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1. Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries

Author: García-Marín, Luis M., Campos, Adrian I., Diaz-Torres, Santiago, Rabinowitz, Jill A., Ceja, Zuriel, Mitchell, Brittany L., Grasby, Katrina L., Thorp, Jackson G., Agartz, Ingrid, Alhusaini, Saud, Ames, David, Amouyel, Philippe, Andreassen, Ole A., Arfanakis, Konstantinos, Arias-Vasquez, Alejandro, Armstrong, Nicola J., Athanasiu, Lavinia, Bastin, Mark E., Beiser, Alexa S., Bennett, David A., Bis, Joshua C., Boks, Marco P. M., Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Burkhardt, Ralph, Cahn, Wiepke, Calhoun, Vince D., Carmichael, Owen T., Chakravarty, Mallar, Chen, Qiang, Ching, Christopher R. K., Cichon, Sven, Crespo-Facorro, Benedicto, Crivello, Fabrice, Dale, Anders M., Smith, George Davey, de Geus, Eco J. C., De Jager, Philip L., de Zubicaray, Greig I., Debette, Stéphanie, DeCarli, Charles, Depondt, Chantal, Desrivières, Sylvane, Djurovic, Srdjan, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fernández, Guillén, Filippi, Irina, Fisher, Simon E., Fleischman, Debra A., Fletcher, Evan, Fornage, Myriam, Forstner, Andreas J., Francks, Clyde, Franke, Barbara, Ge, Tian, Goldman, Aaron L., Grabe, Hans J., Green, Robert C., Grimm, Oliver, Groenewold, Nynke A., Gruber, Oliver, Gudnason, Vilmundur, Håberg, Asta K., Haukvik, Unn K., Heinz, Andreas, Hibar, Derrek P., Hilal, Saima, Himali, Jayandra J., Ho, Beng-Choon, Hoehn, David F., Hoekstra, Pieter J., Hofer, Edith, Hoffmann, Wolfgang, Holmes, Avram J., Homuth, Georg, Hosten, Norbert, Ikram, M. Kamran, Ipser, Jonathan C., Jack Jr, Clifford R., Jahanshad, Neda, Jönsson, Erik G., Kahn, Rene S., Kanai, Ryota, Klein, Marieke, Knol, Maria J., Launer, Lenore J., Lawrie, Stephen M., Hellard, Stephanie Le, Lee, Phil H., Lemaître, Hervé, Li, Shuo, Liewald, David C. M., Lin, Honghuang, Longstreth, Jr, W. T., Lopez, Oscar L., Luciano, Michelle, Maillard, Pauline, Marquand, Andre F., Martin, Nicholas G., Martinot, Jean-Luc, Mather, Karen A., Mattay, Venkata S., McMahon, Katie L., Mecocci, Patrizia, Melle, Ingrid, Meyer-Lindenberg, Andreas, Mirza-Schreiber, Nazanin, Milaneschi, Yuri, Mosley, Thomas H., Mühleisen, Thomas W., Müller-Myhsok, Bertram, Maniega, Susana Muñoz, Nauck, Matthias, Nho, Kwangsik, Niessen, Wiro J., Nöthen, Markus M., Nyquist, Paul A., Oosterlaan, Jaap, Pandolfo, Massimo, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda W. J. H., Pike, G. Bruce, Psaty, Bruce M., Pütz, Benno, Reppermund, Simone, Rietschel, Marcella D., Risacher, Shannon L., Romanczuk-Seiferth, Nina, Romero-Garcia, Rafael, Roshchupkin, Gennady V., Rotter, Jerome I., Sachdev, Perminder S., Sämann, Philipp G., Saremi, Arvin, Sargurupremraj, Muralidharan, Saykin, Andrew J., Schmaal, Lianne, Schmidt, Helena, Schmidt, Reinhold, Schofield, Peter R., Scholz, Markus, Schumann, Gunter, Schwarz, Emanuel, Shen, Li, Shin, Jean, Sisodiya, Sanjay M., Smith, Albert V., Smoller, Jordan W., Soininen, Hilkka S., Steen, Vidar M., Stein, Dan J., Stein, Jason L., Thomopoulos, Sophia I., Toga, Arthur W., Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Valdes-Hernandez, Maria C., van ′t Ent, Dennis, van Bokhoven, Hans, van der Meer, Dennis, van der Wee, Nic J. A., Vázquez-Bourgon, Javier, Veltman, Dick J., Vernooij, Meike W., Villringer, Arno, Vinke, Louis N., Völzke, Henry, Walter, Henrik, Wardlaw, Joanna M., Weinberger, Daniel R., Weiner, Michael W., Wen, Wei, Westlye, Lars T., Westman, Eric, White, Tonya, Witte, A. Veronica, Wolf, Christiane, Yang, Jingyun, Zwiers, Marcel P., Ikram, M. Arfan, Seshadri, Sudha, Thompson, Paul M., Satizabal, Claudia L., Medland, Sarah E., and Rentería, Miguel E.
Published: 2024
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2. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: Brouwer, Rachel M, Klein, Marieke, Grasby, Katrina L, Schnack, Hugo G, Jahanshad, Neda, Teeuw, Jalmar, Thomopoulos, Sophia I, Sprooten, Emma, Franz, Carol E, Gogtay, Nitin, Kremen, William S, Panizzon, Matthew S, Olde Loohuis, Loes M, Whelan, Christopher D, Aghajani, Moji, Alloza, Clara, Alnæs, Dag, Artiges, Eric, Ayesa-Arriola, Rosa, Barker, Gareth J, Bastin, Mark E, Blok, Elisabet, Bøen, Erlend, Breukelaar, Isabella A, Bright, Joanna K, Buimer, Elizabeth EL, Bülow, Robin, Cannon, Dara M, Ciufolini, Simone, Crossley, Nicolas A, Damatac, Christienne G, Dazzan, Paola, de Mol, Casper L, de Zwarte, Sonja MC, Desrivières, Sylvane, Díaz-Caneja, Covadonga M, Doan, Nhat Trung, Dohm, Katharina, Fröhner, Juliane H, Goltermann, Janik, Grigis, Antoine, Grotegerd, Dominik, Han, Laura KM, Harris, Mathew A, Hartman, Catharina A, Heany, Sarah J, Heindel, Walter, Heslenfeld, Dirk J, Hohmann, Sarah, Ittermann, Bernd, Jansen, Philip R, Janssen, Joost, Jia, Tianye, Jiang, Jiyang, Jockwitz, Christiane, Karali, Temmuz, Keeser, Daniel, Koevoets, Martijn GJC, Lenroot, Rhoshel K, Malchow, Berend, Mandl, René CW, Medel, Vicente, Meinert, Susanne, Morgan, Catherine A, Mühleisen, Thomas W, Nabulsi, Leila, Opel, Nils, de la Foz, Víctor Ortiz-García, Overs, Bronwyn J, Paillère Martinot, Marie-Laure, Redlich, Ronny, Marques, Tiago Reis, Repple, Jonathan, Roberts, Gloria, Roshchupkin, Gennady V, Setiaman, Nikita, Shumskaya, Elena, Stein, Frederike, Sudre, Gustavo, Takahashi, Shun, Thalamuthu, Anbupalam, Tordesillas-Gutiérrez, Diana, van der Lugt, Aad, van Haren, Neeltje EM, Wardlaw, Joanna M, Wen, Wei, Westeneng, Henk-Jan, Wittfeld, Katharina, Zhu, Alyssa H, Zugman, Andre, Armstrong, Nicola J, Bonfiglio, Gaia, Bralten, Janita, Dalvie, Shareefa, Davies, Gail, Di Forti, Marta, Ding, Linda, Donohoe, Gary, Forstner, Andreas J, and Gonzalez-Peñas, Javier
Subjects: Biological Psychology, Psychology, Genetics, Biomedical Imaging, Mental Health, Biotechnology, Human Genome, Prevention, Aging, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Brain, Genome-Wide Association Study, Humans, Longevity, Magnetic Resonance Imaging, IMAGEN Consortium, Cognitive Sciences, Neurology & Neurosurgery, Biological psychology
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Published: 2022

3. Intelligence, educational attainment, and brain structure in those at familial high‐risk for schizophrenia or bipolar disorder

Author: Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso‐Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales‐Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro‐Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Bonnin, Caterina Mar, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó‐Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Ongun, Ceren Hidiroglu, Hillegers, Manon HJ, Houenou, Josselin, Pol, Hilleke E Hulshoff, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer‐Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol‐Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Aydogan, Aybala Saricicek, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon‐Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, Erp, Theo GM, Jahanshad, Neda, and Thompson, Paul M
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Brain Disorders, Bipolar Disorder, Clinical Research, Serious Mental Illness, Neurosciences, Schizophrenia, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, 2.1 Biological and endogenous factors, Mental health, Cognitive Dysfunction, Educational Status, Family, Genetic Predisposition to Disease, Humans, Intelligence, Magnetic Resonance Imaging, Neuroimaging, bipolar disorder, education, intelligence, neuroimaging, relatives, schizophrenia, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract: First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
Published: 2022

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

Author: Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim-Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dannlowski, Udo, Dale, Anders M, Davey, Christopher, de Geus, Eco JC, de Haan, Lieuwe, de Zubicaray, Greig I, den Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros-Bergman, Helena, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Frodl, Thomas, Fuentes-Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng-Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kahn, Rene, and Kalnin, Andrew
Subjects: Karolinska Schizophrenia Project, Amygdala, Hippocampus, Thalamus, Corpus Striatum, Humans, Human Development, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Child, Child, Preschool, Female, Male, Young Adult, Neuroimaging, ENIGMA, brain morphometry, longitudinal trajectories, multisite, Neurosciences, Aging, Aetiology, 2.1 Biological and endogenous factors, Mental health, Cognitive Sciences, Experimental Psychology
Abstract: Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
Published: 2022

5. Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3–90 years

Author: Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven CR, Papachristou, Efstathios, Doucet, Gaelle E, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes‐Eizagirre, Anton, Alnæs, Dag, Alpert, Kathryn I, Andersson, Micael, Andreasen, Nancy C, Andreassen, Ole A, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur‐Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Buckner, Randy L, Calhoun, Vincent, Canales‐Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Cervenka, Simon, Chaim‐Avancini, Tiffany M, Ching, Christopher RK, Chubar, Victoria, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crespo‐Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A, Dale, Anders M, Dannlowski, Udo, Davey, Christopher, Geus, Eco JC, Haan, Lieuwe, Zubicaray, Greig I, Braber, Anouk, Dickie, Erin W, Di Giorgio, Annabella, Doan, Nhat Trung, Dørum, Erlend S, Ehrlich, Stefan, Erk, Susanne, Espeseth, Thomas, Fatouros‐Bergman, Helena, Fisher, Simon E, Fouche, Jean‐Paul, Franke, Barbara, Frodl, Thomas, Fuentes‐Claramonte, Paola, Glahn, David C, Gotlib, Ian H, Grabe, Hans‐Jörgen, Grimm, Oliver, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E, Gur, Ruben C, Hahn, Tim, Harrison, Ben J, Hartman, Catharine A, Hatton, Sean N, Heinz, Andreas, Heslenfeld, Dirk J, Hibar, Derrek P, Hickie, Ian B, Ho, Beng‐Choon, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Pol, Hilleke E Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, and Kahn, Rene
Subjects: Behavioral and Social Science, Neurosciences, Aging, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Cross-Sectional Studies, Female, Human Development, Humans, Male, Middle Aged, Neuroimaging, Young Adult, aging, cortical thickness, development, trajectories, Karolinska Schizophrenia Project, Cognitive Sciences, Experimental Psychology
Abstract: Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
Published: 2022

6. What we learn about bipolar disorder from large‐scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Author: Ching, Christopher RK, Hibar, Derrek P, Gurholt, Tiril P, Nunes, Abraham, Thomopoulos, Sophia I, Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M, Cannon, Dara M, Zwarte, Sonja MC, Eyler, Lisa T, Favre, Pauline, Hajek, Tomas, Haukvik, Unn K, Houenou, Josselin, Landén, Mikael, Lett, Tristram A, McDonald, Colm, Nabulsi, Leila, Patel, Yash, Pauling, Melissa E, Paus, Tomas, Radua, Joaquim, Soeiro‐de‐Souza, Marcio G, Tronchin, Giulia, Haren, Neeltje EM, Vieta, Eduard, Walter, Henrik, Zeng, Ling‐Li, Alda, Martin, Almeida, Jorge, Alnæs, Dag, Alonso‐Lana, Silvia, Altimus, Cara, Bauer, Michael, Baune, Bernhard T, Bearden, Carrie E, Bellani, Marcella, Benedetti, Francesco, Berk, Michael, Bilderbeck, Amy C, Blumberg, Hilary P, Bøen, Erlend, Bollettini, Irene, Bonnin, Caterina Mar, Brambilla, Paolo, Canales‐Rodríguez, Erick J, Caseras, Xavier, Dandash, Orwa, Dannlowski, Udo, Delvecchio, Giuseppe, Díaz‐Zuluaga, Ana M, Dima, Danai, Duchesnay, Édouard, Elvsåshagen, Torbjørn, Fears, Scott C, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goikolea, Jose M, Green, Melissa J, Grotegerd, Dominik, Gruber, Oliver, Haarman, Bartholomeus CM, Henry, Chantal, Howells, Fleur M, Ives‐Deliperi, Victoria, Jansen, Andreas, Kircher, Tilo TJ, Knöchel, Christian, Kramer, Bernd, Lafer, Beny, López‐Jaramillo, Carlos, Machado‐Vieira, Rodrigo, MacIntosh, Bradley J, Melloni, Elisa MT, Mitchell, Philip B, Nenadic, Igor, Nery, Fabiano, Nugent, Allison C, Oertel, Viola, Ophoff, Roel A, Ota, Miho, Overs, Bronwyn J, Pham, Daniel L, Phillips, Mary L, Pineda‐Zapata, Julian A, Poletti, Sara, Polosan, Mircea, Pomarol‐Clotet, Edith, Pouchon, Arnaud, Quidé, Yann, Rive, Maria M, Roberts, Gloria, Ruhe, Henricus G, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Schene, Aart H, and Sim, Kang
Subjects: Serious Mental Illness, Brain Disorders, Biomedical Imaging, Bipolar Disorder, Clinical Research, Behavioral and Social Science, Mental Health, Neurosciences, Mental health, Neurological, Good Health and Well Being, Cerebral Cortex, Humans, Magnetic Resonance Imaging, Meta-Analysis as Topic, Multicenter Studies as Topic, Neuroimaging, bipolar disorder, cortical surface area, cortical thickness, ENIGMA, mega-analysis, meta-analysis, MRI, neuroimaging, psychiatry, volume, ENIGMA Bipolar Disorder Working Group, Cognitive Sciences, Experimental Psychology
Abstract: MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
Published: 2022

7. Active Selection of Classification Features

Author: Kok, Thomas T., Brouwer, Rachel M., Mandl, Rene M., Schnack, Hugo G., and Krempl, Georg
Subjects: Computer Science - Machine Learning
Abstract: Some data analysis applications comprise datasets, where explanatory variables are expensive or tedious to acquire, but auxiliary data are readily available and might help to construct an insightful training set. An example is neuroimaging research on mental disorders, specifically learning a diagnosis/prognosis model based on variables derived from expensive Magnetic Resonance Imaging (MRI) scans, which often requires large sample sizes. Auxiliary data, such as demographics, might help in selecting a smaller sample that comprises the individuals with the most informative MRI scans. In active learning literature, this problem has not yet been studied, despite promising results in related problem settings that concern the selection of instances or instance-feature pairs. Therefore, we formulate this complementary problem of Active Selection of Classification Features (ASCF): Given a primary task, which requires to learn a model f: x-> y to explain/predict the relationship between an expensive-to-acquire set of variables x and a class label y. Then, the ASCF-task is to use a set of readily available selection variables z to select these instances, that will improve the primary task's performance most when acquiring their expensive features z and including them to the primary training set. We propose two utility-based approaches for this problem, and evaluate their performance on three public real-world benchmark datasets. In addition, we illustrate the use of these approaches to efficiently acquire MRI scans in the context of neuroimaging research on mental disorders, based on a simulated study design with real MRI data., Comment: Accepted for publication at the 19th Intelligent Data Analysis Symposium, 2021. The final authenticated publication will be made available online at springer.com
Published: 2021

8. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Author: Sønderby, Ida E, van der Meer, Dennis, Moreau, Clara, Kaufmann, Tobias, Walters, G Bragi, Ellegaard, Maria, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Micael, Armstrong, Nicola J, Bernard, Manon, Blackburn, Nicholas B, Blangero, John, Boomsma, Dorret I, Brodaty, Henry, Brouwer, Rachel M, Bülow, Robin, Bøen, Rune, Cahn, Wiepke, Calhoun, Vince D, Caspers, Svenja, Ching, Christopher RK, Cichon, Sven, Ciufolini, Simone, Crespo-Facorro, Benedicto, Curran, Joanne E, Dale, Anders M, Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco JC, de Zubicaray, Greig I, de Zwarte, Sonja MC, Desrivieres, Sylvane, Doherty, Joanne L, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Eising, Else, Espeseth, Thomas, Fejgin, Kim, Fisher, Simon E, Fladby, Tormod, Frei, Oleksandr, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Ge, Tian, Glahn, David C, Grabe, Hans J, Groenewold, Nynke A, Gústafsson, Ómar, Haavik, Jan, Haberg, Asta K, Hall, Jeremy, Hashimoto, Ryota, Hehir-Kwa, Jayne Y, Hibar, Derrek P, Hillegers, Manon HJ, Hoffmann, Per, Holleran, Laurena, Holmes, Avram J, Homuth, Georg, Hottenga, Jouke-Jan, Hulshoff Pol, Hilleke E, Ikeda, Masashi, Jahanshad, Neda, Jockwitz, Christiane, Johansson, Stefan, Jönsson, Erik G, Jørgensen, Niklas R, Kikuchi, Masataka, Knowles, Emma EM, Kumar, Kuldeep, Le Hellard, Stephanie, Leu, Costin, Linden, David EJ, Liu, Jingyu, Lundervold, Arvid, Lundervold, Astri Johansen, Maillard, Anne M, Martin, Nicholas G, Martin-Brevet, Sandra, Mather, Karen A, Mathias, Samuel R, McMahon, Katie L, McRae, Allan F, Medland, Sarah E, Meyer-Lindenberg, Andreas, Moberget, Torgeir, Modenato, Claudia, Sánchez, Jennifer Monereo, Morris, Derek W, Mühleisen, Thomas W, Murray, Robin M, Nielsen, Jacob, Nordvik, Jan E, Nyberg, Lars, Loohuis, Loes M Olde, and Ophoff, Roel A
Subjects: ENIGMA-CNV working group, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
Published: 2021

9. The genetic architecture of the human cerebral cortex

Author: Grasby, Katrina L, Jahanshad, Neda, Painter, Jodie N, Colodro-Conde, Lucía, Bralten, Janita, Hibar, Derrek P, Lind, Penelope A, Pizzagalli, Fabrizio, Ching, Christopher RK, McMahon, Mary Agnes B, Shatokhina, Natalia, Zsembik, Leo CP, Thomopoulos, Sophia I, Zhu, Alyssa H, Strike, Lachlan T, Agartz, Ingrid, Alhusaini, Saud, Almeida, Marcio AA, Alnæs, Dag, Amlien, Inge K, Andersson, Micael, Ard, Tyler, Armstrong, Nicola J, Ashley-Koch, Allison, Atkins, Joshua R, Bernard, Manon, Brouwer, Rachel M, Buimer, Elizabeth EL, Bülow, Robin, Bürger, Christian, Cannon, Dara M, Chakravarty, Mallar, Chen, Qiang, Cheung, Joshua W, Couvy-Duchesne, Baptiste, Dale, Anders M, Dalvie, Shareefa, de Araujo, Tânia K, de Zubicaray, Greig I, de Zwarte, Sonja MC, Braber, Anouk den, Doan, Nhat Trung, Dohm, Katharina, Ehrlich, Stefan, Engelbrecht, Hannah-Ruth, Erk, Susanne, Fan, Chun Chieh, Fedko, Iryna O, Foley, Sonya F, Ford, Judith M, Fukunaga, Masaki, Garrett, Melanie E, Ge, Tian, Giddaluru, Sudheer, Goldman, Aaron L, Green, Melissa J, Groenewold, Nynke A, Grotegerd, Dominik, Gurholt, Tiril P, Gutman, Boris A, Hansell, Narelle K, Harris, Mathew A, Harrison, Marc B, Haswell, Courtney C, Hauser, Michael, Herms, Stefan, Heslenfeld, Dirk J, Ho, New Fei, Hoehn, David, Hoffmann, Per, Holleran, Laurena, Hoogman, Martine, Hottenga, Jouke-Jan, Ikeda, Masashi, Janowitz, Deborah, Jansen, Iris E, Jia, Tianye, Jockwitz, Christiane, Kanai, Ryota, Karama, Sherif, Kasperaviciute, Dalia, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Klein, Marieke, Knapp, Michael, Knodt, Annchen R, Krämer, Bernd, Lam, Max, Lancaster, Thomas M, Lee, Phil H, Lett, Tristram A, Lewis, Lindsay B, Lopes-Cendes, Iscia, Luciano, Michelle, Macciardi, Fabio, Marquand, Andre F, Mathias, Samuel R, Melzer, Tracy R, and Milaneschi, Yuri
Subjects: Biological Sciences, Genetics, Neurosciences, Mental Health, Brain Disorders, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Neurological, Attention Deficit Disorder with Hyperactivity, Brain Mapping, Cerebral Cortex, Cognition, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Organ Size, Parkinson Disease, Alzheimer’s Disease Neuroimaging Initiative, CHARGE Consortium, EPIGEN Consortium, IMAGEN Consortium, SYS Consortium, Parkinson’s Progression Markers Initiative, Enhancing NeuroImaging Genetics through Meta-Analysis Consortium (ENIGMA)—Genetics working group, General Science & Technology
Abstract: The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
Published: 2020

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

Author: Thompson, Paul M, Jahanshad, Neda, Ching, Christopher RK, Salminen, Lauren E, Thomopoulos, Sophia I, Bright, Joanna, Baune, Bernhard T, Bertolín, Sara, Bralten, Janita, Bruin, Willem B, Bülow, Robin, Chen, Jian, Chye, Yann, Dannlowski, Udo, de Kovel, Carolien GF, Donohoe, Gary, Eyler, Lisa T, Faraone, Stephen V, Favre, Pauline, Filippi, Courtney A, Frodl, Thomas, Garijo, Daniel, Gil, Yolanda, Grabe, Hans J, Grasby, Katrina L, Hajek, Tomas, Han, Laura KM, Hatton, Sean N, Hilbert, Kevin, Ho, Tiffany C, Holleran, Laurena, Homuth, Georg, Hosten, Norbert, Houenou, Josselin, Ivanov, Iliyan, Jia, Tianye, Kelly, Sinead, Klein, Marieke, Kwon, Jun Soo, Laansma, Max A, Leerssen, Jeanne, Lueken, Ulrike, Nunes, Abraham, Neill, Joseph O', Opel, Nils, Piras, Fabrizio, Piras, Federica, Postema, Merel C, Pozzi, Elena, Shatokhina, Natalia, Soriano-Mas, Carles, Spalletta, Gianfranco, Sun, Daqiang, Teumer, Alexander, Tilot, Amanda K, Tozzi, Leonardo, van der Merwe, Celia, Van Someren, Eus JW, van Wingen, Guido A, Völzke, Henry, Walton, Esther, Wang, Lei, Winkler, Anderson M, Wittfeld, Katharina, Wright, Margaret J, Yun, Je-Yeon, Zhang, Guohao, Zhang-James, Yanli, Adhikari, Bhim M, Agartz, Ingrid, Aghajani, Moji, Aleman, André, Althoff, Robert R, Altmann, Andre, Andreassen, Ole A, Baron, David A, Bartnik-Olson, Brenda L, Marie Bas-Hoogendam, Janna, Baskin-Sommers, Arielle R, Bearden, Carrie E, Berner, Laura A, Boedhoe, Premika SW, Brouwer, Rachel M, Buitelaar, Jan K, Caeyenberghs, Karen, Cecil, Charlotte AM, Cohen, Ronald A, Cole, James H, Conrod, Patricia J, De Brito, Stephane A, de Zwarte, Sonja MC, Dennis, Emily L, Desrivieres, Sylvane, Dima, Danai, Ehrlich, Stefan, Esopenko, Carrie, Fairchild, Graeme, Fisher, Simon E, Fouche, Jean-Paul, and Francks, Clyde
Subjects: ENIGMA Consortium, Brain, Humans, Magnetic Resonance Imaging, Reproducibility of Results, Depressive Disorder, Major, Neuroimaging, Neurosciences, Clinical Research, Mental Health, Brain Disorders, Behavioral and Social Science, Genetics, Basic Behavioral and Social Science, Prevention, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Mental health, Neurological, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
Published: 2020

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

Author: Sønderby, Ida E, Gústafsson, Ómar, Doan, Nhat Trung, Hibar, Derrek P, Martin-Brevet, Sandra, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Michael, Armstrong, Nicola J, Bernard, Manon, Blackburn, Nicholas, Blangero, John, Boomsma, Dorret I, Bralten, Janita, Brattbak, Hans-Richard, Brodaty, Henry, Brouwer, Rachel M, Bülow, Robin, Calhoun, Vince, Caspers, Svenja, Cavalleri, Gianpiero, Chen, Chi-Hua, Cichon, Sven, Ciufolini, Simone, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Dale, Anders M, Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco JC, de Zubicaray, Greig I, de Zwarte, Sonja MC, Delanty, Norman, den Braber, Anouk, Desrivières, Sylvane, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Espeseth, Thomas, Fisher, Simon E, Franke, Barbara, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Glahn, David C, Grabe, Hans, Groenewold, Nynke A, Haavik, Jan, Håberg, Asta, Hashimoto, Ryota, Hehir-Kwa, Jayne Y, Heinz, Andreas, Hillegers, Manon HJ, Hoffmann, Per, Holleran, Laurena, Hottenga, Jouke-Jan, Hulshoff, Hilleke E, Ikeda, Masashi, Jahanshad, Neda, Jernigan, Terry, Jockwitz, Christiane, Johansson, Stefan, Jonsdottir, Gudrun A, Jönsson, Erik G, Kahn, Rene, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Knowles, Emma EM, Kolskår, Knut K, Kwok, John B, Hellard, Stephanie Le, Leu, Costin, Liu, Jingyu, Lundervold, Astri J, Lundervold, Arvid, Martin, Nicholas G, Mather, Karen, Mathias, Samuel R, McCormack, Mark, McMahon, Katie L, McRae, Allan, Milaneschi, Yuri, Moreau, Clara, Morris, Derek, Mothersill, David, Mühleisen, Thomas W, Murray, Robin, Nordvik, Jan E, Nyberg, Lars, Olde Loohuis, Loes M, Ophoff, Roel, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda, Peralta, Juan M, Pike, Bruce, and Prieto, Carlos
Subjects: Intellectual and Developmental Disabilities (IDD), Neurosciences, Brain Disorders, Autism, Biomedical Imaging, Mental Health, Mental health, Adult, Autism Spectrum Disorder, Autistic Disorder, Basal Ganglia, Brain, Chromosome Deletion, Chromosome Disorders, Chromosome Duplication, Chromosomes, Human, Pair 16, DNA Copy Number Variations, Databases, Factual, Female, Globus Pallidus, Humans, Image Processing, Computer-Assisted, Intellectual Disability, Magnetic Resonance Imaging, Male, Middle Aged, Neurodevelopmental Disorders, Organ Size, Putamen, Schizophrenia, 16p11.2 European Consortium, for the ENIGMA-CNV working group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P
Published: 2020

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

Author: Sønderby, Ida E, Gústafsson, Ómar, Doan, Nhat Trung, Hibar, Derrek P, Martin-Brevet, Sandra, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Michael, Armstrong, Nicola J, Bernard, Manon, Blackburn, Nicholas, Blangero, John, Boomsma, Dorret I, Bralten, Janita, Brattbak, Hans-Richard, Brodaty, Henry, Brouwer, Rachel M, Bülow, Robin, Calhoun, Vince, Caspers, Svenja, Cavalleri, Gianpiero, Chen, Chi-Hua, Cichon, Sven, Ciufolini, Simone, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E, Dale, Anders M, Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco JC, de Zubicaray, Greig I, de Zwarte, Sonja MC, Delanty, Norman, den Braber, Anouk, Desrivières, Sylvane, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Espeseth, Thomas, Fisher, Simon E, Franke, Barbara, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Glahn, David C, Grabe, Hans, Groenewold, Nynke A, Haavik, Jan, Håberg, Asta, Hashimoto, Ryota, Hehir-Kwa, Jayne Y, Heinz, Andreas, Hillegers, Manon HJ, Hoffmann, Per, Holleran, Laurena, Hottenga, Jouke-Jan, Hulshoff, Hilleke E, Ikeda, Masashi, Jahanshad, Neda, Jernigan, Terry, Jockwitz, Christiane, Johansson, Stefan, Jonsdottir, Gudrun A, Jönsson, Erik G, Kahn, Rene, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Knowles, Emma EM, Kolskår, Knut K, Kwok, John B, Hellard, Stephanie Le, Leu, Costin, Liu, Jingyu, Lundervold, Astri J, Lundervold, Arvid, Martin, Nicholas G, Mather, Karen, Mathias, Samuel R, McCormack, Mark, McMahon, Katie L, McRae, Allan, Milaneschi, Yuri, Moreau, Clara, Morris, Derek, Mothersill, David, Mühleisen, Thomas W, Murray, Robin, Nordvik, Jan E, Nyberg, Lars, Olde Loohuis, Loes M, Ophoff, Roel, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda, Peralta, Juan M, Pike, Bruce, and Prieto, Carlos
Subjects: 16p11.2 European Consortium, for the ENIGMA-CNV working group, Neurosciences, Psychiatry, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences
Abstract: Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.
Published: 2020

13. The Association Between Familial Risk and Brain Abnormalities Is Disease Specific: An ENIGMA-Relatives Study of Schizophrenia and Bipolar Disorder

Author: de Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Aleman, André, Alpert, Kathryn I, Bearden, Carrie E, Bertolino, Alessandro, Bois, Catherine, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Frankland, Andrew, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, de Haan, Lieuwe, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Hillegers, Manon HJ, Pol, Hilleke E Hulshoff, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krabbendam, Lydia, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Marsman, Jan-Bernard C, Mattay, Venkata S, McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Najt, Pablo, Neilson, Emma, Newport, Jason, van Os, Jim, Overs, Bronwyn, Ozerdem, Aysegul, Picchioni, Marco M, Richter, Anja, Roberts, Gloria, Aydogan, Aybala Saricicek, Schofield, Peter R, Simsek, Fatma, Soares, Jair C, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Walter, Henrik, Wang, Lei, Weinberger, Daniel R, Whalley, Heather C, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, van Erp, Theo GM, Turner, Jessica A, Jahanshad, Neda, Thompson, Paul M, Kahn, René S, and van Haren, Neeltje EM
Subjects: Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Mental Health, Brain Disorders, Serious Mental Illness, Schizophrenia, Genetics, Neurosciences, Clinical Research, Bipolar Disorder, 2.3 Psychological, social and economic factors, Aetiology, 2.1 Biological and endogenous factors, Mental health, Adult, Brain, Cohort Studies, Female, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Young Adult, Bipolar disorder, Familial risk, Imaging, Meta-analysis, Neurodevelopment, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract: BackgroundSchizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects.MethodsWe performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects.ResultsFDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d
Published: 2019

14. Genetic overlap between schizophrenia and height implicates pituitary and immune response

Author: Romero, Cato, primary, de Leeuw, Christiaan, additional, Schipper, Marijn, additional, Maciel, Bernardo de A.P.C., additional, van den Heuvel, Martijn P., additional, Brouwer, Rachel M., additional, Posthuma, Danielle, additional, and van der Sluis, Sophie, additional
Published: 2024
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15. Normative modelling of brain morphometry across the lifespan with CentileBrain: algorithm benchmarking and model optimisation

Author: Ge, Ruiyang, primary, Yu, Yuetong, additional, Qi, Yi Xuan, additional, Fan, Yu-nan, additional, Chen, Shiyu, additional, Gao, Chuntong, additional, Haas, Shalaila S, additional, New, Faye, additional, Boomsma, Dorret I, additional, Brodaty, Henry, additional, Brouwer, Rachel M, additional, Buckner, Randy, additional, Caseras, Xavier, additional, Crivello, Fabrice, additional, Crone, Eveline A, additional, Erk, Susanne, additional, Fisher, Simon E, additional, Franke, Barbara, additional, Glahn, David C, additional, Dannlowski, Udo, additional, Grotegerd, Dominik, additional, Gruber, Oliver, additional, Hulshoff Pol, Hilleke E, additional, Schumann, Gunter, additional, Tamnes, Christian K, additional, Walter, Henrik, additional, Wierenga, Lara M, additional, Jahanshad, Neda, additional, Thompson, Paul M, additional, Frangou, Sophia, additional, Agartz, Ingrid, additional, Asherson, Philip, additional, Ayesa-Arriola, Rosa, additional, Banaj, Nerisa, additional, Banaschewski, Tobias, additional, Baumeister, Sarah, additional, Bertolino, Alessandro, additional, Borgwardt, Stefan, additional, Bourque, Josiane, additional, Brandeis, Daniel, additional, Breier, Alan, additional, Buitelaar, Jan K, additional, Cannon, Dara M, additional, Cervenka, Simon, additional, Conrod, Patricia J, additional, Crespo-Facorro, Benedicto, additional, Davey, Christopher G, additional, de Haan, Lieuwe, additional, de Zubicaray, Greig I, additional, Di Giorgio, Annabella, additional, Frodl, Thomas, additional, Gruner, Patricia, additional, Gur, Raquel E, additional, Gur, Ruben C, additional, Harrison, Ben J, additional, Hatton, Sean N, additional, Hickie, Ian, additional, Howells, Fleur M, additional, Huyser, Chaim, additional, Jernigan, Terry L, additional, Jiang, Jiyang, additional, Joska, John A, additional, Kahn, René S, additional, Kalnin, Andrew J, additional, Kochan, Nicole A, additional, Koops, Sanne, additional, Kuntsi, Jonna, additional, Lagopoulos, Jim, additional, Lazaro, Luisa, additional, Lebedeva, Irina S, additional, Lochner, Christine, additional, Martin, Nicholas G, additional, Mazoyer, Bernard, additional, McDonald, Brenna C, additional, McDonald, Colm, additional, McMahon, Katie L, additional, Medland, Sarah, additional, Modabbernia, Amirhossein, additional, Mwangi, Benson, additional, Nakao, Tomohiro, additional, Nyberg, Lars, additional, Piras, Fabrizio, additional, Portella, Maria J, additional, Qiu, Jiang, additional, Roffman, Joshua L, additional, Sachdev, Perminder S, additional, Sanford, Nicole, additional, Satterthwaite, Theodore D, additional, Saykin, Andrew J, additional, Sellgren, Carl M, additional, Sim, Kang, additional, Smoller, Jordan W, additional, Soares, Jair C, additional, Sommer, Iris E, additional, Spalletta, Gianfranco, additional, Stein, Dan J, additional, Thomopoulos, Sophia I, additional, Tomyshev, Alexander S, additional, Tordesillas-Gutiérrez, Diana, additional, Trollor, Julian N, additional, van 't Ent, Dennis, additional, van den Heuvel, Odile A, additional, van Erp, Theo GM, additional, van Haren, Neeltje EM, additional, Vecchio, Daniela, additional, Veltman, Dick J, additional, Wang, Yang, additional, Weber, Bernd, additional, Wei, Dongtao, additional, Wen, Wei, additional, Westlye, Lars T, additional, Williams, Steven CR, additional, Wright, Margaret J, additional, Wu, Mon-Ju, additional, and Yu, Kevin, additional
Published: 2024
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16. Structural Methods in Gray Matter

Author: Mandl, René C. W., Schnack, Hugo G., Brouwer, Rachel M., Hulshoff Pol, Hilleke E., Kubicki, Marek, editor, and Shenton, Martha E., editor
Published: 2020
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17. Diffusion MRI derived free-water imaging measures in patients with schizophrenia and their non-psychotic siblings

Author: Chang, Xiao, Mandl, René C.W., Pasternak, Ofer, Brouwer, Rachel M., Cahn, Wiepke, and Collin, Guusje
Published: 2021
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18. Reliability modelling of resting-state functional connectivity

Author: Teeuw, Jalmar, Hulshoff Pol, Hilleke E., Boomsma, Dorret I., and Brouwer, Rachel M.
Published: 2021
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19. Accelerated aging in the brain, epigenetic aging in blood, and polygenic risk for schizophrenia

Author: Teeuw, Jalmar, Ori, Anil P.S., Brouwer, Rachel M., de Zwarte, Sonja M.C., Schnack, Hugo G., Hulshoff Pol, Hilleke E., and Ophoff, Roel A.
Published: 2021
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20. ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide

Author: Thompson, Paul M, Andreassen, Ole A, Arias-Vasquez, Alejandro, Bearden, Carrie E, Boedhoe, Premika S, Brouwer, Rachel M, Buckner, Randy L, Buitelaar, Jan K, Bulayeva, Kazima B, Cannon, Dara M, Cohen, Ronald A, Conrod, Patricia J, Dale, Anders M, Deary, Ian J, Dennis, Emily L, de Reus, Marcel A, Desrivieres, Sylvane, Dima, Danai, Donohoe, Gary, Fisher, Simon E, Fouche, Jean-Paul, Francks, Clyde, Frangou, Sophia, Franke, Barbara, Ganjgahi, Habib, Garavan, Hugh, Glahn, David C, Grabe, Hans J, Guadalupe, Tulio, Gutman, Boris A, Hashimoto, Ryota, Hibar, Derrek P, Holland, Dominic, Hoogman, Martine, Pol, Hilleke E Hulshoff, Hosten, Norbert, Jahanshad, Neda, Kelly, Sinead, Kochunov, Peter, Kremen, William S, Lee, Phil H, Mackey, Scott, Martin, Nicholas G, Mazoyer, Bernard, McDonald, Colm, Medland, Sarah E, Morey, Rajendra A, Nichols, Thomas E, Paus, Tomas, Pausova, Zdenka, Schmaal, Lianne, Schumann, Gunter, Shen, Li, Sisodiya, Sanjay M, Smit, Dirk JA, Smoller, Jordan W, Stein, Dan J, Stein, Jason L, Toro, Roberto, Turner, Jessica A, van den Heuvel, Martijn P, van den Heuvel, Odile L, van Erp, Theo GM, van Rooij, Daan, Veltman, Dick J, Walter, Henrik, Wang, Yalin, Wardlaw, Joanna M, Whelan, Christopher D, Wright, Margaret J, Ye, Jieping, and Consortium, for the ENIGMA
Subjects: Biomedical and Clinical Sciences, Health Sciences, Genetics, Mental Health, Prevention, Brain Disorders, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Mental health, Neurological, Good Health and Well Being, Brain Diseases, Genome-Wide Association Study, Humans, Mental Disorders, Multicenter Studies as Topic, ENIGMA Consortium, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Abstract: 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 others1, 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

21. Normative modelling of brain morphometry across the lifespan with CentileBrain:algorithm benchmarking and model optimisation

Author: Ge, Ruiyang, Yu, Yuetong, Qi, Yi Xuan, Fan, Yu nan, Chen, Shiyu, Gao, Chuntong, Haas, Shalaila S., New, Faye, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buckner, Randy, Caseras, Xavier, Crivello, Fabrice, Crone, Eveline A., Erk, Susanne, Fisher, Simon E., Franke, Barbara, Glahn, David C., Dannlowski, Udo, Grotegerd, Dominik, Gruber, Oliver, Hulshoff Pol, Hilleke E., Schumann, Gunter, Tamnes, Christian K., Walter, Henrik, Wierenga, Lara M., Jahanshad, Neda, Thompson, Paul M., Frangou, Sophia, Agartz, Ingrid, Asherson, Philip, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Baumeister, Sarah, Bertolino, Alessandro, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Buitelaar, Jan K., Cannon, Dara M., Cervenka, Simon, Conrod, Patricia J., Crespo-Facorro, Benedicto, Davey, Christopher G., de Haan, Lieuwe, de Zubicaray, Greig I., van Haren, Neeltje EM, Ge, Ruiyang, Yu, Yuetong, Qi, Yi Xuan, Fan, Yu nan, Chen, Shiyu, Gao, Chuntong, Haas, Shalaila S., New, Faye, Boomsma, Dorret I., Brodaty, Henry, Brouwer, Rachel M., Buckner, Randy, Caseras, Xavier, Crivello, Fabrice, Crone, Eveline A., Erk, Susanne, Fisher, Simon E., Franke, Barbara, Glahn, David C., Dannlowski, Udo, Grotegerd, Dominik, Gruber, Oliver, Hulshoff Pol, Hilleke E., Schumann, Gunter, Tamnes, Christian K., Walter, Henrik, Wierenga, Lara M., Jahanshad, Neda, Thompson, Paul M., Frangou, Sophia, Agartz, Ingrid, Asherson, Philip, Ayesa-Arriola, Rosa, Banaj, Nerisa, Banaschewski, Tobias, Baumeister, Sarah, Bertolino, Alessandro, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Buitelaar, Jan K., Cannon, Dara M., Cervenka, Simon, Conrod, Patricia J., Crespo-Facorro, Benedicto, Davey, Christopher G., de Haan, Lieuwe, de Zubicaray, Greig I., and van Haren, Neeltje EM
Abstract: The value of normative models in research and clinical practice relies on their robustness and a systematic comparison of different modelling algorithms and parameters; however, this has not been done to date. We aimed to identify the optimal approach for normative modelling of brain morphometric data through systematic empirical benchmarking, by quantifying the accuracy of different algorithms and identifying parameters that optimised model performance. We developed this framework with regional morphometric data from 37 407 healthy individuals (53% female and 47% male; aged 3–90 years) from 87 datasets from Europe, Australia, the USA, South Africa, and east Asia following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The multivariate fractional polynomial regression (MFPR) emerged as the preferred algorithm, optimised with non-linear polynomials for age and linear effects of global measures as covariates. The MFPR models showed excellent accuracy across the lifespan and within distinct age-bins and longitudinal stability over a 2-year period. The performance of all MFPR models plateaued at sample sizes exceeding 3000 study participants. This model can inform about the biological and behavioural implications of deviations from typical age-related neuroanatomical changes and support future study designs. The model and scripts described here are freely available through CentileBrain.
Published: 2024

22. Changes in the intracranial volume from early adulthood to the sixth decade of life: A longitudinal study

Author: Caspi, Yaron, Brouwer, Rachel M., Schnack, Hugo G., van de Nieuwenhuijzen, Marieke E., Cahn, Wiepke, Kahn, René S., Niessen, Wiro J., van der Lugt, Aad, and Pol, Hilleke Hulshoff
Published: 2020
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23. Contributing factors to advanced brain aging in depression and anxiety disorders

Author: Han, Laura K. M., Schnack, Hugo G., Brouwer, Rachel M., Veltman, Dick J., van der Wee, Nic J. A., van Tol, Marie-José, Aghajani, Moji, and Penninx, Brenda W. J. H.
Published: 2021
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24. Genetic and environmental influences on functional connectivity within and between canonical cortical resting-state networks throughout adolescent development in boys and girls

Author: Teeuw, Jalmar, Brouwer, Rachel M., Guimarães, João P.O.F.T., Brandner, Philip, Koenis, Marinka M.G., Swagerman, Suzanne C., Verwoert, Maxime, Boomsma, Dorret I., and Hulshoff Pol, Hilleke E.
Published: 2019
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25. Active Selection of Classification Features

Author: Kok, Thomas T., primary, Brouwer, Rachel M., additional, Mandl, Rene M., additional, Schnack, Hugo G., additional, and Krempl, Georg, additional
Published: 2021
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26. The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data

Author: Thompson, Paul M, Stein, Jason L, Medland, Sarah E, Hibar, Derrek P, Vasquez, Alejandro Arias, Renteria, Miguel E, Toro, Roberto, Jahanshad, Neda, Schumann, Gunter, Franke, Barbara, Wright, Margaret J, Martin, Nicholas G, Agartz, Ingrid, Alda, Martin, Alhusaini, Saud, Almasy, Laura, Almeida, Jorge, Alpert, Kathryn, Andreasen, Nancy C, Andreassen, Ole A, Apostolova, Liana G, Appel, Katja, Armstrong, Nicola J, Aribisala, Benjamin, Bastin, Mark E, Bauer, Michael, Bearden, Carrie E, Bergmann, Ørjan, Binder, Elisabeth B, Blangero, John, Bockholt, Henry J, Bøen, Erlend, Bois, Catherine, Boomsma, Dorret I, Booth, Tom, Bowman, Ian J, Bralten, Janita, Brouwer, Rachel M, Brunner, Han G, Brohawn, David G, Buckner, Randy L, Buitelaar, Jan, Bulayeva, Kazima, Bustillo, Juan R, Calhoun, Vince D, Cannon, Dara M, Cantor, Rita M, Carless, Melanie A, Caseras, Xavier, Cavalleri, Gianpiero L, Chakravarty, M Mallar, Chang, Kiki D, Ching, Christopher RK, Christoforou, Andrea, Cichon, Sven, Clark, Vincent P, Conrod, Patricia, Coppola, Giovanni, Crespo-Facorro, Benedicto, Curran, Joanne E, Czisch, Michael, Deary, Ian J, de Geus, Eco JC, den Braber, Anouk, Delvecchio, Giuseppe, Depondt, Chantal, de Haan, Lieuwe, de Zubicaray, Greig I, Dima, Danai, Dimitrova, Rali, Djurovic, Srdjan, Dong, Hongwei, Donohoe, Gary, Duggirala, Ravindranath, Dyer, Thomas D, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Emsell, Louise, Erk, Susanne, Espeseth, Thomas, Fagerness, Jesen, Fears, Scott, Fedko, Iryna, Fernández, Guillén, Fisher, Simon E, Foroud, Tatiana, Fox, Peter T, Francks, Clyde, Frangou, Sophia, Frey, Eva Maria, Frodl, Thomas, Frouin, Vincent, Garavan, Hugh, Giddaluru, Sudheer, Glahn, David C, Godlewska, Beata, Goldstein, Rita Z, Gollub, Randy L, and Grabe, Hans J
Subjects: Biological Psychology, Health Sciences, Psychology, Brain Disorders, Schizophrenia, Human Genome, Biomedical Imaging, Genetics, Mental Illness, Mental Health, Neurosciences, 2.1 Biological and endogenous factors, Neurological, Mental health, Good Health and Well Being, Brain Mapping, Cooperative Behavior, Genome-Wide Association Study, Humans, Meta-Analysis as Topic, Neuroimaging, MRI, GWAS, Consortium, Meta-analysis, Multi-site, Alzheimer’s Disease Neuroimaging Initiative, EPIGEN Consortium, IMAGEN Consortium, Saguenay Youth Study (SYS) Group, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology, Biomedical and clinical sciences, Health sciences
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.
Published: 2014

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

Author: Satizabal, Claudia L., Adams, Hieab H. H., Hibar, Derrek P., White, Charles C., Knol, Maria J., Stein, Jason L., Scholz, Markus, Sargurupremraj, Muralidharan, Jahanshad, Neda, Roshchupkin, Gennady V., Smith, Albert V., Bis, Joshua C., Jian, Xueqiu, Luciano, Michelle, Hofer, Edith, Teumer, Alexander, van der Lee, Sven J., Yang, Jingyun, Yanek, Lisa R., Lee, Tom V., Li, Shuo, Hu, Yanhui, Koh, Jia Yu, Eicher, John D., Desrivières, Sylvane, Arias-Vasquez, Alejandro, Chauhan, Ganesh, Athanasiu, Lavinia, Rentería, Miguel E., Kim, Sungeun, Hoehn, David, Armstrong, Nicola J., Chen, Qiang, Holmes, Avram J., den Braber, Anouk, Kloszewska, Iwona, Andersson, Micael, Espeseth, Thomas, Grimm, Oliver, Abramovic, Lucija, Alhusaini, Saud, Milaneschi, Yuri, Papmeyer, Martina, Axelsson, Tomas, Ehrlich, Stefan, Roiz-Santiañez, Roberto, Kraemer, Bernd, Håberg, Asta K., Jones, Hannah J., Pike, G. Bruce, Stein, Dan J., Stevens, Allison, Bralten, Janita, Vernooij, Meike W., Harris, Tamara B., Filippi, Irina, Witte, A. Veronica, Guadalupe, Tulio, Wittfeld, Katharina, Mosley, Thomas H., Becker, James T., Doan, Nhat Trung, Hagenaars, Saskia P., Saba, Yasaman, Cuellar-Partida, Gabriel, Amin, Najaf, Hilal, Saima, Nho, Kwangsik, Mirza-Schreiber, Nazanin, Arfanakis, Konstantinos, Becker, Diane M., Ames, David, Goldman, Aaron L., Lee, Phil H., Boomsma, Dorret I., Lovestone, Simon, Giddaluru, Sudheer, Le Hellard, Stephanie, Mattheisen, Manuel, Bohlken, Marc M., Kasperaviciute, Dalia, Schmaal, Lianne, Lawrie, Stephen M., Agartz, Ingrid, Walton, Esther, Tordesillas-Gutierrez, Diana, Davies, Gareth E., Shin, Jean, Ipser, Jonathan C., Vinke, Louis N., Hoogman, Martine, Jia, Tianye, Burkhardt, Ralph, Klein, Marieke, Crivello, Fabrice, Janowitz, Deborah, Carmichael, Owen, Haukvik, Unn K., Aribisala, Benjamin S., Schmidt, Helena, Strike, Lachlan T., Cheng, Ching-Yu, Risacher, Shannon L., Pütz, Benno, Fleischman, Debra A., Assareh, Amelia A., Mattay, Venkata S., Buckner, Randy L., Mecocci, Patrizia, Dale, Anders M., Cichon, Sven, Boks, Marco P., Matarin, Mar, Penninx, Brenda W. J. H., Calhoun, Vince D., Chakravarty, M. Mallar, Marquand, Andre F., Macare, Christine, Kharabian Masouleh, Shahrzad, Oosterlaan, Jaap, Amouyel, Philippe, Hegenscheid, Katrin, Rotter, Jerome I., Schork, Andrew J., Liewald, David C. M., de Zubicaray, Greig I., Wong, Tien Yin, Shen, Li, Sämann, Philipp G., Brodaty, Henry, Roffman, Joshua L., de Geus, Eco J. C., Tsolaki, Magda, Erk, Susanne, van Eijk, Kristel R., Cavalleri, Gianpiero L., van der Wee, Nic J. A., McIntosh, Andrew M., Gollub, Randy L., Bulayeva, Kazima B., Bernard, Manon, Richards, Jennifer S., Himali, Jayandra J., Loeffler, Markus, Rommelse, Nanda, Hoffmann, Wolfgang, Westlye, Lars T., Valdés Hernández, Maria C., Hansell, Narelle K., van Erp, Theo G. M., Wolf, Christiane, Kwok, John B. J., Vellas, Bruno, Heinz, Andreas, Olde Loohuis, Loes M., Delanty, Norman, Ho, Beng-Choon, Ching, Christopher R. K., Shumskaya, Elena, Singh, Baljeet, Hofman, Albert, van der Meer, Dennis, Homuth, Georg, Psaty, Bruce M., Bastin, Mark E., Montgomery, Grant W., Foroud, Tatiana M., Reppermund, Simone, Hottenga, Jouke-Jan, Simmons, Andrew, Meyer-Lindenberg, Andreas, Cahn, Wiepke, Whelan, Christopher D., van Donkelaar, Marjolein M. J., Yang, Qiong, Hosten, Norbert, Green, Robert C, Thalamuthu, Anbupalam, Mohnke, Sebastian, Hulshoff Pol, Hilleke E., Lin, Honghuang, Jack, Jr, Clifford R., Schofield, Peter R., Mühleisen, Thomas W., Maillard, Pauline, Potkin, Steven G., Wen, Wei, Fletcher, Evan, Toga, Arthur W., Gruber, Oliver, Huentelman, Matthew, Davey Smith, George, Launer, Lenore J., Nyberg, Lars, Jönsson, Erik G., Crespo-Facorro, Benedicto, Koen, Nastassja, Greve, Douglas N., Uitterlinden, André G., Weinberger, Daniel R., Steen, Vidar M., Fedko, Iryna O., Groenewold, Nynke A., Niessen, Wiro J., Toro, Roberto, Tzourio, Christophe, Longstreth, Jr, William T., Ikram, M. Kamran, Smoller, Jordan W., van Tol, Marie-Jose, Sussmann, Jessika E., Paus, Tomas, Lemaître, Hervé, Schroeter, Matthias L., Mazoyer, Bernard, Andreassen, Ole A., Holsboer, Florian, Depondt, Chantal, Veltman, Dick J., Turner, Jessica A., Pausova, Zdenka, Schumann, Gunter, van Rooij, Daan, Djurovic, Srdjan, Deary, Ian J., McMahon, Katie L., Müller-Myhsok, Bertram, Brouwer, Rachel M., Soininen, Hilkka, Pandolfo, Massimo, Wassink, Thomas H., Cheung, Joshua W., Wolfers, Thomas, Martinot, Jean-Luc, Zwiers, Marcel P., Nauck, Matthias, Melle, Ingrid, Martin, Nicholas G., Kanai, Ryota, Westman, Eric, Kahn, René S., Sisodiya, Sanjay M., White, Tonya, Saremi, Arvin, van Bokhoven, Hans, Brunner, Han G., Völzke, Henry, Wright, Margaret J., van ‘t Ent, Dennis, Nöthen, Markus M., Ophoff, Roel A., Buitelaar, Jan K., Fernández, Guillén, Sachdev, Perminder S., Rietschel, Marcella, van Haren, Neeltje E. M., Fisher, Simon E., Beiser, Alexa S., Francks, Clyde, Saykin, Andrew J., Mather, Karen A., Romanczuk-Seiferth, Nina, Hartman, Catharina A., DeStefano, Anita L., Heslenfeld, Dirk J., Weiner, Michael W., Walter, Henrik, Hoekstra, Pieter J., Nyquist, Paul A., Franke, Barbara, Bennett, David A., Grabe, Hans J., Johnson, Andrew D., Chen, Christopher, van Duijn, Cornelia M., Lopez, Oscar L., Fornage, Myriam, Wardlaw, Joanna M., Schmidt, Reinhold, DeCarli, Charles, De Jager, Philip L., Villringer, Arno, Debette, Stéphanie, Gudnason, Vilmundur, Medland, Sarah E., Shulman, Joshua M., Thompson, Paul M., Seshadri, Sudha, and Ikram, M. Arfan
Published: 2019
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28. Detailed T1-Weighted Profiles from the Human Cortex Measured in Vivo at 3 Tesla MRI

Author: Ferguson, Bart, Petridou, Natalia, Fracasso, Alessio, van den Heuvel, Martijn P., Brouwer, Rachel M., Hulshoff Pol, Hilleke E., Kahn, René S., and Mandl, René C.W.
Published: 2018
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29. Heritability of cortical thickness changes over time in twin pairs discordant for schizophrenia

Author: Hedman, Anna M., van Haren, Neeltje E.M., van Baal, G. Caroline M., Brouwer, Rachel M., Brans, Rachel G.H., Schnack, Hugo G., Kahn, René S., and Hulshoff Pol, Hilleke E.
Published: 2016
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30. Increased risk of psychosis in patients with hearing impairment: Review and meta-analyses

Author: Linszen, Mascha M.J., Brouwer, Rachel M., Heringa, Sophie M., and Sommer, Iris E.
Published: 2016
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31. Contribution of genes and unique environment to cross-sectional and longitudinal measures of subcortical volumes in bipolar disorder

Author: Bootsman, Florian, Brouwer, Rachel M., Kemner, Sanne M., Schnack, Hugo G., van der Schot, Astrid C., Vonk, Ronald, Hillegers, Manon H.J., Boomsma, Dorret I., Hulshoff Pol, Hilleke E., Nolen, Willem A., Kahn, René S., and van Haren, Neeltje E.M.
Published: 2015
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32. Normative Modeling of Brain Morphometry Across the Lifespan using CentileBrain: Algorithm Benchmarking and Model Optimization

Author: Ge, Ruiyang, primary, Yu, Yuetong, additional, Qi, Yi Xuan, additional, Fan, Yunan Vera, additional, Chen, Shiyu, additional, Gao, Chuntong, additional, Haas, Shalaila S, additional, Modabbernia, Amirhossein, additional, New, Faye, additional, Agartz, Ingrid, additional, Asherson, Philip, additional, Ayesa-Arriola, Rosa, additional, Banaj, Nerisa, additional, Banaschewski, Tobias, additional, Baumeister, Sarah, additional, Bertolino, Alessandro, additional, Boomsma, Dorret I, additional, Borgwardt, Stefan, additional, Bourque, Josiane, additional, Brandeis, Daniel, additional, Breier, Alan, additional, Brodaty, Henry, additional, Brouwer, Rachel M, additional, Buckner, Randy, additional, Buitelaar, Jan K, additional, Cannon, Dara M, additional, Caseras, Xavier, additional, Cervenka, Simon, additional, Conrod, Patricia J, additional, Crespo-Facorro, Benedicto, additional, Crivello, Fabrice, additional, Crone, Eveline A, additional, de Haan, Liewe, additional, de Zubicaray, Greig I, additional, Di Giorgio, Annabella, additional, Erk, Susanne, additional, Fisher, Simon E, additional, Franke, Barbara, additional, Frodl, Thomas, additional, Glahn, David C, additional, Grotegerd, Dominik, additional, Gruber, Oliver, additional, Gruner, Patricia, additional, Gur, Raquel E, additional, Gur, Ruben C, additional, Harrison, Ben J, additional, Hatton, Sean N, additional, Hickie, Ian, additional, Howells, Fleur M, additional, Hulshoff Pol, Hilleke E, additional, Huyser, Chaim, additional, Jernigan, Terry L, additional, Jiang, Jiyang, additional, Joska, John A, additional, Kahn, Rene S, additional, Kalnin, Andrew J, additional, Kochan, Nicole A, additional, Koops, Sanne, additional, Kuntsi, Jonna, additional, Lagopoulos, Jim, additional, Lazaro, Luisa, additional, Lebedeva, Irina S, additional, Lochner, Christine, additional, Martin, Nicholas G, additional, Mazoyer, Bernard, additional, McDonald, Brenna C, additional, McDonald, Colm, additional, McMahon, Katie L, additional, Nakao, Tomohiro, additional, Nyberg, Lars, additional, Piras, Fabrizio, additional, Portella, Maria J, additional, Qiu, Jiang, additional, Roffman, Joshua L, additional, Sachdev, Perminder S, additional, Sanford, Nicole, additional, Saykin, Andrew J, additional, Satterthwaite, Theodore D, additional, Thomopolous, Sophia I, additional, Sellgren, Carl M, additional, Sim, Kang, additional, Smoller, Jordan W, additional, Soares, Jair, additional, Sommer, Iris E, additional, Spalletta, Gianfranco, additional, Stein, Dan J, additional, Tamnes, Christian K, additional, Tomyshev, Alexander S, additional, van Erp, Theo GM, additional, Tordesillas-Gutierrez, Diana, additional, Trollor, Julian N, additional, van 't Ent, Dennis, additional, van den Heuvel, Odile A, additional, van Haren, Neeltje EM, additional, Vecchio, Daniela, additional, Veltman, Dick J, additional, Wei, Dongtao, additional, Walter, Henrik, additional, Wang, Yang, additional, Weber, Bernd, additional, Wright, Margaret J, additional, Wen, Wei, additional, Westlye, Lars T, additional, Wierenga, Lara M, additional, Thompson, Paul M, additional, Williams, Steven CR, additional, Medland, Sarah, additional, Wu, Mon-Ju, additional, Yu, Kevin, additional, Jahanshad, Neda, additional, and Frangou, Sophia, additional
Published: 2023
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33. Adverse childhood experiences and fronto-subcortical structures in the developing brain

Author: Buimer, Elizabeth E. L., primary, Brouwer, Rachel M., additional, Mandl, René C. W., additional, Pas, Pascal, additional, Schnack, Hugo G., additional, and Hulshoff Pol, Hilleke E., additional
Published: 2022
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34. Association between structural brain network efficiency and intelligence increases during adolescence

Author: Koenis, Marinka M.G., Brouwer, Rachel M., Swagerman, Suzanne C., van Soelen, Inge L.C., Boomsma, Dorret I., and Hulshoff Pol, Hilleke E.
Published: 2018
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35. Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA–DTI working group

Author: Jahanshad, Neda, Kochunov, Peter V., Sprooten, Emma, Mandl, René C., Nichols, Thomas E., Almasy, Laura, Blangero, John, Brouwer, Rachel M., Curran, Joanne E., de Zubicaray, Greig I., Duggirala, Ravi, Fox, Peter T., Hong, L. Elliot, Landman, Bennett A., Martin, Nicholas G., McMahon, Katie L., Medland, Sarah E., Mitchell, Braxton D., Olvera, Rene L., Peterson, Charles P., Starr, John M., Sussmann, Jessika E., Toga, Arthur W., Wardlaw, Joanna M., Wright, Margaret J., Hulshoff Pol, Hilleke E., Bastin, Mark E., McIntosh, Andrew M., Deary, Ian J., Thompson, Paul M., and Glahn, David C.
Published: 2013
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36. Family-wise automatic classification in schizophrenia

Author: Mandl, René C.W., Brouwer, Rachel M., Cahn, Wiepke, Kahn, René S., and Hulshoff Pol, Hilleke E.
Published: 2013
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37. Exercise therapy, cardiorespiratory fitness and their effect on brain volumes: A randomised controlled trial in patients with schizophrenia and healthy controls

Author: Scheewe, Thomas W., van Haren, Neeltje E.M., Sarkisyan, Gayane, Schnack, Hugo G., Brouwer, Rachel M., de Glint, Maria, Hulshoff Pol, Hilleke E., Backx, Frank J.G., Kahn, René S., and Cahn, Wiepke
Published: 2013
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38. A Genetic Analysis of Brain Volumes and IQ in Children

Author: van Leeuwen, Marieke, Peper, Jiska S., van den Berg, Stephanie M., Brouwer, Rachel M., Hulshoff Pol, Hilleke E., Kahn, Rene S., and Boomsma, Dorret I.
Abstract: In a population-based sample of 112 nine-year old twin pairs, we investigated the association among total brain volume, gray matter and white matter volume, intelligence as assessed by the Raven IQ test, verbal comprehension, perceptual organization and perceptual speed as assessed by the Wechsler Intelligence Scale for Children-III. Phenotypic correlations between the brain volumes and intelligence traits ranged between 0.20 and 0.33. Processing speed and brain volume did not correlate. The relation between brain volume and intelligence was entirely explained by a common set of genes influencing both sets of phenotypes. (Contains 3 figures and 8 tables.)
Published: 2009
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39. Brain SCALE: Brain structure and cognition: An adolescent longitudinal twin study into the genetic etiology of individual differences

Author: van Soelen, Inge LC, Brouwer, Rachel M, Peper, Jiska S, van Leeuwen, Marieke, Koenis, Marinka MG, van Beijsterveldt, Toos CEM, Swagerman, Suzanne C, Kahn, Rene S, Hulshoff Pol, Hilleke E, and Boomsma, Dorret I
Published: 2012

40. Multivariate Genetic Structure of Externalizing Behavior and Structural Brain Development in a Longitudinal Adolescent Twin Sample

Author: Teeuw, Jalmar, Klein, Marieke, Roth Mota, Nina, Brouwer, Rachel M., Van‘t Ent, Dennis, Al-Hassaan, Zyneb, Franke, Barbara, Boomsma, Dorret I., Hulshoff Pol, Hilleke E., Teeuw, Jalmar, Klein, Marieke, Roth Mota, Nina, Brouwer, Rachel M., Van‘t Ent, Dennis, Al-Hassaan, Zyneb, Franke, Barbara, Boomsma, Dorret I., and Hulshoff Pol, Hilleke E.
Abstract: Externalizing behavior in its more extreme form is often considered a problem to the individual, their families, teachers, and society as a whole. Several brain structures have been linked to externalizing behavior and such associations may arise if the (co)development of externalizing behavior and brain structures share the same genetic and/or environmental factor(s). We assessed externalizing behavior with the Child Behavior Checklist and Youth Self Report, and the brain volumes and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD]) with magnetic resonance imaging in the BrainSCALE cohort, which consisted of twins and their older siblings from 112 families measured longitudinally at ages 10, 13, and 18 years for the twins. Genetic covariance modeling based on the classical twin design, extended to also include siblings of twins, showed that genes influence externalizing behavior and changes therein (h2 up to 88%). More pronounced externalizing behavior was associated with higher FA (observed correlation rph up to +0.20) and lower MD (rph up to –0.20), with sizeable genetic correlations (FA ra up to +0.42; MD ra up to –0.33). The cortical gray matter (CGM; rph up to –0.20) and cerebral white matter (CWM; rph up to +0.20) volume were phenotypically but not genetically associated with externalizing behavior. These results suggest a potential mediating role for global brain structures in the display of externalizing behavior during adolescence that are both partially explained by the influence of the same genetic factor.
Published: 2022

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

Author: Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, Tamnes, Christian K., Wierenga, Lara M., Doucet, Gaelle E., Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn, I, Andreassen, Ole A., Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret, I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M., Buitelaar, Jan K., Busatto, Geraldo F., Calhoun, Vince D., Canales-Rodriguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Clark, Vincent P., Conrod, Patricia J., Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G., Dickie, Erin W., Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E., Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco J. C., Di Giorgio, Annabella, Glahn, David C., Gotlib, Ian H., Grabe, Hans J., Gruber, Oliver, Gruner, Patricia, Gur, Raquel E., Gur, Ruben C., Gurholt, Tiril P., de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J., Hartman, Catharina A., Hatton, Sean N., Heslenfeld, Dirk J., van den Heuvel, Odile A., Hickie, Ian B., Hoekstra, Pieter J., Hohmann, Sarah, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Pol, Hilleke E. Hulshoff, Huyser, Chaim, Jahanshad, Neda, James, Anthony C., Jiang, Jiyang, Jonsson, Erik G., Joska, John A., Kalnin, Andrew J., Klein, Marieke, Koenders, Laura, Kolskar, Knut K., Kramer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S., Lee, Phil H., Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martinez-Zalacain, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C., McDonald, Colm, McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, van der Meer, Dennis, Menchon, Jose M., Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Radua, Joaquim, Reif, Andreas, Richard, Genevieve, Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sarro, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Sim, Kang, Simmons, Andrew, Smoller, Jordan W., Sommer, Iris E., Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Szeszko, Philip R., Temmingh, Henk S., Thomopoulos, Sophia, I, Tomyshev, Alexander S., Trollor, Julian N., Uhlmann, Anne, Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Volzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather C., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Wright, Margaret J., Yoncheva, Yuliya N., Zanetti, Marcus, V, Ziegler, Georg C., de Zubicaray, Greig, I, Thompson, Paul M., Crone, Eveline A., Frangou, Sophia, and Tamnes, Christian K.
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022
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42. Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder.

Author: de Zwarte, Sonja MC, de Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales-Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon HJ, Houenou, Josselin, Hulshoff Pol, Hilleke E, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, van Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, van Erp, Theo GM, Jahanshad, Neda, Thompson, Paul M, de Zwarte, Sonja MC, de Zwarte, Sonja MC, Brouwer, Rachel M, Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E, Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth EL, Cahn, Wiepke, Canales-Rodríguez, Erick J, Cannon, Dara M, Cannon, Tyrone D, Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E, Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C, Foley, Sonya F, Frangou, Sophia, Fullerton, Janice M, Glahn, David C, Goghari, Vina M, Goikolea, Jose M, Goldman, Aaron L, Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L, Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon HJ, Houenou, Josselin, Hulshoff Pol, Hilleke E, Hultman, Christina M, Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G, Kane, Fergus, Kempton, Matthew J, Koenis, Marinka MG, Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M, Lenroot, Rhoshel K, Marcelis, Machteld, Mattay, Venkata S, McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B, Moreno, Dolores, Murray, Robin M, Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A, van Os, Jim, Overs, Bronwyn J, Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M, Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S, Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R, Simsek, Esma M, Simsek, Fatma, Soares, Jair C, Sponheim, Scott R, Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R, Whalley, Heather C, Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A, Ching, Christopher RK, Thomopoulos, Sophia I, van Erp, Theo GM, Jahanshad, Neda, and Thompson, Paul M
Abstract: First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
Published: 2022

43. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: Brouwer, Rachel M., Klein, M., Grasby, Katrina L., Schnack, Hugo G., Jahanshad, Neda, Teeuw, Jalmar, Sprooten, E., Damatac, C.G., Bralten, J.B., Guimaraes, J.P.O.F.T., Buitelaar, J.K., Franke, B., Thompson, Paul M., Hulshoff Pol, Hilleke E., Brouwer, Rachel M., Klein, M., Grasby, Katrina L., Schnack, Hugo G., Jahanshad, Neda, Teeuw, Jalmar, Sprooten, E., Damatac, C.G., Bralten, J.B., Guimaraes, J.P.O.F.T., Buitelaar, J.K., Franke, B., Thompson, Paul M., and Hulshoff Pol, Hilleke E.
Abstract: Item does not contain fulltext
Published: 2022

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

Author: Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher Rk, Clark, Vincent P, Conrod, Patricia J, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G, Dickie, Erin W, Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco Jc, Giorgio, Annabella Di, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise Wj, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro Gp, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven Cr, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M., Crone, Eveline A, Frangou, Sophia, Tamnes, Christian K, Wierenga, Lara M, Doucet, Gaelle E, Dima, Danai, Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N, Albajes-Eizagirre, Anton, Alnaes, Dag, Alpert, Kathryn I, Andreassen, Ole A, Anticevic, Alan, Asherson, Philip, Banaschewski, Tobias, Bargallo, Nuria, Baumeister, Sarah, Baur-Streubel, Ramona, Bertolino, Alessandro, Bonvino, Aurora, Boomsma, Dorret I, Borgwardt, Stefan, Bourque, Josiane, den Braber, Anouk, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Brouwer, Rachel M, Buitelaar, Jan K, Busatto, Geraldo F, Calhoun, Vince D, Canales-Rodríguez, Erick J, Cannon, Dara M, Caseras, Xavier, Castellanos, Francisco X, Chaim-Avancini, Tiffany M, Ching, Christopher Rk, Clark, Vincent P, Conrod, Patricia J, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher G, Dickie, Erin W, Ehrlich, Stefan, Van't Ent, Dennis, Fisher, Simon E, Fouche, Jean-Paul, Franke, Barbara, Fuentes-Claramonte, Paola, de Geus, Eco Jc, Giorgio, Annabella Di, Glahn, David C, Gotlib, Ian H, Grabe, Hans J, Gruber, Oliver, Gruner, Patricia, Gur, Raquel E, Gur, Ruben C, Gurholt, Tiril P, de Haan, Lieuwe, Haatveit, Beathe, Harrison, Ben J, Hartman, Catharina A, Hatton, Sean N, Heslenfeld, Dirk J, van den Heuvel, Odile A, Hickie, Ian B, Hoekstra, Pieter J, Hohmann, Sarah, Holmes, Avram J, Hoogman, Martine, Hosten, Norbert, Howells, Fleur M, Hulshoff Pol, Hilleke E, Huyser, Chaim, Jahanshad, Neda, James, Anthony C, Jiang, Jiyang, Jönsson, Erik G, Joska, John A, Kalnin, Andrew J, Klein, Marieke, Koenders, Laura, Kolskår, Knut K, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lazaro, Luisa, Lebedeva, Irina S, Lee, Phil H, Lochner, Christine, Machielsen, Marise Wj, Maingault, Sophie, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Brenna C, McDonald, Colm, McIntosh, Andrew M, McMahon, Katie L, McPhilemy, Genevieve, van der Meer, Dennis, Menchón, José M, Naaijen, Jilly, Nyberg, Lars, Oosterlaan, Jaap, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J, Radua, Joaquim, Reif, Andreas, Richard, Geneviève, Roffman, Joshua L, Rosa, Pedro Gp, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Sarró, Salvador, Satterthwaite, Theodore D, Saykin, Andrew J, Serpa, Mauricio H, Sim, Kang, Simmons, Andrew, Smoller, Jordan W, Sommer, Iris E, Soriano-Mas, Carles, Stein, Dan J, Strike, Lachlan T, Szeszko, Philip R, Temmingh, Henk S, Thomopoulos, Sophia I, Tomyshev, Alexander S, Trollor, Julian N, Uhlmann, Anne, Veer, Ilya M, Veltman, Dick J, Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Wang, Lei, Wang, Yang, Weber, Bernd, Wen, Wei, West, John D, Westlye, Lars T, Whalley, Heather C, Williams, Steven Cr, Wittfeld, Katharina, Wolf, Daniel H, Wright, Margaret J, Yoncheva, Yuliya N, Zanetti, Marcus V, Ziegler, Georg C, de Zubicaray, Greig I, Thompson, Paul M., Crone, Eveline A, Frangou, Sophia, and Tamnes, Christian K
Abstract: For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
Published: 2022

45. Intelligence, educational attainment, and brain structure in those at familial high-risk for schizophrenia or bipolar disorder

Author: de Zwarte, Sonja M. C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E., Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E. L., Cahn, Wiepke, Canales-Rodríguez, Erick J., Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goikolea, Jose M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon H.J., Houenou, Josselin, Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M. G., Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A., van Os, Jim, Overs, Bronwyn J., Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M., Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S., Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R., Simsek, Esma M., Simsek, Fatma, Soares, Jair C., Sponheim, Scott R., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R., Whalley, Heather C., Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R. K., Thomopoulos, Sophia I., van Erp, Theo G. M., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., van Haren, Neeltje E. M., de Zwarte, Sonja M. C., Brouwer, Rachel M., Agartz, Ingrid, Alda, Martin, Alonso-Lana, Silvia, Bearden, Carrie E., Bertolino, Alessandro, Bonvino, Aurora, Bramon, Elvira, Buimer, Elizabeth E. L., Cahn, Wiepke, Canales-Rodríguez, Erick J., Cannon, Dara M., Cannon, Tyrone D., Caseras, Xavier, Castro-Fornieles, Josefina, Chen, Qiang, Chung, Yoonho, De la Serna, Elena, Del Mar Bonnin, Caterina, Demro, Caroline, Di Giorgio, Annabella, Doucet, Gaelle E., Eker, Mehmet Cagdas, Erk, Susanne, Fatjó-Vilas, Mar, Fears, Scott C., Foley, Sonya F., Frangou, Sophia, Fullerton, Janice M., Glahn, David C., Goghari, Vina M., Goikolea, Jose M., Goldman, Aaron L., Gonul, Ali Saffet, Gruber, Oliver, Hajek, Tomas, Hawkins, Emma L., Heinz, Andreas, Hidiroglu Ongun, Ceren, Hillegers, Manon H.J., Houenou, Josselin, Hulshoff Pol, Hilleke E., Hultman, Christina M., Ingvar, Martin, Johansson, Viktoria, Jönsson, Erik G., Kane, Fergus, Kempton, Matthew J., Koenis, Marinka M. G., Kopecek, Miloslav, Krämer, Bernd, Lawrie, Stephen M., Lenroot, Rhoshel K., Marcelis, Machteld, Mattay, Venkata S., McDonald, Colm, Meyer-Lindenberg, Andreas, Michielse, Stijn, Mitchell, Philip B., Moreno, Dolores, Murray, Robin M., Mwangi, Benson, Nabulsi, Leila, Newport, Jason, Olman, Cheryl A., van Os, Jim, Overs, Bronwyn J., Ozerdem, Aysegul, Pergola, Giulio, Picchioni, Marco M., Piguet, Camille, Pomarol-Clotet, Edith, Radua, Joaquim, Ramsay, Ian S., Richter, Anja, Roberts, Gloria, Salvador, Raymond, Saricicek Aydogan, Aybala, Sarró, Salvador, Schofield, Peter R., Simsek, Esma M., Simsek, Fatma, Soares, Jair C., Sponheim, Scott R., Sugranyes, Gisela, Toulopoulou, Timothea, Tronchin, Giulia, Vieta, Eduard, Walter, Henrik, Weinberger, Daniel R., Whalley, Heather C., Wu, Mon-Ju, Yalin, Nefize, Andreassen, Ole A., Ching, Christopher R. K., Thomopoulos, Sophia I., van Erp, Theo G. M., Jahanshad, Neda, Thompson, Paul M., Kahn, René S., and van Haren, Neeltje E. M.
Abstract: First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
Published: 2022
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46. Multivariate Genetic Structure of Externalizing Behavior and Structural Brain Development in a Longitudinal Adolescent Twin Sample

Author: Leerstoel Hulshoff, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Teeuw, Jalmar, Klein, Marieke, Roth Mota, Nina, Brouwer, Rachel M., Van‘t Ent, Dennis, Al-Hassaan, Zyneb, Franke, Barbara, Boomsma, Dorret I., Hulshoff Pol, Hilleke E., Leerstoel Hulshoff, Helmholtz Institute, Experimental Psychology (onderzoeksprogramma PF), Teeuw, Jalmar, Klein, Marieke, Roth Mota, Nina, Brouwer, Rachel M., Van‘t Ent, Dennis, Al-Hassaan, Zyneb, Franke, Barbara, Boomsma, Dorret I., and Hulshoff Pol, Hilleke E.
Published: 2022

47. Genetic variants associated with longitudinal changes in brain structure across the lifespan

Author: European Commission, European Research Council, Comunidad de Madrid, Instituto de Salud Carlos III, Fundación Mutua Madrileña, Fundación Alicia Koplowitz, Brouwer, Rachel M., Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Hulshoff Pol, Hilleke E., European Commission, European Research Council, Comunidad de Madrid, Instituto de Salud Carlos III, Fundación Mutua Madrileña, Fundación Alicia Koplowitz, Brouwer, Rachel M., Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, and Hulshoff Pol, Hilleke E.
Abstract: Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
Published: 2022

48. Heritability of specific cognitive functions and associations with schizophrenia spectrum disorders using CANTAB:a nation-wide twin study

Author: Lemvigh, Cecilie K., Brouwer, Rachel M, Pantelis, Christos, Jensen, Maria H., Hilker, Rikke W., Legind, Christian S., Anhøj, Simon J., Robbins, Trevor W, Sahakian, Barbara J, Glenthøj, Birte Y., Fagerlund, Birgitte, Lemvigh, Cecilie K., Brouwer, Rachel M, Pantelis, Christos, Jensen, Maria H., Hilker, Rikke W., Legind, Christian S., Anhøj, Simon J., Robbins, Trevor W, Sahakian, Barbara J, Glenthøj, Birte Y., and Fagerlund, Birgitte
Abstract: BACKGROUND: Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown.METHODS: We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling.RESULTS: Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = -0.34), self-ordered spatial working memory (rph = -0.24), sustained attention (rph = -0.23), and set-shifting (rph = -0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ.CONCLUSIONS: This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia.
Published: 2022

49. Schizophrenia and Bipolar Polygenic Risk Scores in Relation to Intracranial Volume

Author: de Zwarte, Sonja M.C., Brouwer, Rachel M., Kahn, René S., van Haren, Neeltje E.M., de Zwarte, Sonja M.C., Brouwer, Rachel M., Kahn, René S., and van Haren, Neeltje E.M.
Abstract: Schizophrenia and bipolar disorder are neurodevelopmental disorders with overlapping symptoms and a shared genetic background. Deviations in intracranial volume (ICV)—a marker for neurodevelopment—differ between schizophrenia and bipolar disorder. Here, we investigated whether genetic risk for schizophrenia and bipolar disorder is related to ICV in the general population by using the UK Biobank data (n = 20,196). Polygenic risk scores for schizophrenia (SZ‐ PRS) and bipolar disorder (BD‐PRS) were computed for 12 genome wide association study P‐value thresholds (PT) for each individual and correlations with ICV were investigated. Partial correlations were performed at each PT to investigate whether disease specific genetic risk variants for schizophrenia and bipolar disorder show different relationships with ICV. ICV showed a negative correlation with SZ‐PRS at PT ≥ 0.005 (r < -0.02, P < 0.005). ICV was not associated with BD‐PRS; however, a positive correlation between BD‐PRS and ICV at PT = 0.2 and PT = 0.4 (r = +0.02, P < 0.005) appeared when the genetic overlap between schizophrenia and bipolar disorder was accounted for. Despite small effect sizes, a higher load of schizophrenia risk genes is associated with a smaller ICV in the general population, while risk genes specific for bipolar disorder are correlated with a larger ICV. These findings suggest that schizophrenia and bipolar disorder risk genes, when accounting for the genetic overlap between both disorders, have opposite effects on early brain development.
Published: 2022

50. What we learn about bipolar disorder from large-scale neuroimaging:Findings and future directions from the ENIGMA Bipolar Disorder Working Group

Author: Ching, Christopher R.K., Hibar, Derrek P., Gurholt, Tiril P., Nunes, Abraham, Thomopoulos, Sophia I., Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M., Cannon, Dara M., de Zwarte, Sonja M.C., Eyler, Lisa T., Favre, Pauline, Hajek, Tomas, Haukvik, Unn K., Houenou, Josselin, Landén, Mikael, Lett, Tristram A., McDonald, Colm, Nabulsi, Leila, Patel, Yash, Pauling, Melissa E., Paus, Tomas, Radua, Joaquim, Soeiro-de-Souza, Marcio G., Tronchin, Giulia, van Haren, Neeltje E.M., Vieta, Eduard, Walter, Henrik, Zeng, Ling Li, Alda, Martin, Almeida, Jorge, Alnæs, Dag, Alonso-Lana, Silvia, Altimus, Cara, Bauer, Michael, Baune, Bernhard T., Bearden, Carrie E., Bellani, Marcella, Benedetti, Francesco, Berk, Michael, Bilderbeck, Amy C., Blumberg, Hilary P., Bøen, Erlend, Bollettini, Irene, del Mar Bonnin, Caterina, Brambilla, Paolo, Canales-Rodríguez, Erick J., Caseras, Xavier, Dandash, Orwa, Ophoff, Roel A., Ching, Christopher R.K., Hibar, Derrek P., Gurholt, Tiril P., Nunes, Abraham, Thomopoulos, Sophia I., Abé, Christoph, Agartz, Ingrid, Brouwer, Rachel M., Cannon, Dara M., de Zwarte, Sonja M.C., Eyler, Lisa T., Favre, Pauline, Hajek, Tomas, Haukvik, Unn K., Houenou, Josselin, Landén, Mikael, Lett, Tristram A., McDonald, Colm, Nabulsi, Leila, Patel, Yash, Pauling, Melissa E., Paus, Tomas, Radua, Joaquim, Soeiro-de-Souza, Marcio G., Tronchin, Giulia, van Haren, Neeltje E.M., Vieta, Eduard, Walter, Henrik, Zeng, Ling Li, Alda, Martin, Almeida, Jorge, Alnæs, Dag, Alonso-Lana, Silvia, Altimus, Cara, Bauer, Michael, Baune, Bernhard T., Bearden, Carrie E., Bellani, Marcella, Benedetti, Francesco, Berk, Michael, Bilderbeck, Amy C., Blumberg, Hilary P., Bøen, Erlend, Bollettini, Irene, del Mar Bonnin, Caterina, Brambilla, Paolo, Canales-Rodríguez, Erick J., Caseras, Xavier, Dandash, Orwa, and Ophoff, Roel A.
Abstract: MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
Published: 2022

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