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1. Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive-Behavioral Therapy in Children With Obsessive-Compulsive Disorder.

Author: Bertolín, Sara, Alonso, Pino, Martínez-Zalacaín, Ignacio, Menchón, Jose, Jimenez-Murcia, Susana, Baker, Justin, Bargalló, Nuria, Batistuzzo, Marcelo, Boedhoe, Premika, Brennan, Brian, Feusner, Jamie, Fitzgerald, Kate, Fontaine, Martine, Hansen, Bjarne, Hirano, Yoshiyuki, Hoexter, Marcelo, Huyser, Chaim, Jahanshad, Neda, Jaspers-Fayer, Fern, Kuno, Masaru, Kvale, Gerd, Lazaro, Luisa, Machado-Sousa, Mafalda, Marsh, Rachel, Morgado, Pedro, Nakagawa, Akiko, Norman, Luke, Nurmi, Erika, ONeill, Joseph, Ortiz, Ana, Perriello, Chris, Picó-Pérez, Maria, Shavitt, Roseli, Shimizu, Eiji, Simpson, Helen, Stewart, S, Thomopoulos, Sophia, Thorsen, Anders, Walitza, Susanne, Wolters, Lidewij, Thompson, Paul, van den Heuvel, Odile, Stein, Dan, Soriano-Mas, Carles, and Piacentini, John
Subjects: anxiety disorders, cognitive-behavioral therapy, magnetic resonance imaging, neuroimaging, obsessive-compulsive disorder, Adult, Adolescent, Humans, Child, Child, Preschool, Prefrontal Cortex, Obsessive-Compulsive Disorder, Magnetic Resonance Imaging, Frontal Lobe, Cognitive Behavioral Therapy
Abstract: OBJECTIVE: Cognitive-behavioral therapy (CBT) is considered a first-line treatment for obsessive-compulsive disorder (OCD) in pediatric and adult populations. Nevertheless, some patients show partial or null response. The identification of predictors of CBT response may improve clinical management of patients with OCD. Here, we aimed to identify structural magnetic resonance imaging (MRI) predictors of CBT response in 2 large series of children and adults with OCD from the worldwide ENIGMA-OCD consortium. METHOD: Data from 16 datasets from 13 international sites were included in the study. We assessed which variations in baseline cortical thickness, cortical surface area, and subcortical volume predicted response to CBT (percentage of baseline to post-treatment symptom reduction) in 2 samples totaling 168 children and adolescents (age range 5-17.5 years) and 318 adult patients (age range 18-63 years) with OCD. Mixed linear models with random intercept were used to account for potential cross-site differences in imaging values. RESULTS: Significant results were observed exclusively in the pediatric sample. Right prefrontal cortex thickness was positively associated with the percentage of CBT response. In a post hoc analysis, we observed that the specific changes accounting for this relationship were a higher thickness of the frontal pole and the rostral middle frontal gyrus. We observed no significant effects of age, sex, or medication on our findings. CONCLUSION: Higher cortical thickness in specific right prefrontal cortex regions may be important for CBT response in children with OCD. Our findings suggest that the right prefrontal cortex plays a relevant role in the mechanisms of action of CBT in children.
Published: 2023

2. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author: Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle C., Boomsma, Dorret I., Roessner, Veit, Wolanczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, Dietrich, Andrea, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., and Paschou, Peristera
Published: 2023
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3. 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

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. Investigation of gene-environment interactions in relation to tic severity.

Author: Abdulkadir, Mohamed, Yu, Dongmei, Osiecki, Lisa, King, Robert A, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Plessen, Kerstin J, Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Visscher, Frank, Zinner, Samuel H, Mathews, Carol A, Scharf, Jeremiah M, Tischfield, Jay A, Heiman, Gary A, Dietrich, Andrea, and Hoekstra, Pieter J
Subjects: Humans, Tourette Syndrome, Tics, Severity of Illness Index, Attention Deficit Disorder with Hyperactivity, Pregnancy, Female, Genome-Wide Association Study, Gene-Environment Interaction, Autism Spectrum Disorder, Gene–environment interaction, Pre- and perinatal complications, Tic severity, Tourette syndrome, Mental Health, Autism, Genetics, Pediatric, Neurosciences, Serious Mental Illness, Brain Disorders, Human Genome, Neurodegenerative, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Mental health, Gene-environment interaction, Psychology, Neurology & Neurosurgery
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.
Published: 2021

7. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium: medication matters.

Author: Bruin, Willem B, Taylor, Luke, Thomas, Rajat M, Shock, Jonathan P, Zhutovsky, Paul, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Assogna, Francesca, Benedetti, Francesco, Beucke, Jan C, Boedhoe, Premika SW, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P, Buitelaar, Jan K, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A, Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Gürsel, Deniz A, Hauser, Tobias U, Hirano, Yoshiyuki, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Ivanov, Iliyan, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Liu, Yanni, Lochner, Christine, Lázaro, Luisa, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O'Neill, Joseph, Pariente, Jose C, Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Rus-Oswald, Oana G, Sakai, Yuki, Sato, João R, Schmaal, Lianne, Shimizu, Eiji, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Szeszko, Philip R, Tolin, David F, Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, ENIGMA-OCD Working Group, Thompson, Paul M, van den Heuvel, Odile A, Stein, Dan J, and van Wingen, Guido A
Subjects: ENIGMA-OCD Working Group, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
Published: 2020

8. Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups

Author: Boedhoe, Premika SW, van Rooij, Daan, Hoogman, Martine, Twisk, Jos WR, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anikin, Anatoly, Anticevic, Alan, Arango, Celso, Arnold, Paul D, Asherson, Philip, Assogna, Francesca, Auzias, Guillaume, Banaschewski, Tobias, Baranov, Alexander, Batistuzzo, Marcelo C, Baumeister, Sarah, Baur-Streubel, Ramona, Behrmann, Marlene, Bellgrove, Mark A, Benedetti, Francesco, Beucke, Jan C, Biederman, Joseph, Bollettini, Irene, Bose, Anushree, Bralten, Janita, Bramati, Ivanei E, Brandeis, Daniel, Brem, Silvia, Brennan, Brian P, Busatto, Geraldo F, Calderoni, Sara, Calvo, Anna, Calvo, Rosa, Castellanos, Francisco X, Cercignani, Mara, Chaim-Avancini, Tiffany M, Chantiluke, Kaylita C, Cheng, Yuqi, Cho, Kang Ik K, Christakou, Anastasia, Coghill, David, Conzelmann, Annette, Cubillo, Ana I, Dale, Anders M, Dallaspezia, Sara, Daly, Eileen, Denys, Damiaan, Deruelle, Christine, Di Martino, Adriana, Dinstein, Ilan, Doyle, Alysa E, Durston, Sarah, Earl, Eric A, Ecker, Christine, Ehrlich, Stefan, Ely, Benjamin A, Epstein, Jeffrey N, Ethofer, Thomas, Fair, Damien A, Fallgatter, Andreas J, Faraone, Stephen V, Fedor, Jennifer, Feng, Xin, Feusner, Jamie D, Fitzgerald, Jackie, Fitzgerald, Kate D, Fouche, Jean-Paul, Freitag, Christine M, Fridgeirsson, Egill A, Frodl, Thomas, Gabel, Matt C, Gallagher, Louise, Gogberashvili, Tinatin, Gori, Ilaria, Gruner, Patricia, Gürsel, Deniz A, Haar, Shlomi, Haavik, Jan, Hall, Geoffrey B, Harrison, Neil A, Hartman, Catharina A, Heslenfeld, Dirk J, Hirano, Yoshiyuki, Hoekstra, Pieter J, Hoexter, Marcelo Q, Hohmann, Sarah, Høvik, Marie F, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, Jalbrzikowski, Maria, James, Anthony, Janssen, Joost, Jaspers-Fayer, Fern, Jernigan, Terry L, Kapilushniy, Dmitry, and Kardatzki, Bernd
Subjects: Attention Deficit Hyperactivity Disorder (ADHD), Behavioral and Social Science, Clinical Research, Mental Health, Neurosciences, Pediatric, Autism, Intellectual and Developmental Disabilities (IDD), Brain Disorders, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Aetiology, Mental health, Neurological, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Cerebrum, Child, Female, Human Development, Humans, Male, Neuroimaging, Obsessive-Compulsive Disorder, Organ Size, Psychopathology, Research Report, Systems Analysis, ENIGMA ADHD working group, ENIGMA ASD working group, ENIGMA OCD working group, Attention Deficit Hyperactivity Disorder, ENIGMA, Structural MRI, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectiveAttention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data.MethodsStructural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures).ResultsNo shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood.ConclusionsThe study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.
Published: 2020

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

Author: Kong, Xiang-Zhen, Boedhoe, Premika SW, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Arnold, Paul D, Assogna, Francesca, Baker, Justin T, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P, Buitelaar, Jan, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A, Feusner, Jamie, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Glahn, David C, Gruner, Patricia, Gürsel, Deniz A, Hauser, Tobias U, Hirano, Yoshiyuki, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Lazaro, Luisa, Liu, Yanni, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Medland, Sarah E, Menchón, José M, Minuzzi, Luciano, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O'Neill, Joseph, Pariente, Jose C, Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, YC Janardhan, Rus-Oswald, Oana Georgiana, Sakai, Yuki, Sato, Joao R, Schmaal, Lianne, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Szeszko, Philip R, Tolin, David F, Tsuchiyagaito, Aki, van Rooij, Daan, van Wingen, Guido A, Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, Group, ENIGMA OCD Working, Anticevic, Alan, Banaj, Nerisa, and Bargalló, Nuria
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Serious Mental Illness, Mental Health, Neurosciences, Brain Disorders, Clinical Research, Anxiety Disorders, Neurological, Mental health, Adult, Brain, Brain Mapping, Child, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Obsessive-Compulsive Disorder, Thalamus, Brain asymmetry, Laterality, Mega-analysis, Obsessive-compulsive disorder, Pallidum, ENIGMA OCD Working Group, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract: BackgroundLateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD.MethodsWe studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status.ResultsIn the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets.ConclusionsThe results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.
Published: 2020

10. Corrigendum

Author: Yun, Je-Yeon, Boedhoe, Premika SW, Vriend, Chris, Jahanshad, Neda, Abe, Yoshinari, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D, Fouche, Jean-Paul, Gimenez, Monica, Gruner, Patricia, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Lazaro, Luisa, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martinez-Zalacain, Ignacio, Mataix-Cols, David, Menchon, Jose M, Minuzzi, Luciano, Morgado, Pedro, Moreira, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O'Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C, Szeszko, Philip R, Tolin, David F, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, van Wingen, Guido A, Xu, Jian, Xu, Xiufeng, Zhao, Qing, Thompson, Paul M, Stein, Dan J, van den Heuvel, Odile A, and Kwon, Jun Soo
Subjects: Biomedical and Clinical Sciences, Health Sciences, Psychology, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery, Biomedical and clinical sciences, Health sciences
Published: 2020

11. Brain structural covariance networks in obsessive-compulsive disorder: a graph analysis from the ENIGMA Consortium

Author: Yun, Je-Yeon, Boedhoe, Premika SW, Vriend, Chris, Jahanshad, Neda, Abe, Yoshinari, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D, Fouche, Jean-Paul, Giménez, Mònica, Gruner, Patricia, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Lazaro, Luisa, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morgado, Pedro, Moreira, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, O’Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C, Szeszko, Philip R, Tolin, David F, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, van Wingen, Guido A, Xu, Jian, Xu, Xiufeng, Zhao, Qing, van den Heuvel, Odile3 A, Stein, Dan J, Thompson, Paul M, Ik, Kang, and Cho, K
Subjects: Mental Health, Brain Disorders, Serious Mental Illness, Clinical Research, Neurosciences, Neurological, Mental health, Adult, Brain, Cerebral Cortex, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Neural Pathways, Obsessive-Compulsive Disorder, brain structural covariance network, graph theory, obsessive-compulsive disorder, pharmacotherapy, illness duration, ENIGMA-OCD working group, Medical and Health Sciences, Psychology and Cognitive Sciences, Neurology & Neurosurgery
Abstract: Brain structural covariance networks reflect covariation in morphology of different brain areas and are thought to reflect common trajectories in brain development and maturation. Large-scale investigation of structural covariance networks in obsessive-compulsive disorder (OCD) may provide clues to the pathophysiology of this neurodevelopmental disorder. Using T1-weighted MRI scans acquired from 1616 individuals with OCD and 1463 healthy controls across 37 datasets participating in the ENIGMA-OCD Working Group, we calculated intra-individual brain structural covariance networks (using the bilaterally-averaged values of 33 cortical surface areas, 33 cortical thickness values, and six subcortical volumes), in which edge weights were proportional to the similarity between two brain morphological features in terms of deviation from healthy controls (i.e. z-score transformed). Global networks were characterized using measures of network segregation (clustering and modularity), network integration (global efficiency), and their balance (small-worldness), and their community membership was assessed. Hub profiling of regional networks was undertaken using measures of betweenness, closeness, and eigenvector centrality. Individually calculated network measures were integrated across the 37 datasets using a meta-analytical approach. These network measures were summated across the network density range of K = 0.10-0.25 per participant, and were integrated across the 37 datasets using a meta-analytical approach. Compared with healthy controls, at a global level, the structural covariance networks of OCD showed lower clustering (P
Published: 2020

12. Error Processing and Inhibitory Control in Obsessive-Compulsive Disorder: A Meta-analysis Using Statistical Parametric Maps

Author: Norman, Luke J, Taylor, Stephan F, Liu, Yanni, Radua, Joaquim, Chye, Yann, De Wit, Stella J, Huyser, Chaim, Karahanoglu, F Isik, Luks, Tracy, Manoach, Dara, Mathews, Carol, Rubia, Katya, Suo, Chao, van den Heuvel, Odile A, Yücel, Murat, and Fitzgerald, Kate
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Clinical Research, Neurosciences, Brain Disorders, Serious Mental Illness, Mental health, Adolescent, Adult, Brain, Brain Mapping, Female, Humans, Inhibition, Psychological, Magnetic Resonance Imaging, Male, Neural Pathways, Obsessive-Compulsive Disorder, Young Adult, Error processing, fMRI, Inhibitory control, Meta-analysis, OCD, Performance monitoring, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biological sciences, Biomedical and clinical sciences
Abstract: BackgroundError processing and inhibitory control enable the adjustment of behaviors to meet task demands. Functional magnetic resonance imaging studies report brain activation abnormalities in patients with obsessive-compulsive disorder (OCD) during both processes. However, conclusions are limited by inconsistencies in the literature and small sample sizes. Therefore, the aim here was to perform a meta-analysis of the existing literature using unthresholded statistical maps from previous studies.MethodsA voxelwise seed-based d mapping meta-analysis was performed using t-maps from studies comparing patients with OCD and healthy control subjects (HCs) during error processing and inhibitory control. For the error processing analysis, 239 patients with OCD (120 male; 79 medicated) and 229 HCs (129 male) were included, while the inhibitory control analysis included 245 patients with OCD (120 male; 91 medicated) and 239 HCs (135 male).ResultsPatients with OCD, relative to HCs, showed longer inhibitory control reaction time (standardized mean difference = 0.20, p = .03, 95% confidence interval = 0.016, 0.393) and more inhibitory control errors (standardized mean difference = 0.22, p = .02, 95% confidence interval = 0.039, 0.399). In the brain, patients showed hyperactivation in the bilateral dorsal anterior cingulate cortex, supplementary motor area, and pre-supplementary motor area as well as right anterior insula/frontal operculum and anterior lateral prefrontal cortex during error processing but showed hypoactivation during inhibitory control in the rostral and ventral anterior cingulate cortices and bilateral thalamus/caudate, as well as the right anterior insula/frontal operculum, supramarginal gyrus, and medial orbitofrontal cortex (all seed-based d mapping z value >2, p < .001).ConclusionsA hyperactive error processing mechanism in conjunction with impairments in implementing inhibitory control may underlie deficits in stopping unwanted compulsive behaviors in the disorder.
Published: 2019

13. An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Boedhoe, Premika SW, Heymans, Martijn W, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Hanna, Gregory L, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nishida, Seiji, Nurmi, Erika L, O'Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Reess, Tim J, Sakai, Yuki, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C, Szeszko, Philip R, Tolin, David F, van Wingen, Guido A, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Yun, Je-Yeon, Working-Group, ENIGMA-OCD, Thompson, Paul M, Stein, Dan J, van den Heuvel, Odile A, and Twisk, Jos WR
Subjects: Biomedical and Clinical Sciences, Information and Computing Sciences, Neurosciences, Applied Computing, Machine Learning, neuroimaging, MRI, IPD meta-analysis, mega-analysis, linear mixed-effect models, ENIGMA-OCD Working-Group, Cognitive Sciences, Applied computing, Machine learning
Abstract: Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.
Published: 2019

14. The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Author: Weeland, Cees J., Kasprzak, Selina, de Joode, Niels T., Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Balachander, Srinivas, Banaj, Nerisa, Bargallo, Nuria, Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Brecke, Vilde, Brem, Silvia, Cappi, Carolina, Cheng, Yuqi, Cho, Kang Ik K., Costa, Daniel L. C., Dallaspezia, Sara, Denys, Damiaan, Eng, Goi Khia, Ferreira, Sónia, Feusner, Jamie D., Fontaine, Martine, Fouche, Jean-Paul, Grazioplene, Rachael G., Gruner, Patricia, He, Mengxin, Hirano, Yoshiyuki, Hoexter, Marcelo Q., Huyser, Chaim, Hu, Hao, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Kim, Minah, Koch, Kathrin, Bin Kwak, Yoo, Kwon, Jun Soo, Lazaro, Luisa, Li, Chiang-shan R., Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, Jose M., Minnuzi, Luciano, Moreira, Pedro Silva, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Narayanaswamy, Janardhanan C., Nurmi, Erika L., Ortiz, Ana E., Pariente, Jose C., Piacentini, John, Picó-Pérez, Maria, Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, Y. C. Janardhan, Rodriguez-Manrique, Daniela, Sakai, Yuki, Shimizu, Eiji, Shivakumar, Venkataram, Simpson, Helen Blair, Soreni, Noam, Soriano-Mas, Carles, Sousa, Nuno, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Stewart, S. Evelyn, Szeszko, Philip R., Takahashi, Jumpei, Tanamatis, Tais, Tang, Jinsong, Thorsen, Anders Lillevik, Tolin, David, van der Werf, Ysbrand D., van Marle, Hein, van Wingen, Guido A., Vecchio, Daniela, Venkatasubramanian, G., Walitza, Susanne, Wang, Jicai, Wang, Zhen, Watanabe, Anri, Wolters, Lidewij H., Xu, Xiufeng, Yun, Je-Yeon, Zhao, Qing, White, Tonya, Thompson, Paul M., Stein, Dan J., van den Heuvel, Odile A., and Vriend, Chris
Published: 2022
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15. Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Boedhoe, Premika SW, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Hanna, Gregory L, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nishida, Seiji, Nurmi, Erika, O’Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, YC Janardhan, Reess, Tim J, Sakai, Yuki, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C, Szeszko, Philip R, Tolin, David F, van Wingen, Guido A, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Yun, Je-Yeon, Thompson, Paul M, Stein, Dan J, van den Heuvel, Odile A, Bargalló, Nuria, Brandeis, Daniel, Buimer, Elizabeth, Busatto, Geraldo F, de Vries, Froukje E, de Wit, Stella J, Drechsler, Renate, and Falini, Andrea
Subjects: Biological Psychology, Biomedical and Clinical Sciences, Psychology, Pediatric, Neurosciences, Mental Health, Serious Mental Illness, Brain Disorders, Neurological, Mental health, Adolescent, Adult, Age of Onset, Cerebral Cortex, Child, Frontal Lobe, Humans, Magnetic Resonance Imaging, Obsessive-Compulsive Disorder, Parietal Lobe, Reference Values, Temporal Lobe, Young Adult, ENIGMA-OCD Working Group, ENIGMA OCD Working Group, Cortical Thickness, FreeSurfer, MRI, Surface Area, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract: ObjectiveBrain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.MethodT1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.ResultsIn adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.ConclusionsThe parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
Published: 2018

16. Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Author: Abdulkadir, Mohamed, Londono, Douglas, Gordon, Derek, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, Elzerman, Lonneke, Fremer, Carolin, Fründt, Odette, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Jakubovski, Ewgeni, Kim, Young Key, Kim, Young Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Ludolph, Andrea G, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Müller-Vahl, Kirsten, Münchau, Alexander, Murphy, Tara L, Plessen, Kerstin J, Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Tübing, Jennifer, van den Ban, Els, Visscher, Frank, Wanderer, Sina, Woods, Martin, Zinner, Samuel H, King, Robert A, Tischfield, Jay A, Heiman, Gary A, Hoekstra, Pieter J, and Dietrich, Andrea
Subjects: Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Autism, Genetics, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), Tourette Syndrome, Neurodegenerative, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adolescent, Adult, Child, Child, Preschool, Family Health, Female, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Microtubule-Associated Proteins, Middle Aged, Polymorphism, Single Nucleotide, Severity of Illness Index, Tic Disorders, Tryptophan Hydroxylase, Young Adult, Attention-deficit/hyperactivity disorder, Candidate gene study, Obsessive-compulsive disorder, Tourette syndrome, Transmission Disequilibrium Test, Obsessive–compulsive disorder, Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology
Abstract: Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.
Published: 2018

17. An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group.

Author: Boedhoe, Premika, Heymans, Martijn, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie, Anticevic, Alan, Arnold, Paul, Batistuzzo, Marcelo, Benedetti, Francesco, Beucke, Jan, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang, Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie, Fitzgerald, Kate, Fouche, Jean-Paul, Fridgeirsson, Egill, Gruner, Patricia, Hanna, Gregory, Hibar, Derrek, Hoexter, Marcelo, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José, Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan, Nishida, Seiji, Nurmi, Erika, Oneill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, Y, Reess, Tim, Sakai, Yuki, Sato, Joao, Simpson, H, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael, Szeszko, Philip, Tolin, David, van Wingen, Guido, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Yun, Je-Yeon, Thompson, Paul, Stein, Dan, van den Heuvel, Odile, and Twisk, Jos
Subjects: IPD meta-analysis, MRI, linear mixed-effect models, mega-analysis, neuroimaging
Abstract: Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.
Published: 2018

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

Author: Guadalupe, Tulio, Mathias, Samuel R, vanErp, Theo GM, Whelan, Christopher D, Zwiers, Marcel P, Abe, Yoshinari, Abramovic, Lucija, Agartz, Ingrid, Andreassen, Ole A, Arias-Vásquez, Alejandro, Aribisala, Benjamin S, Armstrong, Nicola J, Arolt, Volker, Artiges, Eric, Ayesa-Arriola, Rosa, Baboyan, Vatche G, Banaschewski, Tobias, Barker, Gareth, Bastin, Mark E, Baune, Bernhard T, Blangero, John, Bokde, Arun LW, Boedhoe, Premika SW, Bose, Anushree, Brem, Silvia, Brodaty, Henry, Bromberg, Uli, Brooks, Samantha, Büchel, Christian, Buitelaar, Jan, Calhoun, Vince D, Cannon, Dara M, Cattrell, Anna, Cheng, Yuqi, Conrod, Patricia J, Conzelmann, Annette, Corvin, Aiden, Crespo-Facorro, Benedicto, Crivello, Fabrice, Dannlowski, Udo, de Zubicaray, Greig I, de Zwarte, Sonja MC, Deary, Ian J, Desrivières, Sylvane, Doan, Nhat Trung, Donohoe, Gary, Dørum, Erlend S, Ehrlich, Stefan, Espeseth, Thomas, Fernández, Guillén, Flor, Herta, Fouche, Jean-Paul, Frouin, Vincent, Fukunaga, Masaki, Gallinat, Jürgen, Garavan, Hugh, Gill, Michael, Suarez, Andrea Gonzalez, Gowland, Penny, Grabe, Hans J, Grotegerd, Dominik, Gruber, Oliver, Hagenaars, Saskia, Hashimoto, Ryota, Hauser, Tobias U, Heinz, Andreas, Hibar, Derrek P, Hoekstra, Pieter J, Hoogman, Martine, Howells, Fleur M, Hu, Hao, Hulshoff Pol, Hilleke E, Huyser, Chaim, Ittermann, Bernd, Jahanshad, Neda, Jönsson, Erik G, Jurk, Sarah, Kahn, Rene S, Kelly, Sinead, Kraemer, Bernd, Kugel, Harald, Kwon, Jun Soo, Lemaitre, Herve, Lesch, Klaus-Peter, Lochner, Christine, Luciano, Michelle, Marquand, Andre F, Martin, Nicholas G, Martínez-Zalacaín, Ignacio, Martinot, Jean-Luc, Mataix-Cols, David, Mather, Karen, McDonald, Colm, McMahon, Katie L, Medland, Sarah E, Menchón, José M, Morris, Derek W, Mothersill, Omar, Maniega, Susana Munoz, and Mwangi, Benson
Subjects: Brain, Humans, Magnetic Resonance Imaging, Organ Size, Aging, Sex Characteristics, Quantitative Trait, Heritable, Adolescent, Adult, Aged, Middle Aged, Female, Male, Functional Laterality, Meta-Analysis as Topic, Young Adult, Age, Enigma, Handedness, Heritability, Meta-analysis, Sex, Subcortical brain asymmetry, Quantitative Trait, Heritable, Medical and Health Sciences, Psychology and Cognitive Sciences, Experimental Psychology
Abstract: The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.
Published: 2017

20. Pre- and perinatal complications in relation to Tourette syndrome and co-occurring obsessive-compulsive disorder and attention-deficit/hyperactivity disorder

Author: Abdulkadir, Mohamed, Tischfield, Jay A, King, Robert A, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, de Bruijn, Sebastian FTM, Elzerman, Lonneke, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Lamerz, Andreas, Leventhal, Bennett, Ludolph, Andrea G, Madruga-Garrido, Marcos, Maras, Athanasios, Messchendorp, Marieke D, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Murphy, Tara L, Openneer, Thaïra JC, Plessen, Kerstin J, Rath, Judith JG, Roessner, Veit, Fründt, Odette, Shin, Eun-Young, Sival, Deborah A, Song, Dong-Ho, Song, Jungeun, Stolte, Anne-Marie, Tübing, Jennifer, van den Ban, Els, Visscher, Frank, Wanderer, Sina, Woods, Martin, Zinner, Samuel H, State, Matthew W, Heiman, Gary A, Hoekstra, Pieter J, and Dietrich, Andrea
Subjects: Clinical and Health Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Tourette Syndrome, Neurosciences, Neurodegenerative, Pediatric, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Infant Mortality, Serious Mental Illness, Perinatal Period - Conditions Originating in Perinatal Period, Preterm, Low Birth Weight and Health of the Newborn, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Child, Child, Preschool, Europe, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Parent-Child Relations, Pregnancy, Pregnancy Complications, Psychiatric Status Rating Scales, Republic of Korea, Retrospective Studies, Severity of Illness Index, Sex Factors, Tic Disorders, United States, Young Adult, Attention-deficit hyperactivity disorder, Delivery, Obsessive-compulsive disorder, Prenatal, Tourette syndrome, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract: Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.
Published: 2016

21. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author: National Institutes of Health (US), Lundbeck Foundation, German Research Foundation, Royal Netherlands Academy of Arts and Sciences, National Science Centre (Poland), National Institute for Health and Care Research (US), NIHR Biomedical Research Centre (UK), Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle, Boomsma, Dorret I., Roessner, Veit, Wolańczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya‑Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Münchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), The EMTICS collaborative group, Dietrich, Andrea, The TS-EUROTRAIN Network, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., Paschou, Peristera, National Institutes of Health (US), Lundbeck Foundation, German Research Foundation, Royal Netherlands Academy of Arts and Sciences, National Science Centre (Poland), National Institute for Health and Care Research (US), NIHR Biomedical Research Centre (UK), Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle, Boomsma, Dorret I., Roessner, Veit, Wolańczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya‑Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Münchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), The EMTICS collaborative group, Dietrich, Andrea, The TS-EUROTRAIN Network, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., and Paschou, Peristera
Abstract: Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.
Published: 2023

22. Reproducibility in the absence of selective reporting : An illustration from large-scale brain asymmetry research

Author: Kong, Xiang-Zhen, Francks, Clyde, Allen, Nicholas B., Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C., Hoekstra, Pieter J., Holst, Ruth J., Hoogman, Martine, Høvik, Marie F., Howells, Fleur M., Ames, David, Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L., Jönsson, Erik G, Kaleda, Vasily, Kelly, Clare, Andreassen, Ole A., Kerich, Michael, Keshavan, Matcheri S., Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Krämer, Bernd, Krug, Axel, Kuntsi, Jonna, Vasquez, Alejandro Arias, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Lim, Kelvin O., Liu, Jia, Armstrong, Nicola J., Lochner, Christine, London, Edythe D., Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J., Mackey, Scott, MacMaster, Frank P., Maingault, Sophie, Malpas, Charles B., Asherson, Phil, Malt, Ulrik F., Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R., McCarthy, Hazel, Medland, Sarah, Metha, Mitul, Mitchell, Philip B., Mueller, Bryon A., Maniega, Susana Muñoz, Bergo, Felipe, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L., McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M., Narayanaswamy, Janardhanan C., Moreira, José Carlos Vasques, Nerland, Stener, Bastin, Mark E., Nestor, Liam, Newman, Erik, Nigg, Joel T., Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Orr, Catherine, Batalla, Albert, Overs, Bronwyn, Paloyelis, Yannis, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, Polier, Georg G., Pomarol-Clotet, Edith, Portella, Maria J., Qiu, Jiang, Radua, Joaquim, Bauer, Jochen, Ramos-Quiroga, Josep Antoni, Reddy, Y. C. Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Schmaal, Lianne, Baune, Bernhard T, Schulte-Rüther, Martin, Schweren, Lizanne, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J., Simmons, Alan N., Simulionyte, Egle, Sinha, Rajita, Baur-Streubel, Ramona, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R., Stein, Dan J., Stein, Elliot A., Stevens, Michael, Strike, Lachlan T., Biederman, Joseph, Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S., Thoma, Robert J., Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Erp, Theo G. M., Blaine, Sara K., Heuvel, Odile A., Meer, Dennis, Eijk, Liza, Vance, Alasdair, Veer, Ilya M., Veltman, Dick J., Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Voineskos, Aristotle N, Boedhoe, Premika, Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., White, Tonya, Bøen, Erlend, Wiers, Reinout W., Wright, Margaret J., Wittfeld, Katharina, Yang, Tony T., Yasuda, Clarissa L., Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Zhen, Zonglei, Bose, Anushree, Zhu, Xing-xing, Ziegler, Georg C., Zubicaray, Greig I., Zwiers, Marcel, Project, Karolinska Schizophrenia, Glahn, David C., Crivello, Fabrice, Fisher, Simon E., Thompson, Paul M., Bralten, Janita, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Collste, Karin, Brandeis, Daniel, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl, Brem, Silvia, Mathias, Samuel R., Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J., Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Cannon, Dara M., Guadalupe, Tulio, Caparelli, Elisabeth C., Castellanos, Francisco X., Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Clark, Vincent P., Abé, Christoph, Coghill, David, Connolly, Colm G., Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, Bruttopilo, Sara Ambrosino, Zeeuw, Patrick, Deary, Ian J., Demeter, Damion V., Di Martino, Adriana, Dickie, Erin W, Dietsche, Bruno, Doan, Nhat Trung, Doherty, Colin P., Doyle, Alysa, Durston, Sarah, Earl, Eric, Akudjedu, Theophilus N., Ehrlich, Stefan, Ekman, Carl Johan, Elvsåshagen, Torbjørn, Epstein, Jeffery N., Fair, Damien A., Faraone, Stephen V., Fernández, Guillén, Flint, Claas, Filho, Geraldo Busatto, Förster, Katharina, Aleman, Andre, Fouche, Jean-Paul, Foxe, John J., Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice M., Garavan, Hugh, Santos Garcia, Danielle, Gotlib, Ian H., Goudriaan, Anna E., Grabe, Hans Jörgen, Alhusaini, Saud, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K., Harris, Mathew A., Hartman, Catharina A., Carmen Valdés Hernández, Maria, Alhusaini, Saud, Del Carmen Valdés Hernández, Maria, Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C., Hoekstra, Pieter J., van Holst, Ruth J., Hoogman, Martine, Høvik, Marie F., Allen, Nicholas B., Howells, Fleur M., Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L., Jönsson, Erik G., Kaleda, Vasily, Ames, David, Kelly, Clare, Kerich, Michael, Keshavan, Matcheri S., Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Krämer, Bernd, Krug, Axel, Andreassen, Ole A., Kuntsi, Jonna, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Lim, Kelvin O., Vasquez, Alejandro Arias, Liu, Jia, Lochner, Christine, London, Edythe D., Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J., Mackey, Scott, MacMaster, Frank P., Maingault, Sophie, Armstrong, Nicola J., Malpas, Charles B., Malt, Ulrik F., Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R., McCarthy, Hazel, Medland, Sarah, Metha, Mitul, Mitchell, Philip B., Mueller, Bryon A., Asherson, Phil, Maniega, Susana Muñoz, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L., McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M., Narayanaswamy, Janardhanan C., Moreira, José Carlos Vasques, Bergo, Felipe, Nerland, Stener, Nestor, Liam, Newman, Erik, Nigg, Joel T., Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L., Oosterlaan, Jaap, Oranje, Bob, Bastin, Mark E., Orr, Catherine, Overs, Bronwyn, Paloyelis, Yannis, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, von Polier, Georg G., Pomarol-Clotet, Edith, Portella, Maria J., Qiu, Jiang, Batalla, Albert, Radua, Joaquim, Ramos-Quiroga, Josep Antoni, Reddy, Y. C. Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Bauer, Jochen, Schmaal, Lianne, Schulte-Rüther, Martin, Schweren, Lizanne, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J., Simmons, Alan N., Simulionyte, Egle, Baune, Bernhard T., Sinha, Rajita, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R., Stein, Dan J., Stein, Elliot A., Stevens, Michael, Baur-Streubel, Ramona, Strike, Lachlan T., Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S., Thoma, Robert J., Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Biederman, Joseph, van Erp, Theo G. M., van den Heuvel, Odile A., van der Meer, Dennis, van Eijk, Liza, Vance, Alasdair, Veer, Ilya M., Veltman, Dick J., Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Blaine, Sara K., Voineskos, Aristotle N., Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M., Wen, Wei, Westlye, Lars T., Whelan, Christopher D., Boedhoe, Premika, White, Tonya, Wiers, Reinout W., Wright, Margaret J., Wittfeld, Katharina, Yang, Tony T., Yasuda, Clarissa L., Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Bøen, Erlend, Zhen, Zonglei, Zhu, Xing-Xing, Ziegler, Georg C., de Zubicaray, Greig I., Zwiers, Marcel, Project, Karolinska Schizophrenia, Glahn, David C., Crivello, Fabrice, Fisher, Simon E., Thompson, Paul M., Bose, Anushree, Francks, Clyde, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Piehl, Fredrik, Agartz, Ingrid, Bralten, Janita, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Sellgren, Carl, Brandeis, Daniel, Kong, Xiang-Zhen, Brem, Silvia, Brodaty, Henry, Yüksel, Dilara, Brooks, Samantha J., Buitelaar, Jan, Bürger, Christian, Bülow, Robin, Calhoun, Vince, Calvo, Anna, Canales-Rodríguez, Erick Jorge, Mathias, Samuel R., Cannon, Dara M., Caparelli, Elisabeth C., Castellanos, Francisco X., Cendes, Fernando, Chaim-Avancini, Tiffany Moukbel, Chantiluke, Kaylita, Chen, Qun-Lin, Chen, Xiayu, Cheng, Yuqi, Christakou, Anastasia, Guadalupe, Tulio, Clark, Vincent P., Coghill, David, Connolly, Colm G., Conzelmann, Annette, Córdova-Palomera, Aldo, Cousijn, Janna, Crow, Tim, Cubillo, Ana, Dannlowski, Udo, de Bruttopilo, Sara Ambrosino, Abé, Christoph, de Zeeuw, Patrick, Deary, Ian J., Demeter, Damion V., Di Martino, Adriana, Dickie, Erin W., Dietsche, Bruno, Doan, Nhat 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, Flint, Claas, Filho, Geraldo Busatto, Akudjedu, Theophilus N., Förster, Katharina, Fouche, Jean-Paul, Foxe, John J., Frodl, Thomas, Fuentes-Claramonte, Paola, Fullerton, Janice M., Garavan, Hugh, do Santos Garcia, Danielle, Gotlib, Ian H., Goudriaan, Anna E., Aleman, Andre, Grabe, Hans Jörgen, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K., Harris, Mathew A., Hartman, Catharina A., Ontwikkelingspsychologie (Psychologie, FMG), Adult Psychiatry, APH - Mental Health, ANS - Compulsivity, Impulsivity & Attention, Child and Adolescent Psychiatry & Psychosocial Care, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, Laboratory Genetic Metabolic Diseases, Paediatrics, General Paediatrics, ARD - Amsterdam Reproduction and Development, Paediatric Pulmonology, Graduate School, and APH - Digital Health
Subjects: P‐hacking, Datasets as Topic, Publication bias, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Statistics, team science, Brain asymmetry, Multicenter Studies as Topic, Cervell, Research Articles, Cerebral Cortex, Radiological and Ultrasound Technology, P-hacking, 05 social sciences, Brain, Cerebral cortex, Middle Aged, Magnetic Resonance Imaging, Discoveries in science, Escorça cerebral, Neurology, Biaix de publicació, Anatomy, Psychology, Research Article, Neuroinformatics, Adult, Adolescent, Neuroimaging, Descobriments científics, 050105 experimental psychology, Statistical power, 03 medical and health sciences, Young Adult, Magnetic resonance imaging, Imatges per ressonància magnètica, multisite collaboration, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, reproducibility, Aged, publication bias, Reproducibility, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Perspective (graphical), Reproducibility of Results, Brain Cortical Thickness, Research data, Sample size determination, Dades de recerca, Neurology (clinical), Scale (map), Developmental Psychopathology, 030217 neurology & neurosurgery
Abstract: The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p‐hacking. Low statistical power in individual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% (SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used sample sizes., Region‐wise effect sizes and reproducibility rates of hemispheric asymmetry effects. In general, effects with higher effect sizes showed higher reproducibility, given the same conditions (e.g., sample size and data heterogeneity).
Published: 2022

23. Effectiveness of ‘Tackle Your Tics’, a brief, intensive group-based exposure therapy programme for children with tic disorders: study protocol of a randomised controlled trial

Author: Heijerman-Holtgrefe, Annet, primary, Huyser, Chaim, additional, Verdellen, Cara, additional, van de Griendt, Jolande, additional, Beljaars, Laura, additional, Kan, Kees-Jan, additional, Lindauer, Ramón, additional, Cath, Daniëlle, additional, Hoekstra, Pieter, additional, and Utens, Lisbeth, additional
Published: 2022
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24. Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

Author: Schrag, Anette-Eleonore, Martino, Davide, Wang, Hanyuying, Ambler, Gareth, Benaroya-Milstein, Noa, Buttiglione, Maura, Cardona, Francesco, Creti, Roberta, Efstratiou, Androulla, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Mir, Pablo, Morer, Astrid, Moll, Natalie, Müller, Norbert E, Müller-Vahl, Kirsten R, Plessen, Kerstin J, Porcelli, Cesare, Rizzo, Renata, Roessner, Veit, Schwarz, Markus, Tarnok, Zsanett, Walitza, Susanne, Dietrich, Andrea, Hoekstra, Pieter J, European Multicentre Tics in Children Study (EMTICS), Clinical Cognitive Neuropsychiatry Research Program (CCNP), and European Commission
Subjects: Male, Incidence, Streptococcal Infections, Tic Disorders, Tics, Humans, Female, Neurology (clinical), Prospective Studies, Child
Abstract: [Background and Objectives] The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs)., [Methods] In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti–streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses., [Results] A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2–0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037–2.590; definition 2: HR 0.561, 95% CI 0.219–1.436; definition 3: HR 0.853, 95% CI 0.466–1.561; definition 4: HR 0.725, 95% CI 0.384–1.370)., [Discussion] These results do not suggest an association between GAS exposure and development of tics., This project has received funding from the European Union’s Seventh Framework Program for research and technological development under grant agreement No. 278367.
Published: 2022

25. 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

26. Tic disorders in children and adolescents:does the clinical presentation differ in males and females? A report by the EMTICS group

Author: Garcia-Delgar, Blanca, Servera, Mateu, Coffey, Barbara J, Lázaro, Luisa, Openneer, Thaïra J C, Benaroya-Milshtein, Noa, Steinberg, Tami, Hoekstra, Pieter J, Dietrich, Andrea, Morer, Astrid, Apter, Alan, Baglioni, Valentina, Ball, Juliane, Bognar, Emese, Burger, Bianka, Buse, Judith, Cardona, Francesco, Vela, Marta Correa, Debes, Nanette M., Ferro, Maria Cristina, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Hedderly, Tammy J., Heyman, Isobel, Huyser, Chaim, Madruga-Garrido, Marcos, Marotta, Anna, Martino, Davide, Mir, Pablo, Müller, Norbert, Müller-Vahl, Kirsten, Münchau, Alexander, Nagy, Peter, Neri, Valeria, Openneer, Thaïra J.C., Pellico, Alessandra, Plessen, Kerstin J., Porcelli, Cesare, Rizzo, Renata, Roessner, Veit, Ruhrman, Daphna, Schnell, Jaana M.L., Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Tarnok, Zsanett, Garcia-Delgar, Blanca, Servera, Mateu, Coffey, Barbara J, Lázaro, Luisa, Openneer, Thaïra J C, Benaroya-Milshtein, Noa, Steinberg, Tami, Hoekstra, Pieter J, Dietrich, Andrea, Morer, Astrid, Apter, Alan, Baglioni, Valentina, Ball, Juliane, Bognar, Emese, Burger, Bianka, Buse, Judith, Cardona, Francesco, Vela, Marta Correa, Debes, Nanette M., Ferro, Maria Cristina, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Hedderly, Tammy J., Heyman, Isobel, Huyser, Chaim, Madruga-Garrido, Marcos, Marotta, Anna, Martino, Davide, Mir, Pablo, Müller, Norbert, Müller-Vahl, Kirsten, Münchau, Alexander, Nagy, Peter, Neri, Valeria, Openneer, Thaïra J.C., Pellico, Alessandra, Plessen, Kerstin J., Porcelli, Cesare, Rizzo, Renata, Roessner, Veit, Ruhrman, Daphna, Schnell, Jaana M.L., Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, and Tarnok, Zsanett
Abstract: Tic disorders have a strong male predominance, with a male-to-female ratio of 4:1 in Tourette syndrome (TS) and 2:1 in persistent tic disorders. In other neurodevelopmental conditions, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), the disparity in sex distribution has been partially related to differences in symptom presentation between males and females. In tic disorders, however, little research has been conducted on this topic, probably due to the limited access to large samples with a significant proportion of females. The aim of this study was to describe sex differences in the clinical presentation of tic disorders in children and adolescents in one of the largest pediatric samples with TS/persistent tic disorders (n = 709, 23.3% females) recruited as part of the European Multicenter Tics in Children Study (EMTICS). Validated measures assessed the severity of tics and comorbid psychiatric symptoms. Using mixed-effect models, we found that sex had a significant influence on the severity of tics, ADHD symptoms, ASD symptoms, and emotional problems. Males had more severe symptoms than females, except for emotional problems. We also observed a statistically significant interaction between sex and age on the severity of tics and compulsions, with females showing higher symptom severity with increasing age than males. These findings indicate that the clinical presentation of TS/persistent tic disorders varies with sex. Males seem to exhibit a more noticeable pattern of clinical symptoms at a younger age that may contribute to their earlier detection in comparison to females.
Published: 2022

27. Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children Study

Author: European Commission, Schrag, Anette-Eleonore, Martino, Davide, Wang, Hanyuying, Ambler, Gareth, Benaroya-Milstein, Noa, Buttiglione, Maura, Cardona, Francesco, Creti, Roberta, Efstratiou, Androulla, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Mir, Pablo, Morer, Astrid, Moll, Natalie, Müller, Norbert, Müller-Vahl, Kirsten R., Plessen, Kerstin J., Porcelli, Cesare, Rizzo, Renata, Roessner, Veit, Schwarz, Markus, Tarnok, Zsanett, Walitza, Susanne, Dietrich, Andrea, Hoekstra, Pieter J., European Commission, Schrag, Anette-Eleonore, Martino, Davide, Wang, Hanyuying, Ambler, Gareth, Benaroya-Milstein, Noa, Buttiglione, Maura, Cardona, Francesco, Creti, Roberta, Efstratiou, Androulla, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Mir, Pablo, Morer, Astrid, Moll, Natalie, Müller, Norbert, Müller-Vahl, Kirsten R., Plessen, Kerstin J., Porcelli, Cesare, Rizzo, Renata, Roessner, Veit, Schwarz, Markus, Tarnok, Zsanett, Walitza, Susanne, Dietrich, Andrea, and Hoekstra, Pieter J.
Abstract: [Background and Objectives] The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs)., [Methods] In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti–streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses., [Results] A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2–0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037–2.590; definition 2: HR 0.561, 95% CI 0.219–1.436; definition 3: HR 0.853, 95% CI 0.466–1.561; definition 4: HR 0.725, 95% CI 0.384–1.370)., [Discussion] These results do not suggest an association between GAS exposure and development of tics.
Published: 2022

28. Effectiveness of 'Tackle Your Tics', a brief, intensive group-based exposure therapy programme for children with tic disorders:Study protocol of a randomised controlled trial

Author: Heijerman-Holtgrefe, Annet, Huyser, Chaim, Verdellen, Cara, Van De Griendt, Jolande, Beljaars, Laura, Kan, Kees Jan, Lindauer, Ramón, Cath, Daniëlle, Hoekstra, Pieter, Utens, Lisbeth, Heijerman-Holtgrefe, Annet, Huyser, Chaim, Verdellen, Cara, Van De Griendt, Jolande, Beljaars, Laura, Kan, Kees Jan, Lindauer, Ramón, Cath, Daniëlle, Hoekstra, Pieter, and Utens, Lisbeth
Abstract: Introduction This paper outlines the study protocol for the Dutch Tackle Your Tics study in youth with tic disorders. Tourette syndrome and chronic tic disorders are prevalent neurodevelopmental disorders, placing considerable burden on youth and their families. Behavioural treatment is the first-line, evidence-based intervention for tic disorders, but tic reduction and availability remain relatively low. Patient associations stress the need for more accessible high-quality treatments, also focusing on improving quality of life. Therefore, the brief, intensive group-based treatment Tackle Your Tics was developed. Methods and analysis Tackle Your Tics is a 4-day intensive and comprehensive group-based intervention for children and adolescents (9-17 years) with Tourette syndrome or a chronic tic disorder. The programme encompasses exposure and response prevention treatment and additional supporting components (coping strategies, relaxation exercises and parent support). To study the effectiveness of Tackle Your Tics and identify predictors/moderators at baseline, a single-blinded randomised controlled trial (n=104) is conducted, comparing Tackle Your Tics (n=52) with a waiting list condition lasting 3 months (n=52). Assessments are performed at similar time points for both groups: At baseline, after 4 weeks, and at 3 and 6 months of follow-up, on tic severity, quality of life and other psychosocial variables. Ethics and dissemination Ethics approval has been obtained from the medical ethical committee of the Amsterdam Medical Centre (METC nr NL66340.018.18, v3 June 2020). Findings will be presented on national and international conferences, peer-reviewed scientific journals, patient organisation meetings and public media. Patient representatives are fully integrated as part of the research team. If Tackle Your Tics proves to be effective, it can expand evidence-based treatment possibilities for children and adolescents with tic disorders. Identifying the psychosoci
Published: 2022

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

Author: European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Bertolino, Alessandro, Wen, Wei, Kalnin, Andrew, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Bonvino, Aurora, Kanai, Ryota, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Karolinska Schizophrenia Project, Thompson, Paul M., Dima, Danai, Boomsma, Dorret I., Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Klein, Marieke, 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, Klyushnik, Tatyana P., Castellanos, Francisco X., Cervenka, Simon, Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Koenders, Laura, Crone, Eveline A., Dale, Anders M., Dannlowski, Udo, Davey, Christopher, Geus, Eco J. C. de, Haan, Lieuwe de, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Koops, Sanne, 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, Krämer, Bernd, 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., Kuntsi, Jonna, 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, Lagopoulos, Jim, 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, Lázaro, Luisa, Jernigan, Terry L., Jiang, Jiyang, Jönsson, Erik G., Joska, John A., Kahn, René S., Andersson, Micael, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, Andreasen, Nancy C., McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Andreassen, Ole A., Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Asherson, Philip, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Banaschewski, Tobias, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Bargalló, Núria, Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Baumeister, Sarah, Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van 't Ent, Dennis, van Erp, Theo G. M., Baur-Streubel, Ramona, Veer, Ilya M., Veltman, Dick J., European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Bertolino, Alessandro, Wen, Wei, Kalnin, Andrew, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Bonvino, Aurora, Kanai, Ryota, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Karolinska Schizophrenia Project, Thompson, Paul M., Dima, Danai, Boomsma, Dorret I., Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Klein, Marieke, 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, Klyushnik, Tatyana P., Castellanos, Francisco X., Cervenka, Simon, Chaim-Avancini, Tiffany M., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Koenders, Laura, Crone, Eveline A., Dale, Anders M., Dannlowski, Udo, Davey, Christopher, Geus, Eco J. C. de, Haan, Lieuwe de, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Koops, Sanne, 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, Krämer, Bernd, 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., Kuntsi, Jonna, 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, Lagopoulos, Jim, 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, Lázaro, Luisa, Jernigan, Terry L., Jiang, Jiyang, Jönsson, Erik G., Joska, John A., Kahn, René S., Andersson, Micael, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, Andreasen, Nancy C., McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Andreassen, Ole A., Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Asherson, Philip, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Banaschewski, Tobias, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Bargalló, Núria, Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Baumeister, Sarah, Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van 't Ent, Dennis, van Erp, Theo G. M., Baur-Streubel, Ramona, Veer, Ilya M., and Veltman, Dick J.
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

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

Author: National Institute of Mental Health (US), Karolinska Institute, Stockholm County Council, South-Eastern Norway Regional Health Authority, German Centre for Cardiovascular Research, Siemens Healthcare, University of Queensland, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Health and Medical Research Council (Australia), National Institute on Drug Abuse (US), Indiana State Department of Health, Parents of children with epilepsy, Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures, Epilepsy Foundation, American Epilepsy Society, Knut and Alice Wallenberg Foundation, European Commission, Dutch Research Council, Netherlands Organization for Scientific Research, Netherlands Brain Foundation, Utrecht University, European Research Council, National Center for Advancing Translational Sciences (US), National Institutes of Health (US), National Center for Research Resources (US), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, Kings College London, South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre (UK), National Institute for Health Research (UK), Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Andersson, Micael, Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Tordesillas-Gutiérrez, Diana, Ehrlich, Stefan, Bargalló, Núria, Weber, Bernd, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Erk, Susanne, West, John D., Smoller, Jordan W., Sommer, Iris, Wen, Wei, Baumeister, Sarah, Hartman, Catharine A., Trollor, Julian N., Baur-Streubel, Ramona, Turner, Jessica A., Uhlmann, Anne, Espeseth, Thomas, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Hatton, Sean N., Bonvino, Aurora, Veer, Ilya M., Veltman, Dick J., Fatouros-Bergman, Helena, Bertolino, Alessandro, Voineskos, Aristotle, Kanai, Ryota, Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Williams, Steven C. R., Heinz, Andreas, Wittfeld, Katharina, Wolf, Daniel H., Fisher, Simon E., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Klein, Marieke, Boomsma, Dorret I., Zanetti, Marcus V., Ziegler, Georg C., Heslenfeld, Dirk J., Thompson, Paul M., Fouche, Jean-Paul, Frangou, Sophia, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Klyushnik, Tatyana P., Brouwer, Rachel M., Buitelaar, Jan K., Hibar, Derrek P., Franke, Barbara, Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodríguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Cervenka, Simon, Koenders, Laura, Chaim-Avancini, Tiffany M., Frodl, Thomas, Hickie, Ian B., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dannlowski, Udo, Fuentes-Claramonte, Paola, Koops, Sanne, Ho, Beng-Choon, Dale, Anders M., Davey, Christopher, Geus, Eco J. C. de, de Haan, Lieuwe, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Hohmann, Sarah, Doan, Nhat Trung, Dørum, Erlend S., Hoekstra, Pieter J., Krämer, Bernd, Soriano-Mas, Carles, Glahn, David C., Kuntsi, Jonna, Gotlib, Ian H., Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Stein, Dan J., Lázaro, Luisa, Gur, Ruben C., Hahn, Tim, Lagopoulos, Jim, Harrison, Ben J., Völzke, Henry, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Strike, Lachlan T., Hulshoff Pol, Hilleke E., Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L., Jiang, Jiyang, Walter, Henrik, Lebedeva, Irina, Jönsson, Erik G., Joska, John A., Swagerman, Suzanne C., Kahn, René S., Kalnin, Andrew, Andreasen, Nancy C., Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Walton, Esther, Maingault, Sophie, Martin, Nicholas G., Tamnes, Christian K., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, Andreassen, Ole A., McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., Wang, Lei, McPhilemy, Genevieve, Temmingh, Henk S., Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Asherson, Philip, Nakao, Tomohiro, Nordvik, Jan E., Wang, Yang, Thomopoulos, Sophia I., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Banaschewski, Tobias, Potkin, Steven G., Tomyshev, Alexander S., Wassink, Thomas H., National Institute of Mental Health (US), Karolinska Institute, Stockholm County Council, South-Eastern Norway Regional Health Authority, German Centre for Cardiovascular Research, Siemens Healthcare, University of Queensland, Eunice Kennedy Shriver National Institute of Child Health and Human Development (US), National Health and Medical Research Council (Australia), National Institute on Drug Abuse (US), Indiana State Department of Health, Parents of children with epilepsy, Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures, Epilepsy Foundation, American Epilepsy Society, Knut and Alice Wallenberg Foundation, European Commission, Dutch Research Council, Netherlands Organization for Scientific Research, Netherlands Brain Foundation, Utrecht University, European Research Council, National Center for Advancing Translational Sciences (US), National Institutes of Health (US), National Center for Research Resources (US), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, Kings College London, South London and Maudsley NHS Foundation Trust, NIHR Biomedical Research Centre (UK), National Institute for Health Research (UK), Dima, Danai, Modabbernia, Amirhossein, Papachristou, Efstathios, Doucet, Gaelle E., Agartz, Ingrid, Aghajani, Moji, Akudjedu, Theophilus N., Albajes-Eizagirre, Antón, Alnæs, Dag, Alpert, Kathryn I., Andersson, Micael, Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Tordesillas-Gutiérrez, Diana, Ehrlich, Stefan, Bargalló, Núria, Weber, Bernd, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Erk, Susanne, West, John D., Smoller, Jordan W., Sommer, Iris, Wen, Wei, Baumeister, Sarah, Hartman, Catharine A., Trollor, Julian N., Baur-Streubel, Ramona, Turner, Jessica A., Uhlmann, Anne, Espeseth, Thomas, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Hatton, Sean N., Bonvino, Aurora, Veer, Ilya M., Veltman, Dick J., Fatouros-Bergman, Helena, Bertolino, Alessandro, Voineskos, Aristotle, Kanai, Ryota, Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Williams, Steven C. R., Heinz, Andreas, Wittfeld, Katharina, Wolf, Daniel H., Fisher, Simon E., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Klein, Marieke, Boomsma, Dorret I., Zanetti, Marcus V., Ziegler, Georg C., Heslenfeld, Dirk J., Thompson, Paul M., Fouche, Jean-Paul, Frangou, Sophia, Borgwardt, Stefan, Bourque, Josiane, Brandeis, Daniel, Breier, Alan, Brodaty, Henry, Klyushnik, Tatyana P., Brouwer, Rachel M., Buitelaar, Jan K., Hibar, Derrek P., Franke, Barbara, Busatto, Geraldo F., Buckner, Randy L., Calhoun, Vincent, Canales-Rodríguez, Erick J., Cannon, Dara M., Caseras, Xavier, Castellanos, Francisco X., Cervenka, Simon, Koenders, Laura, Chaim-Avancini, Tiffany M., Frodl, Thomas, Hickie, Ian B., Ching, Christopher R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dannlowski, Udo, Fuentes-Claramonte, Paola, Koops, Sanne, Ho, Beng-Choon, Dale, Anders M., Davey, Christopher, Geus, Eco J. C. de, de Haan, Lieuwe, Zubicaray, Greig I. de, den Braber, Anouk, Dickie, Erin W., Di Giorgio, Annabella, Hohmann, Sarah, Doan, Nhat Trung, Dørum, Erlend S., Hoekstra, Pieter J., Krämer, Bernd, Soriano-Mas, Carles, Glahn, David C., Kuntsi, Jonna, Gotlib, Ian H., Grabe, Hans-Jörgen, Grimm, Oliver, Groenewold, Nynke A., Grotegerd, Dominik, Gruber, Oliver, Gruner, Patricia, Gur, Rachel E., Stein, Dan J., Lázaro, Luisa, Gur, Ruben C., Hahn, Tim, Lagopoulos, Jim, Harrison, Ben J., Völzke, Henry, Holmes, Avram J., Hoogman, Martine, Hosten, Norbert, Howells, Fleur M., Strike, Lachlan T., Hulshoff Pol, Hilleke E., Huyser, Chaim, Jahanshad, Neda, James, Anthony, Jernigan, Terry L., Jiang, Jiyang, Walter, Henrik, Lebedeva, Irina, Jönsson, Erik G., Joska, John A., Swagerman, Suzanne C., Kahn, René S., Kalnin, Andrew, Andreasen, Nancy C., Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Walton, Esther, Maingault, Sophie, Martin, Nicholas G., Tamnes, Christian K., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, Andreassen, Ole A., McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., Wang, Lei, McPhilemy, Genevieve, Temmingh, Henk S., Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Asherson, Philip, Nakao, Tomohiro, Nordvik, Jan E., Wang, Yang, Thomopoulos, Sophia I., Nyberg, Lars, Oosterlaan, Jaap, Ortiz-Garcia de la Foz, Victor, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Banaschewski, Tobias, Potkin, Steven G., Tomyshev, Alexander S., and Wassink, Thomas H.
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

31. 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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32. Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

Author: Koenders, Laura, Machielsen, Marise W.J., van der Meer, Floor J., van Gasselt, Angelique C.M., Meijer, Carin J., van den Brink, Wim, Koeter, Maarten W.J., Caan, Matthan W.A., Cousijn, Janna, den Braber, Anouk, van't Ent, Dennis, Rive, Maaike M., Schene, Aart H., van de Giessen, Elsmarieke, Huyser, Chaim, de Kwaasteniet, Bart P., Veltman, Dick J., and de Haan, Lieuwe
Subjects: Brain -- Physiological aspects, Schizophrenia -- Physiological aspects, Cannabis -- Health aspects -- Psychological aspects, Health, Psychology and mental health
Abstract: Background: Schizophrenia is highly comorbid with cannabis use disorders (CUDs), and this comorbidity is associated with an unfavourable course. Early onset or frequent cannabis use may influence brain structure. A key question is whether comorbid CUDs modulate brain morphology alterations associated with schizophrenia. Methods: We used surface-based analysis to measure the brain volume, cortical thickness and cortical surface area of a priori-defined brain regions (hippocampus, amygdala, thalamus, caudate, putamen, orbitofrontal cortex, anterior cingulate cortex, insula, parahippocampus and fusiform gyrus) in male patients with schizophrenia or related disorders with and without comorbid CUDs and matched healthy controls. Associations between age at onset and frequency of cannabis use with regional grey matter volume were explored. Results: We included 113 patients with (CUD, n = 80) and without (NCUD, n = 33) CUDs and 84 controls in our study. As expected, patients with schizophrenia (with or without a CUD) had smaller volumes of most brain regions (amygdala, putamen, insula, parahippocampus and fusiform gyrus) than healthy controls, and differences in cortical volume were mainly driven by cortical thinning. Compared with the NCUD group, the CUD group had a larger volume of the putamen, possibly driven by polysubstance use. No associations between age at onset and frequency of use with regional grey matter volumes were found. Limitations: We were unable to correct for possible confounding effects of smoking or antipsychotic medication. Conclusion: Patients with psychotic disorders and comorbid CUDs have larger putamen volumes than those without CUDs. Future studies should elaborate whether a large putamen represents a risk factor for the development of CUDs or whether (poly)substance use causes changes in putamen volume., Introduction In patients with recent onset schizophrenia, cannabis use disorders (CUDs) are highly comorbid and associated with an unfavourable outcome. (1-3) In several studies, patients who used cannabis were found [...]
Published: 2015
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33. Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years

Author: Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., 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 R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dale, Anders M., Dannlowski, Udo, Davey, Christopher, de Geus, Eco J. C., 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, Kalnin, Andrew, Kanai, Ryota, Klein, Marieke, Klyushnik, Tatyana P., Koenders, Laura, Koops, Sanne, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lázaro, Luisa, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, de la Foz, Víctor Ortiz-García, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van 't Ent, Dennis, van Erp, Theo G. M., Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Thompson, Paul M., Dima, Danai, Universitat Autònoma de Barcelona, Frangou, Sophia, Modabbernia, Amirhossein, Williams, Steven C. R., 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 R. K., Chubar, Victoria, Clark, Vincent P., Conrod, Patricia, Conzelmann, Annette, Crespo-Facorro, Benedicto, Crivello, Fabrice, Crone, Eveline A., Dale, Anders M., Dannlowski, Udo, Davey, Christopher, de Geus, Eco J. C., 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, Kalnin, Andrew, Kanai, Ryota, Klein, Marieke, Klyushnik, Tatyana P., Koenders, Laura, Koops, Sanne, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lázaro, Luisa, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, de la Foz, Víctor Ortiz-García, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van 't Ent, Dennis, van Erp, Theo G. M., Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Thompson, Paul M., Dima, Danai, and Universitat Autònoma de Barcelona
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. 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.
Published: 2021

34. 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, 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 R. K., 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 J. C., 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, Kalnin, Andrew, Kanai, Ryota, Klein, Marieke, Klyushnik, Tatyana P., Koenders, Laura, Koops, Sanne, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lázaro, Luisa, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, de la Foz, Víctor Ortiz-García, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Thompson, Paul M., Frangou, Sophia, Universitat Autònoma de Barcelona, Dima, Danai, Modabbernia, Amirhossein, 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 R. K., 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 J. C., 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, Kalnin, Andrew, Kanai, Ryota, Klein, Marieke, Klyushnik, Tatyana P., Koenders, Laura, Koops, Sanne, Krämer, Bernd, Kuntsi, Jonna, Lagopoulos, Jim, Lázaro, Luisa, Lebedeva, Irina, Lee, Won Hee, Lesch, Klaus-Peter, Lochner, Christine, Machielsen, Marise W. J., Maingault, Sophie, Martin, Nicholas G., Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mazoyer, Bernard, McDonald, Colm, McDonald, Brenna C., McIntosh, Andrew M., McMahon, Katie L., McPhilemy, Genevieve, Meinert, Susanne, Menchón, José M., Medland, Sarah E., Meyer-Lindenberg, Andreas, Naaijen, Jilly, Najt, Pablo, Nakao, Tomohiro, Nordvik, Jan E., Nyberg, Lars, Oosterlaan, Jaap, de la Foz, Víctor Ortiz-García, Paloyelis, Yannis, Pauli, Paul, Pergola, Giulio, Pomarol-Clotet, Edith, Portella, Maria J., Potkin, Steven G., Radua, Joaquim, Reif, Andreas, Rinker, Daniel A., Roffman, Joshua L., Rosa, Pedro G. P., Sacchet, Matthew D., Sachdev, Perminder S., Salvador, Raymond, Sánchez-Juan, Pascual, Sarró, Salvador, Satterthwaite, Theodore D., Saykin, Andrew J., Serpa, Mauricio H., Schmaal, Lianne, Schnell, Knut, Schumann, Gunter, Sim, Kang, Smoller, Jordan W., Sommer, Iris, Soriano-Mas, Carles, Stein, Dan J., Strike, Lachlan T., Swagerman, Suzanne C., Tamnes, Christian K., Temmingh, Henk S., Thomopoulos, Sophia I., Tomyshev, Alexander S., Tordesillas-Gutiérrez, Diana, Trollor, Julian N., Turner, Jessica A., Uhlmann, Anne, van den Heuvel, Odile A., van den Meer, Dennis, van der Wee, Nic J. A., van Haren, Neeltje E. M., van't Ent, Dennis, van Erp, Theo G. M., Veer, Ilya M., Veltman, Dick J., Voineskos, Aristotle, Völzke, Henry, Walter, Henrik, Walton, Esther, Wang, Lei, Wang, Yang, Wassink, Thomas H., Weber, Bernd, Wen, Wei, West, John D., Westlye, Lars T., Whalley, Heather, Wierenga, Lara M., Williams, Steven C. R., Wittfeld, Katharina, Wolf, Daniel H., Worker, Amanda, Wright, Margaret J., Yang, Kun, Yoncheva, Yulyia, Zanetti, Marcus V., Ziegler, Georg C., Thompson, Paul M., Frangou, Sophia, and Universitat Autònoma de Barcelona
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. We analyzed subcortical volumes from 18,605 healthy individuals from multiple cross-sectional cohorts to infer age-related trajectories between the ages of 3 and 90 years.
Published: 2021

35. Investigation of gene–environment interactions in relation to tic severity

Author: National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, Judah Foundation, Tourette Association of America, National Institutes of Health (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, Generalitat de Catalunya, German Research Foundation, National Institute of Environmental Health Sciences (US), Abdulkadir, Mohamed, Yu, Dongmei, Osiecki, Lisa, King, Robert A., Fernández, Thomas V., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., García-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibáñez-Gómez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Madruga, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Plessen, Kerstin J., Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Visscher, Frank, Zinner, Samuel H., Mathews, Carol A., Scharf, Jeremiah M., Tischfield, Jay A., Heiman, Gary A., Dietrich, Andrea, Hoekstra, Pieter J., National Institute of Mental Health (US), Tourette Syndrome Association of New Jersey, Judah Foundation, Tourette Association of America, National Institutes of Health (US), Instituto de Salud Carlos III, Junta de Andalucía, Sociedad Andaluza de Neurología, Fundación Alicia Koplowitz, Fundación Mutua Madrileña, Jacques and Gloria Gossweiler Foundation, Generalitat de Catalunya, German Research Foundation, National Institute of Environmental Health Sciences (US), Abdulkadir, Mohamed, Yu, Dongmei, Osiecki, Lisa, King, Robert A., Fernández, Thomas V., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., García-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibáñez-Gómez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Madruga, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Plessen, Kerstin J., Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Visscher, Frank, Zinner, Samuel H., Mathews, Carol A., Scharf, Jeremiah M., Tischfield, Jay A., Heiman, Gary A., Dietrich, Andrea, and Hoekstra, Pieter J.
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive–compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene–environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene–environment studies.
Published: 2021

36. Erratum: Brain structural covariance networks in obsessive-compulsive disorder: A graph analysis from the ENIGMA Consortium (Brain (2020) 143 (684-700) DOI: 10.1093/brain/awaa001)

Author: Yun, Je-Yeon, Boedhoe, Premika S. W., Vriend, Chris, Jahanshad, Neda, Abe, Yoshinari, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik K., Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D., Fouche, Jean-Paul, Giménez, M. nica, Gruner, Patricia, Hibar, Derrek P., Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Lazaro, Luisa, Lochner, Christine, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Morgado, Pedro, Moreira, Pedro, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erika L., O'Neill, Joseph, Piacentini, John, Piras, Fabrizio, van Wingen, Guido A., Adult Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Child Psychiatry
Abstract: The authors apologize for misspelling the first name of the author Erika L. Nurmi. This has now been corrected.
Published: 2020

37. The Premonitory Urge for Tics Scale in a large sample of children and adolescents:psychometric properties in a developmental context. An EMTICS study

Author: Openneer, Thaïra J.C., Tárnok, Zsanett, Bognar, Emese, Benaroya-Milshtein, Noa, Garcia-Delgar, Blanca, Morer, Astrid, Steinberg, Tamar, Hoekstra, Pieter J., Dietrich, Andrea, Apter, Alan, Baglioni, Valentina, Ball, Juliane, Bodmer, Benjamin, Burger, Bianka, Buse, Judith, Cardona, Francesco, Correa Vela, Marta, Debes, Nanette M., Ferro, Maria Cristina, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Hedderly, Tammy J., Heyman, Isobel, Huyser, Chaim, Madruga-Garrido, Marcos, Marotta, Anna, Mir, Pablo, Müller, Norbert, Müller-Vahl, Kirsten, Münchau, Alexander, Nagy, Peter, Neri, Valeria, Pellico, Alessandra, Plessen, Kerstin J., Porcelli, Cesare, Redondo, Marina, Rizzo, Renata, Roessner, Veit, Ruhrman, Daphna, Schnell, Jaana M.L., Silvestri, Paola Rosaria, Skov, Liselotte, Tagwerker Gloor, Friederike, Tübing, Jennifer, Turner, Victoria L., Visscher, Frank, and the EMTICS collaborative group, Apter, A., Baglioni, V., Ball, J., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Cardona, F., Correa Vela, M., Debes, N.M., Dietrich, A., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Madruga-Garrido, M., Marotta, A., Mir, P., Morer, A., Müller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Pellico, A., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roessner, V., Ruhrman, D., Schnell, JML, Silvestri, P.R., Skov, L., Steinberg, T., Tagwerker Gloor, F., Tárnok, Z., Tübing, J., Turner, V.L., Visscher, F., ANS - Cellular & Molecular Mechanisms, Child Psychiatry, ANS - Amsterdam Neuroscience, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Sensory phenomena, Male, Tourette syndrome, THERAPY, Severity of Illness Index, Obsessive-compulsive symptoms, 0302 clinical medicine, Quality of life, QUALITY-OF-LIFE, Developmental and Educational Psychology, Child and adolescent psychiatry, 030212 general & internal medicine, ADULT PATIENTS, Child, Premonitory Urge for Tics Scale (PUTS), Obsessive–compulsive symptoms, Premonitory urges, Psychometric properties, General Medicine, Original Contribution, Psychiatry and Mental health, Child, Preschool, Female, medicine.symptom, Psychology, Clinical psychology, medicine.medical_specialty, Tics, Adolescent, Psychometrics, DISORDERS, QUESTIONNAIRE, Context (language use), 03 medical and health sciences, OBSESSIVE-COMPULSIVE SCALE, medicine, SENSORY PHENOMENA, Humans, TOURETTE-SYNDROME, HABIT REVERSAL, Reproducibility of Results, medicine.disease, SEVERITY, Sample size determination, Tic Disorders, Pediatrics, Perinatology and Child Health, Chronic Tic Disorder, 030217 neurology & neurosurgery
Abstract: Premonitory urges are uncomfortable physical sensations preceding tics that occur in most individuals with a chronic tic disorder. The Premonitory Urge for Tics Scale (PUTS) is the most frequently used self-report measure to assess the severity of premonitory urges. We aimed to evaluate the psychometric properties of the PUTS in the largest sample size to date (n = 656), in children aged 3–16 years, from the baseline measurement of the longitudinal European Multicenter Tics in Children Study (EMTICS). Our psychometric evaluation was done in three age-groups: children aged 3–7 years (n = 103), children between 8 and 10 years (n = 253), and children aged 11–16 years (n = 300). The PUTS exhibited good internal reliability in children and adolescents, also under the age of 10, which is younger than previously thought. We observed significant but small correlations between the severity of urges and severity of tics and obsessive–compulsive symptoms, and between severity of urges and ratings of attention-deficit/hyperactivity disorder and internalizing and externalizing behaviors, however, only in children of 8–10 years. Consistent with previous results, the 10th item of the PUTS correlated less with the rest of the scale compared to the other items and, therefore, should not be used as part of the questionnaire. We found a two-factor structure of the PUTS in children of 11 years and older, distinguishing between sensory phenomena related to tics, and mental phenomena as often found in obsessive–compulsive disorder. The age-related differences observed in this study may indicate the need for the development of an age-specific questionnaire to assess premonitory urges. Electronic supplementary material The online version of this article (10.1007/s00787-019-01450-1) contains supplementary material, which is available to authorized users.
Published: 2020

38. 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: 2020
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39. 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 S.W., 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, Y.C. 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., van den Heuvel, Odile A., Boedhoe, Premika S.W., 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, Y.C. 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., and Stein, Dan J.
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: 2020

40. Structural neuroimaging biomarkers for obsessive-compulsive disorder in the ENIGMA-OCD consortium : medication matters

Author: Bruin, Willem B., Taylor, Luke, Thomas, Rajat M., Shock, Jonathan P., Zhutovsky, Paul, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Assogna, Francesca, Benedetti, Francesco, Beucke, Jan C., Boedhoe, Premika S. W., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P., Buitelaar, Jan K., Calvo-Escalona, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A., Feusner, Jamie D., Fitzgerald, Kate D., Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Gürsel, Deniz A., Hauser, Tobias U., Hirano, Yoshiyuki, Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ivanov, Iliyan, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Liu, Yanni, Lochner, Christine, Lázaro, Luisa, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón Magriñá, José Manuel, Minuzzi, Luciano, Moreira, Pedro S., Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erika L., O'Neill, Joseph, Pariente, Jose C., Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, Y. C. Janardhan, Rus-Oswald, Oana G., Sakai, Yuki, Sato, João R., Schmaal, Lianne, Shimizu, Eiji, Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Stewart, S. Evelyn, Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, Thompson, Paul M., van den Heuvel, Odile A., Stein, Dan J., van Wingen, Guido A., Bruin, Willem B., Taylor, Luke, Thomas, Rajat M., Shock, Jonathan P., Zhutovsky, Paul, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Assogna, Francesca, Benedetti, Francesco, Beucke, Jan C., Boedhoe, Premika S. W., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Brennan, Brian P., Buitelaar, Jan K., Calvo-Escalona, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Dallaspezia, Sara, Denys, Damiaan, Ely, Benjamin A., Feusner, Jamie D., Fitzgerald, Kate D., Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Gürsel, Deniz A., Hauser, Tobias U., Hirano, Yoshiyuki, Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ivanov, Iliyan, James, Anthony, Jaspers-Fayer, Fern, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kuno, Masaru, Kvale, Gerd, Kwon, Jun Soo, Liu, Yanni, Lochner, Christine, Lázaro, Luisa, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón Magriñá, José Manuel, Minuzzi, Luciano, Moreira, Pedro S., Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nurmi, Erika L., O'Neill, Joseph, Pariente, Jose C., Perriello, Chris, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, Y. C. Janardhan, Rus-Oswald, Oana G., Sakai, Yuki, Sato, João R., Schmaal, Lianne, Shimizu, Eiji, Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Stewart, S. Evelyn, Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, Thompson, Paul M., van den Heuvel, Odile A., Stein, Dan J., and van Wingen, Guido A.
Abstract: No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.
Published: 2020

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, Alnæs, 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 R. K, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher, 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, 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, Alnæs, 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 R. K, Clark, Vincent P, Conrod, Patricia, Conzelmann, Annette, Crivello, Fabrice, Davey, Christopher, 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, 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: Altres ajuts: The Marató TV3 Foundation #091710, 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: 2020

42. Anti-dopamine D2 receptor antibodies in chronic tic disorders

Author: Addabbo, Francesco, Baglioni, Valentina, Schrag, Anette, Schwarz, Markus J., Dietrich, Andrea, Hoekstra, Pieter J., Martino, Davide, Buttiglione, Maura, Anastasiou, Zacharias, Apter, Alan, Ball, Juliane, Bartolini, Erika, Benaroya-Milshtein, Noa, Bodmer, Benjamin, Bognar, Emese, Burger, Bianka, Buse, Judith, Cardona, Francesco, Correa Vela, Marta, Creti, Roberta, Debes, Nanette M., Efstratiou, Androulla, Ferro, Maria Cristina, Fremer, Carolin, Garcia-Delgar, Blanca, Gariup, Maria, Georgitsi, Marianthi, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Hedderly, Tammy J., Heyman, Isobel, Huyser, Chaim, Imperi, Monica, Karagiannidis, Iordanis, Laviola, Giovanni, Macri, Simone, Madruga-Garrido, Marcos, Margarit, Immaculada, Marotta, Anna, Meier, Ute C., Mir, Pablo, Moll, Natalie, Morer, Astrid, Müller-Vahl, Kirsten, Münchau, Alexander, Nagy, Peter, Neri, Valeria, Openneer, Thaïra J.C., Plessen, Kerstin, Addabbo, Francesco, Baglioni, Valentina, Schrag, Anette, Schwarz, Markus J., Dietrich, Andrea, Hoekstra, Pieter J., Martino, Davide, Buttiglione, Maura, Anastasiou, Zacharias, Apter, Alan, Ball, Juliane, Bartolini, Erika, Benaroya-Milshtein, Noa, Bodmer, Benjamin, Bognar, Emese, Burger, Bianka, Buse, Judith, Cardona, Francesco, Correa Vela, Marta, Creti, Roberta, Debes, Nanette M., Efstratiou, Androulla, Ferro, Maria Cristina, Fremer, Carolin, Garcia-Delgar, Blanca, Gariup, Maria, Georgitsi, Marianthi, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Hedderly, Tammy J., Heyman, Isobel, Huyser, Chaim, Imperi, Monica, Karagiannidis, Iordanis, Laviola, Giovanni, Macri, Simone, Madruga-Garrido, Marcos, Margarit, Immaculada, Marotta, Anna, Meier, Ute C., Mir, Pablo, Moll, Natalie, Morer, Astrid, Müller-Vahl, Kirsten, Münchau, Alexander, Nagy, Peter, Neri, Valeria, Openneer, Thaïra J.C., and Plessen, Kerstin
Abstract: Aim: To investigate the association between circulating anti-dopamine D2 receptor (D2R) autoantibodies and the exacerbation of tics in children with chronic tic disorders (CTDs). Method: One hundred and thirty-seven children with CTDs (108 males, 29 females; mean age [SD] 10y 0mo [2y 7mo], range 4–16y) were recruited over 18 months. Patients were assessed at baseline, at tic exacerbation, and at 2 months after exacerbation. Serum anti-D2R antibodies were evaluated using a cell-based assay and blinded immunofluorescence microscopy scoring was performed by two raters. The association between visit type and presence of anti-D2R antibodies was measured with McNemar’s test and repeated-measure logistic regression models, adjusting for potential demographic and clinical confounders. Results: At exacerbation, 11 (8%) participants became anti-D2R-positive (‘early peri-exacerbation seroconverters’), and nine (6.6%) became anti-D2R-positive at post-exacerbation (‘late peri-exacerbation seroconverters’). The anti-D2R antibodies were significantly associated with exacerbations when compared to baseline (McNemar’s odds ratio=11, p=0.003) and conditional logistic regression confirmed this association (Z=3.49, p<0.001) after adjustment for demographic and clinical data and use of psychotropic drugs. Interpretation: There is a potential association between immune mechanisms and the severity course of tics in adolescents with CTDs.
Published: 2020

43. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author: Lee, Phil H., primary, Anttila, Verneri, additional, Won, Hyejung, additional, Feng, Yen-Chen A., additional, Rosenthal, Jacob, additional, Zhu, Zhaozhong, additional, Tucker-Drob, Elliot M., additional, Nivard, Michel G., additional, Grotzinger, Andrew D., additional, Posthuma, Danielle, additional, Wang, Meg M.-J., additional, Yu, Dongmei, additional, Stahl, Eli A., additional, Walters, Raymond K., additional, Anney, Richard J.L., additional, Duncan, Laramie E., additional, Ge, Tian, additional, Adolfsson, Rolf, additional, Banaschewski, Tobias, additional, Belangero, Sintia, additional, Cook, Edwin H., additional, Coppola, Giovanni, additional, Derks, Eske M., additional, Hoekstra, Pieter J., additional, Kaprio, Jaakko, additional, Keski-Rahkonen, Anna, additional, Kirov, George, additional, Kranzler, Henry R., additional, Luykx, Jurjen J., additional, Rohde, Luis A., additional, Zai, Clement C., additional, Agerbo, Esben, additional, Arranz, M.J., additional, Asherson, Philip, additional, Bækvad-Hansen, Marie, additional, Baldursson, Gísli, additional, Bellgrove, Mark, additional, Belliveau, Richard A., additional, Buitelaar, Jan, additional, Burton, Christie L., additional, Bybjerg-Grauholm, Jonas, additional, Casas, Miquel, additional, Cerrato, Felecia, additional, Chambert, Kimberly, additional, Churchhouse, Claire, additional, Cormand, Bru, additional, Crosbie, Jennifer, additional, Dalsgaard, Søren, additional, Demontis, Ditte, additional, Doyle, Alysa E., additional, Dumont, Ashley, additional, Elia, Josephine, additional, Grove, Jakob, additional, Gudmundsson, Olafur O., additional, Haavik, Jan, additional, Hakonarson, Hakon, additional, Hansen, Christine S., additional, Hartman, Catharina A., additional, Hawi, Ziarih, additional, Hervás, Amaia, additional, Hougaard, David M., additional, Howrigan, Daniel P., additional, Huang, Hailiang, additional, Kuntsi, Jonna, additional, Langley, Kate, additional, Lesch, Klaus-Peter, additional, Leung, Patrick W.L., additional, Loo, Sandra K., additional, Martin, Joanna, additional, Martin, Alicia R., additional, McGough, James J., additional, Medland, Sarah E., additional, Moran, Jennifer L., additional, Mors, Ole, additional, Mortensen, Preben B., additional, Oades, Robert D., additional, Palmer, Duncan S., additional, Pedersen, Carsten B., additional, Pedersen, Marianne G., additional, Peters, Triinu, additional, Poterba, Timothy, additional, Poulsen, Jesper B., additional, Ramos-Quiroga, Josep Antoni, additional, Reif, Andreas, additional, Ribasés, Marta, additional, Rothenberger, Aribert, additional, Rovira, Paula, additional, Sánchez-Mora, Cristina, additional, Satterstrom, F. Kyle, additional, Schachar, Russell, additional, Artigas, Maria Soler, additional, Steinberg, Stacy, additional, Stefansson, Hreinn, additional, Turley, Patrick, additional, Walters, G. Bragi, additional, Werge, Thomas, additional, Zayats, Tetyana, additional, Arking, Dan E., additional, Bettella, Francesco, additional, Buxbaum, Joseph D., additional, Christensen, Jane H., additional, Collins, Ryan L., additional, Coon, Hilary, additional, De Rubeis, Silvia, additional, Delorme, Richard, additional, Grice, Dorothy E., additional, Hansen, Thomas F., additional, Holmans, Peter A., additional, Hope, Sigrun, additional, Hultman, Christina M., additional, Klei, Lambertus, additional, Ladd-Acosta, Christine, additional, Magnusson, Pall, additional, Nærland, Terje, additional, Nyegaard, Mette, additional, Pinto, Dalila, additional, Qvist, Per, additional, Rehnström, Karola, additional, Reichenberg, Abraham, additional, Reichert, Jennifer, additional, Roeder, Kathryn, additional, Rouleau, Guy A., additional, Saemundsen, Evald, additional, Sanders, Stephan J., additional, Sandin, Sven, additional, St Pourcain, Beate, additional, Stefansson, Kari, additional, Sutcliffe, James S., additional, Talkowski, Michael E., additional, Weiss, Lauren A., additional, Willsey, A. Jeremy, additional, Agartz, Ingrid, additional, Akil, Huda, additional, Albani, Diego, additional, Alda, Martin, additional, Als, Thomas D., additional, Anjorin, Adebayo, additional, Backlund, Lena, additional, Bass, Nicholas, additional, Bauer, Michael, additional, Baune, Bernhard T., additional, Bellivier, Frank, additional, Bergen, Sarah E., additional, Berrettini, Wade H., additional, Biernacka, Joanna M., additional, Blackwood, Douglas H.R., additional, Bøen, Erlend, additional, Budde, Monika, additional, Bunney, William, additional, Burmeister, Margit, additional, Byerley, William, additional, Byrne, Enda M., additional, Cichon, Sven, additional, Clarke, Toni-Kim, additional, Coleman, Jonathan R.I., additional, Craddock, Nicholas, additional, Curtis, David, additional, Czerski, Piotr M., additional, Dale, Anders M., additional, Dalkner, Nina, additional, Dannlowski, Udo, additional, Degenhardt, Franziska, additional, Di Florio, Arianna, additional, Elvsåshagen, Torbjørn, additional, Etain, Bruno, additional, Fischer, Sascha B., additional, Forstner, Andreas J., additional, Forty, Liz, additional, Frank, Josef, additional, Frye, Mark, additional, Fullerton, Janice M., additional, Gade, Katrin, additional, Gaspar, Héléna A., additional, Gershon, Elliot S., additional, Gill, Michael, additional, Goes, Fernando S., additional, Gordon, Scott D., additional, Gordon-Smith, Katherine, additional, Green, Melissa J., additional, Greenwood, Tiffany A., additional, Grigoroiu-Serbanescu, Maria, additional, Guzman-Parra, José, additional, Hauser, Joanna, additional, Hautzinger, Martin, additional, Heilbronner, Urs, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Holland, Dominic, additional, Jamain, Stéphane, additional, Jones, Ian, additional, Jones, Lisa A., additional, Kandaswamy, Radhika, additional, Kelsoe, John R., additional, Kennedy, James L., additional, Joachim, Oedegaard Ketil, additional, Kittel-Schneider, Sarah, additional, Kogevinas, Manolis, additional, Koller, Anna C., additional, Lavebratt, Catharina, additional, Lewis, Cathryn M., additional, Li, Qingqin S., additional, Lissowska, Jolanta, additional, Loohuis, Loes M.O., additional, Lucae, Susanne, additional, Maaser, Anna, additional, Malt, Ulrik F., additional, Martin, Nicholas G., additional, Martinsson, Lina, additional, McElroy, Susan L., additional, McMahon, Francis J., additional, McQuillin, Andrew, additional, Melle, Ingrid, additional, Metspalu, Andres, additional, Millischer, Vincent, additional, Mitchell, Philip B., additional, Montgomery, Grant W., additional, Morken, Gunnar, additional, Morris, Derek W., additional, Müller-Myhsok, Bertram, additional, Mullins, Niamh, additional, Myers, Richard M., additional, Nievergelt, Caroline M., additional, Nordentoft, Merete, additional, Adolfsson, Annelie Nordin, additional, Nöthen, Markus M., additional, Ophoff, Roel A., additional, Owen, Michael J., additional, Paciga, Sara A., additional, Pato, Carlos N., additional, Pato, Michele T., additional, Perlis, Roy H., additional, Perry, Amy, additional, Potash, James B., additional, Reinbold, Céline S., additional, Rietschel, Marcella, additional, Rivera, Margarita, additional, Roberson, Mary, additional, Schalling, Martin, additional, Schofield, Peter R., additional, Schulze, Thomas G., additional, Scott, Laura J., additional, Serretti, Alessandro, additional, Sigurdsson, Engilbert, additional, Smeland, Olav B., additional, Stordal, Eystein, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thorgeirsson, Thorgeir E., additional, Treutlein, Jens, additional, Turecki, Gustavo, additional, Vaaler, Arne E., additional, Vieta, Eduard, additional, Vincent, John B., additional, Wang, Yunpeng, additional, Witt, Stephanie H., additional, Zandi, Peter, additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Aschauer, Harald, additional, Baker, Jessica H., additional, Bencko, Vladimir, additional, Bergen, Andrew W., additional, Birgegård, Andreas, additional, Perica, Vesna Boraska, additional, Brandt, Harry, additional, Burghardt, Roland, additional, Carlberg, Laura, additional, Cassina, Matteo, additional, Clementi, Maurizio, additional, Courtet, Philippe, additional, Crawford, Steven, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dina, Christian, additional, Docampo, Elisa, additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Espeseth, Thomas, additional, Fernández-Aranda, Fernando, additional, Fichter, Manfred M., additional, Foretova, Lenka, additional, Forzan, Monica, additional, Gambaro, Giovanni, additional, Giegling, Ina, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Mayora, Monica Gratacos, additional, Guo, Yiran, additional, Halmi, Katherine A., additional, Hatzikotoulas, Konstantinos, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herpertz-Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Hinney, Anke, additional, Imgart, Hartmut, additional, Jiménez-Murcia, Susana, additional, Johnson, Craig, additional, Jordan, Jennifer, additional, Julià, Antonio, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kaye, Walter H., additional, Kennedy, Martin A., additional, Kim, Youl-Ri, additional, Klareskog, Lars, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, Landén, Mikael, additional, Le Hellard, Stephanie, additional, Levitan, Robert D., additional, Li, Dong, additional, Lichtenstein, Paul, additional, Maj, Mario, additional, Marsal, Sara, additional, McDevitt, Sara, additional, Mitchell, James, additional, Monteleone, Palmiero, additional, Monteleone, Alessio Maria, additional, Munn-Chernoff, Melissa A., additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, O’Toole, Julie K., additional, Padyukov, Leonid, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn-Kjennerud, Ted, additional, Ricca, Valdo, additional, Roberts, Marion, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Scherag, André, additional, Schmidt, Ulrike, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slof-Op‘t Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Southam, Lorraine, additional, Strober, Michael, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tziouvas, Konstantinos, additional, van Elburg, Annemarie A., additional, Wade, Tracey D., additional, Wagner, Gudrun, additional, Walton, Esther, additional, Watson, Hunna J., additional, Wichmann, H-Erich, additional, Woodside, D. Blake, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Adams, Mark J., additional, Andlauer, Till F.M., additional, Berger, Klaus, additional, Binder, Elisabeth B., additional, Boomsma, Dorret I., additional, Castelao, Enrique, additional, Colodro-Conde, Lucía, additional, Direk, Nese, additional, Docherty, Anna R., additional, Domenici, Enrico, additional, Domschke, Katharina, additional, Dunn, Erin C., additional, Foo, Jerome C., additional, de. Geus, E.J.C., additional, Grabe, Hans J., additional, Hamilton, Steven P., additional, Horn, Carsten, additional, Hottenga, Jouke-Jan, additional, Howard, David, additional, Ising, Marcus, additional, Kloiber, Stefan, additional, Levinson, Douglas F., additional, Lewis, Glyn, additional, Magnusson, Patrik K.E., additional, Mbarek, Hamdi, additional, Middeldorp, Christel M., additional, Mostafavi, Sara, additional, Nyholt, Dale R., additional, Penninx, Brenda WJH., additional, Peterson, Roseann E., additional, Pistis, Giorgio, additional, Porteous, David J., additional, Preisig, Martin, additional, Quiroz, Jorge A., additional, Schaefer, Catherine, additional, Schulte, Eva C., additional, Shi, Jianxin, additional, Smith, Daniel J., additional, Thomson, Pippa A., additional, Tiemeier, Henning, additional, Uher, Rudolf, additional, van der Auwera, Sandra, additional, Weissman, Myrna M., additional, Alexander, Madeline, additional, Begemann, Martin, additional, Bramon, Elvira, additional, Buccola, Nancy G., additional, Cairns, Murray J., additional, Campion, Dominique, additional, Carr, Vaughan J., additional, Cloninger, C. Robert, additional, Cohen, David, additional, Collier, David A., additional, Corvin, Aiden, additional, DeLisi, Lynn E., additional, Donohoe, Gary, additional, Dudbridge, Frank, additional, Duan, Jubao, additional, Freedman, Robert, additional, Gejman, Pablo V., additional, Golimbet, Vera, additional, Godard, Stephanie, additional, Ehrenreich, Hannelore, additional, Hartmann, Annette M., additional, Henskens, Frans A., additional, Ikeda, Masashi, additional, Iwata, Nakao, additional, Jablensky, Assen V., additional, Joa, Inge, additional, Jönsson, Erik G., additional, Kelly, Brian J., additional, Knight, Jo, additional, Konte, Bettina, additional, Laurent-Levinson, Claudine, additional, Lee, Jimmy, additional, Lencz, Todd, additional, Lerer, Bernard, additional, Loughland, Carmel M., additional, Malhotra, Anil K., additional, Mallet, Jacques, additional, McDonald, Colm, additional, Mitjans, Marina, additional, Mowry, Bryan J., additional, Murphy, Kieran C., additional, Murray, Robin M., additional, O’Neill, F. Anthony, additional, Oh, Sang-Yun, additional, Palotie, Aarno, additional, Pantelis, Christos, additional, Pulver, Ann E., additional, Petryshen, Tracey L., additional, Quested, Digby J., additional, Riley, Brien, additional, Sanders, Alan R., additional, Schall, Ulrich, additional, Schwab, Sibylle G., additional, Scott, Rodney J., additional, Sham, Pak C., additional, Silverman, Jeremy M., additional, Sim, Kang, additional, Steixner, Agnes A., additional, Tooney, Paul A., additional, van Os, Jim, additional, Vawter, Marquis P., additional, Walsh, Dermot, additional, Weiser, Mark, additional, Wildenauer, Dieter B., additional, Williams, Nigel M., additional, Wormley, Brandon K., additional, Zhang, Fuquan, additional, Androutsos, Christos, additional, Arnold, Paul D., additional, Barr, Cathy L., additional, Barta, Csaba, additional, Bey, Katharina, additional, Bienvenu, O. Joseph, additional, Black, Donald W., additional, Brown, Lawrence W., additional, Budman, Cathy, additional, Cath, Danielle, additional, Cheon, Keun-Ah, additional, Ciullo, Valentina, additional, Coffey, Barbara J., additional, Cusi, Daniele, additional, Davis, Lea K., additional, Denys, Damiaan, additional, Depienne, Christel, additional, Dietrich, Andrea, additional, Eapen, Valsamma, additional, Falkai, Peter, additional, Fernandez, Thomas V., additional, Garcia-Delgar, Blanca, additional, Geller, Daniel A., additional, Gilbert, Donald L., additional, Grados, Marco A., additional, Greenberg, Erica, additional, Grünblatt, Edna, additional, Hagstrøm, Julie, additional, Hanna, Gregory L., additional, Hartmann, Andreas, additional, Hedderly, Tammy, additional, Heiman, Gary A., additional, Heyman, Isobel, additional, Hong, Hyun Ju, additional, Huang, Alden, additional, Huyser, Chaim, additional, Ibanez-Gomez, Laura, additional, Khramtsova, Ekaterina A., additional, Kim, Young Key, additional, Kim, Young-Shin, additional, King, Robert A., additional, Koh, Yun-Joo, additional, Konstantinidis, Anastasios, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L., additional, Lochner, Christine, additional, Ludolph, Andrea G., additional, Madruga-Garrido, Marcos, additional, Malaty, Irene, additional, Maras, Athanasios, additional, McCracken, James T., additional, Meijer, Inge A., additional, Mir, Pablo, additional, Morer, Astrid, additional, Müller-Vahl, Kirsten R., additional, Münchau, Alexander, additional, Murphy, Tara L., additional, Naarden, Allan, additional, Nagy, Peter, additional, Nestadt, Gerald, additional, Nestadt, Paul S., additional, Nicolini, Humberto, additional, Nurmi, Erika L., additional, Okun, Michael S., additional, Paschou, Peristera, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Pittenger, Christopher, additional, Plessen, Kerstin J., additional, Richter, Margaret A., additional, Rizzo, Renata, additional, Robertson, Mary, additional, Roessner, Veit, additional, Ruhrmann, Stephan, additional, Samuels, Jack F., additional, Sandor, Paul, additional, Schlögelhofer, Monika, additional, Shin, Eun-Young, additional, Singer, Harvey, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, Spalletta, Gianfranco, additional, Stein, Dan J., additional, Stewart, S Evelyn, additional, Storch, Eric A., additional, Stranger, Barbara, additional, Stuhrmann, Manfred, additional, Tarnok, Zsanett, additional, Tischfield, Jay A., additional, Tübing, Jennifer, additional, Visscher, Frank, additional, Vulink, Nienke, additional, Wagner, Michael, additional, Walitza, Susanne, additional, Wanderer, Sina, additional, Woods, Martin, additional, Worbe, Yulia, additional, Zai, Gwyneth, additional, Zinner, Samuel H., additional, Sullivan, Patrick F., additional, Franke, Barbara, additional, Daly, Mark J., additional, Bulik, Cynthia M., additional, McIntosh, Andrew M., additional, O’Donovan, Michael C., additional, Zheutlin, Amanda, additional, Andreassen, Ole A., additional, Børglum, Anders D., additional, Breen, Gerome, additional, Edenberg, Howard J., additional, Fanous, Ayman H., additional, Faraone, Stephen V., additional, Gelernter, Joel, additional, Mathews, Carol A., additional, Mattheisen, Manuel, additional, Mitchell, Karen S., additional, Neale, Michael C., additional, Nurnberger, John I., additional, Ripke, Stephan, additional, Santangelo, Susan L., additional, Scharf, Jeremiah M., additional, Stein, Murray B., additional, Thornton, Laura M., additional, Walters, James T.R., additional, Wray, Naomi R., additional, Geschwind, Daniel H., additional, Neale, Benjamin M., additional, Kendler, Kenneth S., additional, and Smoller, Jordan W., additional
Published: 2019
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44. Analysis of shared heritability in common disorders of the brain

Author: Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M, Freilinger, Tobias, Ran, Caroline, Gordon, Scott D, Borck, Guntram, Adams, Hieab HH, Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E, Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D, Belin, Andrea C, Van Den Maagdenberg, Arn MJM, Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell J, Catarino, Claudia B, Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N, French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S, Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S, Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M, Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G Neil, Visscher, Frank, Whelan, Christopher D, Zara, Federico, Heinzen, Erin L, Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R, Sharma, Manu, Ryten, Mina, Mok, Kin Y, Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Boraska Perica, Vesna, Thornton, Laura M, Huckins, Laura M, William Rayner, N, Lewis, Cathryn M, Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I, Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H, O'Toole, Julie K, Trace, Sara E, Davis, Oliver SP, Helder, Sietske G, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N, Van Elburg, Annemarie A, Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julià, Antonio, Rabionet, Raquel, Dick, Danielle M, Ripatti, Samuli, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri J, Steen, Vidar M, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A, Mitchell, James, Strober, Michael, Bergen, Andrew W, Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D, Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K, Arias Vasquez, Alejandro, Doyle, Alysa E, Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H, Dalsgaard, Soeren, Børglum, Anders D, Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton HD, Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K, McGough, James J, Grevet, Eugenio H, Medland, Sarah E, Robinson, Elise, Weiss, Lauren A, Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M, Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, De-Luca, Daniel Moreno, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Rogé, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G, Thompson, Robert C, Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E, Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B, Reinbold, Céline S, Fullerton, Janice M, Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B, Gershon, Elliot S, Rice, John, Potash, James B, Zandi, Peter P, Craddock, Nick, Ferrier, I Nicol, Alda, Martin, Rouleau, Guy A, Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M, Cruceanu, Cristiana, Jones, Ian R, Posthuma, Danielle, Andlauer, Till FM, Forstner, Andreas J, Streit, Fabian, Baune, Bernhard T, Air, Tracy, Sinnamon, Grant, Wray, Naomi R, MacIntyre, Donald J, Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M, Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H, Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S, Nauck, Matthias, Schoevers, Robert A, Beekman, Aartjan Tf, Knowles, James A, Viktorin, Alexander, Arnold, Paul, Barr, Cathy L, Bedoya-Berrio, Gabriel, Bienvenu, O Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M, Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L, Hartmann, Andreas, Hirschtritt, Matthew E, Hoekstra, Pieter J, Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J, Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A, Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C, Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S, Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M, Reus, Victor, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Roessner, Veit, Rosário, Maria, Samuels, Jack F, Sandor, Paul, Stein, Dan J, Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R, Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S, McLaughlin, Nicole, Nestadt, Paul S, Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A, Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Lee Chee Keong, Jimmy, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C, Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R, Schall, Ulrich, Schwab, Sibylle G, Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V, Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M, Daly, Mark, Dichgans, Martin, Faraone, Stephen V, Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S, Koeleman, Bobby, Mathews, Carol A, Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W, Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W, Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M, Schott, Jonathan M, Anney, Richard, Elia, Josephine, Grigoroiu-Serbanescu, Maria, Edenberg, Howard J, Murray, Robin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), School of Psychology [Cardiff University], Cardiff University, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), New Jersey Institute of Technology [Newark] (NJIT), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University [New York], Dpt of Neuroscience [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Washington [Seattle], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Children’s Hospital of Philadelphia (CHOP ), University of Kentucky (UK), School of medicine, Duke University [Durham], College of medicine, Brigham Young University (BYU), Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Department of Neurology, Emory University [Atlanta, GA], Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Health sciences center, The University of New Mexico [Albuquerque], Institute for Memory Impairments and Neurological Disorders [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of South Florida [Tampa] (USF), University of Utah School of Medicine [Salt Lake City], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania, Dublin City University [Dublin] (DCU), Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Aristotle University of Thessaloniki, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Dementia Research Centre [London] (DRC), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, MRC Prion Unit [London], Queen's University [Belfast] (QUB), School of Life Sciences, University of Nottingham, UK (UON), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), School of Medicine [Dublin], Trinity College Dublin, Department of Medicine, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), School of Public Health [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University Medical Center (CUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Saarland University [Saarbrücken], Universität Leipzig, School of Medicine [Los Angeles], Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], School of Medecine, Washington University in Saint Louis (WUSTL), Oslo University Hospital [Oslo], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, 23andMe Inc., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Leiden University Medical Center (LUMC), Universiteit Leiden, University-Hospital Munich-Großhadern [München], Karolinska Institutet [Stockholm], Universität Ulm - Ulm University [Ulm, Allemagne], Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Landspitali National University Hospital of Iceland, VU University Medical Center [Amsterdam], Boston VA Research Institute (BVARI), Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Christian-Albrechts-Universität zu Kiel (CAU), Institute of Clinical Molecular Biology, Kiel University, National Institute for Health and Welfare [Helsinki], Harvard T.H. Chan School of Public Health, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], University of Tartu, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Human and Clinical Genetics, Universiteit Leiden-Universiteit Leiden, University of Copenhagen = Københavns Universitet (UCPH), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Discipline of Psychiatry [Dublin], Trinity College Dublin-Trinity College Dublin, Institute of Neurology [London], The University of Hong Kong (HKU), University of Melbourne, Cooper Medical School of Rowan University [Camden] (CMSRU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Antwerp (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Eastern Finland, Universitätsklinikum Bonn (UKB), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Royal College of Surgeons in Ireland (RCSI), University of Southern Denmark (SDU), United Christian Hospital [Hong Kong] (UCH), University of Cincinnati (UC), University of Cologne, Inselspital Bern, University of Wales, Jefferson University Hospitals, University of Liverpool, Medizinische Universität Wien = Medical University of Vienna, National Institutes of Health [Bethesda] (NIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lincoln, University of Newcastle [Callaghan, Australia] (UoN), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Virginia, University of Maryland [Baltimore County] (UMBC), University of Maryland System, Royal Holloway [University of London] (RHUL), University of Edinburgh, Universidade de Lisboa = University of Lisbon (ULISBOA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Split, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), McLean Hospital [Belmont, Ma.], Norwegian Institute of Public Health [Oslo] (NIPH), Università degli Studi di Salerno = University of Salerno (UNISA), University of Bristol [Bristol], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Utrecht University [Utrecht], Azienda Ospedaliera di Padova, Université de Liège, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, National and Kapodistrian University of Athens (NKUA), Charles University [Prague] (CU), SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Flinders University [Adelaide, Australia], Virginia Commonwealth University (VCU), University of Oslo (UiO), University of Bergen (UiB), Weill Medical College of Cornell University [New York], University of North Dakota [Grand Forks] (UND), Oregon Research Institute (ORI), University of California [San Diego] (UC San Diego), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hospital Universitario Mutua de Terrassa, School of Computer Science and Communication [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Jefferson (Philadelphia University + Thomas Jefferson University), University Medical Center Göttingen (UMG), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Universitätsklinikum Frankfurt, Maastricht University [Maastricht], Institute of Psychological Medicine and Clinical Neurosciences, Aarhus University [Aarhus], University of Iowa [Iowa City], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), The Hospital for sick children [Toronto] (SickKids), Hospital de Clínicas de Porto Alegre (HCPA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of British Columbia (UBC), IRCCS Fondazione Stella Maris [Pisa], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Our Lady's Children's Hospital Crumlin (OLCHC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Children’s Hospital Los Angeles [Los Angeles], Yale University [New Haven], Brown University, Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Department of Medical Epidemiology and Biostatistics (MEB), Division of Medical Genetics [Seattle], University of Illinois [Chicago] (UIC), University of Illinois System, Maine Medical Center Research Institute (MMCRI), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Johns Hopkins University School of Medicine [Baltimore], Ludwig Maximilian University [Munich] (LMU), University of Michigan System, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, University of Dundee, National University of Ireland [Galway] (NUI Galway), University Hospital Basel [Basel], Neuroscience Research Australia (NeuRA), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Chicago, Johns Hopkins University (JHU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Dalhousie University [Halifax], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], State University of New York (SUNY), University Hospital of Cologne [Cologne], University of Adelaide, James Cook University (JCU), Institute for Molecular Bioscience, University of Queensland [Brisbane], Greifswald University Hospital, The University of Sydney, University Medical Center Groningen [Groningen] (UMCG), University of Calgary, University Health Network, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidade de São Paulo = University of São Paulo (USP), Ospedale San Raffaele, University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Yale School of Medicine [New Haven, Connecticut] (YSM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cape Town, Cold Spring Harbor Laboratory (CSHL), Universidad de Sevilla / University of Sevilla, University of Florida [Gainesville] (UF), University of Denver, Purdue University [West Lafayette], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Moscow Institute of Physics and Technology [Moscow] (MIPT), Sunnybrook Health Sciences Centre, Federal Institute of São Paulo (IFSP), Democritus University of Thrace (DUTH), Universiteit Gent = Ghent University (UGENT), Medical University of Warsaw - Poland, Sorbonne Université - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institute of Mental Health [Singapore], Universidad de Cantabria [Santander], Tel Aviv University (TAU), University College Cork (UCC), University of Rochester [USA], Statens Serum Institut [Copenhagen], Софийски университет = Sofia University, Russian Academy of Sciences [Moscow] (RAS), Latvian Biomedical Research and Study Centre [Rīga], Vilnius University [Vilnius], Nanyang Technological University [Singapour], Department of Life Sciences, Imperial College London, Jena University Hospital [Jena], Oxford University Hospitals NHS Trust, Schizophrenia Research Institute [Sydney], Faculty of Science, Medicine and Health [Wollongong], University of Wollongong [Australia], City University of Hong Kong [Hong Kong] (CUHK), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials ('Study-specific acknowledgments')., Brainstorm Consortium, University of Kentucky, University of California [Irvine] (UCI), University of California-University of California, University of Pennsylvania [Philadelphia], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig [Leipzig], Johannes Kepler University Linz [Linz] (JKU), University of Helsinki-University of Helsinki, University of Helsinki, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Newcastle [Australia] (UoN), University of Virginia [Charlottesville], Universidade de Lisboa (ULISBOA), Università degli Studi di Salerno (UNISA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Università degli Studi di Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli', Universität Heidelberg [Heidelberg], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, VU University Amsterdam, Universidade de São Paulo (USP), Yale University School of Medicine, Universidad de Sevilla, Universiteit Gent = Ghent University [Belgium] (UGENT), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Tel Aviv University [Tel Aviv], University of Sofia, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Françoi, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S.K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johanne, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthia, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlo, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nichola, Kurth, Tobia, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobia, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H.H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Marku, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfon, Pozo-Rosich, Patricia, Hansen, Thoma, Werge, Thoma, Kaprio, Jaakko, Metspalu, Andre, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. 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Duque, F, Green, A, Klauck, S, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, Moreno-De-Luca, D, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Roge, B, Magalhaes, T, Arking, D, Schulze, T, Thompson, R, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, Mcintosh, A, Bergen, S, Schalling, M, Jamain, S, Maaser, A, Fischer, S, Reinbold, C, Fullerton, J, Guzman-Parra, J, Mayoral, F, Schofield, P, Cichon, S, Mühleisen, T, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, P, Gershon, E, Rice, J, Potash, J, Zandi, P, Craddock, N, Nicol Ferrier, I, Alda, M, Rouleau, G, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, P, Cruceanu, C, Jones, I, Posthuma, D, Andlauer, T, Forstner, A, Streit, F, Baune, B, Air, T, Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, J, Wolanczyk, T, Worbe, Y, Zai, G, Goes, F, Mclaughlin, N, Nestadt, P, Grabe, H, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Kauwe, John S. K., Mcquillin, Andrew, Adams, Hieab H. H., Mccormack, Mark, Bau, Claiton H. D., Mcgough, James J., Mcintosh, Andrew, Andlauer, Till F. M., Macintyre, Donald J., Mcgrath, Lauren, Mclaughlin, Nicole, Delisi, Lynn, Mcdonald, Colm, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), RIKEN Center for Integrative Medical Science, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of South Florida (USF), University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Cardiff University-Medical Research Council, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Johannes Kepler University Linz [linz] (JKU), Washington University in St Louis, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Universitat Autònoma de Barcelona [Barcelona] (UAB), Hôpital Erasme (Bruxelles), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Jagiellonian University [Krakow] (UJ), Technische Universität Dresden (TUD), National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Charles University [Prague], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), University Medicine Goettingen, Università di Bologna [Bologna] (UNIBO), Forschungszentrum Jülich GmbH, UNSW Medicine [Sydney], McGill University, Universidad de Antioquia, University of Florida [Gainesville], Universiteit Gent [Ghent], Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Wollongong, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Anttila, Verneri [0000-0002-0073-4675], Finucane, Hilary K [0000-0003-3864-9828], Walters, Raymond K [0000-0001-8422-6530], Duncan, Laramie [0000-0003-1131-661X], Escott-Price, Valentina [0000-0003-1784-5483], Falcone, Guido J [0000-0002-6407-0302], Gormley, Padhraig [0000-0002-8908-6968], Malik, Rainer [0000-0001-9212-2520], Ripke, Stephan [0000-0003-3622-835X], Wei, Zhi [0000-0001-6059-4267], Yu, Dongmei [0000-0001-7901-4365], Lee, Phil H [0000-0003-1770-3100], Breen, Gerome [0000-0003-2053-1792], Bulik, Cynthia M [0000-0001-7772-3264], Daly, Mark [0000-0002-0949-8752], Dichgans, Martin [0000-0002-0654-387X], Faraone, Stephen V [0000-0002-9217-3982], Holmans, Peter [0000-0003-0870-9412], Koeleman, Bobby [0000-0001-7749-182X], Mathews, Carol A [0000-0003-2208-7058], Sklar, Pamela [0000-0001-9715-4943], Williams, Julie [0000-0002-4069-0259], Wood, Nicholas W [0000-0002-9500-3348], Cotsapas, Chris [0000-0002-7772-5910], Smoller, Jordan W [0000-0002-0381-6334], Sullivan, Patrick [0000-0002-6619-873X], Rosand, Jonathan [0000-0002-1014-9138], Corvin, Aiden [0000-0001-6717-4089], Neale, Benjamin M [0000-0003-1513-6077], and Apollo - University of Cambridge Repository
Subjects: Etiology, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, body-mass index, genetics [Mental Disorders], Disorders of the Brain, Risks factors, classification [Mental Disorders], MESH: Quantitative Trait, Heritable, MESH: Risk Factors, Risk Factors, MESH: Genetic Variation, alzheimers-disease, 610 Medicine & health, bipolar disorder, Brain Diseases, deficit hyperactivity disorder, Multidisciplinary, Mental Disorders, genetics [Brain Diseases], Brain Disease, Brain, Genetic Variation, Genome-Wide Association Study, Humans, Phenotype, Quantitative Trait, Heritable, Psychiatric Disorders, anorexia-nervosa, Mental Disorder, Psychiatric Genomics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], long-term survival, Engineering sciences. Technology, Human, General Science & Technology, population-based twin, diagnosis [Mental Disorders], MESH: Phenotype, Neurological Disorders, Quantitative Trait, MD Multidisciplinary, MESH: Mental Disorders, diagnosis [Brain Diseases], Heritable, genetic correlations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, major depressive disorder, Risk Factor, Brain Diseases/classification, Brain Diseases/diagnosis, Brain Diseases/genetics, Mental Disorders/classification, Mental Disorders/diagnosis, Mental Disorders/genetics, classification [Brain Diseases], Perturbações do Desenvolvimento Infantil e Saúde Mental, ddc:320, MESH: Genome-Wide Association Study, genome-wide association, Brainstorm Consortium, Genetic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities’ assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important “scaffolding” to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders.
Published: 2018

45. An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Boedhoe, Premika S. W., Heymans, Martijn W., Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D., Fitzgerald, Kate D., Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Hanna, Gregory L., Hibar, Derrek P., Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nishida, Seiji, Nurmi, Erika L., O'Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, Y. C. Janardhan, Reess, Tim J., Sakai, Yuki, Sato, Joao R., Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C., Szeszko, Philip R., Tolin, David F., van Wingen, Guido A., Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Yun, Je-Yeon, Thompson, Paul M., Stein, Dan J., van den Heuvel, Odile A., Twisk, Jos W. R., Boedhoe, Premika S. W., Heymans, Martijn W., Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H., Anticevic, Alan, Arnold, Paul D., Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K., Ciullo, Valentina, Dallaspezia, Sara, Denys, Damiaan, Feusner, Jamie D., Fitzgerald, Kate D., Fouche, Jean-Paul, Fridgeirsson, Egill A., Gruner, Patricia, Hanna, Gregory L., Hibar, Derrek P., Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Nishida, Seiji, Nurmi, Erika L., O'Neill, Joseph, Piacentini, John, Piras, Fabrizio, Piras, Federica, Reddy, Y. C. Janardhan, Reess, Tim J., Sakai, Yuki, Sato, Joao R., Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carles, Spalletta, Gianfranco, Stevens, Michael C., Szeszko, Philip R., Tolin, David F., van Wingen, Guido A., Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Yun, Je-Yeon, Thompson, Paul M., Stein, Dan J., van den Heuvel, Odile A., and Twisk, Jos W. R.
Abstract: Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data., Peer Reviewed
Published: 2019

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

Author: Kong, Xiang-Zhen, Mathias, Samuel R, Francks, Clyde, Grabe, Hans, Groenewold, Nynke A, Grotegerd, Dominik, Gruber, Oliver, Gurholt, Tiril, Haavik, Jan, Hahn, Tim, Hansell, Narelle K, Harris, Mathew A, Hartman, Catharina A, Hernández, Maria Del Carmen Valdés, Heslenfeld, Dirk, Hester, Robert, Hibar, Derrek Paul, Ho, Beng-Choon, Ho, Tiffany C, Hoekstra, Pieter J, van Holst, Ruth J, Hoogman, Martine, Høvik, Marie F, Howells, Fleur M, Hugdahl, Kenneth, Huyser, Chaim, Ingvar, Martin, Irwin, Lourdes, Ishikawa, Akari, James, Anthony, Jahanshad, Neda, Jernigan, Terry L, Jönsson, Erik G, Guadalupe, Tulio, Kähler, Claas, Kaleda, Vasily, Kelly, Clare, Kerich, Michael, Keshavan, Matcheri S, Khadka, Sabin, Kircher, Tilo, Kohls, Gregor, Konrad, Kerstin, Korucuoglu, Ozlem, Abé, Christoph, Krämer, Bernd, Krug, Axel, Kwon, Jun Soo, Lambregts-Rommelse, Nanda, Landén, Mikael, Lázaro, Luisa, Lebedeva, Irina, Lenroot, Rhoshel, Lesch, Klaus-Peter, Li, Qinqin, Agartz, Ingrid, Lim, Kelvin O, Liu, Jia, Lochner, Christine, London, Edythe D, Lonning, Vera, Lorenzetti, Valentina, Luciano, Michelle, Luijten, Maartje, Lundervold, Astri J, Mackey, Scott, Akudjedu, Theophilus N, MacMaster, Frank P, Maingault, Sophie, Malpas, Charles B, Malt, Ulrik F, Mataix-Cols, David, Martin-Santos, Rocio, Mayer, Andrew R, McCarthy, Hazel, Mitchell, Philip B, Mueller, Bryon A, Aleman, Andre, Maniega, Susana Muñoz, Mazoyer, Bernard, McDonald, Colm, McLellan, Quinn, McMahon, Katie L, McPhilemy, Genevieve, Momenan, Reza, Morales, Angelica M, Narayanaswamy, Janardhanan C, Moreira, José Carlos Vasques, Alhusaini, Saud, Nerland, Stener, Nestor, Liam, Newman, Erik, Nigg, Joel T, Nordvik, Jan Egil, Novotny, Stephanie, Weiss, Eileen Oberwelland, O'Gorman, Ruth L, Oosterlaan, Jaap, Oranje, Bob, Allen, Nicholas B, Orr, Catherine, Overs, Bronwyn, Pauli, Paul, Paulus, Martin, Plessen, Kerstin Jessica, von Polier, Georg G, Pomarol-Clotet, Edith, Portella, Maria J, Qiu, Jiang, Radua, Joaquim, Ames, David, Ramos-Quiroga, Josep Antoni, Reddy, Y C Janardhan, Reif, Andreas, Roberts, Gloria, Rosa, Pedro, Rubia, Katya, Sacchet, Matthew D, Sachdev, Perminder S, Salvador, Raymond, Schmaal, Lianne, Andreassen, Ole A, Schulte-Rüther, Martin, Schweren, Lizanne, Seidman, Larry, Seitz, Jochen, Serpa, Mauricio Henriques, Shaw, Philip, Shumskaya, Elena, Silk, Timothy J, Simmons, Alan N, Simulionyte, Egle, Vasquez, Alejandro Arias, Sinha, Rajita, Sjoerds, Zsuzsika, Smelror, Runar Elle, Soliva, Joan Carlos, Solowij, Nadia, Souza-Duran, Fabio Luisde, Sponheim, Scott R, Stein, Dan J, Stein, Elliot A, Stevens, Michael, Armstrong, Nicola J, Strike, Lachlan T, Sudre, Gustavo, Sui, Jing, Tamm, Leanne, Temmingh, Hendrik S, Thoma, Robert J, Tomyshev, Alexander, Tronchin, Giulia, Turner, Jessica, Uhlmann, Anne, Bergo, Felipe, van Erp, Theo G M, van den Heuvel, Odile A, van der Meer, Dennis, van Eijk, Liza, Vance, Alasdair, Veer, Ilya M, Veltman, Dick J, Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, Bastin, Mark E, Voineskos, Aristotle N, Völzke, Henry, Vuletic, Daniella, Walitza, Susanne, Walter, Henrik, Walton, Esther, Wardlaw, Joanna M, Wen, Wei, Westlye, Lars T, Whelan, Christopher D, Batalla, Albert, White, Tonya, Wiers, Reinout W, Wright, Margaret J, Wittfeld, Katharina, Yang, Tony T, Yasuda, Clarissa L, Yoncheva, Yuliya, Yücel, Murat, Yun, Je-Yeon, Zanetti, Marcus Vinicius, Bauer, Jochen, Zhen, Zonglei, Zhu, Xing-Xing, Ziegler, Georg C, Zierhut, Kathrin, de Zubicaray, Greig I, Zwiers, Marcel, Glahn, David C, Franke, Barbara, Crivello, Fabrice, Tzourio-Mazoyer, Nathalie, Baune, Bernhard T, Fisher, Simon E, Thompson, Paul M, Farde, Lars, Flyckt, Lena, Engberg, Göran, Erhardt, Sophie, Fatouros-Bergman, Helena, Cervenka, Simon, Schwieler, Lilly, Baur-Streubel, Ramona, Piehl, Fredrik, Collste, Karin, Victorsson, Pauliina, Malmqvist, Anna, Hedberg, Mikael, Orhan, Funda, Group, ENIGMA Laterality Working, 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, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Stochastics, Clinical Neuropsychology, Cognitive Psychology, IBBA, APH - Mental Health, Ontwikkelingspsychologie (Psychologie, FMG), Anatomy and neurosciences, Psychiatry, Pediatric surgery, Amsterdam Neuroscience - Brain Imaging, Child Psychiatry, Adult Psychiatry, ANS - Brain Imaging, AGEM - Endocrinology, metabolism and nutrition, Graduate School, AGEM - Inborn errors of metabolism, ARD - Amsterdam Reproduction and Development, General Paediatrics, APH - Digital Health, Radiology & Nuclear Medicine, Child and Adolescent Psychiatry / Psychology, and Universitat de Barcelona
Subjects: Dominància cerebral, Male, Databases, Factual, Planum temporale, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], 0302 clinical medicine, Transverse temporal gyrus, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], 80 and over, Brain asymmetry, Neuroimaging/methods, Child, ENIGMA Laterality Working Group, Aged, 80 and over, Cerebral Cortex, Multidisciplinary, Laterality, 05 social sciences, Human brain, Middle Aged, Databases, Factual/statistics & numerical data, medicine.anatomical_structure, Mental Health, PNAS Plus, Lateralitat, Child, Preschool, Brain size, Neurological, Biomedical Imaging, Female, ddc:500, methods [Neuroimaging], Parahippocampal gyrus, Neuroinformatics, Adult, statistics & numerical data [Databases, Factual], Adolescent, Cerebral Cortex/diagnostic imaging, 1.1 Normal biological development and functioning, BF, Inferior frontal gyrus, Neuroimaging, and over, Biology, 050105 experimental psychology, Lateralization of brain function, 03 medical and health sciences, Databases, Young Adult, All institutes and research themes of the Radboud University Medical Center, Clinical Research, Underpinning research, Journal Article, medicine, Humans, lateralization, 0501 psychology and cognitive sciences, General, Preschool, Factual, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], [SCCO.NEUR]Cognitive science/Neuroscience, Neurosciences, Infant, surface area, cortical thickness, Brain Disorders, meta-analysis, Cerebral dominance, brain asymmetry, Neuroscience, Developmental Psychopathology, 030217 neurology & neurosurgery
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 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 brain size (indexed by 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 modest but highly reliable 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.Significance StatementLeft-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.
Published: 2018

47. Analysis of shared heritability in common disorders of the brain

Author: Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Francois, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Kamboh, M. Ilyas, Larson, Eric B., Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Demirci, F. Yesim, Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S. K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Noethen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Merce, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, van der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobias, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H. H., Lehtimaki, Terho, Wedenoja, Juho, Buring, Julie E., Schuerks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsalainen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hamalainen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Goebel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., van den Maagdenberg, Arn M. J. M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kalviainen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Moller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G. Neil, Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., Rayner, N. William, Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A., Mitchell, James, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Antoni Ramos-Quiroga, Josep, Sanchez-Mora, Cristina, Ribases, Marta, Casas, Miguel, Hervas, Amaia, Jesus Arranz, Maria, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K., Arias Vasquez, Alejandro, Doyle, Alysa E., Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Borglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton H. D., Crosbie, Jennifer, Schachar, Russell, K., Sandra, McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patricia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stephane, Maaser, Anna, Fischer, Sascha B., Reinbold, Celine S., Fullerton, Janice M., Guzman-Parra, Jose, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Muhleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Ferrier, I. Nicol, Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F. M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, de Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthias, Schoevers, Robert A., Beekman, Aartjan T. F., Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Bienvenu, O. Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andreas, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A., Maras, Athanasios, McGrath, Lauren, Miguel, Euripedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosario, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kucinskas, Vaidutis, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lonnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stoegmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M., Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Francois, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Kamboh, M. Ilyas, Larson, Eric B., Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Demirci, F. Yesim, Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S. K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Noethen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Merce, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, van der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobias, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H. H., Lehtimaki, Terho, Wedenoja, Juho, Buring, Julie E., Schuerks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsalainen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hamalainen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Goebel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., van den Maagdenberg, Arn M. J. M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kalviainen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Moller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G. Neil, Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., Rayner, N. William, Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A., Mitchell, James, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Antoni Ramos-Quiroga, Josep, Sanchez-Mora, Cristina, Ribases, Marta, Casas, Miguel, Hervas, Amaia, Jesus Arranz, Maria, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K., Arias Vasquez, Alejandro, Doyle, Alysa E., Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Borglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton H. D., Crosbie, Jennifer, Schachar, Russell, K., Sandra, McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patricia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stephane, Maaser, Anna, Fischer, Sascha B., Reinbold, Celine S., Fullerton, Janice M., Guzman-Parra, Jose, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Muhleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Ferrier, I. Nicol, Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F. M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, de Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthias, Schoevers, Robert A., Beekman, Aartjan T. F., Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Bienvenu, O. Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andreas, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A., Maras, Athanasios, McGrath, Lauren, Miguel, Euripedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosario, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kucinskas, Vaidutis, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lonnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stoegmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, and Neale, Benjamin M.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
Published: 2018

48. Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Boedhoe, Premika S W, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, D., Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Hanna, Gregory L, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nishida, Seiji, Nurmi, Erika, O'Neill, Joseph, ENIGMA-OCD Working Group, Boedhoe, Premika S W, Schmaal, Lianne, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Anticevic, Alan, Arnold, Paul D, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Ciullo, Valentina, Dallaspezia, Sara, Denys, D., Feusner, Jamie D, Fitzgerald, Kate D, Fouche, Jean-Paul, Fridgeirsson, Egill A, Gruner, Patricia, Hanna, Gregory L, Hibar, Derrek P, Hoexter, Marcelo Q, Hu, Hao, Huyser, Chaim, Jahanshad, Neda, James, Anthony, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nishida, Seiji, Nurmi, Erika, O'Neill, Joseph, and ENIGMA-OCD Working Group
Abstract: OBJECTIVE: Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken.METHOD: T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume.RESULTS: In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33.CONCLUSIONS: The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
Published: 2018

49. Analysis of shared heritability in common disorders of the brain

Author: Anttila, V, Bulik-Sullivan, B, Finucane, H, Walters, R, Bras, J, Duncan, L, Escott-Price, V, Falcone, G, Gormley, P, Malik, R, Patsopoulos, N, Ripke, S, Wei, Z, Yu, D, Lee, P, Turley, P, Grenier-Boley, B, Chouraki, V, Kamatani, Y, Berr, C, Letenneur, L, Hannequin, D, Amouyel, P, Boland, A, Deleuze, J, Duron, E, Vardarajan, B, Reitz, C, Goate, A, Huentelman, M, Ilyas Kamboh, M, Larson, E, Rogaeva, E, George-Hyslop, P, Hakonarson, H, Kukull, W, Farrer, L, Barnes, L, Beach, T, Yesim Demirci, F, Head, E, Hulette, C, Jicha, G, Kauwe, J, Kaye, J, Leverenz, J, Levey, A, Lieberman, A, Pankratz, V, Poon, W, Quinn, J, Saykin, A, Schneider, L, Smith, A, Sonnen, J, Stern, R, Van Deerlin, V, Van Eldik, L, Harold, D, Russo, G, Rubinsztein, D, Bayer, A, Tsolaki, M, Proitsi, P, Fox, N, Hampel, H, Owen, M, Mead, S, Passmore, P, Morgan, K, Nöthen, M, Rossor, M, Lupton, M, Hoffmann, P, Kornhuber, J, Lawlor, B, Mcquillin, A, Al-Chalabi, A, Bis, J, Ruiz, A, Boada, M, Seshadri, S, Beiser, A, Rice, K, Van Der Lee, S, De Jager, P, Geschwind, D, Riemenschneider, M, Riedel-Heller, S, Rotter, J, Ransmayr, G, Hyman, B, Cruchaga, C, Alegret, M, Winsvold, B, Palta, P, Farh, K, Cuenca-Leon, E, Furlotte, N, Kurth, T, Ligthart, L, Terwindt, G, Freilinger, T, Ran, C, Gordon, S, Borck, G, Adams, H, Lehtimäki, T, Wedenoja, J, Buring, J, Schürks, M, Hrafnsdottir, M, Hottenga, J, Penninx, B, Artto, V, Kaunisto, M, Vepsäläinen, S, Martin, N, Montgomery, G, Kurki, M, Hämäläinen, E, Huang, H, Huang, J, Sandor, C, Webber, C, Muller-Myhsok, B, Schreiber, S, Salomaa, V, Loehrer, E, Göbel, H, Macaya, A, Pozo-Rosich, P, Hansen, T, Werge, T, Kaprio, J, Metspalu, A, Kubisch, C, Ferrari, M, Belin, A, Van Den Maagdenberg, A, Zwart, J, Boomsma, D, Eriksson, N, Olesen, J, Chasman, D, Nyholt, D, Avbersek, A, Baum, L, Berkovic, S, Bradfield, J, Buono, R, Catarino, C, Cossette, P, De Jonghe, P, Depondt, C, Dlugos, D, Ferraro, T, French, J, Hjalgrim, H, Jamnadas-Khoda, J, Kälviäinen, R, Kunz, W, Lerche, H, Leu, C, Lindhout, D, Lo, W, Lowenstein, D, Mccormack, M, Møller, R, Molloy, A, Ng, P, Oliver, K, Privitera, M, Radtke, R, Ruppert, A, Sander, T, Schachter, S, Schankin, C, Scheffer, I, Schoch, S, Sisodiya, S, Smith, P, Sperling, M, Striano, P, Surges, R, Neil Thomas, G, Visscher, F, Whelan, C, Zara, F, Heinzen, E, Marson, A, Becker, F, Stroink, H, Zimprich, F, Gasser, T, Gibbs, R, Heutink, P, Martinez, M, Morris, H, Sharma, M, Ryten, M, Mok, K, Pulit, S, Bevan, S, Holliday, E, Attia, J, Battey, T, Boncoraglio, G, Thijs, V, Chen, W, Mitchell, B, Rothwell, P, Sharma, P, Sudlow, C, Vicente, A, Markus, H, Kourkoulis, C, Pera, J, Raffeld, M, Silliman, S, Perica, V, Thornton, L, Huckins, L, William Rayner, N, Lewis, C, Gratacos, M, Rybakowski, F, Keski-Rahkonen, A, Raevuori, A, Hudson, J, Reichborn-Kjennerud, T, Monteleone, P, Karwautz, A, Mannik, K, Baker, J, O'Toole, J, Trace, S, Davis, O, Helder, S, Ehrlich, S, Herpertz-Dahlmann, B, Danner, U, Van Elburg, A, Clementi, M, Forzan, M, Docampo, E, Lissowska, J, Hauser, J, Tortorella, A, Maj, M, Gonidakis, F, Tziouvas, K, Papezova, H, Yilmaz, Z, Wagner, G, Cohen-Woods, S, Herms, S, Julia, A, Rabionet, R, Dick, D, Ripatti, S, Andreassen, O, Espeseth, T, Lundervold, A, Steen, V, Pinto, D, Scherer, S, Aschauer, H, Schosser, A, Alfredsson, L, Padyukov, L, Halmi, K, Mitchell, J, Strober, M, Bergen, A, Kaye, W, Szatkiewicz, J, Cormand, B, Ramos-Quiroga, J, Sánchez-Mora, C, Ribasés, M, Casas, M, Hervas, A, Arranz, M, Haavik, J, Zayats, T, Johansson, S, Williams, N, Dempfle, A, Rothenberger, A, Kuntsi, J, Oades, R, Banaschewski, T, Franke, B, Buitelaar, J, Vasquez, A, Doyle, A, Reif, A, Lesch, K, Freitag, C, Rivero, O, Palmason, H, Romanos, M, Langley, K, Rietschel, M, Witt, S, Dalsgaard, S, Børglum, A, Waldman, I, Wilmot, B, Molly, N, Bau, C, Crosbie, J, Schachar, R, Loo, S, Mcgough, J, Grevet, E, Medland, S, Robinson, E, Weiss, L, Bacchelli, E, Bailey, A, Bal, V, Battaglia, A, Betancur, C, Bolton, P, Cantor, R, Celestino-Soper, P, Dawson, G, De Rubeis, S, Duque, F, Green, A, Klauck, S, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, Moreno-De-Luca, D, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Roge, B, Magalhaes, T, Arking, D, Schulze, T, Thompson, R, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, Mcintosh, A, Bergen, S, Schalling, M, Jamain, S, Maaser, A, Fischer, S, Reinbold, C, Fullerton, J, Guzman-Parra, J, Mayoral, F, Schofield, P, Cichon, S, Mühleisen, T, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, P, Gershon, E, Rice, J, Potash, J, Zandi, P, Craddock, N, Nicol Ferrier, I, Alda, M, Rouleau, G, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, P, Cruceanu, C, Jones, I, Posthuma, D, Andlauer, T, Forstner, A, Streit, F, Baune, B, Air, T, Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, J, Wolanczyk, T, Worbe, Y, Zai, G, Goes, F, Mclaughlin, N, Nestadt, P, Grabe, H, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S. K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobias, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H. H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. J. M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Neil Thomas, G., Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, BONCORAGLIO, GIORGIO BATTISTA, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., William Rayner, N., Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., Van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A., Mitchell, James, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K., Vasquez, Alejandro Arias, Doyle, Alysa E., Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Børglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton H. 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Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, 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M., Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I., Nyholt, Dale R., Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell, Catarino, Claudia B., Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N., French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S., Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S., Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M., Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Neil Thomas, G., Visscher, Frank, Whelan, Christopher D., Zara, Federico, Heinzen, Erin L., Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R., Sharma, Manu, Ryten, Mina, Mok, Kin Y., Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, BONCORAGLIO, GIORGIO BATTISTA, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Perica, Vesna Boraska, Thornton, Laura M., Huckins, Laura M., William Rayner, N., Lewis, Cathryn M., Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I., Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H., O'Toole, Julie K., Trace, Sara E., Davis, Oliver S. P., Helder, Sietske G., Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N., Van Elburg, Annemarie A., Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julia, Antonio, Rabionet, Raquel, Dick, Danielle M., Ripatti, Samuli, Andreassen, Ole A., Espeseth, Thomas, Lundervold, Astri J., Steen, Vidar M., Pinto, Dalila, Scherer, Stephen W., Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A., Mitchell, James, Strober, Michael, Bergen, Andrew W., Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D., Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K., Vasquez, Alejandro Arias, Doyle, Alysa E., Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H., Dalsgaard, Soeren, Børglum, Anders D., Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton H. D., Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K., McGough, James J., Grevet, Eugenio H., Medland, Sarah E., Robinson, Elise, Weiss, Lauren A., Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M., Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, Moreno-De-Luca, Daniel, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Roge, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G., Thompson, Robert C., Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E., Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B., Reinbold, Céline S., Fullerton, Janice M., Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R., Cichon, Sven, Mühleisen, Thomas W., Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B., Gershon, Elliot S., Rice, John, Potash, James B., Zandi, Peter P., Craddock, Nick, Nicol Ferrier, I., Alda, Martin, Rouleau, Guy A., Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M., Cruceanu, Cristiana, Jones, Ian R., Posthuma, Danielle, Andlauer, Till F. M., Forstner, Andreas J., Streit, Fabian, Baune, Bernhard T., Air, Tracy, Sinnamon, Grant, Wray, Naomi R., MacIntyre, Donald J., Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M., Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H., Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S., Nauck, Matthias, Schoevers, Robert A., Beekman, Aartjan TF, Knowles, James A., Viktorin, Alexander, Arnold, Paul, Barr, Cathy L., Bedoya-Berrio, Gabriel, Joseph Bienvenu, O., Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M., Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L., Hartmann, Andreas, Hirschtritt, Matthew E., Hoekstra, Pieter J., Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J., Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A., Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C., Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S., Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M., Reus, Victor, Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Roessner, Veit, Rosário, Maria, Samuels, Jack F., Sandor, Paul, Stein, Dan J., Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R., Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S., McLaughlin, Nicole, Nestadt, Paul S., Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A., Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Keong, Jimmy Lee Chee, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C., Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R., Schall, Ulrich, Schwab, Sibylle G., Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V., Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M., Daly, Mark, Dichgans, Martin, Faraone, Stephen V., Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S., Koeleman, Bobby, Mathews, Carol A., Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W., Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W., Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, and Neale, Benjamin M.
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.
Published: 2018

50. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author: Wang, Sheng, primary, Mandell, Jeffrey D., additional, Kumar, Yogesh, additional, Sun, Nawei, additional, Morris, Montana T., additional, Arbelaez, Juan, additional, Nasello, Cara, additional, Dong, Shan, additional, Duhn, Clif, additional, Zhao, Xin, additional, Yang, Zhiyu, additional, Padmanabhuni, Shanmukha S., additional, Yu, Dongmei, additional, King, Robert A., additional, Dietrich, Andrea, additional, Khalifa, Najah, additional, Dahl, Niklas, additional, Huang, Alden Y., additional, Neale, Benjamin M., additional, Coppola, Giovanni, additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, Fernandez, Thomas V., additional, Buxbaum, Joseph D., additional, De Rubeis, Silvia, additional, Grice, Dorothy E., additional, Xing, Jinchuan, additional, Heiman, Gary A., additional, Tischfield, Jay A., additional, Paschou, Peristera, additional, Willsey, A. Jeremy, additional, State, Matthew W., additional, Abdulkadir, Mohamed, additional, Bodmer, Benjamin, additional, Bromberg, Yana, additional, Brown, Lawrence W., additional, Cheon, Keun-Ah, additional, Coffey, Barbara J., additional, Deng, Li, additional, Elzerman, Lonneke, additional, Fremer, Carolin, additional, Garcia-Delgar, Blanca, additional, Gilbert, Donald L., additional, Hagstrøm, Julie, additional, Hedderly, Tammy, additional, Heyman, Isobel, additional, Hoekstra, Pieter J., additional, Hong, Hyun Ju, additional, Huyser, Chaim, additional, Kim, Eun-Joo, additional, Kim, Young Key, additional, Kim, Young-Shin, additional, Koh, Yun-Joo, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L, additional, Ludolph, Andrea G., additional, Madruga-Garrido, Marcos, additional, Maras, Athanasios, additional, Mir, Pablo, additional, Morer, Astrid, additional, Morris, Montana T, additional, Müller-Vahl, Kirsten, additional, Münchau, Alexander, additional, Murphy, Tara L., additional, Plessen, Kerstin J., additional, Poisner, Hannah, additional, Roessner, Veit, additional, Sanders, Stephan J., additional, Shin, Eun-Young, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, Thackray, Joshua K., additional, Tübing, Jennifer, additional, Visscher, Frank, additional, Wanderer, Sina, additional, Wang, Sheng, additional, Willsey, A Jeremy, additional, Woods, Martin, additional, Zhang, Yeting, additional, Zinner, Samuel H., additional, Androutsos, Christos, additional, Barta, Csaba, additional, Farkas, Luca, additional, Fichna, Jakub, additional, Georgitsi, Marianthi, additional, Janik, Piotr, additional, Karagiannidis, Iordanis, additional, Koumoula, Anastasia, additional, Nagy, Peter, additional, Puchala, Joanna, additional, Rizzo, Renata, additional, Szejko, Natalia, additional, Szymanska, Urszula, additional, Tarnok, Zsanett, additional, Tsironi, Vaia, additional, Wolanczyk, Tomasz, additional, Zekanowski, Cezary, additional, Barr, Cathy L., additional, Batterson, James R., additional, Berlin, Cheston, additional, Bruun, Ruth D., additional, Budman, Cathy L., additional, Cath, Danielle C., additional, Chouinard, Sylvain, additional, Cox, Nancy J., additional, Darrow, Sabrina, additional, Davis, Lea K., additional, Dion, Yves, additional, Freimer, Nelson B., additional, Grados, Marco A., additional, Hirschtritt, Matthew E., additional, Illmann, Cornelia, additional, Kurlan, Roger, additional, Leckman, James F., additional, Lyon, Gholson J., additional, Malaty, Irene A., additional, MacMahon, William M., additional, Okun, Michael S., additional, Osiecki, Lisa, additional, Pauls, David L., additional, Posthuma, Danielle, additional, Ramensky, Vasily, additional, Robertson, Mary M., additional, Rouleau, Guy A., additional, Sandor, Paul, additional, Singer, Harvey S., additional, Smit, Jan, additional, and Sul, Jae-Hoon, additional
Published: 2018
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