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1. Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

Author

Georgiadis, Foivos, Larivière, Sara, Glahn, David, Hong, L. Elliot, Kochunov, Peter, Mowry, Bryan, Loughland, Carmel, Pantelis, Christos, Henskens, Frans A., Green, Melissa J., Cairns, Murray J., Michie, Patricia T., Rasser, Paul E., Catts, Stanley, Tooney, Paul, Scott, Rodney J., Schall, Ulrich, Carr, Vaughan, Quidé, Yann, Krug, Axel, Stein, Frederike, Nenadić, Igor, Brosch, Katharina, Kircher, Tilo, Gur, Raquel, Gur, Ruben, Satterthwaite, Theodore D., Karuk, Andriana, Pomarol- Clotet, Edith, Radua, Joaquim, Fuentes-Claramonte, Paola, Salvador, Raymond, Spalletta, Gianfranco, Voineskos, Aristotle, Sim, Kang, Crespo-Facorro, Benedicto, Tordesillas Gutiérrez, Diana, Ehrlich, Stefan, Crossley, Nicolas, Grotegerd, Dominik, Repple, Jonathan, Lencer, Rebekka, Dannlowski, Udo, Calhoun, Vince, Rootes-Murdy, Kelly, Demro, Caroline, Ramsay, Ian S., Sponheim, Scott R., Schmidt, Andre, Borgwardt, Stefan, Tomyshev, Alexander, Lebedeva, Irina, Höschl, Cyril, Spaniel, Filip, Preda, Adrian, Nguyen, Dana, Uhlmann, Anne, Stein, Dan J., Howells, Fleur, Temmingh, Henk S., Diaz Zuluaga, Ana M., López Jaramillo, Carlos, Iasevoli, Felice, Ji, Ellen, Homan, Stephanie, Omlor, Wolfgang, Homan, Philipp, Kaiser, Stefan, Seifritz, Erich, Misic, Bratislav, Valk, Sofie L., Thompson, Paul, van Erp, Theo G. M., Turner, Jessica A., Bernhardt, Boris, and Kirschner, Matthias

Published
2024
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3. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium.

Author

Schijven, Dick, Postema, Merel C, Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja MC, van Haren, Neeltje EM, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T, Agartz, Ingrid, Andreassen, Ole A, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E, Schall, Ulrich, Scott, Rodney J, Carr, Vaughan J, Green, Melissa J, Henskens, Frans A, Loughland, Carmel M, Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo TJ, Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D, Bustillo, Juan, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D, Ford, Judith M, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N, Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, and Antonucci, Linda A

Subjects
Brain, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Case-Control Studies, Schizophrenia, Female, Male, Functional Laterality, asymmetry, brain imaging, cortical, subcortical, Clinical Research, Mental Health, Neurosciences, Brain Disorders, Mental health
Abstract

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

Published
2023

4. Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium.

Author

Constantinides, Constantinos, Han, Laura KM, Alloza, Clara, Antonucci, Linda Antonella, Arango, Celso, Ayesa-Arriola, Rosa, Banaj, Nerisa, Bertolino, Alessandro, Borgwardt, Stefan, Bruggemann, Jason, Bustillo, Juan, Bykhovski, Oleg, Calhoun, Vince, Carr, Vaughan, Catts, Stanley, Chung, Young-Chul, Crespo-Facorro, Benedicto, Díaz-Caneja, Covadonga M, Donohoe, Gary, Plessis, Stefan Du, Edmond, Jesse, Ehrlich, Stefan, Emsley, Robin, Eyler, Lisa T, Fuentes-Claramonte, Paola, Georgiadis, Foivos, Green, Melissa, Guerrero-Pedraza, Amalia, Ha, Minji, Hahn, Tim, Henskens, Frans A, Holleran, Laurena, Homan, Stephanie, Homan, Philipp, Jahanshad, Neda, Janssen, Joost, Ji, Ellen, Kaiser, Stefan, Kaleda, Vasily, Kim, Minah, Kim, Woo-Sung, Kirschner, Matthias, Kochunov, Peter, Kwak, Yoo Bin, Kwon, Jun Soo, Lebedeva, Irina, Liu, Jingyu, Mitchie, Patricia, Michielse, Stijn, Mothersill, David, Mowry, Bryan, de la Foz, Víctor Ortiz-García, Pantelis, Christos, Pergola, Giulio, Piras, Fabrizio, Pomarol-Clotet, Edith, Preda, Adrian, Quidé, Yann, Rasser, Paul E, Rootes-Murdy, Kelly, Salvador, Raymond, Sangiuliano, Marina, Sarró, Salvador, Schall, Ulrich, Schmidt, André, Scott, Rodney J, Selvaggi, Pierluigi, Sim, Kang, Skoch, Antonin, Spalletta, Gianfranco, Spaniel, Filip, Thomopoulos, Sophia I, Tomecek, David, Tomyshev, Alexander S, Tordesillas-Gutiérrez, Diana, van Amelsvoort, Therese, Vázquez-Bourgon, Javier, Vecchio, Daniela, Voineskos, Aristotle, Weickert, Cynthia S, Weickert, Thomas, Thompson, Paul M, Schmaal, Lianne, van Erp, Theo GM, Turner, Jessica, Cole, James H, ENIGMA Schizophrenia Consortium, Dima, Danai, and Walton, Esther

Subjects
ENIGMA Schizophrenia Consortium, Brain, Humans, Magnetic Resonance Imaging, Prospective Studies, Schizophrenia, Aging, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Mental Health, Serious Mental Illness, Brain Disorders, Neurosciences, Biomedical Imaging, Clinical Research, Behavioral and Social Science, Neurological, Mental health, Good Health and Well Being, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.55 years (95% CI: 2.91, 4.19; I2 = 57.53%) compared to controls, after adjusting for age, sex and site (Cohen's d = 0.48). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Published
2023

5. The Relationship Between White Matter Microstructure and General Cognitive Ability in Patients With Schizophrenia and Healthy Participants in the ENIGMA Consortium

Author

Holleran, Laurena, Kelly, Sinead, Alloza, Clara, Agartz, Ingrid, Andreassen, Ole A, Arango, Celso, Banaj, Nerisa, Calhoun, Vince, Cannon, Dara, Carr, Vaughan, Corvin, Aiden, Glahn, David C, Gur, Ruben, Hong, Elliot, Hoschl, Cyril, Howells, Fleur M, James, Anthony, Janssen, Joost, Kochunov, Peter, Lawrie, Stephen M, Liu, Jingyu, Martinez, Covadonga, McDonald, Colm, Morris, Derek, Mothersill, David, Pantelis, Christos, Piras, Fabrizio, Potkin, Steven, Rasser, Paul E, Roalf, David, Rowland, Laura, Satterthwaite, Theodore, Schall, Ulrich, Spalletta, Gianfranco, Spaniel, Filip, Stein, Dan J, Uhlmann, Anne, Voineskos, Aristotle, Zalesky, Andrew, van Erp, Theo GM, Turner, Jessica A, Deary, Ian J, Thompson, Paul M, Jahanshad, Neda, and Donohoe, Gary

Subjects
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Prevention, Neurosciences, Behavioral and Social Science, Clinical Research, Brain Disorders, Serious Mental Illness, Schizophrenia, Mental Health, Mental health, Adult, Anisotropy, Brain, Case-Control Studies, Cognition, Diffusion Tensor Imaging, Factor Analysis, Statistical, Female, Healthy Volunteers, Humans, Intelligence, Male, Middle Aged, Neural Pathways, Principal Component Analysis, Schizophrenic Psychology, Wechsler Scales, White Matter, ENIGMA, Meta-Analysis, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

ObjectiveSchizophrenia has recently been associated with widespread white matter microstructural abnormalities, but the functional effects of these abnormalities remain unclear. Widespread heterogeneity of results from studies published to date preclude any definitive characterization of the relationship between white matter and cognitive performance in schizophrenia. Given the relevance of deficits in cognitive function to predicting social and functional outcomes in schizophrenia, the authors carried out a meta-analysis of available data through the ENIGMA Consortium, using a common analysis pipeline, to elucidate the relationship between white matter microstructure and a measure of general cognitive performance, IQ, in patients with schizophrenia and healthy participants.MethodsThe meta-analysis included 760 patients with schizophrenia and 957 healthy participants from 11 participating ENIGMA Consortium sites. For each site, principal component analysis was used to calculate both a global fractional anisotropy component (gFA) and a fractional anisotropy component for six long association tracts (LA-gFA) previously associated with cognition.ResultsMeta-analyses of regression results indicated that gFA accounted for a significant amount of variation in cognition in the full sample (effect size [Hedges' g]=0.27, CI=0.17-0.36), with similar effects sizes observed for both the patient (effect size=0.20, CI=0.05-0.35) and healthy participant groups (effect size=0.32, CI=0.18-0.45). Comparable patterns of association were also observed between LA-gFA and cognition for the full sample (effect size=0.28, CI=0.18-0.37), the patient group (effect size=0.23, CI=0.09-0.38), and the healthy participant group (effect size=0.31, CI=0.18-0.44).ConclusionsThis study provides robust evidence that cognitive ability is associated with global structural connectivity, with higher fractional anisotropy associated with higher IQ. This association was independent of diagnosis; while schizophrenia patients tended to have lower fractional anisotropy and lower IQ than healthy participants, the comparable size of effect in each group suggested a more general, rather than disease-specific, pattern of association.

Published
2020

6. 10Kin1day: A Bottom-Up Neuroimaging Initiative

Author

van den Heuvel, Martijn P, Scholtens, Lianne H, van der Burgh, Hannelore K, Agosta, Federica, Alloza, Clara, Arango, Celso, Auyeung, Bonnie, Baron-Cohen, Simon, Basaia, Silvia, Benders, Manon JNL, Beyer, Frauke, Booij, Linda, Braun, Kees PJ, Filho, Geraldo Busatto, Cahn, Wiepke, Cannon, Dara M, Chaim-Avancini, Tiffany M, Chan, Sandra SM, Chen, Eric YH, Crespo-Facorro, Benedicto, Crone, Eveline A, Dannlowski, Udo, de Zwarte, Sonja MC, Dietsche, Bruno, Donohoe, Gary, Du Plessis, Stefan, Durston, Sarah, Díaz-Caneja, Covadonga M, Díaz-Zuluaga, Ana M, Emsley, Robin, Filippi, Massimo, Frodl, Thomas, Gorges, Martin, Graff, Beata, Grotegerd, Dominik, Gąsecki, Dariusz, Hall, Julie M, Holleran, Laurena, Holt, Rosemary, Hopman, Helene J, Jansen, Andreas, Janssen, Joost, Jodzio, Krzysztof, Jäncke, Lutz, Kaleda, Vasiliy G, Kassubek, Jan, Masouleh, Shahrzad Kharabian, Kircher, Tilo, Koevoets, Martijn GJC, Kostic, Vladimir S, Krug, Axel, Lawrie, Stephen M, Lebedeva, Irina S, Lee, Edwin HM, Lett, Tristram A, Lewis, Simon JG, Liem, Franziskus, Lombardo, Michael V, Lopez-Jaramillo, Carlos, Margulies, Daniel S, Markett, Sebastian, Marques, Paulo, Martínez-Zalacaín, Ignacio, McDonald, Colm, McIntosh, Andrew M, McPhilemy, Genevieve, Meinert, Susanne L, Menchón, José M, Montag, Christian, Moreira, Pedro S, Morgado, Pedro, Mothersill, David O, Mérillat, Susan, Müller, Hans-Peter, Nabulsi, Leila, Najt, Pablo, Narkiewicz, Krzysztof, Naumczyk, Patrycja, Oranje, Bob, de la Foz, Victor Ortiz-Garcia, Peper, Jiska S, Pineda, Julian A, Rasser, Paul E, Redlich, Ronny, Repple, Jonathan, Reuter, Martin, Rosa, Pedro GP, Ruigrok, Amber NV, Sabisz, Agnieszka, Schall, Ulrich, Seedat, Soraya, Serpa, Mauricio H, Skouras, Stavros, Soriano-Mas, Carles, Sousa, Nuno, Szurowska, Edyta, Tomyshev, Alexander S, Tordesillas-Gutierrez, Diana, Valk, Sofie L, and van den Berg, Leonard H

Subjects
Biological Psychology, Psychology, Biomedical Imaging, Brain Disorders, Neurosciences, Neurological, MRI, connectome analysis, diffusion weighted MRI, brain, network, Clinical Sciences, Clinical sciences, Biological psychology
Abstract

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

Published
2019

7. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

Author

van Erp, Theo GM, Walton, Esther, Hibar, Derrek P, Schmaal, Lianne, Jiang, Wenhao, Glahn, David C, Pearlson, Godfrey D, Yao, Nailin, Fukunaga, Masaki, Hashimoto, Ryota, Okada, Naohiro, Yamamori, Hidenaga, Bustillo, Juan R, Clark, Vincent P, Agartz, Ingrid, Mueller, Bryon A, Cahn, Wiepke, de Zwarte, Sonja MC, Hulshoff Pol, Hilleke E, Kahn, René S, Ophoff, Roel A, van Haren, Neeltje EM, Andreassen, Ole A, Dale, Anders M, Doan, Nhat Trung, Gurholt, Tiril P, Hartberg, Cecilie B, Haukvik, Unn K, Jørgensen, Kjetil N, Lagerberg, Trine V, Melle, Ingrid, Westlye, Lars T, Gruber, Oliver, Kraemer, Bernd, Richter, Anja, Zilles, David, Calhoun, Vince D, Crespo-Facorro, Benedicto, Roiz-Santiañez, Roberto, Tordesillas-Gutiérrez, Diana, Loughland, Carmel, Carr, Vaughan J, Catts, Stanley, Cropley, Vanessa L, Fullerton, Janice M, Green, Melissa J, Henskens, Frans A, Jablensky, Assen, Lenroot, Rhoshel K, Mowry, Bryan J, Michie, Patricia T, Pantelis, Christos, Quidé, Yann, Schall, Ulrich, Scott, Rodney J, Cairns, Murray J, Seal, Marc, Tooney, Paul A, Rasser, Paul E, Cooper, Gavin, Shannon Weickert, Cynthia, Weickert, Thomas W, Morris, Derek W, Hong, Elliot, Kochunov, Peter, Beard, Lauren M, Gur, Raquel E, Gur, Ruben C, Satterthwaite, Theodore D, Wolf, Daniel H, Belger, Aysenil, Brown, Gregory G, Ford, Judith M, Macciardi, Fabio, Mathalon, Daniel H, O'Leary, Daniel S, Potkin, Steven G, Preda, Adrian, Voyvodic, James, Lim, Kelvin O, McEwen, Sarah, Yang, Fude, Tan, Yunlong, Tan, Shuping, Wang, Zhiren, Fan, Fengmei, Chen, Jingxu, Xiang, Hong, Tang, Shiyou, Guo, Hua, Wan, Ping, Wei, Dong, Bockholt, Henry J, Ehrlich, Stefan, Wolthusen, Rick PF, King, Margaret D, Shoemaker, Jody M, Sponheim, Scott R, De Haan, Lieuwe, and Koenders, Laura

Subjects
Karolinska Schizophrenia Project, Brain, Frontal Lobe, Prefrontal Cortex, Temporal Lobe, Humans, Magnetic Resonance Imaging, Severity of Illness Index, Linear Models, Case-Control Studies, Schizophrenia, Age of Onset, Adolescent, Adult, Aged, Middle Aged, Child, Female, Male, Young Adult, Neuroimaging, Cortical, Imaging, Meta-analysis, Surface area, Thickness, Serious Mental Illness, Biomedical Imaging, Mental Health, Clinical Research, Neurosciences, Brain Disorders, Mental health, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundThe profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group.MethodsThe study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide.ResultsCompared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset.ConclusionsThe findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Published
2018

10. Cortical similarities in psychiatric and mood disorders identified in federated VBM analysis via COINSTAC

Author

Rootes-Murdy, Kelly, Panta, Sandeep, Kelly, Ross, Romero, Javier, Quidé, Yann, Cairns, Murray J., Loughland, Carmel, Carr, Vaughan J., Catts, Stanley V., Jablensky, Assen, Green, Melissa J., Henskens, Frans, Kiltschewskij, Dylan, Michie, Patricia T., Mowry, Bryan, Pantelis, Christos, Rasser, Paul E., Reay, William R., Schall, Ulrich, Scott, Rodney J., Watkeys, Oliver J., Roberts, Gloria, Mitchell, Philip B., Fullerton, Janice M., Overs, Bronwyn J., Kikuchi, Masataka, Hashimoto, Ryota, Matsumoto, Junya, Fukunaga, Masaki, Sachdev, Perminder S., Brodaty, Henry, Wen, Wei, Jiang, Jiyang, Fani, Negar, Ely, Timothy D., Lorio, Adriana, Stevens, Jennifer S., Ressler, Kerry, Jovanovic, Tanja, van Rooij, Sanne J.H., Federmann, Lydia M., Jockwitz, Christiane, Teumer, Alexander, Forstner, Andreas J., Caspers, Svenja, Cichon, Sven, Plis, Sergey M., Sarwate, Anand D., and Calhoun, Vince D.

Abstract

Structural neuroimaging studies have identified a combination of shared and disorder-specific patterns of gray matter (GM) deficits across psychiatric disorders. Pooling large data allows for examination of a possible common neuroanatomical basis that may identify a certain vulnerability for mental illness. Large-scale collaborative research is already facilitated by data repositories, institutionally supported databases, and data archives. However, these data-sharing methodologies can suffer from significant barriers. Federated approaches augment these approaches by enabling access or more sophisticated, shareable and scaled-up analyses of large-scale data. We examined GM alterations using Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymous Computation, an open-source, decentralized analysis application. Through federated analysis of eight sites, we identified significant overlap in the GM patterns (n = 4,102) of individuals with schizophrenia, major depressive disorder, and autism spectrum disorder. These results show cortical and subcortical regions that may indicate a shared vulnerability to psychiatric disorders.

Published
2024
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13. Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.

Author

Jalbrzikowski, Maria, Hayes, Rebecca A., Wood, Stephen J., Nordholm, Dorte, Zhou, Juan H., Fusar-Poli, Paolo, Uhlhaas, Peter J., Takahashi, Tsutomu, Sugranyes, Gisela, Kwak, Yoo Bin, Mathalon, Daniel H., Katagiri, Naoyuki, Hooker, Christine I., Smigielski, Lukasz, Colibazzi, Tiziano, Via, Esther, Tang, Jinsong, Koike, Shinsuke, Rasser, Paul E., and Michel, Chantal

Subjects
MAGNETIC resonance imaging, PSYCHOSES, 22Q11 deletion syndrome, NEURAL development, DIAGNOSIS, CURIOSITIES & wonders, RELATIVE medical risk, DISEASE progression, RESEARCH, AGE distribution, RESEARCH methodology, CASE-control method, EVALUATION research, COMPARATIVE studies, DISEASE susceptibility, RESEARCH funding, NEURORADIOLOGY, CEREBRAL cortex, LONGITUDINAL method, EARLY diagnosis
Abstract

Importance: The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.Objective: To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).Design, Setting, and Participants: In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.Main Outcomes and Measures: Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).Results: Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001).Conclusions and Relevance: This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes. [ABSTRACT FROM AUTHOR]

Published
2021
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14. Genetic variants for head size share genes and pathways with cancer

Author

Knol, Maria J., Poot, Raymond A., Evans, Tavia E., Satizabal, Claudia L., Mishra, Aniket, Sargurupremraj, Muralidharan, van der Auwera, Sandra, Duperron, Marie-Gabrielle, Jian, Xueqiu, Hostettler, Isabel C., van Dam-Nolen, Dianne H.K., Lamballais, Sander, Pawlak, Mikolaj A., Lewis, Cora E., Carrion-Castillo, Amaia, van Erp, Theo G.M., Reinbold, Céline S., Shin, Jean, Scholz, Markus, Håberg, Asta K., Kämpe, Anders, Li, Gloria H.Y., Avinun, Reut, Atkins, Joshua R., Hsu, Fang-Chi, Amod, Alyssa R., Lam, Max, Tsuchida, Ami, Teunissen, Mariël W.A., Aygün, Nil, Patel, Yash, Liang, Dan, Beiser, Alexa S., Beyer, Frauke, Bis, Joshua C., Bos, Daniel, Bryan, R. Nick, Bülow, Robin, Caspers, Svenja, Catheline, Gwenaëlle, Cecil, Charlotte A.M., Dalvie, Shareefa, Dartigues, Jean-François, DeCarli, Charles, Enlund-Cerullo, Maria, Ford, Judith M., Franke, Barbara, Freedman, Barry I., Friedrich, Nele, Green, Melissa J., Haworth, Simon, Helmer, Catherine, Hoffmann, Per, Homuth, Georg, Ikram, M. Kamran, Jack, Clifford R., Jahanshad, Neda, Jockwitz, Christiane, Kamatani, Yoichiro, Knodt, Annchen R., Li, Shuo, Lim, Keane, Longstreth, W.T., Macciardi, Fabio, Amouyel, Philippe, Arfanakis, Konstantinos, Aribisala, Benjamin S., Bastin, Mark E., Chauhan, Ganesh, Chen, Christopher, Cheng, Ching-Yu, de Jager, Philip L., Deary, Ian J., Fleischman, Debra A., Gottesman, Rebecca F., Gudnason, Vilmundur, Hilal, Saima, Hofer, Edith, Janowitz, Deborah, Jukema, J. Wouter, Liewald, David C.M., Lopez, Lorna M., Lopez, Oscar, Luciano, Michelle, Martinez, Oliver, Niessen, Wiro J., Nyquist, Paul, Rotter, Jerome I., Rundek, Tatjana, Sacco, Ralph L., Schmidt, Helena, Tiemeier, Henning, Trompet, Stella, van der Grond, Jeroen, Völzke, Henry, Wardlaw, Joanna M., Yanek, Lisa, Yang, Jingyun, Agartz, Ingrid, Alhusaini, Saud, Almasy, Laura, Ames, David, Amunts, Katrin, Andreassen, Ole A., Armstrong, Nicola, Bernard, Manon, Blangero, John, Blanken, Laura M.E., Boks, Marco P., Boomsma, Dorret I., Brickman, Adam M., Brodaty, Henry, Buckner, Randy L., Buitelaar, Jan K., Cannon, Dara M., Carr, Vaughan J., Catts, Stanley V., Chakravarty, M. Mallar, Chen, Qiang, Ching, Christopher R.K., Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Davies, Gareth E., de Geus, Eco J.C., de Zubicaray, Greig I., den Braber, Anouk, Desrivières, Sylvane, Dillman, Allissa, Djurovic, Srdjan, Drevets, Wayne C., Duggirala, Ravi, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fedko, Iryna O., Fernández, Guillén, Fisher, Simon E., Foroud, Tatiana M., Ge, Tian, Giddaluru, Sudheer, Glahn, David C., Goldman, Aaron L., Green, Robert C., Greven, Corina U., Grimm, Oliver, Hansell, Narelle K., Hartman, Catharina A., Hashimoto, Ryota, Heinz, Andreas, Henskens, Frans, Hibar, Derrek P., Ho, Beng-Choon, Hoekstra, Pieter J., Holmes, Avram J., Hoogman, Martine, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E., Jablensky, Assen, Jenkinson, Mark, Jia, Tianye, Jöckel, Karl-Heinz, Jönsson, Erik G., Kim, Sungeun, Klein, Marieke, Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Le Hellard, Stephanie, Lemaître, Hervé, Loughland, Carmel, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Matarin, Mar, Mathalon, Daniel H., Mather, Karen A., Mattay, Venkata S., McDonald, Colm, McMahon, Francis J., McMahon, Katie L., E, Rebekah, McWhirter, Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Michie, Patricia T., Milaneschi, Yuri, Morris, Derek W., Mowry, Bryan, Nho, Kwangsik, Nichols, Thomas E., Nöthen, Markus N., Olvera, Rene L., Oosterlaan, Jaap, Ophoff, Roel A., Pandolfo, Massimo, Pantelis, Christos, Pappa, Irene, Penninx, Brenda, Pike, G. Bruce, Rasser, Paul E., Rentería, Miguel E., Reppermund, Simone, Rietschel, Marcella, Risacher, Shannon L., Romanczuk-Seiferth, Nina, Rose, Emma Jane, Sachdev, Perminder S., Sämann, Philipp G., Saykin, Andrew J., Schall, Ulrich, Schofield, Peter R., Schramm, Sara, Schumann, Gunter, Scott, Rodney, Shen, Li, Sisodiya, Sanjay M., Soininen, Hilkka, Sprooten, Emma, Srikanth, Velandai, Steen, Vidar M., Strike, Lachlan T., Thalamuthu, Anbupalam, Toga, Arthur W., Tooney, Paul, Tordesillas-Gutiérrez, Diana, Turner, Jessica A., Valdés Hernández, Maria del C., van der Meer, Dennis, Van der Wee, Nic J.A., Van Haren, Neeltje E.M., van 't Ent, Dennis, Veltman, Dick J., Walter, Henrik, Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, Winkler, Anderson M., Woldehawariat, Girma, Wright, Margaret J., Wu, Jingqin, Mäkitie, Outi, Mazoyer, Bernard, Medland, Sarah E., Miyamoto, Susumu, Moebus, Susanne, Mosley, Thomas H., Muetzel, Ryan, Mühleisen, Thomas W., Nagata, Manabu, Nakahara, Soichiro, Palmer, Nicholette D., Pausova, Zdenka, Preda, Adrian, Quidé, Yann, Reay, William R., Roshchupkin, Gennady V., Schmidt, Reinhold, Schreiner, Pamela J., Setoh, Kazuya, Shapland, Chin Yang, Sidney, Stephen, St Pourcain, Beate, Stein, Jason L., Tabara, Yasuharu, Teumer, Alexander, Uhlmann, Anne, van der Lugt, Aad, Vernooij, Meike W., Werring, David J., Windham, B. Gwen, Witte, A. Veronica, Wittfeld, Katharina, Yang, Qiong, Yoshida, Kazumichi, Brunner, Han G., Le Grand, Quentin, Sim, Kang, Stein, Dan J., Bowden, Donald W., Cairns, Murray J., Hariri, Ahmad R., Cheung, Ching-Lung, Andersson, Sture, Villringer, Arno, Paus, Tomas, Cichon, Sven, Calhoun, Vince D., Crivello, Fabrice, Launer, Lenore J., White, Tonya, Koudstaal, Peter J., Houlden, Henry, Fornage, Myriam, Matsuda, Fumihiko, Grabe, Hans J., Ikram, M. Arfan, Debette, Stéphanie, Thompson, Paul M., Seshadri, Sudha, and Adams, Hieab H.H.

Abstract

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Published
2024
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15. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, primary, Jahanshad, N, additional, Zalesky, A, additional, Kochunov, P, additional, Agartz, I, additional, Alloza, C, additional, Andreassen, O A, additional, Arango, C, additional, Banaj, N, additional, Bouix, S, additional, Bousman, C A, additional, Brouwer, R M, additional, Bruggemann, J, additional, Bustillo, J, additional, Cahn, W, additional, Calhoun, V, additional, Cannon, D, additional, Carr, V, additional, Catts, S, additional, Chen, J, additional, Chen, J-x, additional, Chen, X, additional, Chiapponi, C, additional, Cho, Kl K, additional, Ciullo, V, additional, Corvin, A S, additional, Crespo-Facorro, B, additional, Cropley, V, additional, De Rossi, P, additional, Diaz-Caneja, C M, additional, Dickie, E W, additional, Ehrlich, S, additional, Fan, F-m, additional, Faskowitz, J, additional, Fatouros-Bergman, H, additional, Flyckt, L, additional, Ford, J M, additional, Fouche, J-P, additional, Fukunaga, M, additional, Gill, M, additional, Glahn, D C, additional, Gollub, R, additional, Goudzwaard, E D, additional, Guo, H, additional, Gur, R E, additional, Gur, R C, additional, Gurholt, T P, additional, Hashimoto, R, additional, Hatton, S N, additional, Henskens, F A, additional, Hibar, D P, additional, Hickie, I B, additional, Hong, L E, additional, Horacek, J, additional, Howells, F M, additional, Hulshoff Pol, H E, additional, Hyde, C L, additional, Isaev, D, additional, Jablensky, A, additional, Jansen, P R, additional, Janssen, J, additional, Jönsson, E G, additional, Jung, L A, additional, Kahn, R S, additional, Kikinis, Z, additional, Liu, K, additional, Klauser, P, additional, Knöchel, C, additional, Kubicki, M, additional, Lagopoulos, J, additional, Langen, C, additional, Lawrie, S, additional, Lenroot, R K, additional, Lim, K O, additional, Lopez-Jaramillo, C, additional, Lyall, A, additional, Magnotta, V, additional, Mandl, R C W, additional, Mathalon, D H, additional, McCarley, R W, additional, McCarthy-Jones, S, additional, McDonald, C, additional, McEwen, S, additional, McIntosh, A, additional, Melicher, T, additional, Mesholam-Gately, R I, additional, Michie, P T, additional, Mowry, B, additional, Mueller, B A, additional, Newell, D T, additional, O'Donnell, P, additional, Oertel-Knöchel, V, additional, Oestreich, L, additional, Paciga, S A, additional, Pantelis, C, additional, Pasternak, O, additional, Pearlson, G, additional, Pellicano, G R, additional, Pereira, A, additional, Pineda Zapata, J, additional, Piras, F, additional, Potkin, S G, additional, Preda, A, additional, Rasser, P E, additional, Roalf, D R, additional, Roiz, R, additional, Roos, A, additional, Rotenberg, D, additional, Satterthwaite, T D, additional, Savadjiev, P, additional, Schall, U, additional, Scott, R J, additional, Seal, M L, additional, Seidman, L J, additional, Shannon Weickert, C, additional, Whelan, C D, additional, Shenton, M E, additional, Kwon, J S, additional, Spalletta, G, additional, Spaniel, F, additional, Sprooten, E, additional, Stäblein, M, additional, Stein, D J, additional, Sundram, S, additional, Tan, Y, additional, Tan, S, additional, Tang, S, additional, Temmingh, H S, additional, Westlye, L T, additional, Tønnesen, S, additional, Tordesillas-Gutierrez, D, additional, Doan, N T, additional, Vaidya, J, additional, van Haren, N E M, additional, Vargas, C D, additional, Vecchio, D, additional, Velakoulis, D, additional, Voineskos, A, additional, Voyvodic, J Q, additional, Wang, Z, additional, Wan, P, additional, Wei, D, additional, Weickert, T W, additional, Whalley, H, additional, White, T, additional, Whitford, T J, additional, Wojcik, J D, additional, Xiang, H, additional, Xie, Z, additional, Yamamori, H, additional, Yang, F, additional, Yao, N, additional, Zhang, G, additional, Zhao, J, additional, van Erp, T G M, additional, Turner, J, additional, Thompson, P M, additional, and Donohoe, G, additional

Published
2017
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16. The in vivo topography of cortical changes in healthy aging and prodromal Alzheimer's disease

Author

Prestia, A., Baglieri, A., Pievani, M., Bonetti, M., Rasser, P. E., Thompson, P. M., Marino, Silvia, Bramanti, Placido, and Frisoni, G. B.

Subjects
Adult, Aged, 80 and over, Cerebral Cortex, Male, Mild Cognitive Impairment, Aging, Analysis of Variance, Brain Mapping, Statistics, Middle Aged, Neuropsychological Tests, Magnetic Resonance Imaging, Statistics, Nonparametric, Alzheimer Disease, Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, pathology, Analysis of Variance, Atrophy, pathology, Brain Mapping, Cerebral Cortex, pathology, Female, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Mild Cognitive Impairment, pathology, Neuropsychological Tests, Statistics, Nonparametric, 80 and over, Humans, pathology, Cognitive Dysfunction, Female, Atrophy, Mental Status Schedule, Aged
Abstract

Gray matter atrophy is regarded as a valid marker of neurodegeneration in Alzheimer's disease (AD), but few studies have investigated in detail the topographic changes associated with normal aging. In addition, few studies have compared the changes in the earliest clinical stage of AD (prodromal AD (pAD)) with those of healthy aging. Here we aimed to investigate the topographical distribution of age-related cortical atrophy and to compare it with that associated with prodromal and estabilished AD.Structural T1-weighted high-resolution brain magnetic resonance imaging scans were acquired from 60 healthy volunteers (20 young adults, YA: age 32.7 +/- 4.5 years; 40 elderly subjects, HE: age 71.3 +/- 6.2 years), 16 mild cognitive impairment subjects who converted to AD within 2 years (prodromal AD, pAD: age 72.8 +/- 5.4), and 20 mild to moderate AD patients (mAD, age 72.5 +/- 10.3). Cortical gray matter differences were investigated using a surface-based anatomical mesh modeling technique (cortical pattern matching) and region-of-interest (ROI) analyses based on hypothesized brain networks taught to have a functional and a structural link to each other. Differences in cortical atrophy were assessed between groups, as well as the effect of age within groups.HE compared to YA showed a 10-30% deficit in cortical gray matter in widespread frontal, temporal, and parietal regions (p = 0.0001 by permutation testing), 6-13% loss in the visual and sensorimotor cortices (p0.01) and up to 13% loss in the direct hippocampal pathway ROIs (p0.001). pAD patients showed on average 8-9% cortical loss compared to HE (p0.0001), mainly in the left (up to 6% loss, p = 0.06) and right polysynaptic hippocampal pathway ROIs (up to 8% loss, p = 0.01), and in the left and right olfactory/orbitofrontal cortex (up to 12-15% loss, p0.001). The pattern of cortical atrophy in mAD versus HE was similar to that in pAD, but was more severe in the direct hippocampal pathway ROIs and sensorimotor, visual and temporal cortices (13-15% loss compared with HE, p0.0001).Gray matter loss occurs during aging with rates of atrophy even more severe than that observed during the course of AD. These changes may be caused by normal mechanisms. In pAD, cortical atrophy due to disease is milder than that due to aging, maybe resulting from a slowed down velocity of cell loss, but affects specific brain areas. These findings are consistent with the view that AD is not merely accelerated aging.

Published
2013

17. Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group

Author

Kelly, S, Jahanshad, N, Zalesky, A, Kochunov, P, Agartz, I, Alloza, C, Andreassen, O A, Arango, C, Banaj, N, Bouix, S, Bousman, C A, Brouwer, R M, Bruggemann, J, Bustillo, J, Cahn, W, Calhoun, V, Cannon, D, Carr, V, Catts, S, Chen, J, Chen, J-x, Chen, X, Chiapponi, C, Cho, Kl K, Ciullo, V, Corvin, A S, Crespo-Facorro, B, Cropley, V, De Rossi, P, Diaz-Caneja, C M, Dickie, E W, Ehrlich, S, Fan, F-m, Faskowitz, J, Fatouros-Bergman, H, Flyckt, L, Ford, J M, Fouche, J-P, Fukunaga, M, Gill, M, Glahn, D C, Gollub, R, Goudzwaard, E D, Guo, H, Gur, R E, Gur, R C, Gurholt, T P, Hashimoto, R, Hatton, S N, Henskens, F A, Hibar, D P, Hickie, I B, Hong, L E, Horacek, J, Howells, F M, Hulshoff Pol, H E, Hyde, C L, Isaev, D, Jablensky, A, Jansen, P R, Janssen, J, Jönsson, E G, Jung, L A, Kahn, R S, Kikinis, Z, Liu, K, Klauser, P, Knöchel, C, Kubicki, M, Lagopoulos, J, Langen, C, Lawrie, S, Lenroot, R K, Lim, K O, Lopez-Jaramillo, C, Lyall, A, Magnotta, V, Mandl, R C W, Mathalon, D H, McCarley, R W, McCarthy-Jones, S, McDonald, C, McEwen, S, McIntosh, A, Melicher, T, Mesholam-Gately, R I, Michie, P T, Mowry, B, Mueller, B A, Newell, D T, O'Donnell, P, Oertel-Knöchel, V, Oestreich, L, Paciga, S A, Pantelis, C, Pasternak, O, Pearlson, G, Pellicano, G R, Pereira, A, Pineda Zapata, J, Piras, F, Potkin, S G, Preda, A, Rasser, P E, Roalf, D R, Roiz, R, Roos, A, Rotenberg, D, Satterthwaite, T D, Savadjiev, P, Schall, U, Scott, R J, Seal, M L, Seidman, L J, Shannon Weickert, C, Whelan, C D, Shenton, M E, Kwon, J S, Spalletta, G, Spaniel, F, Sprooten, E, Stäblein, M, Stein, D J, Sundram, S, Tan, Y, Tan, S, Tang, S, Temmingh, H S, Westlye, L T, Tønnesen, S, Tordesillas-Gutierrez, D, Doan, N T, Vaidya, J, van Haren, N E M, Vargas, C D, Vecchio, D, Velakoulis, D, Voineskos, A, Voyvodic, J Q, Wang, Z, Wan, P, Wei, D, Weickert, T W, Whalley, H, White, T, Whitford, T J, Wojcik, J D, Xiang, H, Xie, Z, Yamamori, H, Yang, F, Yao, N, Zhang, G, Zhao, J, van Erp, T G M, Turner, J, Thompson, P M, and Donohoe, G

Abstract

The regional distribution of white matter (WM) abnormalities in schizophrenia remains poorly understood, and reported disease effects on the brain vary widely between studies. In an effort to identify commonalities across studies, we perform what we believe is the first ever large-scale coordinated study of WM microstructural differences in schizophrenia. Our analysis consisted of 2359 healthy controls and 1963 schizophrenia patients from 29 independent international studies; we harmonized the processing and statistical analyses of diffusion tensor imaging (DTI) data across sites and meta-analyzed effects across studies. Significant reductions in fractional anisotropy (FA) in schizophrenia patients were widespread, and detected in 20 of 25 regions of interest within a WM skeleton representing all major WM fasciculi. Effect sizes varied by region, peaking at (d=0.42) for the entire WM skeleton, driven more by peripheral areas as opposed to the core WM where regions of interest were defined. The anterior corona radiata (d=0.40) and corpus callosum (d=0.39), specifically its body (d=0.39) and genu (d=0.37), showed greatest effects. Significant decreases, to lesser degrees, were observed in almost all regions analyzed. Larger effect sizes were observed for FA than diffusivity measures; significantly higher mean and radial diffusivity was observed for schizophrenia patients compared with controls. No significant effects of age at onset of schizophrenia or medication dosage were detected. As the largest coordinated analysis of WM differences in a psychiatric disorder to date, the present study provides a robust profile of widespread WM abnormalities in schizophrenia patients worldwide. Interactive three-dimensional visualization of the results is available at www.enigma-viewer.org.

Published
2018
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25. Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders

Author

Committee, Writing, Disorder, Autism Spectrum, French, Leon, Grevet, Eugenio H, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Guerrero-Pedraza, Amalia, Gur, Raquel E, Gur, Ruben C, Haar, Shlomi, Haarman, Bartholomeus C M, Thomopoulos, Sophia I, Haavik, Jan, Hahn, Tim, Hajek, Tomas, Harrison, Benjamin J, Harrison, Neil A, Hartman, Catharina A, Whalley, Heather C, Heslenfeld, Dirk J, Hibar, Derrek P, Hilland, Eva, Pozzi, Elena, Hirano, Yoshiyuki, Ho, Tiffany C, Hoekstra, Pieter J, Hoekstra, Liesbeth, Hohmann, Sarah, Hong, L. E., Höschl, Cyril, Høvik, Marie F, Howells, Fleur M, Nenadic, Igor, Abe, Yoshinari, Jalbrzikowski, Maria, James, Anthony C, Janssen, Joost, Jaspers-Fayer, Fern, Xu, Jian, Jonassen, Rune, Karkashadze, Georgii, King, Joseph A, Kircher, Tilo, Kirschner, Matthias, Abé, Christoph, Koch, Kathrin, Kochunov, Peter, Kohls, Gregor, Konrad, Kerstin, Krämer, Bernd, Krug, Axel, Kuntsi, Jonna, Kwon, Jun Soo, Landén, Mikael, Landrø, Nils I, Anticevic, Alan, Lazaro, Luisa, Lebedeva, Irina S, Leehr, Elisabeth J, Lera-Miguel, Sara, Lesch, Klaus-Peter, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, MacMaster, Frank P, Alda, Martin, Maglanoc, Luigi A, Malpas, Charles B, Portella, Maria J, Marsh, Rachel, Martyn, Fiona M, Mataix-Cols, David, Mathalon, Daniel H, McCarthy, Hazel, McDonald, Colm, McPhilemy, Genevieve, Aleman, Andre, Meinert, Susanne, Menchón, José M, Minuzzi, Luciano, Mitchell, Philip B, Moreno, Carmen, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan, Mwangi, Benson, Alloza, Clara, Nabulsi, Leila, Nakagawa, Akiko, Nakamae, Takashi, Namazova, Leyla, Narayanaswamy, Janardhanan, Jahanshad, Neda, Nguyen, Danai D, Nicolau, Rosa, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, Alonso-Lana, Silvia, Oosterlaan, Jaap, Opel, Nils, Ophoff, Roel A, Oranje, Bob, García de la Foz, Victor Ortiz, Overs, Bronwyn J, Paloyelis, Yannis, Pantelis, Christos, Parellada, Mara, Pauli, Paul, Disorder, Bipolar, Ameis, Stephanie H, Picó-Pérez, Maria, Picon, Felipe A, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Pomarol-Clotet, Edith, Preda, Adrian, Puig, Olga, Quidé, Yann, Radua, Joaquim, Anagnostou, Evdokia, Ramos-Quiroga, J Antoni, Rasser, Paul E, Rauer, Lisa, Reddy, Janardhan, Redlich, Ronny, Reif, Andreas, Reneman, Liesbeth, Repple, Jonathan, Retico, Alessandra, Richarte, Vanesa, McIntosh, Andrew A, Richter, Anja, Rosa, Pedro G P, Rubia, Katya K, Hashimoto, Ryota, Sacchet, Matthew D, Salvador, Raymond, Santonja, Javier, Sarink, Kelvin, Sarró, Salvador, Satterthwaite, Theodore D, Arango, Celso, Sawa, Akira, Schall, Ulrich, Schofield, Peter R, Schrantee, Anouk, Seitz, Jochen, Serpa, Mauricio H, Setién-Suero, Esther, Shaw, Philip, Shook, Devon, Silk, Tim J, Arnold, Paul D, Sim, Kang, Simon, Schmitt, Simpson, Helen Blair, Singh, Aditya, Skoch, Antonin, Skokauskas, Norbert, Soares, Jair C, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Asherson, Philip, Spaniel, Filip, Lawrie, Stephen M, Stern, Emily R, Stewart, S Evelyn, Takayanagi, Yoichiro, Temmingh, Henk S, Tolin, David F, Tomecek, David, Tordesillas-Gutiérrez, Diana, Tosetti, Michela, Assogna, Francesca, Uhlmann, Anne, van Amelsvoort, Therese, van der Wee, Nic J A, van der Werff, Steven J A, van Haren, Neeltje E M, van Wingen, Guido A, Vance, Alasdair, Vázquez-Bourgon, Javier, Vecchio, Daniela, Venkatasubramanian, Ganesan, Auzias, Guillaume, Vieta, Eduard, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Voineskos, Aristotle N, Völzke, Henry, von Polier, Georg G, Walton, Esther, Weickert, Thomas W, Weickert, Cynthia Shannon, Weideman, Andrea S, Ayesa-Arriola, Rosa, Wittfeld, Katharina, Wolf, Daniel H, Wu, Mon-Ju, Yang, T. T., Yang, Sikun, Yoncheva, Yuliya, Yun, Je-Yeon, Cheng, Yuqi, Zanetti, Marcus V, Ziegler, Georg C, Bakker, Geor, Franke, Barbara, Hoogman, Martine, Buitelaar, Jan K, van Rooij, Daan, Andreassen, Ole A, Ching, Christopher R K, Veltman, Dick J, Schmaal, Lianne, Stein, Dan J, van den Heuvel, Odile A, Disorder, Major Depressive, Banaj, Nerisa, Turner, Jessica A, van Erp, Theo G M, Pausova, Zdenka, Thompson, Paul M, Paus, Tomáš, Attention-Deficit/Hyperactivity Disorder, Banaschewski, Tobias, Bandeira, Cibele E, Baranov, Alexandr, Bargalló, Núria, Bau, Claiton H D, Baumeister, Sarah, Baune, Bernhard T, Bellgrove, Mark A, Benedetti, Francesco, Disorder, Obsessive-Compulsive, Bertolino, Alessandro, Boedhoe, Premika S W, Boks, Marco, Bollettini, Irene, Del Mar Bonnin, Caterina, Borgers, Tiana, Borgwardt, Stefan, Brandeis, Daniel, Brennan, Brian P, Bruggemann, Jason M, Groups, Schizophrenia ENIGMA Working, Bülow, Robin, Busatto, Geraldo F, Calderoni, Sara, Calhoun, Vince D, Calvo, Rosa, Canales-Rodríguez, Erick J, Cannon, Dara M, Carr, Vaughan J, Cascella, Nicola, Cercignani, Mara, Patel, Yash, Chaim-Avancini, Tiffany M, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Crespo-Facorro, Benedicto, Cubillo, Ana I, Cullen, Kathryn R, Cupertino, Renata B, Daly, Eileen, Dannlowski, Udo, Parker, Nadine, Davey, Christopher G, Denys, Damiaan, Deruelle, Christine, Di Giorgio, Annabella, Dickie, Erin W, Dima, Danai, Dohm, Katharina, Ehrlich, Stefan, Ely, Benjamin A, Erwin-Grabner, Tracy, Shin, Jean, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas, Faraone, Stephen V, Fatjó-Vilas, Mar, Fedor, Jennifer M, Fitzgerald, Kate D, Ford, Judith M, Frodl, Thomas, Fu, Cynthia H Y, Howard, Derek, Fullerton, Janice M, Gabel, Matt C, Glahn, David C, Roberts, Gloria, Gogberashvili, Tinatin, Goikolea, Jose M, Gotlib, Ian H, Goya-Maldonado, Roberto, Grabe, Hans, Green, Melissa J, Patel, Y., Parker, N., Shin, J., Howard, D., French, L., Thomopoulos, S. I., Pozzi, E., Abe, Y., Abe, C., Anticevic, A., Alda, M., Aleman, A., Alloza, C., Alonso-Lana, S., Ameis, S. H., Anagnostou, E., Mcintosh, A. A., Arango, C., Arnold, P. D., Asherson, P., Assogna, F., Auzias, G., Ayesa-Arriola, R., Bakker, G., Banaj, N., Banaschewski, T., Bandeira, C. E., Baranov, A., Bargallo, N., Bau, C. H. D., Baumeister, S., Baune, B. T., Bellgrove, M. A., Benedetti, F., Bertolino, A., Boedhoe, P. S. W., Boks, M., Bollettini, I., Del Mar Bonnin, C., Borgers, T., Borgwardt, S., Brandeis, D., Brennan, B. P., Bruggemann, J. M., Bulow, R., Busatto, G. F., Calderoni, S., Calhoun, V. D., Calvo, R., Canales-Rodriguez, E. J., Cannon, D. M., Carr, V. J., Cascella, N., Cercignani, M., Chaim-Avancini, T. M., Christakou, A., Coghill, D., Conzelmann, A., Crespo-Facorro, B., Cubillo, A. I., Cullen, K. R., Cupertino, R. B., Daly, E., Dannlowski, U., Davey, C. G., Denys, D., Deruelle, C., Di Giorgio, A., Dickie, E. W., Dima, D., Dohm, K., Ehrlich, S., Ely, B. A., Erwin-Grabner, T., Ethofer, T., Fair, D. A., Fallgatter, A. J., Faraone, S. V., Fatjo-Vilas, M., Fedor, J. M., Fitzgerald, K. D., Ford, J. M., Frodl, T., Fu, C. H. Y., Fullerton, J. M., Gabel, M. C., Glahn, D. C., Roberts, G., Gogberashvili, T., Goikolea, J. M., Gotlib, I. H., Goya-Maldonado, R., Grabe, H. J., Green, M. J., Grevet, E. H., Groenewold, N. A., Grotegerd, D., Gruber, O., Gruner, P., Guerrero-Pedraza, A., Gur, R. E., Gur, R. C., Haar, S., Haarman, B. C. M., Haavik, J., Hahn, T., Hajek, T., Harrison, B. J., Harrison, N. A., Hartman, C. A., Whalley, H. C., Heslenfeld, D. J., Hibar, D. P., Hilland, E., Hirano, Y., Ho, T. C., Hoekstra, P. J., Hoekstra, L., Hohmann, S., Hong, L. E., Hoschl, C., Hovik, M. F., Howells, F. M., Nenadic, I., Jalbrzikowski, M., James, A. C., Janssen, J., Jaspers-Fayer, F., Xu, J., Jonassen, R., Karkashadze, G., King, J. A., Kircher, T., Kirschner, M., Koch, K., Kochunov, P., Kohls, G., Konrad, K., Kramer, B., Krug, A., Kuntsi, J., Kwon, J. S., Landen, M., Landro, N. I., Lazaro, L., Lebedeva, I. S., Leehr, E. J., Lera-Miguel, S., Lesch, K. -P., Lochner, C., Louza, M. R., Luna, B., Lundervold, A. J., Macmaster, F. P., Maglanoc, L. A., Malpas, C. B., Portella, M. J., Marsh, R., Martyn, F. M., Mataix-Cols, D., Mathalon, D. H., Mccarthy, H., Mcdonald, C., Mcphilemy, G., Meinert, S., Menchon, J. M., Minuzzi, L., Mitchell, P. B., Moreno, C., Morgado, P., Muratori, F., Murphy, C. M., Murphy, D., Mwangi, B., Nabulsi, L., Nakagawa, A., Nakamae, T., Namazova, L., Narayanaswamy, J., Jahanshad, N., Nguyen, D. D., Nicolau, R., O'Gorman Tuura, R. L., O'Hearn, K., Oosterlaan, J., Opel, N., Ophoff, R. A., Oranje, B., Garcia De La Foz, V. O., Overs, B. J., Paloyelis, Y., Pantelis, C., Parellada, M., Pauli, P., Pico-Perez, M., Picon, F. A., Piras, F., Plessen, K. J., Pomarol-Clotet, E., Preda, A., Puig, O., Quide, Y., Radua, J., Ramos-Quiroga, J. A., Rasser, P. E., Rauer, L., Reddy, J., Redlich, R., Reif, A., Reneman, L., Repple, J., Retico, A., Richarte, V., Richter, A., Rosa, P. G. P., Rubia, K. K., Hashimoto, R., Sacchet, M. D., Salvador, R., Santonja, J., Sarink, K., Sarro, S., Satterthwaite, T. D., Sawa, A., Schall, U., Schofield, P. R., Schrantee, A., Seitz, J., Serpa, M. H., Setien-Suero, E., Shaw, P., Shook, D., Silk, T. J., Sim, K., Simon, S., Simpson, H. B., Singh, A., Skoch, A., Skokauskas, N., Soares, J. C., Soreni, N., Soriano-Mas, C., Spalletta, G., Spaniel, F., Lawrie, S. M., Stern, E. R., Stewart, S. E., Takayanagi, Y., Temmingh, H. S., Tolin, D. F., Tomecek, D., Tordesillas-Gutierrez, D., Tosetti, M., Uhlmann, A., Van Amelsvoort, T., Van Der Wee, N. J. A., Van Der Werff, S. J. A., Van Haren, N. E. M., Van Wingen, G. A., Vance, A., Vazquez-Bourgon, J., Vecchio, D., Venkatasubramanian, G., Vieta, E., Vilarroya, O., Vives-Gilabert, Y., Voineskos, A. N., Volzke, H., Von Polier, G. G., Walton, E., Weickert, T. W., Weickert, C. S., Weideman, A. S., Wittfeld, K., Wolf, D. H., Wu, M. -J., Yang, T. T., Yang, K., Yoncheva, Y., Yun, J. -Y., Cheng, Y., Zanetti, M. V., Ziegler, G. C., Franke, B., Hoogman, M., Buitelaar, J. K., Van Rooij, D., Andreassen, O. A., Ching, C. R. K., Veltman, D. J., Schmaal, L., Stein, D. J., Van Den Heuvel, O. A., Turner, J. A., Van Erp, T. G. M., Pausova, Z., Thompson, P. M., Paus, T., Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Pediatric surgery, Radiology and nuclear medicine, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Neurodegeneration, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, MUMC+: MA Med Staf Spec Psychiatrie (9), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, ANS - Brain Imaging, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, University of Zurich, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Child and Adolescent Psychiatry / Psychology, IBBA, and Cognitive Psychology

Subjects
Male, Obsessive-Compulsive Disorder, Bipolar Disorder, Autism Spectrum Disorder, Autism, [SDV]Life Sciences [q-bio], Gene Expression, cytology [Cerebral Cortex], Cohort Studies, Fetal Development, physiology [Gene Expression], 2738 Psychiatry and Mental Health, 0302 clinical medicine, diagnostic imaging [Cerebral Cortex], SCHIZOPHRENIA, BRAIN, Child, Obsessive-compulsive disorder (OCD), Original Investigation, Aged, 80 and over, Cerebral Cortex, 0303 health sciences, pathology [Depressive Disorder, Major], Principal Component Analysis, Adolescent psychiatry, 10058 Department of Child and Adolescent Psychiatry, Middle Aged, diagnostic imaging [Obsessive-Compulsive Disorder], REGIONS, Magnetic Resonance Imaging, 3. Good health, FALSE DISCOVERY RATE, Psychiatry and Mental health, Autism spectrum disorder, Schizophrenia, growth & development [Cerebral Cortex], Child, Preschool, Major depressive disorder, diagnostic imaging [Schizophrenia], Esquizofrènia, Female, Psiquiatria infantil, Psiquiatria de l'adolescència, diagnostic imaging [Autism Spectrum Disorder], Adult, medicine.medical_specialty, Adolescent, Human Development, 610 Medicine & health, diagnostic imaging [Bipolar Disorder], pathology [Autism Spectrum Disorder], diagnostic imaging [Depressive Disorder, Major], 03 medical and health sciences, Young Adult, All institutes and research themes of the Radboud University Medical Center, Neuroimaging, SDG 3 - Good Health and Well-being, CEREBRAL-CORTEX, Child psychiatry, medicine, Attention deficit hyperactivity disorder, Humans, Bipolar disorder, ddc:610, Psychiatry, pathology [Schizophrenia], 030304 developmental biology, Aged, Depressive Disorder, Major, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, DENDRITE, Computational Biology, Correction, pathology [Attention Deficit Disorder with Hyperactivity], physiology [Fetal Development], medicine.disease, PATHOLOGY, pathology [Bipolar Disorder], pathology [Obsessive-Compulsive Disorder], 10036 Medical Clinic, Attention Deficit Disorder with Hyperactivity, 10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics, Case-Control Studies, DENSITY, ORIGINS, HIPPOCAMPUS, diagnostic imaging [Attention Deficit Disorder with Hyperactivity], pathology [Cerebral Cortex], Autisme, business, Neuroscience, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract

[Importance] Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood., [Objective] To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia., [Design, Setting, and Participants] Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244., [Main Outcomes and Measures] Interregional profiles of group difference in cortical thickness between cases and controls., [Results] A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders., [Conclusions and Relevance] In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

Published
2021

26. 10Kin1day: A Bottom-Up Neuroimaging Initiative

Author

Martijn P. van den Heuvel, Lianne H. Scholtens, Hannelore K. van der Burgh, Federica Agosta, Clara Alloza, Celso Arango, Bonnie Auyeung, Simon Baron-Cohen, Silvia Basaia, Manon J. N. L. Benders, Frauke Beyer, Linda Booij, Kees P. J. Braun, Geraldo Busatto Filho, Wiepke Cahn, Dara M. Cannon, Tiffany M. Chaim-Avancini, Sandra S. M. Chan, Eric Y. H. Chen, Benedicto Crespo-Facorro, Eveline A. Crone, Udo Dannlowski, Sonja M. C. de Zwarte, Bruno Dietsche, Gary Donohoe, Stefan Du Plessis, Sarah Durston, Covadonga M. Díaz-Caneja, Ana M. Díaz-Zuluaga, Robin Emsley, Massimo Filippi, Thomas Frodl, Martin Gorges, Beata Graff, Dominik Grotegerd, Dariusz Gąsecki, Julie M. Hall, Laurena Holleran, Rosemary Holt, Helene J. Hopman, Andreas Jansen, Joost Janssen, Krzysztof Jodzio, Lutz Jäncke, Vasiliy G. Kaleda, Jan Kassubek, Shahrzad Kharabian Masouleh, Tilo Kircher, Martijn G. J. C. Koevoets, Vladimir S. Kostic, Axel Krug, Stephen M. Lawrie, Irina S. Lebedeva, Edwin H. M. Lee, Tristram A. Lett, Simon J. G. Lewis, Franziskus Liem, Michael V. Lombardo, Carlos Lopez-Jaramillo, Daniel S. Margulies, Sebastian Markett, Paulo Marques, Ignacio Martínez-Zalacaín, Colm McDonald, Andrew M. McIntosh, Genevieve McPhilemy, Susanne L. Meinert, José M. Menchón, Christian Montag, Pedro S. Moreira, Pedro Morgado, David O. Mothersill, Susan Mérillat, Hans-Peter Müller, Leila Nabulsi, Pablo Najt, Krzysztof Narkiewicz, Patrycja Naumczyk, Bob Oranje, Victor Ortiz-Garcia de la Foz, Jiska S. Peper, Julian A. Pineda, Paul E. Rasser, Ronny Redlich, Jonathan Repple, Martin Reuter, Pedro G. P. Rosa, Amber N. V. Ruigrok, Agnieszka Sabisz, Ulrich Schall, Soraya Seedat, Mauricio H. Serpa, Stavros Skouras, Carles Soriano-Mas, Nuno Sousa, Edyta Szurowska, Alexander S. Tomyshev, Diana Tordesillas-Gutierrez, Sofie L. Valk, Leonard H. van den Berg, Theo G. M. van Erp, Neeltje E. M. van Haren, Judith M. C. van Leeuwen, Arno Villringer, Christiaan H. Vinkers, Christian Vollmar, Lea Waller, Henrik Walter, Heather C. Whalley, Marta Witkowska, A. Veronica Witte, Marcus V. Zanetti, Rui Zhang, Siemon C. de Lange, University Medical Center [Utrecht], Center for Nanotechnology Innovation, @NEST (CNI), National Enterprise for nanoScience and nanoTechnology (NEST), Scuola Normale Superiore di Pisa (SNS)-Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP)-Istituto Italiano di Tecnologia (IIT)-Consiglio Nazionale delle Ricerche [Pisa] (CNR PISA)-Scuola Normale Superiore di Pisa (SNS)-Scuola Universitaria Superiore Sant'Anna [Pisa] (SSSUP)-Istituto Italiano di Tecnologia (IIT)-Consiglio Nazionale delle Ricerche [Pisa] (CNR PISA), Psychiatry Department, Adolescent Unit, Hospital General Universitario Gregorio Marañón, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, University of Edinburgh, University of Cambridge [UK] (CAM), Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Psychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), National University of Ireland [Galway] (NUI Galway), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Trinity College Dublin-St. James's Hospital, University Hospital San Raffaele, Psychiatry and Psychotherapy, Universität Zürich [Zürich] = University of Zurich (UZH), Department of Neurology [Ulm], Universität Ulm - Ulm University [Ulm, Allemagne], Max-Planck-Institut für Mathematik in den Naturwissenschaften (MPI-MiS), Max-Planck-Gesellschaft, Dept. of Psychiatry, University of Marburg, Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences [Leipzig] (IMPNSC), Department of Psychology, Laboratory of Neurogenetics, sans affiliation, Division of Psychiatry, University of Edinburgh-Royal Edinburgh Hospital, Centro de Quimica Estrutural (CQE), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), Humboldt-Universität zu Berlin, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Instituto Superior Técnico, Universidade Técnica de Lisboa, Schizophrenia Research Institute [Sydney], Magnetic Resonance Imaging, Universidade do Minho, Metacohorts Consortium, Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf], Department of Psychiatry and Human Behavior [Irvine], University of California [Irvine] (UCI), University of California-University of California, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin School of Mind and Brain [Berlin], Department of Chemistry, Centre for Molecular Simulation, University of Calgary, Child and Adolescent Psychiatry / Psychology, Utrecht University, Wellcome Trust, Medical Research Council (UK), Canadian Institutes of Health Research, European Research Council, European Commission, German Research Foundation, Science Foundation Ireland, Russian Foundation for Basic Research, Fundação para a Ciência e a Tecnologia (Portugal), Instituto de Salud Carlos III, National Institutes of Health (US), Van Den Heuvel, M. P., Scholtens, L. H., Van Der Burgh, H. K., Agosta, F., Alloza, C., Arango, C., Auyeung, B., Baron-Cohen, S., Basaia, S., Benders, M. J. N. L., Beyer, F., Booij, L., Braun, K. P. J., Filho, G. B., Cahn, W., Cannon, D. M., Chaim-Avancini, T. M., Chan, S. S. M., Chen, E. Y. H., Crespo-Facorro, B., Crone, E. A., Dannlowski, U., De Zwarte, S. M. C., Dietsche, B., Donohoe, G., Plessis, S. D., Durston, S., Diaz-Caneja, C. M., Diaz-Zuluaga, A. M., Emsley, R., Filippi, M., Frodl, T., Gorges, M., Graff, B., Grotegerd, D., Gasecki, D., Hall, J. M., Holleran, L., Holt, R., Hopman, H. J., Jansen, A., Janssen, J., Jodzio, K., Jancke, L., Kaleda, V. G., Kassubek, J., Masouleh, S. K., Kircher, T., Koevoets, M. G. J. C., Kostic, V. S., Krug, A., Lawrie, S. M., Lebedeva, I. S., Lee, E. H. M., Lett, T. A., Lewis, S. J. G., Liem, F., Lombardo, M. V., Lopez-Jaramillo, C., Margulies, D. S., Markett, S., Marques, P., Martinez-Zalacain, I., Mcdonald, C., Mcintosh, A. M., Mcphilemy, G., Meinert, S. L., Menchon, J. M., Montag, C., Moreira, P. S., Morgado, P., Mothersill, D. O., Merillat, S., Muller, H. -P., Nabulsi, L., Najt, P., Narkiewicz, K., Naumczyk, P., Oranje, B., De la Foz, V. O. -G., Peper, J. S., Pineda, J. A., Rasser, P. E., Redlich, R., Repple, J., Reuter, M., Rosa, P. G. P., Ruigrok, A. N. V., Sabisz, A., Schall, U., Seedat, S., Serpa, M. H., Skouras, S., Soriano-Mas, C., Sousa, N., Szurowska, E., Tomyshev, A. S., Tordesillas-Gutierrez, D., Valk, S. L., Van Den Berg, L. H., Van Erp, T. G. M., Van Haren, N. E. M., Van Leeuwen, J. M. C., Villringer, A., Vinkers, C. H., Vollmar, C., Waller, L., Walter, H., Whalley, H. C., Witkowska, M., Witte, A. V., Zanetti, M. V., Zhang, R., De Lange, S. C., Baron-Cohen, Simon [0000-0001-9217-2544], Ruigrok, Amber [0000-0001-7711-8056], and Apollo - University of Cambridge Repository

Subjects
Computer science, diffusion weighted MRI, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Network, Brain mapping, lcsh:RC346-429, HUMAN CONNECTOME, Diffusion, 0302 clinical medicine, Medicine and Health Sciences, yttria mould coating, Cervell, Anàlisi, ComputingMilieux_MISCELLANEOUS, Brain network, 0303 health sciences, Event (computing), Brain, Human Connectome, Top-down and bottom-up design, 3. Good health, Neurology, investment casting, Perspective, Connectome, Difusió, PROJECT, MRI, Connectome analysis, AZ91D-1 wt% CaO, brain, Clinical Neurology, 03 medical and health sciences, SDG 17 - Partnerships for the Goals, Neuroimaging, Journal Article, ddc:610, Diffusion weighted MRI, lcsh:Neurology. Diseases of the nervous system, 030304 developmental biology, Connectome analysi, Science & Technology, Assaying, [SCCO.NEUR]Cognitive science/Neuroscience, mould–metal interaction, Biology and Life Sciences, Data science, Clinical neurology, network, Neurology (clinical), HUMAN CEREBRAL-CORTEX, 030217 neurology & neurosurgery
Abstract

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain. Ongoing grand-scale projects like the European Human Brain Project (1), the US Brain Initiative (2), the Human Connectome Project (3), the Chinese Brainnetome (4) and exciting world-wide neuroimaging collaborations such as ENIGMA (5) herald the new era of big neuroscience. In conjunction with these major undertakings, there is an emerging trend for bottom-up initiatives, starting with small-scale projects built upon existing collaborations and infrastructures. As described by Mainen et al. (6), these initiatives are centralized around self-organized groups of researchers working on the same challenges and sharing interests and specialized expertise. These projects could scale and open up to a larger audience and other disciplines over time, eventually lining up and merging their findings with other programs to make the bigger picture., The 10Kin1day workshop was generously sponsored by the Neuroscience and Cognition program Utrecht (NCU) of the Utrecht University (https://www.uu.nl/en/research/ neuroscience-and-cognition-utrecht), the ENIGMA consortium (http://enigma.ini.usc.edu), and personal grants: MvdH: NWOVIDI (452-16-015), MQ Fellowship; SB-C: the Wellcome Trust; Medical Research Council UK; NIHR CLAHRC for Cambridgeshire and Peterborough Foundation National Health Services Trust; Autism Research Trust; LB: New Investigator Award, Canadian Institutes of Health Research; Dara Cannon: Health Research Board (HRB), Ireland (grant code HRA-POR2013-324); SC: Research Grant Council (Hong Kong)-GRF 14101714; Eveline Crone: ERC-2010-StG-263234; UD: DFG, grant FOR2107 DA1151/5-1, DA1151/5-2, SFB-TRR58, Project C09, IZKF, grant Dan3/012/17; SD: MRC-RFA-UFSP-012013 (Shared Roots MRC Flagship grant); TF: Marie Curie Programme, International Training Programme, r’Birth; DG: National Science Centre (UMO-2011/02/A/NZ5/00329); BG: National Science Centre (UMO-2011/02/A/NZ5/00329); JH: Western Sydney University Postgraduate Research Award; LH: Science Foundation Ireland, ERC; HH: Research Grant Council (Hong Kong)-GRF 14101714; LJ: Velux Stiftung, grant 369 & UZH University Research Priority Program Dynamics of Healthy Aging; AJ: DFG, grant FOR2107 JA 1890/7-1; KJ: National Science Centre (UMO-2013/09/N/HS6/02634); VK: The Russian Foundation for Basic Research (grant code 15-06-05758A); TK: DFG, grant FOR2107 KI 588/14-1, DFG, grant FOR2107 KI 588/15-1; AK: DFG, grant FOR2107 KO 4291/4-1, DFG, grant FOR2107 KO 4291/3-1; IL: The Russian Foundation for Basic Research (grant code 15-06-05758A); EL: Health and Medical Research Fund - 11121271; SiL: NHMRC-ARC Dementia Fellowship 1110414, NHMRC Dementia Research Team Grant 1095127, NHMRC Project Grant 1062319; CL-J: 537-2011, 2014849; AM: Wellcome Trust Strategic Award (104036/Z/14/Z), MRC Grant MC_PC_17209; CM: Heisenberg-Grant, German Research Foundation, DFG MO 2363/3-2; PM: Foundation for Science and Technology, Portugal - PDE/BDE/113601/2015; KN: National Science Centre (UMO-2011/02/A/NZ5/00329); PN: National Science Centre (UMO-2013/09/N/HS6/02634); JiP: NWO-Veni 451-10-007; PaR: PER and US would like to thank the Schizophrenia Research Institute and the Chief-Investigators of the Australian Schizophrenia Research Bank V. Carr, U. Schall, R. Scott, A. Jablensky, B. Mowry, P. Michie, S. Catts, F. Henskens, and C. Pantelis; AS: National Science Centre (UMO-2011/02/A/NZ5/00329); SS: European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 707730; CS-M: Carlos III Health Institute (PI13/01958), Carlos III Health Institute (PI16/00889), Carlos III Health Institute (CPII16/00048); ES: National Science Centre (UMO-2011/02/A/NZ5/00329); AT: The Russian Foundation for Basic Research (grant code 1506-05758A); DT-G: PI14/00918, PI14/00639; Leonardo Tozzi: Marie Curie Programme, International Training Programme, r’Birth; SV: IMPRS Neurocom stipend; TvE: National Center for Research Resources at the National Institutes of Health (grant numbers: NIH 1 U24 RR021992 (Function Biomedical Informatics Research Network), NIH 1 U24 RR025736-01 (Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org) and the NIH Big Data to Knowledge (BD2K) award (U54 EB020403 to Paul Thompson). NvH: NWO-VIDI (452-11-014); MW: National Science Centre (UMO-2011/02/A/NZ5/00329); Veronica O’Keane: Meath Foundation; AV and AW: CRC Obesity Mechanism (SFB 1052) Project A1 funded by DFG. The funding sources had no role in the study design, data collection, analysis, and interpretation of the data.

Published
2019

27. Abnormalities in cortical gray matter density in borderline personality disorder.

Author

Rossi R, Lanfredi M, Pievani M, Boccardi M, Rasser PE, Thompson PM, Cavedo E, Cotelli M, Rosini S, Beneduce R, Bignotti S, Magni LR, Rillosi L, Magnaldi S, Cobelli M, Rossi G, and Frisoni GB

Subjects
Adult, Borderline Personality Disorder psychology, Brain Mapping, Female, Frontal Lobe pathology, Gyrus Cinguli pathology, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Borderline Personality Disorder pathology, Cerebral Cortex pathology, Gray Matter pathology, Prefrontal Cortex pathology
Abstract

Background: Borderline personality disorder (BPD) is a chronic condition with a strong impact on patients' affective, cognitive and social functioning. Neuroimaging techniques offer invaluable tools to understand the biological substrate of the disease. We aimed to investigate gray matter alterations over the whole cortex in a group of Borderline Personality Disorder (BPD) patients compared to healthy controls (HC)., Methods: Magnetic resonance-based cortical pattern matching was used to assess cortical gray matter density (GMD) in 26 BPD patients and in their age- and sex-matched HC (age: 38 ± 11; females: 16, 61%)., Results: BPD patients showed widespread lower cortical GMD compared to HC (4% difference) with peaks of lower density located in the dorsal frontal cortex, in the orbitofrontal cortex, the anterior and posterior cingulate, the right parietal lobe, the temporal lobe (medial temporal cortex and fusiform gyrus) and in the visual cortex (P<0.005). Our BPD subjects displayed a symmetric distribution of anomalies in the dorsal aspect of the cortical mantle, but a wider involvement of the left hemisphere in the mesial aspect in terms of lower density. A few restricted regions of higher density were detected in the right hemisphere. All regions remained significant after correction for multiple comparisons via permutation testing., Conclusions: BPD patients feature specific morphology of the cerebral structures involved in cognitive and emotional processing and social cognition/mentalization, consistent with clinical and functional data., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Published
2015
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28. Gray matter deficits, mismatch negativity, and outcomes in schizophrenia.

Author

Rasser PE, Schall U, Todd J, Michie PT, Ward PB, Johnston P, Helmbold K, Case V, Søyland A, Tooney PA, and Thompson PM

Subjects
Acoustic Stimulation methods, Adolescent, Adult, Aged, Case-Control Studies, Cerebral Cortex pathology, Electroencephalography, Evoked Potentials, Auditory, Female, Frontal Lobe pathology, Frontal Lobe physiopathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Temporal Lobe pathology, Temporal Lobe physiopathology, Young Adult, Activities of Daily Living psychology, Cerebral Cortex physiopathology, Contingent Negative Variation, Schizophrenia pathology, Schizophrenia physiopathology, Schizophrenic Psychology
Abstract

Reduced mismatch negativity (MMN) in response to auditory change is a well-established finding in schizophrenia and has been shown to be correlated with impaired daily functioning, rather than with hallmark signs and symptoms of the disorder. In this study, we investigated (1) whether the relationship between reduced MMN and impaired daily functioning is mediated by cortical volume loss in temporal and frontal brain regions in schizophrenia and (2) whether this relationship varies with the type of auditory deviant generating MMN. MMN in response to duration, frequency, and intensity deviants was recorded from 18 schizophrenia subjects and 18 pairwise age- and gender-matched healthy subjects. Patients' levels of global functioning were rated on the Social and Occupational Functioning Assessment Scale. High-resolution structural magnetic resonance scans were acquired to generate average cerebral cortex and temporal lobe models using cortical pattern matching. This technique allows accurate statistical comparison and averaging of cortical measures across subjects, despite wide variations in gyral patterns. MMN amplitude was reduced in schizophrenia patients and correlated with their impaired day-to-day function level. Only in patients, bilateral gray matter reduction in Heschl's gyrus, as well as motor and executive regions of the frontal cortex, correlated with reduced MMN amplitude in response to frequency deviants, while reduced gray matter in right Heschl's gyrus also correlated with reduced MMN to duration deviants. Our findings further support the importance of MMN reduction in schizophrenia by linking frontotemporal cerebral gray matter pathology to an automatically generated event-related potential index of daily functioning.

Published
2011
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29. Mapping the effect of APOE epsilon4 on gray matter loss in Alzheimer's disease in vivo.

Author

Pievani M, Rasser PE, Galluzzi S, Benussi L, Ghidoni R, Sabattoli F, Bonetti M, Binetti G, Thompson PM, and Frisoni GB

Subjects
Aged, Apolipoprotein E4 metabolism, Atrophy pathology, Atrophy physiopathology, Female, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Alzheimer Disease genetics, Alzheimer Disease pathology, Apolipoprotein E4 genetics, Cerebral Cortex pathology, Cerebral Cortex physiopathology, Neurons metabolism, Neurons pathology
Abstract

Previous studies suggest that in Alzheimer's disease (AD) the Apolipoprotein E (APOE) epsilon4 allele is associated with greater vulnerability of medial temporal lobe structures. However, less is known about its effect on the whole cortical mantle. Here we aimed to identify APOE-related patterns of cortical atrophy in AD using an advanced computational anatomy technique. We studied 15 AD patients carriers (epsilon4+, age: 72+/-10 SD years, MMSE: 20+/-3 SD) and 14 non-carriers (epsilon4-, age: 69+/-9, MMSE: 20+/-5) of the epsilon4 allele and compared them to 29 age-and-sex matched controls (age: 70+/-9, MMSE: 28+/-1). Each subject underwent a clinical evaluation, a neuropsychological battery, and high-resolution MRI. UCLA's cortical pattern matching technique was used to identify regions of local cortical atrophy. epsilon4+ and epsilon4- patients showed similar performance on neuropsychological tests (p>.05, t-test). Diffuse cortical atrophy was detected for both epsilon4+ (p=.0001, permutation test) and epsilon4- patients (p=.0001, permutation test) relative to controls, and overall gray matter loss was about 15% in each patients group. Differences in gray matter loss between carriers and non-carriers mapped to the temporal cortex and right occipital pole (20% greater loss in carriers) and to the posterior cingulate, left orbitofrontal and dorsal fronto-parietal cortex (5-15% greater loss in non-carriers). APOE effect in AD was not significant (p>.74, ANOVA), but a significant APOE by region (temporal vs fronto-parietal cortex) interaction was detected (p=.002, ANOVA), in both early and late-onset patients (p<.05, ANOVA). We conclude that the epsilon4 allele modulates disease phenotype in AD, being associated with a pattern of differential temporal and fronto-parietal vulnerability.

Published
2009
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