also sits on the Advisory Boards of Centre of The Urban Mental Health, University of Amsterdam; and Enosis Therapeutics. MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Eisai, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier – all unrelated to this work. MB has received grant/research support from National Health and Medical Research Council, Wellcome Trust, Medical Research Future Fund, Victorian Medical Research Acceleration Fund, Centre for Research Excellence CRE, Victorian Government Department of Jobs, Precincts and Regions and Victorian COVID-19 Research Fund. He received honoraria from Springer, Oxford University Press, Cambridge University Press, Allen and Unwin, Lundbeck, Controversias Barcelona, Servier, Medisquire, HealthEd, ANZJP, EPA, Janssen, Medplan, Milken Institute, RANZCP, Abbott India, ASCP, Headspace and Sandoz. All other authors report no biomedical financial interests or potential conflicts of interest.

Published
2024
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29. A shifting role of thalamocortical connectivity in the emergence of cortical functional organization.

Author

Park S, Haak KV, Oldham S, Cho H, Byeon K, Park BY, Thomson P, Chen H, Gao W, Xu T, Valk S, Milham MP, Bernhardt B, Di Martino A, and Hong SJ

Subjects
Humans, Male, Child, Female, Adolescent, Magnetic Resonance Imaging, Infant, Child, Preschool, Nerve Net physiology, Cross-Sectional Studies, Longitudinal Studies, Thalamus physiology, Cerebral Cortex physiology, Neural Pathways physiology
Abstract

The cortical patterning principle has been a long-standing question in neuroscience, yet how this translates to macroscale functional specialization in the human brain remains largely unknown. Here we examine age-dependent differences in resting-state thalamocortical connectivity to investigate its role in the emergence of large-scale functional networks during early life, using a primarily cross-sectional but also longitudinal approach. We show that thalamocortical connectivity during infancy reflects an early differentiation of sensorimotor networks and genetically influenced axonal projection. This pattern changes in childhood, when connectivity is established with the salience network, while decoupling externally and internally oriented functional systems. A developmental simulation using generative network models corroborated these findings, demonstrating that thalamic connectivity contributes to developing key features of the mature brain, such as functional segregation and the sensory-association axis, especially across 12-18 years of age. Our study suggests that the thalamus plays an important role in functional specialization during development, with potential implications for studying conditions with compromised internal and external processing., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Published
2024
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30. Gaze-Based Detection of Thoughts across Naturalistic Tasks Using a PSO-Optimized Random Forest Algorithm.

Author

Rahnuma T, Jothiraj SN, Kuvar V, Faber M, Knight RT, and Kam JWY

Abstract

One key aspect of the human experience is our ongoing stream of thoughts. These thoughts can be broadly categorized into various dimensions, which are associated with different impacts on mood, well-being, and productivity. While the past literature has often identified eye movements associated with a specific thought dimension (task-relatedness) during experimental tasks, few studies have determined if these various thought dimensions can be classified by oculomotor activity during naturalistic tasks. Employing thought sampling, eye tracking, and machine learning, we assessed the classification of nine thought dimensions (task-relatedness, freely moving, stickiness, goal-directedness, internal-external orientation, self-orientation, others orientation, visual modality, and auditory modality) across seven multi-day recordings of seven participants during self-selected computer tasks. Our analyses were based on a total of 1715 thought probes across 63 h of recordings. Automated binary-class classification of the thought dimensions was based on statistical features extracted from eye movement measures, including fixation and saccades. These features all served as input into a random forest (RF) classifier, which was then improved with particle swarm optimization (PSO)-based selection of the best subset of features for classifier performance. The mean Matthews correlation coefficient (MCC) values from the PSO-based RF classifier across the thought dimensions ranged from 0.25 to 0.54, indicating above-chance level performance in all nine thought dimensions across participants and improved performance compared to the RF classifier without feature selection. Our findings highlight the potential of machine learning approaches combined with eye movement measures for the real-time prediction of naturalistic ongoing thoughts, particularly in ecologically valid contexts.

Published
2024
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31. The contribution of the vascular architecture and cerebrovascular reactivity to the BOLD signal formation across cortical depth.

Author

Roefs ECA, Schellekens W, Báez-Yáñez MG, Bhogal AA, Groen IIA, van Osch MJP, Siero JCW, and Petridou N

Abstract

Assessment of neuronal activity using blood oxygenation level-dependent (BOLD) is confounded by how the cerebrovascular architecture modulates hemodynamic responses. To understand brain function at the laminar level, it is crucial to distinguish neuronal signal contributions from those determined by the cortical vascular organization. Therefore, our aim was to investigate the purely vascular contribution in the BOLD signal by using vasoactive stimuli and compare that with neuronal-induced BOLD responses from a visual task. To do so, we estimated the hemodynamic response function (HRF) across cortical depth following brief visual stimulations under different conditions using ultrahigh-field (7 Tesla) functional (f)MRI. We acquired gradient-echo (GE)-echo-planar-imaging (EPI) BOLD, containing contributions from all vessel sizes, and spin-echo (SE)-EPI BOLD for which signal changes predominately originate from microvessels, to distinguish signal weighting from different vascular compartments. Non-neuronal hemodynamic changes were induced by hypercapnia and hyperoxia to estimate cerebrovascular reactivity and venous cerebral blood volume ( C B V v O 2 ). Results show that increases in GE HRF amplitude from deeper to superficial layers coincided with increased macrovascular C B V v O 2 . C B V v O 2 -normalized GE-HRF amplitudes yielded similar cortical depth profiles as SE, thereby possibly improving specificity to neuronal activation. For GE BOLD, faster onset time and shorter time-to-peak were observed toward the deeper layers. Hypercapnia reduced the amplitude of visual stimulus-induced signal responses as denoted by lower GE-HRF amplitudes and longer time-to-peak. In contrast, the SE-HRF amplitude was unaffected by hypercapnia, suggesting that these responses reflect predominantly neurovascular processes that are less contaminated by macrovascular signal contributions., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Published
2024
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32. The Advanced BRain Imaging on ageing and Memory (ABRIM) data collection: Study design, data processing, and rationale.

Author

Jansen MG, Zwiers MP, Marques JP, Chan KS, Amelink JS, Altgassen M, Oosterman JM, and Norris DG

Subjects
Humans, Male, Female, Aged, Middle Aged, Adult, Aged, 80 and over, Adolescent, Young Adult, Cognition physiology, Cross-Sectional Studies, Neuroimaging methods, Research Design, Data Collection, Magnetic Resonance Imaging methods, Brain diagnostic imaging, Brain physiology, Aging physiology, Memory physiology
Abstract

To understand the neurocognitive mechanisms that underlie heterogeneity in cognitive ageing, recent scientific efforts have led to a growing public availability of imaging cohort data. The Advanced BRain Imaging on ageing and Memory (ABRIM) project aims to add to these existing datasets by taking an adult lifespan approach to provide a cross-sectional, normative database with a particular focus on connectivity, myelinization and iron content of the brain in concurrence with cognitive functioning, mechanisms of reserve, and sleep-wake rhythms. ABRIM freely shares MRI and behavioural data from 295 participants between 18-80 years, stratified by age decade and sex (median age 52, IQR 36-66, 53.20% females). The ABRIM MRI collection consists of both the raw and pre-processed structural and functional MRI data to facilitate data usage among both expert and non-expert users. The ABRIM behavioural collection includes measures of cognitive functioning (i.e., global cognition, processing speed, executive functions, and memory), proxy measures of cognitive reserve (e.g., educational attainment, verbal intelligence, and occupational complexity), and various self-reported questionnaires (e.g., on depressive symptoms, pain, and the use of memory strategies in daily life and during a memory task). In a sub-sample (n = 120), we recorded sleep-wake rhythms using an actigraphy device (Actiwatch 2, Philips Respironics) for a period of 7 consecutive days. Here, we provide an in-depth description of our study protocol, pre-processing pipelines, and data availability. ABRIM provides a cross-sectional database on healthy participants throughout the adult lifespan, including numerous parameters relevant to improve our understanding of cognitive ageing. Therefore, ABRIM enables researchers to model the advanced imaging parameters and cognitive topologies as a function of age, identify the normal range of values of such parameters, and to further investigate the diverse mechanisms of reserve and resilience., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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33. Phase-dependent word perception emerges from region-specific sensitivity to the statistics of language.

Author

Ten Oever S, Titone L, Te Rietmolen N, and Martin AE

Subjects
Humans, Male, Female, Adult, Temporal Lobe physiology, Young Adult, Models, Neurological, Magnetoencephalography, Language, Speech Perception physiology
Abstract

Neural oscillations reflect fluctuations in excitability, which biases the percept of ambiguous sensory input. Why this bias occurs is still not fully understood. We hypothesized that neural populations representing likely events are more sensitive, and thereby become active on earlier oscillatory phases, when the ensemble itself is less excitable. Perception of ambiguous input presented during less-excitable phases should therefore be biased toward frequent or predictable stimuli that have lower activation thresholds. Here, we show such a frequency bias in spoken word recognition using psychophysics, magnetoencephalography (MEG), and computational modelling. With MEG, we found a double dissociation, where the phase of oscillations in the superior temporal gyrus and medial temporal gyrus biased word-identification behavior based on phoneme and lexical frequencies, respectively. This finding was reproduced in a computational model. These results demonstrate that oscillations provide a temporal ordering of neural activity based on the sensitivity of separable neural populations., Competing Interests: Competing interests statement:The authors declare no competing interest.

Published
2024
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34. Delta-band Activity Underlies Referential Meaning Representation during Pronoun Resolution.

Author

Ding R, Ten Oever S, and Martin AE

Abstract

Human language offers a variety of ways to create meaning, one of which is referring to entities, objects, or events in the world. One such meaning maker is understanding to whom or to what a pronoun in a discourse refers to. To understand a pronoun, the brain must access matching entities or concepts that have been encoded in memory from previous linguistic context. Models of language processing propose that internally stored linguistic concepts, accessed via exogenous cues such as phonological input of a word, are represented as (a)synchronous activities across a population of neurons active at specific frequency bands. Converging evidence suggests that delta band activity (1-3 Hz) is involved in temporal and representational integration during sentence processing. Moreover, recent advances in the neurobiology of memory suggest that recollection engages neural dynamics similar to those which occurred during memory encoding. Integrating from these two research lines, we here tested the hypothesis that neural dynamic patterns, especially in delta frequency range, underlying referential meaning representation, would be reinstated during pronoun resolution. By leveraging neural decoding techniques (i.e., representational similarity analysis) on a magnetoencephalogram data set acquired during a naturalistic story-listening task, we provide evidence that delta-band activity underlies referential meaning representation. Our findings suggest that, during spoken language comprehension, endogenous linguistic representations such as referential concepts may be proactively retrieved and represented via activation of their underlying dynamic neural patterns., (© 2024 Massachusetts Institute of Technology.)

Published
2024
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35. "Not" in the brain and behavior.

Author

Coopmans CW, Mai A, and Martin AE

Subjects
Humans, Behavior physiology, Brain physiology, Cognition physiology
Abstract

Negation is key for cognition but has no physical basis, raising questions about its neural origins. A new study in PLOS Biology on the negation of scalar adjectives shows that negation acts in part by altering the response to the adjective it negates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Coopmans et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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36. A fully synthetic three-dimensional human cerebrovascular model based on histological characteristics to investigate the hemodynamic fingerprint of the layer BOLD fMRI signal formation.

Author

Báez-Yáñez MG, Schellekens W, Bhogal AA, Roefs ECA, van Osch MJP, Siero JCW, and Petridou N

Abstract

Recent advances in functional magnetic resonance imaging (fMRI) at ultra-high field (≥7 tesla), novel hardware, and data analysis methods have enabled detailed research on neurovascular function, such as cortical layer-specific activity, in both human and nonhuman species. A widely used fMRI technique relies on the blood oxygen level-dependent (BOLD) signal. BOLD fMRI offers insights into brain function by measuring local changes in cerebral blood volume, cerebral blood flow, and oxygen metabolism induced by increased neuronal activity. Despite its potential, interpreting BOLD fMRI data is challenging as it is only an indirect measurement of neuronal activity. Computational modeling can help interpret BOLD data by simulating the BOLD signal formation. Current developments have focused on realistic 3D vascular models based on rodent data to understand the spatial and temporal BOLD characteristics. While such rodent-based vascular models highlight the impact of the angioarchitecture on the BOLD signal amplitude, anatomical differences between the rodent and human vasculature necessitate the development of human-specific models. Therefore, a computational framework integrating human cortical vasculature, hemodynamic changes, and biophysical properties is essential. Here, we present a novel computational approach: a three-dimensional VAscular MOdel based on Statistics (3D VAMOS), enabling the investigation of the hemodynamic fingerprint of the BOLD signal within a model encompassing a fully synthetic human 3D cortical vasculature and hemodynamics. Our algorithm generates microvascular and macrovascular architectures based on morphological and topological features from the literature on human cortical vasculature. By simulating specific oxygen saturation states and biophysical interactions, our framework characterizes the intravascular and extravascular signal contributions across cortical depth and voxel-wise levels for gradient-echo and spin-echo readouts. Thereby, the 3D VAMOS computational framework demonstrates that using human characteristics significantly affects the BOLD fingerprint, making it an essential step in understanding the fundamental underpinnings of layer-specific fMRI experiments., Competing Interests: DISCLOSURE/CONFLICT OF INTEREST The authors declare that they have no known competing financial interests, conflict of interest or personal relationships that could have appeared to influence the work reported in this paper.

Published
2024
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37. Is a wandering mind a novelty-seeking mind? The curious case of incubation.

Author

Faber M and de Rooij A

Subjects
Humans, Exploratory Behavior physiology, Attention physiology, Creativity
Abstract

The Novelty-Seeking Model can explain incubation's effect on creativity by assuming an adaptive decision threshold. During an impasse, the threshold for novelty becomes too high and biased to previous neural activity, hindering progress. Incubation "resets" this threshold through attentional decoupling, allowing for spontaneous ideas to emerge from subsequent mind wandering or other activities that attract attention, facilitating progress.

Published
2024
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38. Analysis of blurring due to short T 2 decay at different resolutions in 23 Na MRI.

Author

Dergachyova O, Yu Z, Hodono S, Cloos M, and Madelin G

Abstract

The nuclear magnetic resonance signal from sodium ( 23 Na) nuclei demonstrates a fast bi-exponential T 2 decay in biological tissues (T 2,short = 0.5-5 ms and T 2,long = 10-30 ms). Hence, blurring observed in sodium images acquired with center-out sequences is generally assumed to be dominated by signal attenuation at higher k-space frequencies. Most of the studies in the field primarily focus on the impact of readout duration on blurring but neglect the impact of resolution. In this paper, we examine the blurring effect of short T 2 on images at different resolutions. A series of simulations, as well as phantom and in vivo scans were performed at varying resolutions and readout durations in order to evaluate progressive changes in image quality. We demonstrate that, given a fixed readout duration, T 2 decay produces distinct blurring effects at different resolutions. Therefore, in addition to voxel size-dependent partial volume effects, the choice of resolution adds additional T 2 -dependent blurring.

Published
2024

39. Reciprocity in ambiguous situations: Default psychological strategies underlying ambiguity resolution in moral decision-making.

Author

Galvan E and Sanfey A

Subjects
Humans, Morals, Trust psychology, Motivation
Abstract

When deciding whether to reciprocate trust, people are typically strongly influenced by how much trust their interaction partner has originally shown them. If a partner has placed a lot of trust in you, there is a strong motivation to reciprocate, and indeed this factor often outweighs pro-self considerations to maximize one's own financial payout. However, one important unanswered question in this regard is what people decide to do when this prior information is ambiguous; that is, when they do not know for sure exactly how trusting their partner has been. How then do people decide to reciprocate? This study utilizes a novel version of the Trust Game to directly address this question. Here, we develop, and validate, a computational model-based approach to quantify and categorize how participants assessed the trustworthiness of an unfamiliar partner when making reciprocity decisions. We find that participants spontaneously use their prior experience about the trustingness of game partners in general to inform their reciprocity decisions, even when they had the opportunity to strategically assume that their new, unfamiliar, partners were untrusting, and hence could have justified lower reciprocation rates., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Galvan, Sanfey. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Published
2024
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40. Alpha and Beta Oscillations Differentially Support Word Production in a Rule-Switching Task.

Author

Zioga I, Zhou YJ, Weissbart H, Martin AE, and Haegens S

Subjects
Humans, Magnetoencephalography, Comprehension physiology, Linguistics, Alpha Rhythm physiology, Brain physiology, Language
Abstract

Research into the role of brain oscillations in basic perceptual and cognitive functions has suggested that the alpha rhythm reflects functional inhibition while the beta rhythm reflects neural ensemble (re)activation. However, little is known regarding the generalization of these proposed fundamental operations to linguistic processes, such as speech comprehension and production. Here, we recorded magnetoencephalography in participants performing a novel rule-switching paradigm. Specifically, Dutch native speakers had to produce an alternative exemplar from the same category or a feature of a given target word embedded in spoken sentences (e.g., for the word "tuna", an exemplar from the same category-"seafood"-would be "shrimp", and a feature would be "pink"). A cue indicated the task rule-exemplar or feature-either before (pre-cue) or after (retro-cue) listening to the sentence. Alpha power during the working memory delay was lower for retro-cue compared with that for pre-cue in the left hemispheric language-related regions. Critically, alpha power negatively correlated with reaction times, suggestive of alpha facilitating task performance by regulating inhibition in regions linked to lexical retrieval. Furthermore, we observed a different spatiotemporal pattern of beta activity for exemplars versus features in the right temporoparietal regions, in line with the proposed role of beta in recruiting neural networks for the encoding of distinct categories. Overall, our study provides evidence for the generalizability of the role of alpha and beta oscillations from perceptual to more "complex, linguistic processes" and offers a novel task to investigate links between rule-switching, working memory, and word production., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Zioga et al.)

Published
2024
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41. Alzheimer's disease heterogeneity revealed by neuroanatomical normative modeling.

Author

Loreto F, Verdi S, Kia SM, Duvnjak A, Hakeem H, Fitzgerald A, Patel N, Lilja J, Win Z, Perry R, Marquand AF, Cole JH, and Malhotra P

Abstract

Introduction: Overlooking the heterogeneity in Alzheimer's disease (AD) may lead to diagnostic delays and failures. Neuroanatomical normative modeling captures individual brain variation and may inform our understanding of individual differences in AD-related atrophy., Methods: We applied neuroanatomical normative modeling to magnetic resonance imaging from a real-world clinical cohort with confirmed AD ( n  = 86). Regional cortical thickness was compared to a healthy reference cohort ( n  = 33,072) and the number of outlying regions was summed (total outlier count) and mapped at individual- and group-levels., Results: The superior temporal sulcus contained the highest proportion of outliers (60%). Elsewhere, overlap between patient atrophy patterns was low. Mean total outlier count was higher in patients who were non-amnestic, at more advanced disease stages, and without depressive symptoms. Amyloid burden was negatively associated with outlier count., Discussion: Brain atrophy in AD is highly heterogeneous and neuroanatomical normative modeling can be used to explore anatomo-clinical correlations in individual patients., Competing Interests: J.L. is employed by Hermes Medical Solutions and obtains a salary from them; he is Vice President of Research and Development at Hermes Medical Solutions. Z.W. previously participated in the Eli Lilly PET advisory board and was an amyloid‐PET read trainer. R.P. previously sat on an advisory board for Eli Lilly and received support from GE for research imaging from 2014 to 2018. PM gave an educational talk at a meeting organized by GE. None of the authors currently have funding or support from any commercial organization involved in amyloid PET imaging. Author disclosures are available in the supporting information., (© 2024 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Published
2024
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42. Smartphone keyboard dynamics predict affect in suicidal ideation.

Author

Knol L, Nagpal A, Leaning IE, Idda E, Hussain F, Ning E, Eisenlohr-Moul TA, Beckmann CF, Marquand AF, and Leow A

Abstract

While digital phenotyping provides opportunities for unobtrusive, real-time mental health assessments, the integration of its modalities is not trivial due to high dimensionalities and discrepancies in sampling frequencies. We provide an integrated pipeline that solves these issues by transforming all modalities to the same time unit, applying temporal independent component analysis (ICA) to high-dimensional modalities, and fusing the modalities with linear mixed-effects models. We applied our approach to integrate high-quality, daily self-report data with BiAffect keyboard dynamics derived from a clinical suicidality sample of mental health outpatients. Applying the ICA to the self-report data (104 participants, 5712 days of data) revealed components related to well-being, anhedonia, and irritability and social dysfunction. Mixed-effects models (55 participants, 1794 days) showed that less phone movement while typing was associated with more anhedonia (β = -0.12, p = 0.00030). We consider this method to be widely applicable to dense, longitudinal digital phenotyping data., (© 2024. The Author(s).)

Published
2024
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43. Tackling Costly Fearful Avoidance Using Pavlovian Counterconditioning.

Author

Hulsman AM, van de Pavert I, Roelofs K, and Klumpers F

Subjects
Female, Humans, Bayes Theorem, Anxiety, Anxiety Disorders, Avoidance Learning, Fear, Extinction, Psychological
Abstract

Avoidance behavior constitutes a major transdiagnostic symptom that exacerbates anxiety. It hampers fear extinction and predicts poor therapy-outcome. Pavlovian counterconditioning with a reward could alleviate avoidance better than traditional extinction by reducing negative valence of the feared situation. However, previous studies are scarce and did not consider that pathological avoidance is often costly and typically evolves from an approach-avoidance conflict. Therefore, we used an approach-avoidance conflict paradigm to model effects of counterconditioning on costly avoidance (i.e., avoidance that leads to missing out on rewards). Results from our preregistered Bayesian Mixed Model analyses in 51 healthy participants (43 females) indicated that counterconditioning was more effective in reducing negative valuation and decreasing costly avoidance than traditional extinction. This study supports application of a simple counterconditioning technique, shows that its efficacy transfers to more complex avoidance situations, and suggests treatment may benefit from increasing reward drive in combination with extinction to overcome avoidance. Application in a clinical sample is a necessary next step to assess clinical utility of counterconditioning., (Copyright © 2023 Association for Behavioral and Cognitive Therapies. Published by Elsevier Ltd. All rights reserved.)

Published
2024
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44. The effect of negative arousal on declarative memory.

Author

Constantinou M, Karadachka K, Marstaller L, and Burianová H

Subjects
Young Adult, Humans, Emotions, Arousal, Brain Mapping, Semantics, Mental Recall, Brain diagnostic imaging, Memory, Episodic
Abstract

Arousing events influence retrieval success, with a number of studies supporting a context-dependent effect of arousal on episodic memory retrieval. An improvement in speed and accuracy of episodic memories is observed when negative arousal is attached to them. In contrast, enhancing effects of negative arousal have not been reported to improve semantic memory retrieval. Episodic and semantic memory are highly interactive and yet differ based on their embedded contextual content. Although differences in brain activity exist between episodic and semantic memory, the two types of memory retrieval are part of a common long-term memory system. Considering the shared processes between episodic and semantic memory, the objectives of the current study were twofold: i) to examine, employing a novel paradigm, whether performance on episodic and semantic memory retrieval would be influenced differently by varying levels of arousal, between negative and neutral valence; and ii) to explore the neural patterns underlying these processes. Forty-seven healthy young adults were recruited and completed the experiment in the MRI scanner. The results demonstrated a negative arousal effect on the brain circuitry subserving both memory conditions as well as on behavioural performance, as indicated by better accuracy and faster reaction times. The study provides an insight into the role of negative arousal in memory processes and contributes to our understanding of the interplay between cognitive and emotional factors in memory modulation. Our work also highlights the highly interactive nature of episodic and semantic memory, and emphasises the importance in understanding how negative arousal interacts with the contextual content of a memory, on a behavioural and neurofunctional level., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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45. Interdependence of "What" and "When" in the Brain.

Author

Ten Oever S and Martin AE

Subjects
Humans, Brain, Brain Mapping
Abstract

From a brain's-eye-view, when a stimulus occurs and what it is are interrelated aspects of interpreting the perceptual world. Yet in practice, the putative perceptual inferences about sensory content and timing are often dichotomized and not investigated as an integrated process. We here argue that neural temporal dynamics can influence what is perceived, and in turn, stimulus content can influence the time at which perception is achieved. This computational principle results from the highly interdependent relationship of what and when in the environment. Both brain processes and perceptual events display strong temporal variability that is not always modeled; we argue that understanding-and, minimally, modeling-this temporal variability is key for theories of how the brain generates unified and consistent neural representations and that we ignore temporal variability in our analysis practice at the peril of both data interpretation and theory-building. Here, we review what and when interactions in the brain, demonstrate via simulations how temporal variability can result in misguided interpretations and conclusions, and outline how to integrate and synthesize what and when in theories and models of brain computation., (© 2023 Massachusetts Institute of Technology.)

Published
2024
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47. Smartphone keyboard dynamics predict affect in suicidal ideation.

Author

Knol L, Nagpal A, Leaning IE, Idda E, Hussain F, Ning E, Eisenlohr-Moul TA, Beckmann CF, Marquand AF, and Leow A

Abstract

While digital phenotyping provides opportunities for unobtrusive, real-time mental health assessments, the integration of its modalities is not trivial due to high dimensionalities and discrepancies in sampling frequencies. We provide an integrated pipeline that solves these issues by transforming all modalities to the same time unit, applying temporal independent component analysis (ICA) to high-dimensional modalities, and fusing the modalities with linear mixed-effects models. We applied our approach to integrate high-quality, daily self-report data with BiAffect keyboard dynamics derived from a clinical suicidality sample of mental health outpatients. Applying the ICA to the self-report data (104 participants, 5712 days of data) revealed components related to well-being, anhedonia, and irritability and social dysfunction. Mixed-effects models (55 participants, 1794 days) showed that less phone movement while typing was associated with more anhedonia (β = -0.12, p = 0.00030). We consider this method to be widely applicable to dense, longitudinal digital phenotyping data.

Published
2023
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48. Functional neurological disorder is a feminist issue.

Author

McLoughlin C, Hoeritzauer I, Cabreira V, Aybek S, Adams C, Alty J, Ball HA, Baker J, Bullock K, Burness C, Dworetzky BA, Finkelstein S, Garcin B, Gelauff J, Goldstein LH, Jordbru A, Huys AM, Laffan A, Lidstone SC, Linden SC, Ludwig L, Maggio J, Morgante F, Mallam E, Nicholson C, O'Neal M, O'Sullivan S, Pareés I, Petrochilos P, Pick S, Phillips W, Roelofs K, Newby R, Stanton B, Gray C, Joyce EM, Tijssen MA, Chalder T, McCormick M, Gardiner P, Bègue I, Tuttle MC, Williams I, McRae S, Voon V, and McWhirter L

Subjects
Humans, Female, Nervous System Diseases diagnosis, Nervous System Diseases epidemiology, Nervous System Diseases therapy, Conversion Disorder, Biomedical Research
Abstract

Functional neurological disorder (FND) is a common and disabling disorder, often misunderstood by clinicians. Although viewed sceptically by some, FND is a diagnosis that can be made accurately, based on positive clinical signs, with clinical features that have remained stable for over 100 years. Despite some progress in the last decade, people with FND continue to suffer subtle and overt forms of discrimination by clinicians, researchers and the public. There is abundant evidence that disorders perceived as primarily affecting women are neglected in healthcare and medical research, and the course of FND mirrors this neglect. We outline the reasons why FND is a feminist issue, incorporating historical and contemporary clinical, research and social perspectives. We call for parity for FND in medical education, research and clinical service development so that people affected by FND can receive the care they need., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Published
2023
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49. Reappraisal is less effective than distraction in downregulation of neural responses to physical threats-An event-related potential investigation.

Author

Adamczyk AK, Wyczesany M, Roelofs K, and van Peer JM

Subjects
Animals, Female, Down-Regulation, Emotions physiology, Fear, Cognition physiology, Electroencephalography, Evoked Potentials physiology
Abstract

Evolutionary threats (ETs), such as predatory animals and heights, elicit stronger fear responses and are more often the subject of specific phobias, as compared to modern threats (MTs, such as guns and motorcycles). Since processing of ET depends on lower-order, phylogenetically conserved neural fear circuits, it may be less susceptible to higher-order (vs. simpler) cognitive emotion regulation. Given the relevance for treatment of specific phobias, we tested this hypothesis in an ERP study. Sixty-one female participants passively watched high- and low-threat pictures of evolutionary (snakes, lizards) and modern (guns, water-guns) origin, and downregulated responses to the high-threat pictures (snakes and guns) using either cognitive reappraisal or a simpler cognitive distraction strategy. ET elicited stronger early (EPN) and sustained (LPP) attention processing compared to MT. Both strategies successfully downregulated subjective and LPP (but not EPN) responses compared to passive watching. Although reappraisal was more effective subjectively, distraction downregulated the LPP earlier and stronger than reappraisal, irrespective of the threat type. These findings provide novel evidence that neural responses to physical threat might be less susceptible to cognitive emotion regulation via higher-order (reappraisal) versus simpler (distraction) strategies, irrespective of the evolutionary or modern relevance of threat. Combining both strategies could be beneficial for the emotion regulation-enhancing interventions for specific phobias. Distraction could be used during initial exposure, to reduce immediate emotion responding and help endure the contact with the feared stimulus, whereas reappraisal could be used subsequently, when emotions are less intense, to change maladaptive thoughts about the stimulus for future encounters., (© 2023 The Authors. Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Published
2023
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50. Regional, circuit and network heterogeneity of brain abnormalities in psychiatric disorders.

Author

Segal A, Parkes L, Aquino K, Kia SM, Wolfers T, Franke B, Hoogman M, Beckmann CF, Westlye LT, Andreassen OA, Zalesky A, Harrison BJ, Davey CG, Soriano-Mas C, Cardoner N, Tiego J, Yücel M, Braganza L, Suo C, Berk M, Cotton S, Bellgrove MA, Marquand AF, and Fornito A

Subjects
Humans, Magnetic Resonance Imaging, Gray Matter, Brain, Autism Spectrum Disorder, Bipolar Disorder, Obsessive-Compulsive Disorder, Attention Deficit Disorder with Hyperactivity
Abstract

The substantial individual heterogeneity that characterizes people with mental illness is often ignored by classical case-control research, which relies on group mean comparisons. Here we present a comprehensive, multiscale characterization of the heterogeneity of gray matter volume (GMV) differences in 1,294 cases diagnosed with one of six conditions (attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, depression, obsessive-compulsive disorder and schizophrenia) and 1,465 matched controls. Normative models indicated that person-specific deviations from population expectations for regional GMV were highly heterogeneous, affecting the same area in <7% of people with the same diagnosis. However, these deviations were embedded within common functional circuits and networks in up to 56% of cases. The salience-ventral attention system was implicated transdiagnostically, with other systems selectively involved in depression, bipolar disorder, schizophrenia and attention-deficit/hyperactivity disorder. Phenotypic differences between cases assigned the same diagnosis may thus arise from the heterogeneous localization of specific regional deviations, whereas phenotypic similarities may be attributable to the dysfunction of common functional circuits and networks., (© 2023. The Author(s).)

Published
2023
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