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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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4. Topographic divergence of atypical cortical asymmetry and atrophy patterns in temporal lobe epilepsy

Author

Park, Bo-yong, Larivière, Sara, Rodríguez-Cruces, Raul, Royer, Jessica, Tavakol, Shahin, Wang, Yezhou, Caciagli, Lorenzo, Caligiuri, Maria Eugenia, Gambardella, Antonio, Concha, Luis, Keller, Simon S, Cendes, Fernando, Alvim, Marina KM, Yasuda, Clarissa, Bonilha, Leonardo, Gleichgerrcht, Ezequiel, Focke, Niels K, Kreilkamp, Barbara AK, Domin, Martin, von Podewils, Felix, Langner, Soenke, Rummel, Christian, Rebsamen, Michael, Wiest, Roland, Martin, Pascal, Kotikalapudi, Raviteja, Bender, Benjamin, O’Brien, Terence J, Law, Meng, Sinclair, Benjamin, Vivash, Lucy, Kwan, Patrick, Desmond, Patricia M, Malpas, Charles B, Lui, Elaine, Alhusaini, Saud, Doherty, Colin P, Cavalleri, Gianpiero L, Delanty, Norman, Kälviäinen, Reetta, Jackson, Graeme D, Kowalczyk, Magdalena, Mascalchi, Mario, Semmelroch, Mira, Thomas, Rhys H, Soltanian-Zadeh, Hamid, Davoodi-Bojd, Esmaeil, Zhang, Junsong, Lenge, Matteo, Guerrini, Renzo, Bartolini, Emanuele, Hamandi, Khalid, Foley, Sonya, Weber, Bernd, Depondt, Chantal, Absil, Julie, Carr, Sarah JA, Abela, Eugenio, Richardson, Mark P, Devinsky, Orrin, Severino, Mariasavina, Striano, Pasquale, Parodi, Costanza, Tortora, Domenico, Hatton, Sean N, Vos, Sjoerd B, Duncan, John S, Galovic, Marian, Whelan, Christopher D, Bargalló, Núria, Pariente, Jose, Conde-Blanco, Estefania, Vaudano, Anna Elisabetta, Tondelli, Manuela, Meletti, Stefano, Kong, Xiang‐Zhen, Francks, Clyde, Fisher, Simon E, Caldairou, Benoit, Ryten, Mina, Labate, Angelo, Sisodiya, Sanjay M, Thompson, Paul M, McDonald, Carrie R, Bernasconi, Andrea, Bernasconi, Neda, and Bernhardt, Boris C

Subjects
Epilepsy, Neurodegenerative, Clinical Research, Brain Disorders, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Neurological, Adult, Atrophy, Connectome, Epilepsy, Temporal Lobe, Hippocampus, Humans, Magnetic Resonance Imaging, temporal lobe epilepsy, asymmetry, cortical thickness, multi-site, gradients, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract

Temporal lobe epilepsy, a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter structural alterations in temporal lobe epilepsy relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry; or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multisite ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 temporal lobe epilepsy patients and 1418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in temporal lobe epilepsy, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity calculated using 207 healthy controls obtained from Human Connectome Project and an independent dataset containing 23 temporal lobe epilepsy patients and 53 healthy controls and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of temporal lobe epilepsy-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of temporal lobe epilepsy and may inform future discovery and validation of complementary MRI biomarkers in temporal lobe epilepsy.

Published
2022

5. Mapping brain asymmetry in health and disease through the ENIGMA consortium

Author

Kong, Xiang‐Zhen, Postema, Merel C, Guadalupe, Tulio, de Kovel, Carolien, Boedhoe, Premika SW, Hoogman, Martine, Mathias, Samuel R, van Rooij, Daan, Schijven, Dick, Glahn, David C, Medland, Sarah E, Jahanshad, Neda, Thomopoulos, Sophia I, Turner, Jessica A, Buitelaar, Jan, van Erp, Theo GM, Franke, Barbara, Fisher, Simon E, van den Heuvel, Odile A, Schmaal, Lianne, Thompson, Paul M, and Francks, Clyde

Subjects
Biological Psychology, Psychology, Brain Disorders, Mental Health, Neurosciences, Clinical Research, Mental health, Neurological, Autism Spectrum Disorder, Cerebral Cortex, Depressive Disorder, Major, Gray Matter, Humans, Magnetic Resonance Imaging, Multicenter Studies as Topic, Neuroimaging, Obsessive-Compulsive Disorder, autism spectrum disorder, brain asymmetry, brain laterality, major depressive disorder, mega-analysis, meta-analysis, obsessive-compulsive disorder, structural imaging, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. Decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes. There are also open questions surrounding which structures are asymmetrical on average in the healthy population, and how variability in brain asymmetry relates to basic biological variables such as age and sex. Over the last 4 years, the ENIGMA-Laterality Working Group has published six studies of gray matter morphological asymmetry based on total sample sizes from roughly 3,500 to 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. A population-level mapping of average asymmetry was achieved, including an intriguing fronto-occipital gradient of cortical thickness asymmetry in healthy brains. ENIGMA's multi-dataset approach also supported an empirical illustration of reproducibility of hemispheric differences across datasets. Effect sizes were estimated for gray matter asymmetry based on large, international, samples in relation to age, sex, handedness, and brain volume, as well as for three psychiatric disorders: autism spectrum disorder was associated with subtly reduced asymmetry of cortical thickness at regions spread widely over the cortex; pediatric obsessive-compulsive disorder was associated with altered subcortical asymmetry; major depressive disorder was not significantly associated with changes of asymmetry. Ongoing studies are examining brain asymmetry in other disorders. Moreover, a groundwork has been laid for possibly identifying shared genetic contributions to brain asymmetry and disorders.

Published
2022

6. An overview of the first 5 years of the ENIGMA obsessive–compulsive disorder working group: The power of worldwide collaboration

Author

van den Heuvel, Odile A, Boedhoe, Premika SW, Bertolin, Sara, Bruin, Willem B, Francks, Clyde, Ivanov, Iliyan, Jahanshad, Neda, Kong, Xiang‐Zhen, Kwon, Jun Soo, O'Neill, Joseph, Paus, Tomas, Patel, Yash, Piras, Fabrizio, Schmaal, Lianne, Soriano‐Mas, Carles, Spalletta, Gianfranco, van Wingen, Guido A, Yun, Je‐Yeon, Vriend, Chris, Simpson, H Blair, van Rooij, Daan, Hoexter, Marcelo Q, Hoogman, Martine, Buitelaar, Jan K, Arnold, Paul, Beucke, Jan C, Benedetti, Francesco, Bollettini, Irene, Bose, Anushree, Brennan, Brian P, De Nadai, Alessandro S, Fitzgerald, Kate, Gruner, Patricia, Grünblatt, Edna, Hirano, Yoshiyuki, Huyser, Chaim, James, Anthony, Koch, Kathrin, Kvale, Gerd, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Mataix‐Cols, David, Morgado, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika, Pittenger, Christopher, Reddy, YC Janardhan, Sato, João R, Soreni, Noam, Stewart, S Evelyn, Taylor, Stephan F, Tolin, David, Thomopoulos, Sophia I, Veltman, Dick J, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Thompson, Paul M, Stein, Dan J, Abe, Yoshinari, Alonso, Pino, Assogna, Francesca, Banaj, Nerisa, Batistuzzo, Marcelo C, Brem, Silvia, Ciullo, Valentina, Feusner, Jamie, Martínez‐Zalacaín, Ignacio, Menchón, José M, Miguel, Euripedes C, Piacentini, John, Piras, Federica, Sakai, Yuki, Wolters, Lidewij, and Yamada, Kei

Subjects
Biological Psychology, Psychology, Brain Disorders, Clinical Research, Serious Mental Illness, Pediatric, Neurosciences, Mental Health, Mental health, Neurological, Cerebral Cortex, Humans, Machine Learning, Multicenter Studies as Topic, Neuroimaging, Obsessive-Compulsive Disorder, cortical thickness, ENIGMA, mega-analysis, meta-analysis, MRI, obsessive-compulsive disorder, surface area, volume, ENIGMA-OCD working group, Cognitive Sciences, Experimental Psychology, Biological psychology, Cognitive and computational psychology
Abstract

Neuroimaging has played an important part in advancing our understanding of the neurobiology of obsessive-compulsive disorder (OCD). At the same time, neuroimaging studies of OCD have had notable limitations, including reliance on relatively small samples. International collaborative efforts to increase statistical power by combining samples from across sites have been bolstered by the ENIGMA consortium; this provides specific technical expertise for conducting multi-site analyses, as well as access to a collaborative community of neuroimaging scientists. In this article, we outline the background to, development of, and initial findings from ENIGMA's OCD working group, which currently consists of 47 samples from 34 institutes in 15 countries on 5 continents, with a total sample of 2,323 OCD patients and 2,325 healthy controls. Initial work has focused on studies of cortical thickness and subcortical volumes, structural connectivity, and brain lateralization in children, adolescents and adults with OCD, also including the study on the commonalities and distinctions across different neurodevelopment disorders. Additional work is ongoing, employing machine learning techniques. Findings to date have contributed to the development of neurobiological models of OCD, have provided an important model of global scientific collaboration, and have had a number of clinical implications. Importantly, our work has shed new light on questions about whether structural and functional alterations found in OCD reflect neurodevelopmental changes, effects of the disease process, or medication impacts. We conclude with a summary of ongoing work by ENIGMA-OCD, and a consideration of future directions for neuroimaging research on OCD within and beyond ENIGMA.

Published
2022

7. 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

8. Discovery of 42 genome-wide significant loci associated with dyslexia

Author

Doust, Catherine, Fontanillas, Pierre, Eising, Else, Gordon, Scott D., Wang, Zhengjun, Alagöz, Gökberk, Molz, Barbara, Pourcain, Beate St, Francks, Clyde, Marioni, Riccardo E., Zhao, Jingjing, Paracchini, Silvia, Talcott, Joel B., Monaco, Anthony P., Stein, John F., Gruen, Jeffrey R., Olson, Richard K., Willcutt, Erik G., DeFries, John C., Pennington, Bruce F., Smith, Shelley D., Wright, Margaret J., Martin, Nicholas G., Auton, Adam, Bates, Timothy C., Fisher, Simon E., and Luciano, Michelle

Published
2022
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11. Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium

Author

Sha, Zhiqiang, van Rooij, Daan, Anagnostou, Evdokia, Arango, Celso, Auzias, Guillaume, Behrmann, Marlene, Bernhardt, Boris, Bolte, Sven, Busatto, Geraldo F., Calderoni, Sara, Calvo, Rosa, Daly, Eileen, Deruelle, Christine, Duan, Meiyu, Duran, Fabio Luis Souza, Durston, Sarah, Ecker, Christine, Ehrlich, Stefan, Fair, Damien, Fedor, Jennifer, Fitzgerald, Jacqueline, Floris, Dorothea L., Franke, Barbara, Freitag, Christine M., Gallagher, Louise, Glahn, David C., Haar, Shlomi, Hoekstra, Liesbeth, Jahanshad, Neda, Jalbrzikowski, Maria, Janssen, Joost, King, Joseph A., Lazaro, Luisa, Luna, Beatriz, McGrath, Jane, Medland, Sarah E., Muratori, Filippo, Murphy, Declan G. M., Neufeld, Janina, O’Hearn, Kirsten, Oranje, Bob, Parellada, Mara, Pariente, Jose C., Postema, Merel C., Remnelius, Karl Lundin, Retico, Alessandra, Rosa, Pedro Gomes Penteado, Rubia, Katya, Shook, Devon, Tammimies, Kristiina, Taylor, Margot J., Tosetti, Michela, Wallace, Gregory L., Zhou, Fengfeng, Thompson, Paul M., Fisher, Simon E., Buitelaar, Jan K., and Francks, Clyde

Published
2022
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14. Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium

Author

Kong, Xiang-Zhen, Mathias, Samuel R, Guadalupe, Tulio, Glahn, David C, Franke, Barbara, Crivello, Fabrice, Tzourio-Mazoyer, Nathalie, Fisher, Simon E, Thompson, Paul M, Francks, Clyde, Abé, Christoph, Agartz, Ingrid, Akudjedu, Theophilus N, Aleman, Andre, Alhusaini, Saud, Allen, Nicholas B, Ames, David, Andreassen, Ole A, Vasquez, Alejandro Arias, Armstrong, Nicola J, Bergo, Felipe, Bastin, Mark E, Batalla, Albert, Bauer, Jochen, Baune, Bernhard T, Baur-Streubel, Ramona, Biederman, Joseph, Blaine, Sara K, Boedhoe, Premika, Bøen, Erlend, Bose, Anushree, Bralten, Janita, Brandeis, Daniel, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J, Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Canive, Jose M, Cannon, Dara M, Caparelli, Elisabeth C, Castellanos, Francisco X, Cavalleri, Gianpiero L, Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P, Coghill, David, Connolly, Colm G, Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dale, Anders, Dannlowski, Udo, Ambrosino de Bruttopilo, Sara, de Zeeuw, Patrick, Deary, Ian J, Delanty, Norman, Demeter, Damion V, Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, N Trung, Doherty, Colin P, Doyle, Alysa, Durston, Sarah, Earl, Eric, Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N, Fair, Damien A, Faraone, Stephen V, Fernández, Guillén, Filho, Geraldo Busatto, Förster, Katharina, Fouche, Jean-Paul, Foxe, John J, Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice, Garavan, Hugh, Garcia, Danielle do Santos, Gotlib, Ian H, Goudriaan, Anna E, and Grabe, Hans Jörgen

Subjects
Neurosciences, Clinical Research, Brain Disorders, Mental Health, Biomedical Imaging, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Mental health, Adolescent, Adult, Aged, Aged, 80 and over, Cerebral Cortex, Child, Child, Preschool, Databases, Factual, Female, Humans, Infant, Male, Middle Aged, Neuroimaging, Young Adult, brain asymmetry, lateralization, cortical thickness, surface area, meta-analysis, ENIGMA Laterality Working Group
Abstract

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Published
2018

16. Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia

Author

Doust, Catherine, Fontanillas, Pierre, Eising, Else, Gordon, Scott D., Wang, Zhengjun, Alagöz, Gökberk, Molz, Barbara, Pourcain, Beate St, Francks, Clyde, Marioni, Riccardo E., Zhao, Jingjing, Paracchini, Silvia, Talcott, Joel B., Monaco, Anthony P., Stein, John F., Gruen, Jeffrey R., Olson, Richard K., Willcutt, Erik G., DeFries, John C., Pennington, Bruce F., Smith, Shelley D., Wright, Margaret J., Martin, Nicholas G., Auton, Adam, Bates, Timothy C., Fisher, Simon E., and Luciano, Michelle

Published
2023
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17. 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

19. Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia

Author

Gialluisi, Alessandro, Andlauer, Till F. M., Mirza-Schreiber, Nazanin, Moll, Kristina, Becker, Jessica, Hoffmann, Per, Ludwig, Kerstin U., Czamara, Darina, Pourcain, Beate St, Honbolygó, Ferenc, Tóth, Dénes, Csépe, Valéria, Huguet, Guillaume, Chaix, Yves, Iannuzzi, Stephanie, Demonet, Jean-Francois, Morris, Andrew P., Hulslander, Jacqueline, Willcutt, Erik G., DeFries, John C., Olson, Richard K., Smith, Shelley D., Pennington, Bruce F., Vaessen, Anniek, Maurer, Urs, Lyytinen, Heikki, Peyrard-Janvid, Myriam, Leppänen, Paavo H. T., Brandeis, Daniel, Bonte, Milene, Stein, John F., Talcott, Joel B., Fauchereau, Fabien, Wilcke, Arndt, Kirsten, Holger, Müller, Bent, Francks, Clyde, Bourgeron, Thomas, Monaco, Anthony P., Ramus, Franck, Landerl, Karin, Kere, Juha, Scerri, Thomas S., Paracchini, Silvia, Fisher, Simon E., Schumacher, Johannes, Nöthen, Markus M., Müller-Myhsok, Bertram, and Schulte-Körne, Gerd

Published
2021
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20. The neocortical infrastructure for language involves region-specific patterns of laminar gene expression.

Author

Wong, Maggie M. K., Zhiqiang Sha, Lütje, Lukas, Xiang-Zhen Kong, van Heukelum, Sabrina, van de Berg, Wilma D. J., Jonkman, Laura E., Fisher, Simon E., and Francks, Clyde

Subjects
TEMPORAL lobe, GENE expression, FRONTAL lobe, TRANSCRIPTOMES, MEDICAL screening, PEOPLE with schizophrenia
Abstract

The language network of the human brain has core components in the inferior frontal cortex and superior/middle temporal cortex, with left-hemisphere dominance in most people. Functional specialization and interconnectivity of these neocortical regions is likely to be reflected in their molecular and cellular profiles. Excitatory connections between cortical regions arise and innervate according to layer-specific patterns. Here, we generated a gene expression dataset from human postmortem cortical tissue samples from core language network regions, using spatial transcriptomics to discriminate gene expression across cortical layers. Integration of these data with existing single-cell expression data identified 56 genes that showed differences in laminar expression profiles between the frontal and temporal language cortex together with upregulation in layer II/III and/or layer V/VI excitatory neurons. Based on data from large-scale genome-wide screening in the population, DNA variants within these 56 genes showed set-level associations with interindividual variation in structural connectivity between the left-hemisphere frontal and temporal language cortex, and with the brain-related disorders dyslexia and schizophrenia which often involve affected language. These findings identify region-specific patterns of laminar gene expression as a feature of the brain's language network. [ABSTRACT FROM AUTHOR]

Published
2024
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21. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author

Kong, Xiang-Zhen, Boedhoe, Premika S.W., Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Assogna, Francesca, Baker, Justin T., Banaj, Nerisa, Bargalló, Nuria, Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P., Buitelaar, Jan, Busatto, Geraldo F., Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, de Vries, Froukje E., de Wit, Stella J., Dickie, Erin, Drechsler, Renate, Ely, Benjamin A., Esteves, Madalena, Falini, Andrea, Fang, Yu, Feusner, Jamie, Figee, Martijn, Fitzgerald, Kate D., Fontaine, Martine, Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Gürsel, Deniz A., Hall, Geoff, Hamatani, Sayo, Hanna, Gregory L., Hansen, Bjarne, Hauser, Tobias U., Hirano, Yoshiyuki, Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Jahanshad, Neda, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Lazaro, Luisa, Liu, Yanni, Lochner, Christine, Magalhães, Ricardo, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Masuda, Yasutaka, Mataix-Cols, David, Matsumoto, Koji, McCracken, James T., Menchón, José M., Miguel, Euripedes C., Minuzzi, Luciano, Moreira, Pedro S., Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Narumoto, Jin, Nishida, Seiji, Nurmi, Erika L., O'Neill, Joseph, Pariente, Jose C., Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Poletti, Sara, Reddy, Y.C. Janardhan, Reess, Tim, Rus-Oswald, Oana Georgiana, Sakai, Yuki, Sato, Joao R., Schmaal, Lianne, Shimizu, Eiji, Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carles, Sousa, Nuno, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Stewart, S. Evelyn, Szeszko, Philip R., Takahashi, Jumpei, Tang, Jinsong, Thorsen, Anders Lillevik, Tolin, David F., Tsuchiyagaito, Aki, van Rooij, Daan, van Wingen, Guido A., van der Werf, Ysbrand D., Veltman, Dick J., Vecchio, Daniela, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Watanabe, Anri, Xu, Jian, Xu, Xiufeng, Yamada, Kei, Yoshida, Tokiko, Yun, Je-Yeon, Zarei, Mojtaba, Zhao, Qing, Zhou, Cong, Thompson, Paul M., Stein, Dan J., van den Heuvel, Odile A., Francks, Clyde, Glahn, David C., and Medland, Sarah E.

Published
2020
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25. Author Correction: Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Author

Postema, Merel C., van Rooij, Daan, Anagnostou, Evdokia, Arango, Celso, Auzias, Guillaume, Behrmann, Marlene, Filho, Geraldo Busatto, Calderoni, Sara, Calvo, Rosa, Daly, Eileen, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Duran, Fabio Luis S., Durston, Sarah, Ecker, Christine, Ehrlich, Stefan, Fair, Damien, Fedor, Jennifer, Feng, Xin, Fitzgerald, Jackie, Floris, Dorothea L., Freitag, Christine M., Gallagher, Louise, Glahn, David C., Gori, Ilaria, Haar, Shlomi, Hoekstra, Liesbeth, Jahanshad, Neda, Jalbrzikowski, Maria, Janssen, Joost, King, Joseph A., Kong, Xiang Zhen, Lazaro, Luisa, Lerch, Jason P., Luna, Beatriz, Martinho, Mauricio M., McGrath, Jane, Medland, Sarah E., Muratori, Filippo, Murphy, Clodagh M., Murphy, Declan G. M., O’Hearn, Kirsten, Oranje, Bob, Parellada, Mara, Puig, Olga, Retico, Alessandra, Rosa, Pedro, Rubia, Katya, Shook, Devon, Taylor, Margot J., Tosetti, Michela, Wallace, Gregory L., Zhou, Fengfeng, Thompson, Paul M., Fisher, Simon E., Buitelaar, Jan K., and Francks, Clyde

Published
2021
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26. Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

Author

Villanueva, Pía, Nudel, Ron, Hoischen, Alexander, Fernández, María Angélica, Simpson, Nuala H, Gilissen, Christian, Reader, Rose H, Jara, Lillian, Echeverry, María Magdalena, Francks, Clyde, Baird, Gillian, Conti-Ramsden, Gina, O'Hare, Anne, Bolton, Patrick F, Hennessy, Elizabeth R, SLI Consortium, Palomino, Hernán, Carvajal-Carmona, Luis, Veltman, Joris A, Cazier, Jean-Baptiste, De Barbieri, Zulema, Fisher, Simon E, and Newbury, Dianne F

Subjects
SLI Consortium, Humans, Apraxias, Genetic Predisposition to Disease, Carrier Proteins, Membrane Proteins, Genetics, Population, Child, Child, Preschool, Female, Male, Genetic Association Studies, High-Throughput Nucleotide Sequencing, Exome, Preschool, Genetics, Population, Developmental Biology
Abstract

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

Published
2015

27. 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

28. Imaging genetics of language network functional connectivity reveals links with language-related abilities, dyslexia and handedness

Author

Amelink, Jitse S., primary, Postema, Merel C., additional, Kong, Xiang-Zhen, additional, Schijven, Dick, additional, Carrion-Castillo, Amaia, additional, Soheili-Nezhad, Sourena, additional, Sha, Zhiqiang, additional, Molz, Barbara, additional, Joliot, Marc, additional, Fisher, Simon E., additional, and Francks, Clyde E., additional

Published
2023
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29. The universe is asymmetric, the mouse brain too

Author

Rivera-Olvera, Alejandro, primary, Houwing, Danielle J., additional, Ellegood, Jacob, additional, Masifi, Shang, additional, Martina, Stephany LL., additional, Silberfeld, Andrew, additional, Pourquie, Olivier, additional, Lerch, Jason P., additional, Francks, Clyde, additional, Homberg, Judith R., additional, van Heukelum, Sabrina, additional, and Grandjean, Joanes, additional

Published
2023
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31. 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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33. Tracing the development and lifespan change of population-level structural asymmetry in the cerebral cortex

Author

Roe, James M, primary, Vidal-Pineiro, Didac, additional, Amlien, Inge K, additional, Pan, Mengyu, additional, Sneve, Markus H, additional, Thiebaut de Schotten, Michel, additional, Friedrich, Patrick, additional, Sha, Zhiqiang, additional, Francks, Clyde, additional, Eilertsen, Espen M, additional, Wang, Yunpeng, additional, Walhovd, Kristine B, additional, Fjell, Anders M, additional, and Westerhausen, René, additional

Published
2023
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36. Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Author

Postema, Merel C., van Rooij, Daan, Anagnostou, Evdokia, Arango, Celso, Auzias, Guillaume, Behrmann, Marlene, Filho, Geraldo Busatto, Calderoni, Sara, Calvo, Rosa, Daly, Eileen, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Duran, Fabio Luis S., Durston, Sarah, Ecker, Christine, Ehrlich, Stefan, Fair, Damien, Fedor, Jennifer, Feng, Xin, Fitzgerald, Jackie, Floris, Dorothea L., Freitag, Christine M., Gallagher, Louise, Glahn, David C., Gori, Ilaria, Haar, Shlomi, Hoekstra, Liesbeth, Jahanshad, Neda, Jalbrzikowski, Maria, Janssen, Joost, King, Joseph A., Kong, Xiang Zhen, Lazaro, Luisa, Lerch, Jason P., Luna, Beatriz, Martinho, Mauricio M., McGrath, Jane, Medland, Sarah E., Muratori, Filippo, Murphy, Clodagh M., Murphy, Declan G. M., O’Hearn, Kirsten, Oranje, Bob, Parellada, Mara, Puig, Olga, Retico, Alessandra, Rosa, Pedro, Rubia, Katya, Shook, Devon, Taylor, Margot J., Tosetti, Michela, Wallace, Gregory L., Zhou, Fengfeng, Thompson, Paul M., Fisher, Simon E., Buitelaar, Jan K., and Francks, Clyde

Published
2019
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38. Attention deficit hyperactivity disorder: Fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11

Author

Ogdie, Matthew N, Fisher, Simon E, Yang, May, Ishii, Janeen, Francks, Clyde, Loo, Sandra K, Cantor, Rita M, McCracken, James T, McGough, James J, Smalley, Susan L, and Nelson, Stanley F

Abstract

We completed fine mapping of nine positional candidate regions for attention-deficit/hyperactivity disorder (ADHD) in an extended population sample of 308 affected sibling pairs (ASPs), constituting the largest linkage sample of families with ADHD published to date. The candidate chromosomal regions were selected from all three published genomewide scans for ADHD, and fine mapping was done to comprehensively validate these positional candidate regions in our sample. Multipoint maximum LOD score (MLS) analysis yielded significant evidence of linkage on 6q12 (MLS 3.30; empiric) and 17p11 (MLS 3.63; empiric P = .015), as well as suggestive evidence on 5p13 (MLS 2.55; empiric P = .091). In conjunction with the previously reported significant linkage on the basis of fine mapping 16p13 in the same sample as this report, the analyses presented here indicate that four chromosomal regions - 5p13, 6q12, 16p13, and 17p11 - are likely to harbor susceptibility genes for ADHD. The refinement of linkage within each of these regions lays the foundation for subsequent investigations using association methods to detect risk genes of moderate effect size.

Published
2004

40. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author

Schijven, Dick, primary, Postema, Merel C., additional, Fukunaga, Masaki, additional, Matsumoto, Junya, additional, Miura, Kenichiro, additional, de Zwarte, Sonja M. C., additional, van Haren, Neeltje E. M., additional, Cahn, Wiepke, additional, Hulshoff Pol, Hilleke E., additional, Kahn, René S., additional, Ayesa-Arriola, Rosa, additional, Ortiz-García de la Foz, Víctor, additional, Tordesillas-Gutierrez, Diana, additional, Vázquez-Bourgon, Javier, additional, Crespo-Facorro, Benedicto, additional, Alnæs, Dag, additional, Dahl, Andreas, additional, Westlye, Lars T., additional, Agartz, Ingrid, additional, Andreassen, Ole A., additional, Jönsson, Erik G., additional, Kochunov, Peter, additional, Bruggemann, Jason M., additional, Catts, Stanley V., additional, Michie, Patricia T., additional, Mowry, Bryan J., additional, Quidé, Yann, additional, Rasser, Paul E., additional, Schall, Ulrich, additional, Scott, Rodney J., additional, Carr, Vaughan J., additional, Green, Melissa J., additional, Henskens, Frans A., additional, Loughland, Carmel M., additional, Pantelis, Christos, additional, Weickert, Cynthia Shannon, additional, Weickert, Thomas W., additional, de Haan, Lieuwe, additional, Brosch, Katharina, additional, Pfarr, Julia-Katharina, additional, Ringwald, Kai G., additional, Stein, Frederike, additional, Jansen, Andreas, additional, Kircher, Tilo T. J., additional, Nenadić, Igor, additional, Krämer, Bernd, additional, Gruber, Oliver, additional, Satterthwaite, Theodore D., additional, Bustillo, Juan, additional, Mathalon, Daniel H., additional, Preda, Adrian, additional, Calhoun, Vince D., additional, Ford, Judith M., additional, Potkin, Steven G., additional, Chen, Jingxu, additional, Tan, Yunlong, additional, Wang, Zhiren, additional, Xiang, Hong, additional, Fan, Fengmei, additional, Bernardoni, Fabio, additional, Ehrlich, Stefan, additional, Fuentes-Claramonte, Paola, additional, Garcia-Leon, Maria Angeles, additional, Guerrero-Pedraza, Amalia, additional, Salvador, Raymond, additional, Sarró, Salvador, additional, Pomarol-Clotet, Edith, additional, Ciullo, Valentina, additional, Piras, Fabrizio, additional, Vecchio, Daniela, additional, Banaj, Nerisa, additional, Spalletta, Gianfranco, additional, Michielse, Stijn, additional, van Amelsvoort, Therese, additional, Dickie, Erin W., additional, Voineskos, Aristotle N., additional, Sim, Kang, additional, Ciufolini, Simone, additional, Dazzan, Paola, additional, Murray, Robin M., additional, Kim, Woo-Sung, additional, Chung, Young-Chul, additional, Andreou, Christina, additional, Schmidt, André, additional, Borgwardt, Stefan, additional, McIntosh, Andrew M., additional, Whalley, Heather C., additional, Lawrie, Stephen M., additional, du Plessis, Stefan, additional, Luckhoff, Hilmar K., additional, Scheffler, Freda, additional, Emsley, Robin, additional, Grotegerd, Dominik, additional, Lencer, Rebekka, additional, Dannlowski, Udo, additional, Edmond, Jesse T., additional, Rootes-Murdy, Kelly, additional, Stephen, Julia M., additional, Mayer, Andrew R., additional, Antonucci, Linda A., additional, Fazio, Leonardo, additional, Pergola, Giulio, additional, Bertolino, Alessandro, additional, Díaz-Caneja, Covadonga M., additional, Janssen, Joost, additional, Lois, Noemi G., additional, Arango, Celso, additional, Tomyshev, Alexander S., additional, Lebedeva, Irina, additional, Cervenka, Simon, additional, Sellgren, Carl M., additional, Georgiadis, Foivos, additional, Kirschner, Matthias, additional, Kaiser, Stefan, additional, Hajek, Tomas, additional, Skoch, Antonin, additional, Spaniel, Filip, additional, Kim, Minah, additional, Kwak, Yoo Bin, additional, Oh, Sanghoon, additional, Kwon, Jun Soo, additional, James, Anthony, additional, Bakker, Geor, additional, Knöchel, Christian, additional, Stäblein, Michael, additional, Oertel, Viola, additional, Uhlmann, Anne, additional, Howells, Fleur M., additional, Stein, Dan J., additional, Temmingh, Henk S., additional, Diaz-Zuluaga, Ana M., additional, Pineda-Zapata, Julian A., additional, López-Jaramillo, Carlos, additional, Homan, Stephanie, additional, Ji, Ellen, additional, Surbeck, Werner, additional, Homan, Philipp, additional, Fisher, Simon E., additional, Franke, Barbara, additional, Glahn, David C., additional, Gur, Ruben C., additional, Hashimoto, Ryota, additional, Jahanshad, Neda, additional, Luders, Eileen, additional, Medland, Sarah E., additional, Thompson, Paul M., additional, Turner, Jessica A., additional, van Erp, Theo G. M., additional, and Francks, Clyde, additional

Published
2023
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41. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author

Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., Francks, Clyde, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Matsumoto, Junya, Miura, Kenichiro, de Zwarte, Sonja M. C., van Haren, Neeltje E. M., Cahn, Wiepke, Hulshoff Pol, Hilleke E., Kahn, René S., Ayesa-Arriola, Rosa, Ortiz-García de la Foz, Víctor, Tordesillas-Gutierrez, Diana, Vázquez-Bourgon, Javier, Crespo-Facorro, Benedicto, Alnæs, Dag, Dahl, Andreas, Westlye, Lars T., Agartz, Ingrid, Andreassen, Ole A., Jönsson, Erik G., Kochunov, Peter, Bruggemann, Jason M., Catts, Stanley V., Michie, Patricia T., Mowry, Bryan J., Quidé, Yann, Rasser, Paul E., Schall, Ulrich, Scott, Rodney J., Carr, Vaughan J., Green, Melissa J., Henskens, Frans A., Loughland, Carmel M., Pantelis, Christos, Weickert, Cynthia Shannon, Weickert, Thomas W., de Haan, Lieuwe, Brosch, Katharina, Pfarr, Julia-Katharina, Ringwald, Kai G., Stein, Frederike, Jansen, Andreas, Kircher, Tilo T. J., Nenadić, Igor, Krämer, Bernd, Gruber, Oliver, Satterthwaite, Theodore D., Bustillo, Juan, Mathalon, Daniel H., Preda, Adrian, Calhoun, Vince D., Ford, Judith M., Potkin, Steven G., Chen, Jingxu, Tan, Yunlong, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan, Fuentes-Claramonte, Paola, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond, Sarró, Salvador, Pomarol-Clotet, Edith, Ciullo, Valentina, Piras, Fabrizio, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W., Voineskos, Aristotle N., Sim, Kang, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M., Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André, Borgwardt, Stefan, McIntosh, Andrew M., Whalley, Heather C., Lawrie, Stephen M., du Plessis, Stefan, Luckhoff, Hilmar K., Scheffler, Freda, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo, Edmond, Jesse T., Rootes-Murdy, Kelly, Stephen, Julia M., Mayer, Andrew R., Antonucci, Linda A., Fazio, Leonardo, Pergola, Giulio, Bertolino, Alessandro, Díaz-Caneja, Covadonga M., Janssen, Joost, Lois, Noemi G., Arango, Celso, Tomyshev, Alexander S., Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M., Georgiadis, Foivos, Kirschner, Matthias, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin, Spaniel, Filip, Kim, Minah, Kwak, Yoo Bin, Oh, Sanghoon, Kwon, Jun Soo, James, Anthony, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne, Howells, Fleur M., Stein, Dan J., Temmingh, Henk S., Diaz-Zuluaga, Ana M., Pineda-Zapata, Julian A., López-Jaramillo, Carlos, Homan, Stephanie, Ji, Ellen, Surbeck, Werner, Homan, Philipp, Fisher, Simon E., Franke, Barbara, Glahn, David C., Gur, Ruben C., Hashimoto, Ryota, Jahanshad, Neda, Lueders, Eileen, Medland, Sarah E., Thompson, Paul M., Turner, Jessica A., van Erp, Theo G. M., and Francks, Clyde

Abstract

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

Published
2023
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42. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author

National Institutes of Health (US), Instituto de Salud Carlos III, European Commission, European Research Council, Ministerio de Ciencia e Innovación (España), Fundación Marques de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Fundación Alonso Lozano, Fundación Alicia Koplowitz, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, Francks, Clyde, National Institutes of Health (US), Instituto de Salud Carlos III, European Commission, European Research Council, Ministerio de Ciencia e Innovación (España), Fundación Marques de Valdecilla, Instituto de Investigación Marqués de Valdecilla, Fundación Alonso Lozano, Fundación Alicia Koplowitz, Schijven, Dick, Postema, Merel C., Fukunaga, Masaki, Tordesillas-Gutiérrez, Diana, Crespo-Facorro, Benedicto, and Francks, Clyde

Abstract

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

Published
2023

43. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author

Schijven, Dick; https://orcid.org/0000-0001-5190-7241, Postema, Merel C; https://orcid.org/0000-0002-1536-7062, Fukunaga, Masaki; https://orcid.org/0000-0003-1010-2644, Matsumoto, Junya; https://orcid.org/0000-0003-4228-3208, Miura, Kenichiro, de Zwarte, Sonja M C, van Haren, Neeltje E M, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa; https://orcid.org/0000-0003-0570-5352, de la Foz, Víctor Ortiz-García; https://orcid.org/0000-0002-0627-1827, Tordesillas-Gutierrez, Diana; https://orcid.org/0000-0003-1458-3932, Vázquez-Bourgon, Javier; https://orcid.org/0000-0002-5478-3376, Crespo-Facorro, Benedicto, Alnæs, Dag; https://orcid.org/0000-0001-7361-5418, Dahl, Andreas; https://orcid.org/0000-0002-2668-8371, Westlye, Lars T; https://orcid.org/0000-0001-8644-956X, Agartz, Ingrid, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E; https://orcid.org/0000-0003-3482-721X, Schall, Ulrich; https://orcid.org/0000-0001-9041-4562, Scott, Rodney J; https://orcid.org/0000-0001-7724-3404, Carr, Vaughan J; https://orcid.org/0000-0002-8907-5804, Green, Melissa J; https://orcid.org/0000-0002-9361-4874, Henskens, Frans A; https://orcid.org/0000-0003-2358-5630, Loughland, Carmel M, Pantelis, Christos; https://orcid.org/0000-0002-9565-0238, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina; https://orcid.org/0000-0002-0526-8095, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo T J, Nenadić, Igor, Krämer, Bernd; https://orcid.org/0000-0002-1145-9103, Gruber, Oliver; https://orcid.org/0000-0003-1841-7413, Satterthwaite, Theodore D; https://orcid.org/0000-0001-7072-9399, Bustillo, Juan; https://orcid.org/0000-0001-8730-8152, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D; https://orcid.org/0000-0001-9058-0747, Ford, Judith M; https://orcid.org/0000-0002-6500-6548, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong; https://orcid.org/0000-0002-3522-3912, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan; https://orcid.org/0000-0003-2132-4445, Fuentes-Claramonte, Paola; https://orcid.org/0000-0002-1428-7976, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond; https://orcid.org/0000-0001-5557-1562, Sarró, Salvador; https://orcid.org/0000-0003-1835-2189, Pomarol-Clotet, Edith, Ciullo, Valentina; https://orcid.org/0000-0002-6870-6259, Piras, Fabrizio; https://orcid.org/0000-0003-3566-5494, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco; https://orcid.org/0000-0002-7432-4249, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N; https://orcid.org/0000-0003-0156-0395, Sim, Kang; https://orcid.org/0000-0003-3209-9626, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M; https://orcid.org/0000-0003-0829-0519, Kim, Woo-Sung, Chung, Young-Chul, Andreou, Christina, Schmidt, André; https://orcid.org/0000-0001-6055-8397, Borgwardt, Stefan; https://orcid.org/0000-0002-5792-3987, McIntosh, Andrew M, Whalley, Heather C, Lawrie, Stephen M; https://orcid.org/0000-0002-2444-5675, du Plessis, Stefan, Luckhoff, Hilmar K, Scheffler, Freda; https://orcid.org/0000-0002-8898-8599, Emsley, Robin, Grotegerd, Dominik, Lencer, Rebekka, Dannlowski, Udo; https://orcid.org/0000-0002-0623-3759, Edmond, Jesse T, Rootes-Murdy, Kelly, Stephen, Julia M, Mayer, Andrew R, Antonucci, Linda A, Fazio, Leonardo; https://orcid.org/0000-0003-4000-974X, Pergola, Giulio; https://orcid.org/0000-0002-9193-1841, Bertolino, Alessandro, Díaz-Caneja, Covadonga M; https://orcid.org/0000-0001-8538-3175, Janssen, Joost, Lois, Noemi G; https://orcid.org/0000-0002-6600-072X, Arango, Celso; https://orcid.org/0000-0003-3382-4754, Tomyshev, Alexander S, Lebedeva, Irina, Cervenka, Simon, Sellgren, Carl M, Georgiadis, Foivos, Kirschner, Matthias; https://orcid.org/0000-0002-9486-1439, Kaiser, Stefan, Hajek, Tomas, Skoch, Antonin; https://orcid.org/0000-0002-1739-3256, Spaniel, Filip, Kim, Minah; https://orcid.org/0000-0001-8668-0817, Kwak, Yoo Bin, Oh, Sanghoon; https://orcid.org/0000-0002-7394-5211, Kwon, Jun Soo; https://orcid.org/0000-0002-1060-1462, James, Anthony; https://orcid.org/0000-0002-2742-8328, Bakker, Geor, Knöchel, Christian, Stäblein, Michael, Oertel, Viola, Uhlmann, Anne; https://orcid.org/0000-0002-1753-7811, Howells, Fleur M, Stein, Dan J; https://orcid.org/0000-0001-7218-7810, Temmingh, Henk S; https://orcid.org/0000-0002-7688-0759, Diaz-Zuluaga, Ana M, Pineda-Zapata, Julian A, López-Jaramillo, Carlos, Homan, Stephanie; https://orcid.org/0000-0003-1449-7508, Ji, Ellen; https://orcid.org/0000-0003-1527-8868, Surbeck, Werner; https://orcid.org/0000-0002-4733-795X, Homan, Philipp; https://orcid.org/0000-0001-9034-148X, Fisher, Simon E; https://orcid.org/0000-0002-3132-1996, Franke, Barbara; https://orcid.org/0000-0003-4375-6572, Glahn, David C; https://orcid.org/0000-0002-4749-6977, Gur, Ruben C; https://orcid.org/0000-0002-9657-1996, Hashimoto, Ryota, Jahanshad, Neda, Luders, Eileen; https://orcid.org/0000-0001-5659-992X, Medland, Sarah E, Thompson, Paul M; https://orcid.org/0000-0002-4720-8867, Turner, Jessica A, van Erp, Theo G M, Francks, Clyde; https://orcid.org/0000-0002-9098-890X, Schijven, Dick; https://orcid.org/0000-0001-5190-7241, Postema, Merel C; https://orcid.org/0000-0002-1536-7062, Fukunaga, Masaki; https://orcid.org/0000-0003-1010-2644, Matsumoto, Junya; https://orcid.org/0000-0003-4228-3208, Miura, Kenichiro, de Zwarte, Sonja M C, van Haren, Neeltje E M, Cahn, Wiepke, Hulshoff Pol, Hilleke E, Kahn, René S, Ayesa-Arriola, Rosa; https://orcid.org/0000-0003-0570-5352, de la Foz, Víctor Ortiz-García; https://orcid.org/0000-0002-0627-1827, Tordesillas-Gutierrez, Diana; https://orcid.org/0000-0003-1458-3932, Vázquez-Bourgon, Javier; https://orcid.org/0000-0002-5478-3376, Crespo-Facorro, Benedicto, Alnæs, Dag; https://orcid.org/0000-0001-7361-5418, Dahl, Andreas; https://orcid.org/0000-0002-2668-8371, Westlye, Lars T; https://orcid.org/0000-0001-8644-956X, Agartz, Ingrid, Andreassen, Ole A; https://orcid.org/0000-0002-4461-3568, Jönsson, Erik G, Kochunov, Peter, Bruggemann, Jason M, Catts, Stanley V, Michie, Patricia T, Mowry, Bryan J, Quidé, Yann, Rasser, Paul E; https://orcid.org/0000-0003-3482-721X, Schall, Ulrich; https://orcid.org/0000-0001-9041-4562, Scott, Rodney J; https://orcid.org/0000-0001-7724-3404, Carr, Vaughan J; https://orcid.org/0000-0002-8907-5804, Green, Melissa J; https://orcid.org/0000-0002-9361-4874, Henskens, Frans A; https://orcid.org/0000-0003-2358-5630, Loughland, Carmel M, Pantelis, Christos; https://orcid.org/0000-0002-9565-0238, Weickert, Cynthia Shannon, Weickert, Thomas W, de Haan, Lieuwe, Brosch, Katharina; https://orcid.org/0000-0002-0526-8095, Pfarr, Julia-Katharina, Ringwald, Kai G, Stein, Frederike, Jansen, Andreas, Kircher, Tilo T J, Nenadić, Igor, Krämer, Bernd; https://orcid.org/0000-0002-1145-9103, Gruber, Oliver; https://orcid.org/0000-0003-1841-7413, Satterthwaite, Theodore D; https://orcid.org/0000-0001-7072-9399, Bustillo, Juan; https://orcid.org/0000-0001-8730-8152, Mathalon, Daniel H, Preda, Adrian, Calhoun, Vince D; https://orcid.org/0000-0001-9058-0747, Ford, Judith M; https://orcid.org/0000-0002-6500-6548, Potkin, Steven G, Chen, Jingxu, Tan, Yunlong; https://orcid.org/0000-0002-3522-3912, Wang, Zhiren, Xiang, Hong, Fan, Fengmei, Bernardoni, Fabio, Ehrlich, Stefan; https://orcid.org/0000-0003-2132-4445, Fuentes-Claramonte, Paola; https://orcid.org/0000-0002-1428-7976, Garcia-Leon, Maria Angeles, Guerrero-Pedraza, Amalia, Salvador, Raymond; https://orcid.org/0000-0001-5557-1562, Sarró, Salvador; https://orcid.org/0000-0003-1835-2189, Pomarol-Clotet, Edith, Ciullo, Valentina; https://orcid.org/0000-0002-6870-6259, Piras, Fabrizio; https://orcid.org/0000-0003-3566-5494, Vecchio, Daniela, Banaj, Nerisa, Spalletta, Gianfranco; https://orcid.org/0000-0002-7432-4249, Michielse, Stijn, van Amelsvoort, Therese, Dickie, Erin W, Voineskos, Aristotle N; https://orcid.org/0000-0003-0156-0395, Sim, Kang; https://orcid.org/0000-0003-3209-9626, Ciufolini, Simone, Dazzan, Paola, Murray, Robin M; 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Abstract

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

Published
2023

44. The universe is asymmetric, the mouse brain too

Author

Rivera-Olvera, Alejandro, Houwing, Danielle J., Ellegood, Jacob, Masifi, Shang, Martina, Stephany LL., Silberfeld, Andrew, Pourquie, Olivier, Lerch, Jason P., Francks, Clyde, Homberg, Judith R., van Heukelum, Sabrina, and Grandjean, Joanes

Abstract

Hemispheric brain asymmetry is a basic organizational principle of the human brain and has been implicated in various psychiatric conditions, including autism spectrum disorder. Brain asymmetry is not a uniquely human feature and is observed in other species such as the mouse. Yet, asymmetry patterns are generally nuanced, and substantial sample sizes are required to detect these patterns. In this pre-registered study, we use a mouse dataset from the Province of Ontario Neurodevelopmental Network, which comprises structural MRI data from over 2000 mice, including genetic models for autism spectrum disorder, to reveal the scope and magnitude of hemispheric asymmetry in the mouse. Our findings demonstrate the presence of robust hemispheric asymmetry in the mouse brain, such as larger right hemispheric volumes towards the anterior pole and larger left hemispheric volumes toward the posterior pole, opposite to what has been shown in humans. This suggests the existence of species-specific traits. Further clustering analysis identified distinct asymmetry patterns in autism spectrum disorder models, a phenomenon that is also seen in atypically developing participants. Our study shows potential for the use of mouse models to understand the biological bases of typical and atypical brain asymmetry but also warrants caution as asymmetry patterns seem to differ between humans and mice.

Published
2024
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46. Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia

Author

Gialluisi, Alessandro, Andlauer, Till F. M., Mirza-Schreiber, Nazanin, Moll, Kristina, Becker, Jessica, Hoffmann, Per, Ludwig, Kerstin U., Czamara, Darina, St Pourcain, Beate, Brandler, William, Honbolygó, Ferenc, Tóth, Dénes, Csépe, Valéria, Huguet, Guillaume, Morris, Andrew P., Hulslander, Jacqueline, Willcutt, Erik G., DeFries, John C., Olson, Richard K., Smith, Shelley D., Pennington, Bruce F., Vaessen, Anniek, Maurer, Urs, Lyytinen, Heikki, Peyrard-Janvid, Myriam, Leppänen, Paavo H. T., Brandeis, Daniel, Bonte, Milene, Stein, John F., Talcott, Joel B., Fauchereau, Fabien, Wilcke, Arndt, Francks, Clyde, Bourgeron, Thomas, Monaco, Anthony P., Ramus, Franck, Landerl, Karin, Kere, Juha, Scerri, Thomas S., Paracchini, Silvia, Fisher, Simon E., Schumacher, Johannes, Nöthen, Markus M., Müller-Myhsok, Bertram, and Schulte-Körne, Gerd

Published
2019
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49. Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity

Author

Guadalupe, Tulio, Zwiers, Marcel P., Wittfeld, Katharina, Teumer, Alexander, Vasquez, Alejandro Arias, Hoogman, Martine, Hagoort, Peter, Fernandez, Guillen, Buitelaar, Jan, van Bokhoven, Hans, Hegenscheid, Katrin, Völzke, Henry, Franke, Barbara, Fisher, Simon E., Grabe, Hans J., and Francks, Clyde

Published
2015
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