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1. Total and subregional thalamic volumes before and after cognitive behavioral therapy in obsessive-compulsive disorder

Author: Vilde Brecke, Anders Lillevik Thorsen, Chaim Huyser, Niels de Joode, Bjarne Hansen, Kristen Hagen, Gerd Kvale, Chris Vriend, Odile A. van den Heuvel, and Olga Therese Ousdal
Subjects: Obsessive-compulsive disorder, Thalamus, Exposure and response prevention, Treatment outcome, Magnetic resonance imaging, Biomarkers, Mental healing, RZ400-408
Abstract: Background: Thalamic volumetric alterations are frequently reported in children and adults with obsessive-compulsive disorder (OCD). However, whether successful cognitive behavioral therapy (CBT) is accompanied by thalamic macrostructural plasticity is unclear. Methods: Twenty-five pediatric (8–19 years) and 53 adult (16–55 years) OCD patients underwent magnetic resonance imaging before and after CBT with exposure and response prevention (CBT with ERP). The data also included 27 pediatric and 37 adult healthy controls that were scanned at similar time intervals. Thalamic nuclei volumes were estimated from T1-weighted images using the longitudinal stream of FreeSurfer's ThalamicNuclei pipeline and aggregated into five subregions (anterior, lateral, medial, pulvinar and ventral). Repeated measures ANCOVAs and linear models were used to investigate pre-post changes in total or subregional thalamic volumes and their associations with clinical response. Results: There were no significant changes in total or subregional thalamic volumes following CBT with ERP in the pediatric or the adult OCD patients. Moreover, the individual clinical response was not associated with changes in thalamic volume, and baseline thalamic volumes did not predict clinical outcome. Limitations: Low variance in the clinical outcome and power to detect only moderate-to-large effect sizes. Conclusion: The results suggest that total and subregional thalamic volumes remain stable following successful CBT with ERP in OCD patients. Hence, thalamus or its subregions may not serve as feasible biomarkers of CBT outcome in OCD.
Published: 2025
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2. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author: Pritesh Jain, Tyne Miller-Fleming, Apostolia Topaloudi, Dongmei Yu, Petros Drineas, Marianthi Georgitsi, Zhiyu Yang, Renata Rizzo, Kirsten R. Müller-Vahl, Zeynep Tumer, Nanette Mol Debes, Andreas Hartmann, Christel Depienne, Yulia Worbe, Pablo Mir, Danielle C. Cath, Dorret I. Boomsma, Veit Roessner, Tomasz Wolanczyk, Piotr Janik, Natalia Szejko, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Joseph D. Buxbaum, Dorothy Grice, Jeffrey Glennon, Hreinn Stefansson, Bastian Hengerer, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Astrid Morer, Norbert Mueller, Alexander Munchau, Kerstin J. Plessen, Cesare Porcelli, Susanne Walitza, Anette Schrag, Davide Martino, The Psychiatric Genomics Consortium Tourette Syndrome Working Group (PGC-TS), The EMTICS collaborative group, Andrea Dietrich, The TS-EUROTRAIN Network, Carol A. Mathews, Jeremiah M. Scharf, Pieter J. Hoekstra, Lea K. Davis, and Peristera Paschou
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: 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
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3. The thalamus and its subnuclei—a gateway to obsessive-compulsive disorder

Author: Cees J. Weeland, Selina Kasprzak, Niels T. de Joode, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Srinivas Balachander, Nerisa Banaj, Nuria Bargallo, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Vilde Brecke, Silvia Brem, Carolina Cappi, Yuqi Cheng, Kang Ik K. Cho, Daniel L. C. Costa, Sara Dallaspezia, Damiaan Denys, Goi Khia Eng, Sónia Ferreira, Jamie D. Feusner, Martine Fontaine, Jean-Paul Fouche, Rachael G. Grazioplene, Patricia Gruner, Mengxin He, Yoshiyuki Hirano, Marcelo Q. Hoexter, Chaim Huyser, Hao Hu, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Minah Kim, Kathrin Koch, Yoo Bin Kwak, Jun Soo Kwon, Luisa Lazaro, Chiang-shan R. Li, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Jose M. Menchón, Luciano Minnuzi, Pedro Silva Moreira, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Ana E. Ortiz, Jose C. Pariente, John Piacentini, Maria Picó-Pérez, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y. C. Janardhan Reddy, Daniela Rodriguez-Manrique, Yuki Sakai, Eiji Shimizu, Venkataram Shivakumar, Helen Blair Simpson, Noam Soreni, Carles Soriano-Mas, Nuno Sousa, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, Jumpei Takahashi, Tais Tanamatis, Jinsong Tang, Anders Lillevik Thorsen, David Tolin, Ysbrand D. van der Werf, Hein van Marle, Guido A. van Wingen, Daniela Vecchio, G. Venkatasubramanian, Susanne Walitza, Jicai Wang, Zhen Wang, Anri Watanabe, Lidewij H. Wolters, Xiufeng Xu, Je-Yeon Yun, Qing Zhao, ENIGMA OCD Working Group, Tonya White, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, and Chris Vriend
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (
Published: 2022
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4. 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: Danielle Cath, Annet Heijerman-Holtgrefe, Chaim Huyser, Cara Verdellen, Jolande van de Griendt, Laura Beljaars, Kees-Jan Kan, Ramón Lindauer, Pieter Hoekstra, and Lisbeth Utens
Subjects: Medicine
Published: 2022
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5. Synaptic processes and immune-related pathways implicated in Tourette syndrome

Author: Fotis Tsetsos, Dongmei Yu, Jae Hoon Sul, Alden Y. Huang, Cornelia Illmann, Lisa Osiecki, Sabrina M. Darrow, Matthew E. Hirschtritt, Erica Greenberg, Kirsten R. Muller-Vahl, Manfred Stuhrmann, Yves Dion, Guy A. Rouleau, Harald Aschauer, Mara Stamenkovic, Monika Schlögelhofer, Paul Sandor, Cathy L. Barr, Marco A. Grados, Harvey S. Singer, Markus M. Nöthen, Johannes Hebebrand, Anke Hinney, Robert A. King, Thomas V. Fernandez, Csaba Barta, Zsanett Tarnok, Peter Nagy, Christel Depienne, Yulia Worbe, Andreas Hartmann, Cathy L. Budman, Renata Rizzo, Gholson J. Lyon, William M. McMahon, James R. Batterson, Danielle C. Cath, Irene A. Malaty, Michael S. Okun, Cheston Berlin, Douglas W. Woods, Paul C. Lee, Joseph Jankovic, Mary M. Robertson, Donald L. Gilbert, Lawrence W. Brown, Barbara J. Coffey, Andrea Dietrich, Pieter J. Hoekstra, Samuel Kuperman, Samuel H. Zinner, Michael Wagner, James A. Knowles, A. Jeremy Willsey, Jay A. Tischfield, Gary A. Heiman, Nancy J. Cox, Nelson B. Freimer, Benjamin M. Neale, Lea K. Davis, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Peristera Paschou, on behalf of the Tourette Association of America International Consortium for Genetics, Sabrina Darrow, Roger Kurlan, James F. Leckman, Jan H. Smit, the Gilles de la Tourette GWAS Replication Initiative, Harald Aschauer Harald Aschauer, Anastasios Konstantinidis, Kirsten Müller-Vahl, Tomasz Wolanczyk, the Tourette International Collaborative Genetics Study, Lawrence Brown, Keun-Ah Cheon, Blanca Garcia-Delgar, Donald Gilbert, Dorothy E. Grice, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Bennett L. Leventhal, Marcos Madruga-Garrido, Pablo Mir, Astrid Morer, Alexander Münchau, Kerstin J. Plessen, Veit Roessner, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Samuel Zinner, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group, Thomas Fernandez, Gary Heiman, Pieter Hoekstra, Jay Tischfield, and Douglas Woods
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.
Published: 2021
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6. Yale Global Tic Severity Scale (YGTSS): Psychometric Quality of the Gold Standard for Tic Assessment Based on the Large-Scale EMTICS Study

Author: Martina Haas, Ewgeni Jakubovski, Carolin Fremer, Andrea Dietrich, Pieter J. Hoekstra, Burkard Jäger, Kirsten R. Müller-Vahl, The EMTICS Collaborative Group, Alan Apter, Valentina Baglioni, Juliane Ball, Noa Benaroya-Milshtein, Benjamin Bodmer, Emese Bognar, Bianka Burger, Judith Buse, Francesco Cardona, Marta Correa Vela, Nanette M. Debes, Maria Cristina Ferro, Blanca Garcia-Delgar, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Chaim Huyser, Marcos Madruga-Garrido, Anna Marotta, Davide Martino, Pablo Mir, Astrid Morer, Norbert Müller, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Alessandra Pellico, Ángela Periañez Vasco, Kerstin J. Plessen, Cesare Porcelli, Marina Redondo, Renata Rizzo, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Anette Schrag, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Friederike Tagwerker Gloor, Zsanett Tarnok, Jennifer Tübing, Victoria L. Turner, Susanne Walitza, and Elif Weidinger
Subjects: Tourette's syndrome (TS), YGTSS = Yale Global Tic Severity Scale, psychometric properties, internal consistency, confirmatory factor analysis, Psychiatry, RC435-571
Abstract: The Yale Global Tic Severity Scale (YGTSS) is a clinician-rated instrument considered as the gold standard for assessing tics in patients with Tourette's Syndrome and other tic disorders. Previous psychometric investigations of the YGTSS exhibit different limitations such as small sample sizes and insufficient methods. To overcome these shortcomings, we used a subsample of the large-scale “European Multicentre Tics in Children Study” (EMTICS) including 706 children and adolescents with a chronic tic disorder and investigated convergent, discriminant and factorial validity, as well as internal consistency of the YGTSS. Our results confirm acceptable convergent and good to very good discriminant validity, respectively, indicated by a sufficiently high correlation of the YGTSS total tic score with the Clinical Global Impression Scale for tics (rs = 0.65) and only low to medium correlations with clinical severity ratings of attention deficit/hyperactivity symptoms (rs = 0.24), obsessive–compulsive symptoms (rs = 27) as well as internalizing symptoms (rs = 0.27). Internal consistency was found to be acceptable (Ω = 0.58 for YGTSS total tic score). A confirmatory factor analysis supports the concept of the two factors “motor tics” and “phonic tics,” but still demonstrated just a marginal model fit (root mean square error of approximation = 0.09 [0.08; 0.10], comparative fit index = 0.90, and Tucker Lewis index = 0.87). A subsequent analysis of local misspecifications revealed correlated measurement errors, suggesting opportunities for improvement regarding the item wording. In conclusion, our results indicate acceptable psychometric quality of the YGTSS. However, taking the wide use and importance of the YGTSS into account, our results suggest the need for further investigations and improvements of the YGTSS. In addition, our results show limitations of the global severity score as a sum score indicating that the separate use of the total tic score and the impairment rating is more beneficial.
Published: 2021
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7. Associations of medication with subcortical morphology across the lifespan in OCD: Results from the international ENIGMA Consortium

Author: Iliyan Ivanov, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Srinivas Balachander, Justin T. Baker, Nerisa Banaj, Nuria Bargalló, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Juliana B. Diniz, Benjamin A. Ely, Jamie D. Feusner, Sónia Ferreira, Kate D. Fitzgerald, Martine Fontaine, Patricia Gruner, Gregory L. Hanna, Yoshiyuki Hirano, Marcelo Q. Hoexter, Chaim Huyser, Keisuke Ikari, Anthony James, Fern Jaspers-Fayer, Hongyan Jiang, Norbert Kathmann, Christian Kaufmann, Minah Kim, Kathrin Koch, Jun Soo Kwon, Luisa Lázaro, Yanni Liu, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Luciano Minuzzi, Astrid Morer, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Sanghoon Oh, Chris Perriello, John C. Piacentini, Maria Picó-Pérez, Fabrizio Piras, Federica Piras, Y.C. Janardhan Reddy, Daniela Rodriguez Manrique, Yuki Sakai, Eiji Shimizu, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, David F. Tolin, Daan van Rooij, Dick J. Veltman, Ysbrand D. van der Werf, Guido A. van Wingen, Ganesan Venkatasubramanian, Susanne Walitza, Zhen Wang, Anri Watanabe, Lidewij H. Wolters, Xiufeng Xu, Je-Yeon Yun, Mojtaba Zarei, Fengrui Zhang, Qing Zhao, Neda Jahanshad, Sophia I. Thomopoulos, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Joseph O'Neill, Sara Poletti, Egill Axfjord Fridgeirsson, Toshikazu Ikuta, Stella J. de Wit, Chris Vriend, Selina Kasprzak, Masaru Kuno, Jumpei Takahashi, Euripedes C. Miguel, Roseli G. Shavitt, Morgan Hough, Jose C. Pariente, Ana E. Ortiz, Sara Bertolín, Eva Real, Cinto Segalàs, Pedro Silva Moreira, Nuno Sousa, Jin Narumoto, Kei Yamada, Jinsong Tang, Jean-Paul Fouche, Taekwan Kim, Sunah Choi, Minji Ha, Sunghyun Park, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Systems & Network Neuroscience, Amsterdam Neuroscience - Neurodegeneration, Adult Psychiatry, Child Psychiatry, Paediatric Psychosocial Care, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Graduate School, Ivanov, Iliyan, Boedhoe, Premika S W, Abe, Yoshinari, Alonso, Pino, Ameis, Stephanie H, Arnold, Paul D, Balachander, Sriniva, Baker, Justin T, Banaj, Nerisa, Bargalló, Nuria, Batistuzzo, Marcelo C, Benedetti, Francesco, Beucke, Jan C, Bollettini, Irene, Brem, Silvia, Brennan, Brian P, Buitelaar, Jan, Calvo, Rosa, Cheng, Yuqi, Cho, Kang Ik K, Dallaspezia, Sara, Denys, Damiaan, Diniz, Juliana B, Ely, Benjamin A, Feusner, Jamie D, Ferreira, Sónia, Fitzgerald, Kate D, Fontaine, Martine, Gruner, Patricia, Hanna, Gregory L, Hirano, Yoshiyuki, Hoexter, Marcelo Q, Huyser, Chaim, Ikari, Keisuke, James, Anthony, Jaspers-Fayer, Fern, Jiang, Hongyan, Kathmann, Norbert, Kaufmann, Christian, Kim, Minah, Koch, Kathrin, Kwon, Jun Soo, Lázaro, Luisa, Liu, Yanni, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M, Minuzzi, Luciano, Morer, Astrid, Morgado, Pedro, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C, Nurmi, Erika L, Oh, Sanghoon, Perriello, Chri, Piacentini, John C, Picó-Pérez, Maria, Piras, Fabrizio, Piras, Federica, Reddy, Y C Janardhan, Manrique, Daniela Rodriguez, Sakai, Yuki, Shimizu, Eiji, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Szeszko, Philip R, Tolin, David F, van Rooij, Daan, Veltman, Dick J, van der Werf, Ysbrand D, van Wingen, Guido A, Venkatasubramanian, Ganesan, Walitza, Susanne, Wang, Zhen, Watanabe, Anri, Wolters, Lidewij H, Xu, Xiufeng, Yun, Je-Yeon, Zarei, Mojtaba, Zhang, Fengrui, Zhao, Qing, Jahanshad, Neda, Thomopoulos, Sophia I, Thompson, Paul M, Stein, Dan J, van den Heuvel, Odile A, and O'Neill, Joseph
Subjects: Obsessive-Compulsive Disorder, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], OCD, Psychotropics, Longevity, SRIs, Magnetic Resonance Imaging, Benzodiazepines, Psychiatry and Mental health, Clinical Psychology, Age, Cross-Sectional Studies, Subcortical volumes, 130 000 Cognitive Neurology & Memory, Child, Preschool, Serotonin Uptake Inhibitors, Humans, Child, Selective Serotonin Reuptake Inhibitors, Aged, Antipsychotic Agents
Abstract: Background: Widely used psychotropic medications for obsessive-compulsive disorder (OCD) may change the volumes of subcortical brain structures, and differently in children vs. adults. We measured subcortical volumes cross-sectionally in patients finely stratified for age taking various common classes of OCD drugs. Methods: The ENIGMA-OCD consortium sample (1081 medicated/1159 unmedicated OCD patients and 2057 healthy controls aged 6–65) was divided into six successive 6–10-year age-groups. Individual structural MRIs were parcellated automatically using FreeSurfer into 8 regions-of-interest (ROIs). ROI volumes were compared between unmedicated and medicated patients and controls, and between patients taking serotonin reuptake inhibitors (SRIs), tricyclics (TCs), antipsychotics (APs), or benzodiazepines (BZs) and unmedicated patients. Results: Compared to unmedicated patients, volumes of accumbens, caudate, and/or putamen were lower in children aged 6–13 and adults aged 50–65 with OCD taking SRIs (Cohen's d = −0.24 to −0.74). Volumes of putamen, pallidum (d = 0.18–0.40), and ventricles (d = 0.31–0.66) were greater in patients aged 20–29 receiving APs. Hippocampal volumes were smaller in patients aged 20 and older taking TCs and/or BZs (d = −0.27 to −1.31). Conclusions: Results suggest that TCs and BZs could potentially aggravate hippocampal atrophy of normal aging in older adults with OCD, whereas SRIs may reduce striatal volumes in young children and older adults. Similar to patients with psychotic disorders, OCD patients aged 20–29 may experience subcortical nuclear and ventricular hypertrophy in relation to APs. Although cross-sectional, present results suggest that commonly prescribed agents exert macroscopic effects on subcortical nuclei of unknown relation to therapeutic response.
Published: 2022
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8. Thalamic Subregions and Obsessive-Compulsive Symptoms in 2,500 Children From the General Population

Author: Chris Vriend, Cees J. Weeland, Tonya White, Odile A. van den Heuvel, Ysbrand D. van der Werf, Manon H.J. Hillegers, Henning Tiemeier, Chaim Huyser, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Systems & Network Neuroscience, Amsterdam Neuroscience - Neurodegeneration, Child and Adolescent Psychiatry / Psychology, and Epidemiology
Subjects: False discovery rate, Obsessive-Compulsive Disorder, education.field_of_study, Pediatrics, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Thalamus, Population, Magnetic resonance imaging, Magnetic Resonance Imaging, Obsessive compulsive symptoms, Psychiatry and Mental health, SDG 3 - Good Health and Well-being, Neuroimaging, Multiple comparisons problem, Developmental and Educational Psychology, medicine, Humans, Generation R, Child, business, education
Abstract: Objective Pediatric obsessive-compulsive disorder (OCD) and clinically relevant obsessive-compulsive symptoms in the general population are associated with increased thalamic volume. It is unknown whether this enlargement is explained by specific thalamic subregions. The relation between obsessive-compulsive symptoms and volume of thalamic subregions was investigated in a population-based sample of children. Method Obsessive-compulsive symptoms were measured in children (9–12 years of age) from the Generation R Study using the Short Obsessive-Compulsive Disorder Screener (SOCS). Thalamic nuclei volumes were extracted from structural 3T magnetic resonance imaging scans using the ThalamicNuclei pipeline and regrouped into anterior, ventral, intralaminar/medial, lateral, and pulvinar subregions. Volumes were compared between children with symptoms above clinical cutoff (probable OCD cases, SOCS ≥ 6, n = 156) and matched children without symptoms (n = 156). Linear regression models were fitted to investigate the association between continuous SOCS score and subregional volume in the whole sample (N = 2500). Results Children with probable OCD had larger ventral nuclei compared with children without symptoms (d = 0.25, p = .025, false discovery rate adjusted p = .126). SOCS score showed a negative association with pulvinar volume when accounting for overall thalamic volume (β = −0.057, p = .009, false discovery rate adjusted p = .09). However, these associations did not survive multiple testing correction. Conclusion The results suggest that individual nuclei groups contribute in varying degrees to overall thalamic volume in children with probable OCD, although this did not survive multiple comparisons correction. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead toward treatment strategies targeting these circuits.
Published: 2022
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9. Right Prefrontal Cortical Thickness Is Associated With Response to Cognitive?Behavioral Therapy in Children With Obsessive-Compulsive Disorder

Author: Sara Bertolín, Pino Alonso, Ignacio Martínez-Zalacaín, Jose M. Menchón, Susana Jimenez-Murcia, Justin T. Baker, Nuria Bargalló, Marcelo Camargo Batistuzzo, Premika S.W. Boedhoe, Brian P. Brennan, Jamie D. Feusner, Kate D. Fitzgerald, Martine Fontaine, Bjarne Hansen, Yoshiyuki Hirano, Marcelo Q. Hoexter, Chaim Huyser, Neda Jahanshad, Fern Jaspers-Fayer, Masaru Kuno, Gerd Kvale, Luisa Lazaro, Mafalda Machado-Sousa, Rachel Marsh, Pedro Morgado, Akiko Nakagawa, Luke Norman, Erika L. Nurmi, Joseph O’Neill, Ana E. Ortiz, Chris Perriello, John Piacentini, Maria Picó-Pérez, Roseli G. Shavitt, Eiji Shimizu, Helen Blair Simpson, S. Evelyn Stewart, Sophia I. Thomopoulos, Anders Lillevik Thorsen, Susanne Walitza, Lidewij H. Wolters, Paul M. Thompson, Odile A. van den Heuvel, Dan J. Stein, Carles Soriano-Mas, Eva Real, Cinto Segalas, Astrid Morer, Silvia Brem, Sonia Ferreira, Pedro Silva Moreira, Kristen Hagen, Sayo Hamatani, Jumpei Takahashi, Tokiko Yoshida, Maria Alice de Mathis, Euripedes C. Miguel, Jose C. Pariente, Jinsong Tang, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Neurodegeneration
Subjects: Psychiatry and Mental health, Developmental and Educational Psychology
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
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10. Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Author: Fotis Tsetsos, Apostolia Topaloudi, Pritesh Jain, Zhiyu Yang, Dongmei Yu, Petros Kolovos, Zeynep Tumer, Renata Rizzo, Andreas Hartmann, Christel Depienne, Yulia Worbe, Kirsten R. Müller-Vahl, Danielle C. Cath, Dorret I. Boomsma, Tomasz Wolanczyk, Cezary Zekanowski, Csaba Barta, Zsofia Nemoda, Zsanett Tarnok, Shanmukha S. Padmanabhuni, Joseph D. Buxbaum, Dorothy Grice, Jeffrey Glennon, Hreinn Stefansson, Bastian Hengerer, Evangelia Yannaki, John A. Stamatoyannopoulos, Noa Benaroya-Milshtein, Francesco Cardona, Tammy Hedderly, Isobel Heyman, Chaim Huyser, Pablo Mir, Astrid Morer, Norbert Mueller, Alexander Munchau, Kerstin J. Plessen, Cesare Porcelli, Veit Roessner, Susanne Walitza, Anette Schrag, Davide Martino, Jay A. Tischfield, Gary A. Heiman, A. Jeremy Willsey, Andrea Dietrich, Lea K. Davis, James J. Crowley, Carol A. Mathews, Jeremiah M. Scharf, Marianthi Georgitsi, Pieter J. Hoekstra, Peristera Paschou, Cathy L. Barr, James R. Batterson, Cheston Berlin, Cathy L. Budman, Giovanni Coppola, Nancy J. Cox, Sabrina Darrow, Yves Dion, Nelson B. Freimer, Marco A. Grados, Erica Greenberg, Matthew E. Hirschtritt, Alden Y. Huang, Cornelia Illmann, Robert A. King, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, William M. McMahon, Benjamin M. Neale, Michael S. Okun, Lisa Osiecki, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Harvey S. Singer, Jan H. Smit, Jae Hoon Sul, Christos Androutsos, Entela Basha, Luca Farkas, Jakub Fichna, Piotr Janik, Mira Kapisyzi, Iordanis Karagiannidis, Anastasia Koumoula, Peter Nagy, Joanna Puchala, Natalia Szejko, Urszula Szymanska, Vaia Tsironi, Alan Apter, Juliane Ball, Benjamin Bodmer, Emese Bognar, Judith Buse, Marta Correa Vela, Carolin Fremer, Blanca Garcia-Delgar, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Marcos Madruga-Garrido, Alessandra Pellico, Daphna Ruhrman, Jaana Schnell, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Friederike Tagwerker Gloor, Victoria L. Turner, Elif Weidinger, John Alexander, Tamas Aranyi, Wim R. Buisman, Jan K. Buitelaar, Nicole Driessen, Petros Drineas, Siyan Fan, Natalie J. Forde, Sarah Gerasch, Odile A. van den Heuvel, Cathrine Jespersgaard, Ahmad S. Kanaan, Harald E. Möller, Muhammad S. Nawaz, Ester Nespoli, Luca Pagliaroli, Geert Poelmans, Petra J.W. Pouwels, Francesca Rizzo, Dick J. Veltman, Ysbrand D. van der Werf, Joanna Widomska, Nuno R. Zilhäo, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Thomas V. Fernandez, Donald L. Gilbert, Hyun Ju Hong, Laura Ibanez-Gomez, Eun-Joo Kim, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett L. Leventhal, Athanasios Maras, Tara L. Murphy, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Matthew W. State, Frank Visscher, Sheng Wang, Samuel H. Zinner, Psychiatry, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Neurodegeneration, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Systems & Network Neuroscience, Biological Psychology, and Amsterdam Reproduction & Development
Subjects: meta-analysis, Medizin, GWAS, Biological Psychiatry, NR2F1, Tourette Syndrome
Abstract: Background: Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture and is characterized by multiple motor tics and at least one vocal tic persisting for more than 1 year. Methods: We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6133 individuals with TS and 13,565 ancestry-matched control participants. Results: We identified a genome-wide significant locus on chromosome 5q15. Integration of expression quantitative trait locus, Hi-C (high-throughput chromosome conformation capture), and genome-wide association study data implicated the NR2F1 gene and associated long noncoding RNAs within the 5q15 locus. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring of brain volume data identified statistically significant associations with right and left thalamus volumes and right putamen volume. Conclusions: Our work presents novel insights into the neurobiology of TS, thereby opening up new directions for future studies.
Published: 2023
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11. An Empirical Comparison of Meta- and Mega-Analysis With Data From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Premika S. W. Boedhoe, Martijn W. Heymans, Lianne Schmaal, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Alan Anticevic, Paul D. Arnold, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Anna Calvo, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Valentina Ciullo, Sara Dallaspezia, Damiaan Denys, Jamie D. Feusner, Kate D. Fitzgerald, Jean-Paul Fouche, Egill A. Fridgeirsson, Patricia Gruner, Gregory L. Hanna, Derrek P. Hibar, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Neda Jahanshad, Anthony James, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Jun Soo Kwon, Luisa Lazaro, Christine Lochner, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, José M. Menchón, Luciano Minuzzi, Astrid Morer, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Seiji Nishida, Erika L. Nurmi, Joseph O'Neill, John Piacentini, Fabrizio Piras, Federica Piras, Y. C. Janardhan Reddy, Tim J. Reess, Yuki Sakai, Joao R. Sato, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Michael C. Stevens, Philip R. Szeszko, David F. Tolin, Guido A. van Wingen, Ganesan Venkatasubramanian, Susanne Walitza, Zhen Wang, Je-Yeon Yun, ENIGMA-OCD Working-Group, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, and Jos W. R. Twisk
Subjects: neuroimaging, MRI, IPD meta-analysis, mega-analysis, linear mixed-effect models, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
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
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12. Greater male than female variability in regional brain structure across the lifespan

Author: Erick J. Canales-Rodríguez, Hans J. Grabe, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Daniel Brandeis, Yang Wang, Henry Brodaty, Ruben C. Gur, Iris E. C. Sommer, Paul M. Thompson, Knut K. Kolskår, Christopher G. Davey, Dick J. Veltman, Eco J. C. de Geus, Tobias Banaschewski, Greig I. Zubicaray, Xavier Caseras, Sarah Baumeister, Raquel E. Gur, Vincent P. Clark, Maria J. Portella, Simon E. Fisher, Christopher R.K. Ching, Lars T. Westlye, Laura Koenders, Vince D. Calhoun, Carles Soriano-Mas, Nicholas G. Martin, Stefan Ehrlich, Fleur M. Howells, Catharina A. Hartman, Matthew D. Sacchet, Ole A. Andreassen, Josiane Bourque, Fabrice Crivello, Annette Conzelmann, Jaap Oosterlaan, Brenna C. McDonald, Gaelle E. Doucet, Avram J. Holmes, José M. Menchón, Danai Dima, Moji Aghajani, Joshua L. Roffman, Steven Williams, Lei Wang, David Mataix-Cols, Philip R. Szeszko, Bernd Weber, Tiril P. Gurholt, Sarah Hohmann, Ian H. Gotlib, Patricia Gruner, Anthony C. James, Paul Pauli, Lara M. Wierenga, Andrew M. McIntosh, Andrew J. Kalnin, Jim Lagopoulos, Henrik Walter, Andreas Reif, Andrew Simmons, Norbert Hosten, Pieter J. Hoekstra, Aristotle Voineskos, Alexander Tomyshev, Anton Albajes-Eizagirre, Jean-Paul Fouche, Dara M. Cannon, Ignacio Martínez‐Zalacaín, Geneviève Richard, Theophilus N. Akudjedu, David C. Glahn, Patricia J. Conrod, Ben J. Harrison, Alan Anticevic, Martine Hoogman, Francisco X. Castellanos, Bernd Kramer, Neda Jahanshad, Lieuwe de Haan, Dennis van der Meer, John D. West, Alan Breier, Jordan W. Smoller, P. G. P. Rosa, Katharina Wittfeld, Dan J. Stein, Jiyang Jiang, Jilly Naaijen, Christine Lochner, Dorret I. Boomsma, Alessandro Bertolino, Marise W. J. Machielsen, Hilleke E. Hulshoff Pol, Henry Völzke, Christian K. Tamnes, Ingrid Agartz, Georg C. Ziegler, Marieke Klein, Lars Nyberg, Perminder S. Sachdev, Philip Asherson, I.M. Veer, Sean N. Hatton, Núria Bargalló, Annabella Di Giorgio, Henk Temmingh, John A. Joska, Odile A. van den Heuvel, Wei Wen, Eveline A Crone, Kang Sim, Kathryn I. Alpert, Dennis van 't Ent, Jan K. Buitelaar, Joaquim Radua, Julian N. Trollor, B Mazoyer, Chaim Huyser, H. C. Whalley, Irina Lebedeva, Erin W. Dickie, Marcus Vinicus Zanetti, Stefan Borgwardt, Theodore D. Satterthwaite, Daniel H Wolf, Sophia I. Thomopoulos, Giulio Pergola, Luisa Lazaro, Ramona Baur-Streubel, Beathe Haatveit, Yannis Paloyelis, Ian B. Hickie, Jonna Kuntsi, Sophia Frangou, R. Salvador, Geraldo F. Busatto, Margaret J. Wright, Aurora Bonvino, Edith Pomarol-Clotet, Anouk den Braber, Lachlan T. Strike, Phil Lee, Anne Uhlmann, Yuliya N. Yoncheva, Mauricio H. Serpa, Dag Alnæs, Paola Fuentes-Claramonte, Katie L. McMahon, Andrew J. Saykin, Genevieve McPhilemy, Tiffany M. Chaim-Avancini, Sophie Maingault, Barbara Franke, Colm McDonald, Rachel M. Brouwer, Salvador Sarró, Department of Psychology, Education and Child Studies, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, AMS - Ageing & Vitality, AMS - Sports, APH - Personalized Medicine, Cognitive Psychology, Clinical Neuropsychology, IBBA, Karolinska Schizophrenia Project (KaSP) Consortium, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Amsterdam Neuroscience, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Movement Disorder (MD), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Pediatric surgery, and Amsterdam Neuroscience - Brain Imaging
Subjects: Male, Netherlands Twin Register (NTR), SEGMENTATION, Vulnerability, Disease, HM, 0302 clinical medicine, Anàlisi de variància, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], sexual characteristics, Analysis of variance, nuclear magnetic resonance imaging, Cervell, Research Articles, Cerebral Cortex, Sex Characteristics, Radiological and Ultrasound Technology, 05 social sciences, Brain, clinical trial, Brain Structure, Magnetic Resonance Imaging, Early life, Adolescence, medicine.anatomical_structure, Neurology, Cerebral cortex, Healthy individuals, X-CHROMOSOME, anatomy & histology [Cerebral Cortex], Evolution of the brain, Female, Anatomy, Neurovetenskaper, Research Article, Radiology, Nuclear Medicine and Medical Imaging, Neuroinformatics, SEX-DIFFERENCES, diagnostic imaging, brain, Human Development, BF, Neuroimaging, SURFACE-AREA, Evolució del cervell, Regional area, Biology, MULTISAMPLE, 050105 experimental psychology, brain cortex, 03 medical and health sciences, CEREBRAL-CORTEX, Sex differences, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, human, ddc:610, Cortical surface, GENERAL INTELLIGENCE, diagnostic imaging [Brain], METAANALYSIS, biological variation, HUMAN HIPPOCAMPUS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], physiology [Biological Variation, Population], Neurosciences, Gender, Brain Cortical Thickness, multicenter study, Biological Variation, Population, Diferències entre sexes, physiology, RC0321, Radiologi och bildbehandling, Neurology (clinical), anatomy & histology [Brain], 170 000 Motivational & Cognitive Control, 030217 neurology & neurosurgery, anatomy and histology, meta analysis, physiology [Human Development], Demography
Abstract: Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) 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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13. Cortical thickness across the lifespan

Author: Simon E. Fisher, Eveline A. Crone, Dominik Grotegerd, Jilly Naaijen, Anders M. Dale, Sean N. Hatton, Ramona Baur-Streubel, Anthony A. James, Daniel Brandeis, Andrew J. Kalnin, Andreas Reif, Hans-Jörgen Grabe, Pieter J. Hoekstra, Lars Nyberg, Fleur M. Howells, Moji Aghajani, Randy L. Buckner, Daniel A. Rinker, Steven G. Potkin, Dennis van 't Ent, Rachel M. Brouwer, Sophia Frangou, Yang Wang, Nhat Trung Doan, Theodore D. Satterthwaite, Christine Lochner, Geraldo F. Busatto, Lars T. Westlye, Lara M. Wierenga, Calhoun Vd, Henry Brodaty, Carles Soriano-Mas, Annette Conzelmann, Christian K. Tamnes, Julian N. Trollor, Nicholas G. Martin, Neeltje E.M. van Haren, René S. Kahn, Irina Lebedeva, Philip Asherson, Suzanne C. Swagerman, John A. Joska, Theophilus N. Akudjedu, Kang Sim, Lachlan T. Strike, Patricia Gruner, Brenna C. McDonald, Thomas Frodl, Edith Pomarol-Clotet, Víctor Ortiz-García de la Foz, Margaret J. Wright, Norbert Hosten, Jean-Paul Fouche, Bernd Weber, Salvador Sarró, Wei Wen, Dag Alnæs, Greig I. de Zubicaray, Iris E. C. Sommer, Marise W. J. Machielsen, Knut Schnell, Dara M. Cannon, Paola Fuentes-Claramonte, Josiane Bourque, Andreas Meyer-Lindenberg, Anton Albajes-Eizagirre, Sarah Hohmann, Erin W. Dickie, Theo G.M. van Erp, Micael Andersson, Paul Pauli, Thomas Espeseth, Heather C. Whalley, Victoria Chubar, Ruben C. Gur, Tomohiro Nakao, Xavier Caseras, Alessandro Bertolino, Ignacio Martínez-Zalacaín, Katharina Wittfeld, Erick J. Canales-Rodríguez, David C. Glahn, Neda Jahanshad, Jiyang Jiang, Katie L. McMahon, Stefan Borgwardt, Erlend S. Dørum, Jaap Oosterlaan, Won Hee Lee, Alan Breier, Steven Williams, Aristotle N. Voineskos, Bernard Mazoyer, Jordan W. Smoller, Nancy C. Andreasen, Ilya M. Veer, Tiffany M. Chaim-Avancini, Sophie Maingault, Paul M. Thompson, Eco J. C. de Geus, Luisa Lázaro, Giulio Pergola, Efstathios Papachristou, Beng-Choon Ho, David Mataix-Cols, Esther Walton, Ben J. Harrison, Dirk J. Heslenfeld, Pablo Najt, Helena Fatouros-Bergman, Derrek P. Hibar, Gunter Schumann, Raymond Salvador, Lieuwe de Haan, Henry Völzke, Joaquim Radua, Henk Temmingh, Lianne Schmaal, Martine Hoogman, Daniel H. Wolf, Georg C. Ziegler, Marieke Klein, Barbara Franke, Erik G. Jönsson, Laura Koenders, Stefan Ehrlich, Oliver Gruber, Ingrid Agartz, Kun Yang, Ryota Kanai, Sarah Baumeister, Colm McDonald, Annabella Di Giorgio, Amanda Worker, Anne Uhlmann, Marcus V. Zanetti, Danai Dima, Matthew D. Sacchet, Sarah E. Medland, Aurora Bonvino, Benedicto Crespo-Facorro, Jan Egil Nordvik, Joshua L. Roffman, Yannis Paloyelis, Jessica A. Turner, T. P. Klyushnik, Christopher G. Davey, Rachel E. Gur, Ian B. Hickie, Christopher R.K. Ching, Jonna Kuntsi, Tobias Banaschewski, Chaim Huyser, Amirhossein Modabbernia, John D. West, Fabrice Crivello, Núria Bargalló, Patricia J. Conrod, Nic J.A. van der Wee, Mauricio H. Serpa, Thomas H. Wassink, Kathryn I. Alpert, Dick J. Veltman, Andrew J. Saykin, Genevieve McPhilemy, Perminder S. Sachdev, Vincent P. Clark, Ian H. Gotlib, Susanne Erk, Henrik Walter, Dennis van den Meer, Simon Cervenka, Oliver Grimm, Andrew M. McIntosh, Alexander Tomyshev, Francisco X. Castellanos, Bernd Kramer, Klaus-Peter Lesch, Odile A. van den Heuvel, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Terry L. Jernigan, Yulyia Yoncheva, Anouk den Braber, Jim Lagopoulos, Maria J. Portella, Ole A. Andreassen, Gaelle E. Doucet, Avram J. Holmes, Nynke A. Groenewold, Pedro G.P. Rosa, Hilleke E. Hulshoff Pol, Sanne Koops, José M. Menchón, Jan K. Buitelaar, Dan J. Stein, Dorret I. Boomsma, Lei Wang, C.A. Hartman, Pascual Sánchez-Juan, Andreas Heinz, 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), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Karolinska Schizophrenia Project (KaSP), Ontwikkelingspsychologie (Psychologie, FMG), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Epidemiology and Data Science, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Brain Imaging, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Biological Psychology, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, and APH - Personalized Medicine
Subjects: Male, Aging, Neurologi, Audiology, Trajectories, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], Child, Research Articles, Cerebral Cortex, Psychiatry, Aged, 80 and over, Radiological and Ultrasound Technology, Fractional polynomial, 05 social sciences, Radiology, Nuclear Medicine & Medical Imaging, 1. No poverty, Cognition, Middle Aged, Cerebral cortex, Regression, 3. Good health, Escorça cerebral, Neurology, Radiology Nuclear Medicine and imaging, Healthy individuals, Child, Preschool, anatomy & histology [Cerebral Cortex], Female, Analysis of variance, Anatomy, Life Sciences & Biomedicine, Trajectorie, Research Article, Neuroinformatics, Adult, medicine.medical_specialty, Adolescent, Human Development, Clinical Neurology, BF, Neuroimaging, Biology, Development, 050105 experimental psychology, Psykiatri, Cortical thickness, 03 medical and health sciences, Young Adult, Neuroimaging genetics, Envelliment, medicine, Humans, trajectories, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, development, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Brain morphometry, aging, Neurosciences, cortical thickness, Cross-Sectional Studies, RC0321, Neurology (clinical), Neurosciences & Neurology, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract: Special Issue: The ENIGMA Consortium: the first 10 years., 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., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)
Published: 2022
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14. Investigation of gene-environment interactions in relation to tic severity

Author: Frank Visscher, Kerstin J. Plessen, Tammy Hedderly, Jungeun Song, Bennett L. Leventhal, Eun-Young Shin, Lawrence W. Brown, Alexander Münchau, Robert A. King, Young Key Kim, Young Shin Kim, Veit Roessner, Andrea Dietrich, Samuel Kuperman, Thomas V. Fernandez, Keun-Ah Cheon, Carol A. Mathews, Athanasios Maras, Donald L. Gilbert, Yun-Joo Koh, Laura Ibanez-Gomez, Dongmei Yu, Astrid Morer, Sodahm Kook, Marcos Madruga-Garrido, Julie Hagstrøm, Dorothy E. Grice, Jay A. Tischfield, Lisa Osiecki, Mohamed Abdulkadir, Blanca Garcia-Delgar, Samuel H. Zinner, Chaim Huyser, Barbara J. Coffey, Dong-Ho Song, Gary A. Heiman, Pieter J. Hoekstra, Hyun Ju Hong, Pablo Mir, Isobel Heyman, Jeremiah M. Scharf, 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), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, Paediatric Psychosocial Care, and Amsterdam Neuroscience - Cellular & Molecular Mechanisms
Subjects: Candidate gene, Tic severity, Autism Spectrum Disorder, Autism, Intellectual and Developmental Disabilities (IDD), Single-nucleotide polymorphism, Genome-wide association study, Neurodegenerative, Tourette syndrome, Severity of Illness Index, Attention Deficit Disorder with Hyperactivity/genetics, Autism Spectrum Disorder/genetics, Female, Gene-Environment Interaction, Genome-Wide Association Study, Humans, Pregnancy, Tics, Tourette Syndrome, Gene–environment interaction, Pre- and perinatal complications, mental disorders, medicine, Genetics, SNP, 2.1 Biological and endogenous factors, Psychology, Aetiology, Biological Psychiatry, Genetic association, Pediatric, Neurology & Neurosurgery, business.industry, Psychiatry and Preclinical Psychiatric Studies - Original Article, Human Genome, Neurosciences, medicine.disease, Serious Mental Illness, Gene-environment interaction, Brain Disorders, Psychiatry and Mental health, Mental Health, Neurology, Autism spectrum disorder, Attention Deficit Disorder with Hyperactivity, Neurology (clinical), business
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., This research was funded by National Institute of Mental Health (NIMH) grant R01MH092293 (to GAH and JAT) and NJCTS (New Jersey Center for Tourette Syndrome and Associated Disorders; to GAH and JAT). This work was also supported by grants from the Judah Foundation, the Tourette Association of America, National Institute of Health (NIH) Grants NS40024, NS016648, MH079489, MH073250, the American Recovery and Re-investment Act (ARRA) Grants NS040024-07S1; NS16648-29S1; NS040024-09S1; MH092289; MH092290; MH092291; MH092292; R01MH092293; MH092513; MH092516; MH092520; MH071507; MH079489; MH079487; MH079488; and MH079494. Dr. Mir has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña and the Jaques and Gloria Gossweiler Foundation. Dr. Morer has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. Dr. Münchau has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1 and FOR 2698). This study was also supported by a Grant from the National Institute for Environmental Health Science (R01 ES021462).
Published: 2021
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15. Normative Modeling of Brain Morphometry Across the Lifespan using CentileBrain: Algorithm Benchmarking and Model Optimization

Author: Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yunan Vera Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Amirhossein Modabbernia, Faye New, Ingrid Agartz, Philip Asherson, Rosa Ayesa-Arriola, Nerisa Banaj, Tobias Banaschewski, Sarah Baumeister, Alessandro Bertolino, Dorret I Boomsma, Stefan Borgwardt, Josiane Bourque, Daniel Brandeis, Alan Breier, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Jan K Buitelaar, Dara M Cannon, Xavier Caseras, Simon Cervenka, Patricia J Conrod, Benedicto Crespo-Facorro, Fabrice Crivello, Eveline A Crone, Liewe de Haan, Greig I de Zubicaray, Annabella Di Giorgio, Susanne Erk, Simon E Fisher, Barbara Franke, Thomas Frodl, David C Glahn, Dominik Grotegerd, Oliver Gruber, Patricia Gruner, Raquel E Gur, Ruben C Gur, Ben J Harrison, Sean N Hatton, Ian Hickie, Fleur M Howells, Hilleke E Hulshoff Pol, Chaim Huyser, Terry L Jernigan, Jiyang Jiang, John A Joska, Rene S Kahn, Andrew J Kalnin, Nicole A Kochan, Sanne Koops, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Christine Lochner, Nicholas G Martin, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, Katie L McMahon, Tomohiro Nakao, Lars Nyberg, Fabrizio Piras, Maria J Portella, Jiang Qiu, Joshua L Roffman, Perminder S Sachdev, Nicole Sanford, Andrew J Saykin, Theodore D Satterthwaite, Sophia I Thomopolous, Carl M Sellgren, Kang Sim, Jordan W Smoller, Jair Soares, Iris E Sommer, Gianfranco Spalletta, Dan J Stein, Christian K Tamnes, Alexander S Tomyshev, Theo GM van Erp, Diana Tordesillas-Gutierrez, Julian N Trollor, Dennis van 't Ent, Odile A van den Heuvel, Neeltje EM van Haren, Daniela Vecchio, Dick J Veltman, Dongtao Wei, Henrik Walter, Yang Wang, Bernd Weber, Margaret J Wright, Wei Wen, Lars T Westlye, Lara M Wierenga, Paul M Thompson, Steven CR Williams, Sarah Medland, Mon-Ju Wu, Kevin Yu, Neda Jahanshad, and Sophia Frangou
Abstract: Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR
Published: 2023
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16. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author: Susanne Walitza, Andrea Dietrich, Chaim Huyser, Pritesh R Jain, and Anette Schrag
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: 2022
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17. Vitamin D levels in children and adolescents with chronic tic disorders: a multicentre study

Author: Molly, Bond, Natalie, Moll, Alicia, Rosello, Rod, Bond, Jaana, Schnell, Bianka, Burger, Pieter, J Hoekstra, Andrea, Dietrich, Anette, Schrag, Eva, Kocovska, Martino, Davide, Norbert, Mueller, Markus, Schwarz, Ute-Christiane, Meier, EMTICS Collaborative Group: Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Benjamin, Bodmer, Emese, Bognar, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Nanette, M Debes, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga-Garrido, Anna, Marotta, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, R Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra Jc Openneer, Pellico, Alessandra, Ángela Periañez Vasco, Kerstin, J Plessen, Cesare, Porcelli, Marina, Redondo, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Jaana Ml Schnell, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Jennifer, Tübing, Victoria, L Turner, Susanne, Walitza, Elif, Weidinger, Clinical Cognitive Neuropsychiatry Research Program (CCNP), EMTICS Collaborative Group, Bruun, J.E., Grejsen, J., Ommundsen, C.L., Rubæk, M., Enghardt, S., Bokemeyer, S., Driedger-Garbe, C., Reichert, C., Schmalfeld, J., Duffield, T., Gergye, F., Kovacs, M., Vidomusz, R., Carmel, M., Fennig, S., Gev, E., Keller, N., Michaelovsky, E., Nahon, M., Regev, C., Simcha, T., Smollan, G., Weizman, A., Gagliardi, G., Tallon, M., Roazzi, P., van den Ban, E., de Bruijn, SFTM, Driessen, N., Lamerz, A., Messchendorp, M., Rath, JJG, Sival, NSD, Tromp, N., Visscher, F., de la Tourettes, S.G., Cáceres, M.T., Carrillo, F., Gómez-Garre, P., Vargas, L., Gariup, M., Stöber, S., Apter, A., Baglioni, V., Ball, J., Benaroya-Milshtein, N., Bodmer, B., Bond, M., Bognar, E., Burger, B., Buse, J., Cardona, F., Vela, M.C., Dietrich, A., Debes, N.M., 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., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Mueller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Pellico, A., Vasco, Á.P., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Gloor, F.T., Tarnok, Z., Tübing, J., Turner, V.L., Walitza, S., Weidinger, E., and Woods, M.L.
Subjects: Obsessive-Compulsive Disorder, Tic disorder, medicine.medical_specialty, Adolescent, Tics, Comorbidity, Severity of Illness Index, Pediatrics, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, mental disorders, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Vitamin D and neurology, Humans, ADHD, Vitamin D, Child, OCD, business.industry, Tourette, Symptom severity, General Medicine, Attention Deficit Disorder with Hyperactivity/psychology, Cross-Sectional Studies, Obsessive-Compulsive Disorder/epidemiology, Obsessive-Compulsive Disorder/psychology, Tic Disorders/metabolism, Tic Disorders/psychology, Tics/complications, Tics/metabolism, Tourette Syndrome/psychology, Vitamin D/metabolism, medicine.disease, 030227 psychiatry, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Cohort, CTD, business, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: This study investigated whether vitamin D is associated with the presence or severity of chronic tic disorders and their psychiatric comorbidities. This cross-sectional study compared serum 25-hydroxyvitamin D [25(OH)D] (ng/ml) levels among three groups: children and adolescents (3–16 years) with CTD (n = 327); first-degree relatives (3–10 years) of individuals with CTD who were assessed for a period of up to 7 years for possible onset of tics and developed tics within this period (n = 31); and first-degree relatives who did not develop tics and were ≥ 10 years old at their last assessment (n = 93). The relationship between 25(OH)D and the presence and severity of tics, as well as comorbid obsessive–compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD), were analysed controlling for age, sex, season, centre, latitude, family relatedness, and comorbidities. When comparing the CTD cohort to the unaffected cohort, the observed result was contrary to the one expected: a 10 ng/ml increase in 25(OH)D was associated with higher odds of having CTD (OR 2.08, 95% CI 1.27–3.42, p p = 0.01) and was inversely associated with ADHD symptom severity (β = − 2.52, 95% CI − 4.16–0.88, p
Published: 2022

18. Hair cortisol-a stress marker in children and adolescents with chronic tic disorders? A large European cross-sectional study

Author: Judith, Buse, Josefine, Rothe, Anne, Uhlmann, Benjamin, Bodmer, Clemens, Kirschbaum, Hoekstra, Pieter J., Andrea, Dietrich, Veit, Roessner, EMTICS collaborative group: Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Emese, Bognar, Bianka, Burger, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Maria Cristina Ferro, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Hedderly, Tammy J., Isobel, Heyman, Chaim, Huyser, Marcos, Madruga-Garrido, Martino, Davide, Pablo, Mir, Astrid, Morer, Kirsten, Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Openneer, Thaïra J. C., Pellico, Alessandra, Plessen, Kerstin J., Cesare, Porcelli, Rizzo, Renata, Daphna, Ruhrman, Schnell, Jaana M. L., Anette, Schrag, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett Tarnok &amp, Elif, Weidinger, EMTICS collaborative group, Apter, A., Baglioni, V., Ball, J., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Cardona, F., Vela, M.C., Dietrich, A., Ferro, M.C., Garcia-Delgar, B., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Madruga-Garrido, M., Martino, D., Mir, P., Morer, A., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Pellico, A., Plessen, K.J., Porcelli, C., Rizzo, R., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Silvestri, P.R., Skov, L., Steinberg, T., Gloor, F.T., Tarnok, Z., Weidinger, E., and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: BIOMARKER, medicine.medical_specialty, Adolescent, Hydrocortisone, GENETICS, Tics, RESPONSIVITY, Cross-sectional study, Chronic tic disorders, Emotional and behavioral problems, Physiological stress marker, Psychosocial stress, Tourette, Tourette syndrome, 03 medical and health sciences, 0302 clinical medicine, Biomarkers, Child, Cross-Sectional Studies, Hair, Humans, Tic Disorders/diagnosis, Developmental and Educational Psychology, Child and adolescent psychiatry, Medicine, ASSOCIATIONS, business.industry, TOURETTE-SYNDROME, Stressor, OBSESSIVE-COMPULSIVE DISORDER, General Medicine, medicine.disease, PREVALENCE, 030227 psychiatry, INDIVIDUALS, Psychiatry and Mental health, PSYCHOMETRIC PROPERTIES, Tic Disorders, Pediatrics, Perinatology and Child Health, Cohort, Biomarker (medicine), STRENGTHS, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract: Background There is clear evidence that tic disorders (TDs) are associated with psychosocial stress as well as emotional and behavioral problems. Studies have shown that individuals with TDs have higher acute physiological stress responses to external, single stressors (as reflected by saliva cortisol). The aim of the present study was to examine a physiological marker of longer-term stress (as reflected by hair cortisol concentration) in children and adolescents with TDs and unaffected siblings of individuals with TDs. Methods Two samples of a European cohort were included in this study. In the COURSE sample, 412 children and adolescents aged 3–16 years with a chronic TD including Tourette syndrome according to DSM IV-TR criteria were included. The ONSET sample included 131 3–10 years old siblings of individuals with TDs, who themselves had no tics. Differences in hair cortisol concentration (HCC) between the two samples were examined. Within the COURSE sample, relations of HCC with tic severity and perceived psychosocial stress as well as potential effects and interaction effects of comorbid emotional and behavioral problems and psychotropic medication on HCC were investigated. Results There were no differences in HCC between the two samples. In participants with TDs, there were no associations between HCC and tic severity or perceived psychosocial stress. No main effects of sex, psychotropic medication status and comorbid emotional and behavioral problems on HCC were found in participants with TDs. Conclusion A link between HCC and TDs is not supported by the present results.
Published: 2021
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19. Tics behandelen met een korte, intensieve groepstraining

Author: Pieter J. Hoekstra, Laura Beljaars, Chaim Huyser, Kees-Jan Kan, Annet Heijerman-holtgrefe, Marjolein Bus, Cara Verdellen, Danielle C. Cath, Lisbeth Utens, and Jolande van de Griendt
Published: 2020
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20. Anti‐dopamine D2 receptor antibodies in chronic tic disorders

Author: Jennifer Tübing, Thaïra J.C. Openneer, Juliane Ball, Erika Bartolini, Anna Marotta, Giovanni Laviola, Peter Nagy, Marco Tallon, Zsanett Tarnok, Renata Rizzo, Alexander Münchau, Davide Martino, Nanette Mol Debes, Paolo Roazzi, Noa Benaroya-Milshtein, Isobel Heyman, Maria Cristina Ferro, Marianthi Georgitsi, Mariangela Gulisano, Julie Hagstrøm, Angela Periañez, Alan Apter, Liselotte Skov, Benjamin Bodmer, Zacharias Anastasiou, Daphna Ruhrman, Veit Roessner, Vasco Alessandra Pellico, Androulla Efstratiou, Annelieke Hagen, Francesco Addabbo, Kerstin J. Plessen, Immaculada Margarit, Carolin Fremer, Anette Schrag, Marta Correa Vela, Bianka Burger, Marcos Madruga-Garrido, Elif Weidinger, Onofrio Petruzzelli, Ute C. Meier, Friederike Tagwerker Gloor, Blanca Garcia-Delgar, Jaana M. L. Schnell, Marina Redondo, Sara Stöber, Francesco Cardona, Simone Macrì, Valeria Neri, Natalie Moll, Paola R. Silvestri, Pablo Mir, Graziella Orefici, Maura Buttiglione, Pieter J. Hoekstra, Cesare Porcelli, Emese Bognar, Astrid Morer, Susanne Walitza, Iordanis Karagiannidis, Monica Imperi, Markus J. Schwarz, Judith Buse, Valentina Baglioni, Chaim Huyser, Roberta Creti, Andrea Dietrich, Gregor A. Schütze, Tamar Steinberg, Peristera Paschou, Maria Gariup, Tammy Hedderly, Kirsten R. Müller-Vahl, Victoria Turner, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, and ANS - Cellular & Molecular Mechanisms
Subjects: tourette syndrome, Male, 030506 rehabilitation, medicine.medical_specialty, Adolescent, Tics, Exacerbation, antiD2R antibodies, Logistic regression, Tourette syndrome, MOVEMENT, 03 medical and health sciences, GPCR, 0302 clinical medicine, McNemar's test, Developmental Neuroscience, tic exacerbations, Internal medicine, medicine, Humans, Child, Autoantibodies, Receptors, Dopamine D2, business.industry, Confounding, Autoantibody, Odds ratio, medicine.disease, tourette syndrome, antiD2R antibodies, tic exacerbations, Child, Preschool, Tic Disorders, Pediatrics, Perinatology and Child Health, Female, Neurology (clinical), 0305 other medical science, business, 030217 neurology & neurosurgery
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
Published: 2020
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21. Tic disorders in children and adolescents: does the clinical presentation differ in males and females? A report by the EMTICS group

Author: Blanca, Garcia‐delgar, Mateu, Servera, Coffey, Barbara J., Luisa, Lázaro, Thaïra, Openneer, Noa, Benaroya‐milshtein, Tami, Steinberg, Hoekstra, Pieter J., Andrea, Dietrich, Astrid Morer EMTICS collaborative group Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Emese, Bognar, Bianka, Burger, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Debes, Nanette M., Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Hedderly, Tammy J., Isobel, Heyman, Chaim, Huyser, Marcos, Madruga-Garrido, Anna, Marotta, Martino, Davide, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Openneer, Thaïra J. C., Pellico, Alessandra, Plessen, Kerstin J., Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Schnell, Jaana M. L., Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Susanne Walitza &amp, Elif, Weidinger, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, Child and Adolescent Psychiatry & Psychosocial Care, and ANS - Cellular & Molecular Mechanisms
Subjects: Male, Pediatrics, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Younger age, Tics, Adolescent, Autism Spectrum Disorder, Comorbidity, Adolescents, Tourette syndrome, Severity of Illness Index, Limited access, 03 medical and health sciences, 0302 clinical medicine, mental disorders, Sex differences, Developmental and Educational Psychology, Child and adolescent psychiatry, Medicine, Humans, 0501 psychology and cognitive sciences, 10. No inequality, Child, Children, business.industry, 05 social sciences, General Medicine, medicine.disease, 030227 psychiatry, body regions, Psychiatry and Mental health, Autism spectrum disorder, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Female, Presentation (obstetrics), business, human activities, 050104 developmental & child psychology, Male predominance
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

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

Author: Anette-Eleonore, Schrag, Martino, Davide, Hanyuying, Wang, Gareth, Ambler, Noa, Benaroya-Milstein, Maura, Buttiglione, Cardona, Francesco Carmelo Giovanni, Roberta, Creti, Androulla, Efstratiou, Tammy, Hedderly, Isobel, Heyman, Chaim, Huyser, Pablo, Mir, Astrid, Morer, Natalie, Moll, Norbert, E Müller, Kirsten, R Müller-Vahl, Kerstin, J Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Markus, Schwarz, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Pieter, J Hoekstra Alan Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Benjamin, Bodmer, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Nanette, M Debes, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Pieter, J Hoekstra, Marcos, Madruga-Garrido, Anna, Marotta, Norbert, Müller, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra Jc Openneer, Pellico, Alessandra, Ángela Periañez Vasco, Marina, Redondo, Daphna, Ruhrman, Jaana Ml Schnell, Anette, Schrag, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Jennifer, Tübing, Victoria, L Turner, and Elif, Weidinger
Subjects: Neuroimmunity, Neuroinflammation, Tic Disorders, Streptococcal infections
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: Annet Heijerman-Holtgrefe, Chaim Huyser, Cara Verdellen, Jolande van de Griendt, Laura Beljaars, Kees-Jan Kan, Ramón Lindauer, Daniëlle Cath, Pieter Hoekstra, Lisbeth Utens, Child and Adolescent Psychiatry / Psychology, Methods and Statistics (RICDE, FMG), Developmental Psychopathology (RICDE, FMG), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Adolescent, RESPONSE PREVENTION, paediatric neurology, ANXIETY DISORDERS, child & adolescent psychiatry, HABIT REVERSAL, Learning and Plasticity, Implosive Therapy, CHILDHOOD ANXIETY, General Medicine, psychiatry, PREVALENCE, SEVERITY, BEHAVIOR-THERAPY, QUALITY-OF-LIFE, Tic Disorders, ADOLESCENTS, Quality of Life, Tics, Humans, Child, Randomized Controlled Trials as Topic, Tourette Syndrome
Abstract: IntroductionThis 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 analysisTackle 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 disseminationEthics 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 psychosocial predictors/moderators for the effectiveness of this intervention can provide personalised treatment advice in the future.Trial registration numberNL8052.
Published: 2022

24. Genome-wide Association Study identifies two novel loci for Gilles de la Tourette Syndrome

Author: Susanne Walitza, Chaim Huyser, Astrid Morer, Pritesh R Jain, Jeffrey Glennon, and Odile Van den Heuvel
Abstract: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. We identified a genome-wide significant locus on chromosome 5q15 and one array-wide significant locus on chromosome 2q24.2. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus, and the RBMS1 gene within the 2q24.2 locus. Polygenic risk scoring using previous GWAS results demonstrated statistically significant ability to predict TS status in the novel cohort. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left putamen volumes. Our work presents novel insights in the neurobiology of TS opening up new directions for future studies.
Published: 2021
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25. The thalamus and its subregions – a gateway to obsessive-compulsive disorder

Author: Weeland C, Vriend C, Van Der Werf Y, Chaim Huyser, Hillegers M, Tiemeier H, White T, De Joode N, Thompson P, Stein D, Van Den Heuvel O, and Kasprzak S
Subjects: Psychiatry and Mental health
Abstract: Introduction Higher thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population (Boedhoe et al. 2017, Weeland et al. 2021a). Functionally distinct thalamic nuclei are an integral part of OCD-relevant brain circuitry. Objectives We aimed to study the thalamic nuclei volume in relation to subclinical and clinical OCD across different age ranges. Understanding the role of thalamic nuclei and their associated circuits in pediatric OCD could lead towards treatment strategies specifically targeting these circuits. Methods We studied the relationship between thalamic nuclei and obsessive-compulsive symptoms (OCS) in a large sample of school-aged children from the Generation R Study (N = 2500) (Weeland et al. 2021b). Using the data from the ENIGMA-OCD working group we conducted mega-analyses to study thalamic subregional volume in OCD across the lifespan in 2,649 OCD patients and 2,774 healthy controls across 29 sites (Weeland et al. 2021c). Thalamic nuclei were grouped into five subregions: anterior, ventral, intralaminar/medial, lateral and pulvinar (Figure 1). Results Both children with subclinical and clinical OCD compared with controls show increased volume across multiple thalamic subregions. Adult OCD patients have decreased volume across all subregions (Figure 2), which was mostly driven by medicated and adult-onset patients. Conclusions Our results suggests that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status. Disclosure No significant relationships.
Published: 2022
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26. Investigation of gene-environment interactions in relation to tic severity

Author: Hyun Ju Hong, Y.-J. Koh, Andrea Dietrich, J. Song, Pablo Mir, Dong-Ho Song, Samuel Kuperman, Keun-Ah Cheon, Pieter J. Hoekstra, Gary A. Heiman, Barbara J. Coffey, Jeremiah M. Scharf, Tammy Hedderly, Young Shin Kim, Jay A. Tischfield, Chaim Huyser, Lawrence W. Brown, Mohamed Abdulkadir, Blanca Garcia-Delgar, Marcos Madruga-Garrido, Laura Ibanez-Gomez, Bennett L. Leventhal, Frank Visscher, Astrid Morer, Robert A. King, Dorothy E. Grice, Carol A. Mathews, Donald L. Gilbert, Dongmei Yu, Veit Roessner, Alexander Münchau, Samuel H. Zinner, Eun-Young Shin, Thomas V. Fernandez, Isobel Heyman, Athanasios Maras, Lisa Osiecki, Kerstin J. Plessen, Sodahm Kook, Yongsun Kim, and J. Hagstroem
Subjects: Genetics, Candidate gene, Autism spectrum disorder, mental disorders, Multiple comparisons problem, medicine, SNP, Genome-wide association study, Single-nucleotide polymorphism, Biology, medicine.disease, Tourette syndrome, Genetic association
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
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27. Brief intensive cognitive behavioral therapy for children and adolescents with OCD: Two international pilot studies

Author: Juliane Ball, Veronika Brezinka, Lidewij H. Wolters, Elisabeth M. W. J. Utens, Chaim Huyser, Marjolein Bus, University of Zurich, Utens, Elisabeth, Child Psychiatry, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Paediatric Psychosocial Care, and Developmental Psychopathology (RICDE, FMG)
Subjects: medicine.medical_specialty, medicine.medical_treatment, Group format, CBT, 610 Medicine & health, Adolescents, behavioral disciplines and activities, 2738 Psychiatry and Mental Health, mental disorders, medicine, Child and adolescent psychiatry, Obsessive compulsive scale, Prospective cohort study, Children, Intensive treatment, 3203 Clinical Psychology, Retrospective cohort study, 10058 Department of Child and Adolescent Psychiatry, Obsessive compulsive disorders, Exposure and response prevention, Cognitive behavioral therapy, Psychiatry and Mental health, Clinical Psychology, Brief intensive treatment, Psychology, Clinical psychology
Abstract: Introduction: This article presents two international pilot studies examining brief intensive group cognitive behavioral therapy (BIG-CBT) for pediatric OCD. Aims: 1) to examine treatment outcome of BIG-CBT in two countries, 2) to explore the influence of potential predictors on treatment outcome. Methods: Study 1 (n = 59) was a retrospective study executed in the Netherlands, study 2 (n = 17) was a prospective study performed in Switzerland (total: 76 participants). The pilot studies were carried out in academic centers for child and adolescent psychiatry. BIG-CBT consisted of 5-day CBT in a group format, with exposure and response prevention as the main element. Results: Both studies showed a significant decrease from pre-to post-treatment on the Children's Yale-Brown Obsessive Compulsive Scale mean scores. In study 1, 44% of participants met the criterion for treatment responder at post-treatment (≥35% improvement), in study 2 this was 59% at post-treatment and 41% at 3-month-follow-up. In both studies, age, gender and baseline OCD severity did not significantly predict treatment outcome. Conclusion: The results of these two international pilots of BIG-CBT indicate that brief, intensive treatment has the potential to become a valuable addition to standard clinical care for pediatric OCD.
Published: 2021
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28. Tackle your Tics

Author: Kees-Jan Kan, Laura Beljaars, Chaim Huyser, Elisabeth M. W. J. Utens, Cara Verdellen, Pieter J. Hoekstra, A. P. Heijerman-Holtgrefe, Danielle C. Cath, J. M. T. M. van de Griendt, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, Child and Adolescent Psychiatry / Psychology, Methods and Statistics (RICDE, FMG), and Developmental Psychopathology (RICDE, FMG)
Subjects: Male, Quality of life, medicine.medical_specialty, Tic disorder, Exposure and response prevention, Adolescent, Tics, RESPONSE PREVENTION, medicine.medical_treatment, Exposure therapy, Implosive Therapy, Pilot Projects, Tourette syndrome, Quality of life (healthcare), SDG 3 - Good Health and Well-being, Behavior Therapy, QUALITY-OF-LIFE, mental disorders, ADOLESCENTS, Developmental and Educational Psychology, medicine, Child and adolescent psychiatry, Humans, Child, SCALE, business.industry, Chronic tic disorder, HABIT REVERSAL, Original Contribution, General Medicine, IMPAIRMENT, medicine.disease, PREVALENCE, Psychiatry and Mental health, Treatment Outcome, EUROPEAN CLINICAL GUIDELINES, Tic Disorders, Pediatrics, Perinatology and Child Health, BEHAVIORAL-THERAPY, Psychotherapy, Group, Chronic Tic Disorder, Female, Intensive behavioral treatment, business, Clinical psychology
Abstract: Tourette syndrome (TS) and other chronic tic disorders (CTD) are prevalent neurodevelopmental disorders, which can have a huge burden on families and society. Behavioral treatment is a first-line intervention for tic disorders. Despite demonstrated efficacy, tic reduction and utilization rates of behavioral treatment remain relatively low. Patient associations point to an urgent need for easy-to-undergo treatments that focus both on tic reduction and improvement of quality of life. To enhance treatment outcome and overcome treatment barriers, this pilot study’s aim was to investigate the feasibility and preliminary results of a brief, intensive group-based treatment. Tackle your Tics is a 4-day intensive and comprehensive group-based program for children and adolescents (9–17 years) with a tic disorder, consisting of exposure and response prevention (ERP) treatment and additional supporting components, such as coping strategies, relaxing activities and parent support. Assessments were performed pre- and post-treatment and at 2 months follow-up, to test outcomes on tic severity and quality of life, and explore premonitory urges, emotional and behavioral functioning and treatment satisfaction (N = 14, of whom 13 completed the treatment). Parents and children rated this treatment positive on a treatment satisfaction questionnaire. On tic severity (Yale Global Tic Severity Scale) and quality of life (Gilles de la Tourette Syndrome Quality of Life Scale for children and adolescents), improvements between pre-treatment and follow-up were found. Intensive ERP in group format is promising as a feasible treatment to improve both tic severity as well as quality of life. Larger controlled trials are needed to establish its effectiveness.
Published: 2021
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29. Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Tiffany M. Chaim-Avancini, Suzanne C. Swagerman, Sophie Maingault, Mauricio H. Serpa, Kang Sim, Patricia Gruner, Dara M. Cannon, Esther Walton, Gunter Schumann, Christopher R.K. Ching, Simon E. Fisher, Tomohiro Nakao, Nhat Trung Doan, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Ilya M. Veer, Lieuwe de Haan, Paul Pauli, Derrek P. Hibar, Kun Yang, Dan J. Stein, Dominik Grotegerd, Víctor Ortiz-García de la Foz, Daniel Brandeis, Sarah Baumeister, Xavier Caseras, Fabrice Crivello, Vincent P. Clark, Maria J. Portella, Salvador Sarró, Dorret I. Boomsma, Henry Völzke, Daniel H. Wolf, Lianne Schmaal, Yannis Paloyelis, Barbara Franke, Matthew D. Sacchet, Anne Uhlmann, Yulyia Yoncheva, Ole A. Andreassen, Erick J. Canales-Rodríguez, Ingrid Agartz, Anouk den Braber, Colm McDonald, Edith Pomarol-Clotet, Anders M. Dale, Calhoun Vd, David Mataix-Cols, Ignacio Martínez-Zalacaín, Joshua L. Roffman, Andrew J. Kalnin, Anton Albajes-Eizagirre, Andreas Reif, Won Hee Lee, Gaelle E. Doucet, Hans-Jörgen Grabe, Pieter J. Hoekstra, Avram J. Holmes, Theophilus N. Akudjedu, Ian H. Gotlib, Fleur M. Howells, Andrew J. Saykin, Genevieve McPhilemy, Moji Aghajani, David C. Glahn, Rachel M. Brouwer, Núria Bargalló, Knut Schnell, Katharina Wittfeld, Thomas Frodl, Josiane Bourque, Ryota Kanai, Raymond Salvador, Sean N. Hatton, Terry L. Jernigan, Helena Fatouros-Bergman, Oliver Grimm, Marise W. J. Machielsen, Victoria Chubar, Henk Temmingh, Andrew M. McIntosh, Georg C. Ziegler, Marieke Klein, T. P. Klyushnik, Iris E. C. Sommer, Heather C. Whalley, Rachel E. Gur, Alan Breier, Jordan W. Smoller, Kathryn I. Alpert, Dick J. Veltman, Neda Jahanshad, Sophia Frangou, Jiyang Jiang, Jessica A. Turner, Eveline A. Crone, Thomas Espeseth, Alexander Tomyshev, Christine Lochner, Anthony A. James, Aristotle N. Voineskos, Julian N. Trollor, Efstathios Papachristou, Beng-Choon Ho, Pablo Najt, Christian K. Tamnes, Geraldo F. Busatto, Stefan Borgwardt, Andreas Meyer-Lindenberg, Philip Asherson, Francisco X. Castellanos, Bernd Kramer, Jim Lagopoulos, Marcus V. Zanetti, Joaquim Radua, John A. Joska, Giulio Pergola, Nynke A. Groenewold, Erlend S. Dørum, Henrik Walter, Jan Egil Nordvik, Alessandro Bertolino, Wei Wen, Klaus-Peter Lesch, Ian B. Hickie, Pedro G.P. Rosa, Randy L. Buckner, Daniel A. Rinker, Hilleke E. Hulshoff Pol, Steven G. Potkin, Odile A. van den Heuvel, Nancy C. Andreasen, Sanne Koops, Amanda Worker, Susanne Erk, Lei Wang, Norbert Hosten, Jean-Paul Fouche, Dennis van 't Ent, Jonna Kuntsi, Dennis van den Meer, Simon Cervenka, C.A. Hartman, Nicholas G. Martin, Carles Soriano-Mas, Neeltje E.M. van Haren, Pascual Sánchez-Juan, Andreas Heinz, Brenna C. McDonald, Thomas H. Wassink, José M. Menchón, Katie L. McMahon, Jan K. Buitelaar, Sarah E. Medland, Aurora Bonvino, Patricia J. Conrod, Nic J.A. van der Wee, Paul M. Thompson, Micael Andersson, Perminder S. Sachdev, Lars Nyberg, Eco J. C. de Geus, Ramona Baur-Streubel, Lachlan T. Strike, Dag Alnæs, Paola Fuentes-Claramonte, Ben J. Harrison, Martine Hoogman, Lars T. Westlye, Annette Conzelmann, Annabella Di Giorgio, Benedicto Crespo-Facorro, Sarah Hohmann, Jilly Naaijen, Yang Wang, Henry Brodaty, Greig I. de Zubicaray, Laura Koenders, Ruben C. Gur, Stefan Ehrlich, Danai Dima, Christopher G. Davey, Tobias Banaschewski, Amirhossein Modabbernia, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Theodore D. Satterthwaite, René S. Kahn, Margaret J. Wright, Jaap Oosterlaan, Steven Williams, Bernard Mazoyer, Lara M. Wierenga, Bernd Weber, Luisa Lázaro, Irina Lebedeva, Erin W. Dickie, Chaim Huyser, John D. West, Theo G.M. van Erp, 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), RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Karolinska Schizophrenia Project (KaSP), Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, APH - Personalized Medicine, Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Amsterdam Neuroscience - Brain Imaging
Subjects: Male, diagnostic imaging [Corpus Striatum], Physiology, Hippocampus, Edat, Morfologia (Biologia), Lateral ventricles, anatomy & histology [Corpus Striatum], 0302 clinical medicine, Thalamus, 130 000 Cognitive Neurology & Memory, Basal ganglia, diagnostic imaging [Amygdala], Child, Cervell, Research Articles, diagnostic imaging [Hippocampus], Aged, 80 and over, Radiological and Ultrasound Technology, Putamen, Radiology, Nuclear Medicine & Medical Imaging, 05 social sciences, ENIGMA, Multisi, Brain, Middle Aged, Amygdala, 3. Good health, Neurology, Child, Preschool, Brain size, Female, Anatomy, Life Sciences & Biomedicine, Neurovetenskaper, Research Article, Neuroinformatics, Adult, Adolescent, anatomy & histology [Hippocampus], Human Development, multisite, BF, Neuroimaging, Nucleus accumbens, Biology, Brain morphometry, Morphology (Biology), 050105 experimental psychology, Young Adult, 03 medical and health sciences, Age, Longitudinal trajectories, brain morphometry, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, anatomy & histology [Thalamus], Aged, diagnostic imaging [Thalamus], Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Neurosciences, Corpus Striatum, nervous system, anatomy & histology [Amygdala], RC0321, Neurosciences & Neurology, longitudinal trajectories, Neurology (clinical), 030217 neurology & neurosurgery, physiology [Human Development]
Abstract: Special Issue: The ENIGMA Consortium: the first 10 years.-- Karolinska Schizophrenia Project (KaSP)., 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., National Institute of Mental Health, Grant/Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research.
Published: 2021
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30. Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders

Author: Martino, Davide, Anette, Schrag, Zacharias, Anastasiou, Alan, Apter, Noa, Benaroya-Milstein, Maura, Buttiglione, Cardona, Francesco Carmelo Giovanni, Roberta, Creti, Androulla, Efstratiou, Tammy, Hedderly, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga, Pablo, Mir, Astrid, Morer, Nanette Mol Debes, Natalie, Moll, Norbert Mu ̈ller, Kirsten Mu ̈ller-Vahl, Alexander, Munchau, Peter, Nagy, Kerstin Jessica Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Jaana, Schnell, Markus, Schwarz, Liselotte, Skov, Tamar, Steinberg, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Hoekstra, Pieter J., Baglioni, Valentina, Juliane, Ball, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Anna, Marotta, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Friederike Tagwerker Gloor, and Susanne Walitza, Elif Weidinger
Subjects: neuroimmunity, Tourette syndrome, tic disorders, neuroimmunity, tic disorders
Published: 2021

31. Clinical precursors of tics: an EMTICS study

Author: Openneer, Tha€ıra J. C., Chaim, Huyser, Martino, Davide, Anette, Schrag, Alan, Apter, Baglioni, Valentina, Juliane, Ball, Noa, Benaroya-Milshtein, Emese, Bognar, Bianka, Burger, Judith, Buse, Cardona, Francesco Carmelo Giovanni, Marta Correa Vela, Nanette, M Debes, Andrea, Dietrich, Maria Cristina Ferro, Carolin, Fremer, Blanca, Garcia-Delgar, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Tammy, J Hedderly, Isobel, Heyman, Marcos, Madruga-Garrido, Pablo, Mir, Astrid, Morer, Norbert, Müller, Kirsten, Müller-Vahl, Alexander, Münchau, Peter, Nagy, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Cesare, Porcelli, Rizzo, Renata, Veit, Roessner, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Liselotte, Skov, Tamar, Steinberg, Friederike Tagwerker Gloor, Zsanett, Tarnok, Susanne, Walitza, Elif, Weidinger, Hoekstra, Pieter J., Child Psychiatry, Child and Adolescent Psychiatry & Psychosocial Care, ANS - Cellular & Molecular Mechanisms, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Male, sex differences, Pediatrics, Longitudinal study, SYMPTOMS, Autism Spectrum Disorder, Comorbidity, Logistic regression, Tourette syndrome, 0302 clinical medicine, Developmental and Educational Psychology, Obsessive compulsive scale, Spectrum disorder, Longitudinal Studies, Child, 05 social sciences, PSYCHIATRIC-DISORDERS, clinical precursors, PREVALENCE, Psychiatry and Mental health, Autism spectrum disorder, Child, Preschool, Compulsions, Tics, Female, Psychology, 050104 developmental & child psychology, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, conduct problems, 03 medical and health sciences, OBSESSIVE-COMPULSIVE SCALE, mental disorders, medicine, Humans, ADHD, 0501 psychology and cognitive sciences, tic onset, SPECTRUM DISORDER, TOURETTE-SYNDROME, medicine.disease, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, SEVERITY, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Pediatrics, Perinatology and Child Health, Selection operator, human activities, 030217 neurology & neurosurgery, DISRUPTIVE BEHAVIOR, Tourette Syndrome
Abstract: Background: Children with Tourette syndrome (TS) often have comorbid disorders, particularly attention-deficit/hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). While subtle premorbid symptoms have been described in various psychiatric disorders, the presence of clinical precursors that may exist before the onset of tics is unknown. This longitudinal study aimed to find clinical precursors of tics by assessing a range of clinical characteristics prior to tic onset in comparison with children without onset of tics.Methods: A sample of 187 3- to 10-year-old first-degree unaffected relatives of children with TS were followed up to 7 years in the European Multicentre Tics in Children Study (EMTICS). We investigated whether clinical characteristics assessed at baseline predicted tic onset, comparing 126 children without tic onset to 61 children who developed tics. We used the least absolute shrinkage and selection operator (LASSO) method, a penalised logistic regression approach. We also explored sex differences and repeated our analyses in an age- and sex-matched subsample.Results: Children with tic onset were more frequently male (beta = -0.36), had higher baseline severity of conduct problems (beta = 0.23), autism spectrum disorder symptoms (ASD; beta = 0.08), compulsions (beta = 0.02) and emotional problems (beta = 0.03) compared to children without tic onset. Conduct and ASD problems were male-specific predictors, whereas severity of compulsions and oppositional (beta = 0.39) and emotional problems were female-specific predictors.Conclusion: This study supports the presence of clinical precursors prior to tic onset and highlights the need of sex-specific monitoring of children at risk of developing tics. This may aid in the earlier detection of tics, particularly in females. We moreover found that tics most often persisted one year after tic onset, in contrast to the common belief that tics are mostly transient.
Published: 2021

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

Author: Jonathan P. Shock, Erika L. Nurmi, Francesco Benedetti, Gianfranco Spalletta, Anthony C. James, Damiaan Denys, Jose C. Pariente, Ignacio Martínez-Zalacaín, Yanni Liu, Paulo Marques, Joseph O'Neill, Ganesan Venkatasubramanian, Benjamin A. Ely, Noam Soreni, Tobias U. Hauser, Michael C. Stevens, Masaru Kuno, Kate D. Fitzgerald, Je-Yeon Yun, Stephanie H. Ameis, John Piacentini, Yuki Sakai, Kang Ik K. Cho, Kathrin Koch, Luciano Minuzzi, Fabrizio Piras, Hao Hu, Chaim Huyser, Philip R. Szeszko, Gerd Kvale, Zhen Wang, Luke Taylor, Jean Paul Fouche, Marcelo Q. Hoexter, Francesca Assogna, Odile A. van den Heuvel, Rachel Marsh, Carles Soriano-Mas, Alan Anticevic, David Mataix-Cols, Eiji Shimizu, Fern Jaspers-Fayer, Rajat M. Thomas, Yoshinari Abe, Pedro Moreira, Norbert Kathmann, Astrid Morer, Rosa Calvo, Guido van Wingen, João Ricardo Sato, Egill A. Fridgeirsson, Chris Perriello, Janardhanan C. Narayanaswamy, Anushree Bose, Pedro Morgado, Oana G. Rus-Oswald, Akiko Nakagawa, Silvia Brem, Luisa Lazaro, Dan J. Stein, Paul D. Arnold, Yoshiyuki Hirano, Premika S.W. Boedhoe, Emily R. Stern, Irene Bollettini, Sara Dallaspezia, Lianne Schmaal, Federica Piras, Willem B Bruin, José M. Menchón, Jan K. Buitelaar, Christian Kaufmann, Christine Lochner, Yuqi Cheng, Brian P. Brennan, H. Blair Simpson, David F. Tolin, Daan van Rooij, Pino Alonso, Iliyan Ivanov, S. Evelyn Stewart, Paul M. Thompson, Takashi Nakamae, Deniz A. Gürsel, Paul Zhutovsky, Jan C. Beucke, Jamie D. Feusner, Patricia Gruner, Tomohiro Nakao, Y.C. Janardhan Reddy, Jun Soo Kwon, Graduate School, ANS - Compulsivity, Impulsivity & Attention, APH - Global Health, APH - Mental Health, Adult Psychiatry, Child Psychiatry, Bruin, Willem B., Taylor, Luke, Thomas, Rajat M., P Shock, Jonathan, 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., K Buitelaar, Jan, 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, Soo Kwon, Jun, 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, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Janardhan Reddy, Y. C., Rus-Oswald, Oana G., Sakai, Yuki, Sato, João R., Schmaal, Lianne, Shimizu, Eiji, Blair Simpson, H., Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R., Stevens, Michael C., Evelyn Stewart, S., Szeszko, Philip R., Tolin, David F., Venkatasubramanian, Ganesan, Wang, Zhen, Yun, Je-Yeon, van Rooij, Daan, Consortium, ENIGMA-OCD, Thompson, Paul M., van den Heuvel, Odile A., Stein, Dan J., van Wingen, Guido A., Netherlands Institute for Neuroscience (NIN), ENIGMA-OCD Working Group, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry
Subjects: Obsessive-Compulsive Disorder, Multivariate analysis, Disease, Neuroimaging biomarkers, 0302 clinical medicine, Obsessive-compulsive disorder, Medicine, Psychology, Prefrontal cortex, screening and diagnosis, medicine.diagnostic_test, Biochemical markers, Brain, Serious Mental Illness, Magnetic Resonance Imaging, 3. Good health, Psychiatry and Mental health, Detection, Mental Health, Marcadors bioquímics, Public Health and Health Services, Biomedical Imaging, Clinical psychology, medicine.drug, medicine.medical_specialty, Clinical Sciences, MEDLINE, Neuroimaging, Article, lcsh:RC321-571, Cellular and Molecular Neuroscience, 03 medical and health sciences, Obsessive compulsive, Clinical Research, Internal medicine, Medical imaging, Diagnostic biomarker, Humans, Clinical significance, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, Fluoxetine, business.industry, Neurosi obsessiva, Neurosciences, Magnetic resonance imaging, Diagnostic markers, 030227 psychiatry, Brain Disorders, 4.1 Discovery and preclinical testing of markers and technologies, Obsessive compulsive disorder, ENIGMA-OCD Working Group, business, 030217 neurology & neurosurgery, Biomarkers, Neuroscience
Abstract: ObjectiveNo diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Magnetic resonance imaging (MRI) studies have provided evidence for structural abnormalities in distinct brain regions, but effect sizes are small and have limited clinical relevance. To investigate whether individual patients can be distinguished from healthy controls, we performed multivariate analysis of structural neuroimaging data from the ENIGMA-OCD consortium.MethodWe included 46 data sets with neuroimaging and clinical data from adult (≥18 years) and pediatric (1images from 2,304 OCD patients and 2,068 healthy controls were analyzed using standardized processing to extract regional measures of cortical thickness, surface area and subcortical volume. Machine learning classification performance was tested using cross-validation, and possible effects of clinical variables were investigated by stratification.ResultsClassification performance for OCD versus controls using the complete sample with different classifiers and cross-validation strategies was poor (AUC—0.57 (standard deviation (SD)=0.02;Pcorr=0.19) to 0.62 (SD=0.03;Pcorrcorr>.99) to 0.54 (SD=0.08;Pcorr>.99)). In contrast, good classification performance (>0.8 AUC) was achieved within subgroups of patients split according to their medication status.ConclusionsParcellated structural MRI data do not enable good distinction between patients with OCD and controls. However, classifying subgroups of patients based on medication status enables good identification at the individual subject level. This underlines the need for longitudinal studies on the short- and long-term effects of medication on brain structure.
Published: 2020
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33. Subcortical brain volume, regional cortical thickness, and cortical surface area across disorders:Findings from the ENIGMA ADHD, ASD, and OCD working groups

Author: Pedro Moreira, Ruth O'Gorman Tuura, Mara Cercignani, Philip Aherson, Maria Jalbrzikowski, Kate D. Fitzgerald, Declan G. Murphy, Bernd Kardatzki, Christine Ecker, David F. Tolin, Fern Jaspers-Fayer, Pedro Morgado, Juan Carlos Soliva Vila, Kang Ik K. Cho, Kathrin Koch, Timothy J. Silk, Philip R. Szeszko, Thomas Frodl, Mara Parellada, Shlomi Haar, Eileen Daly, Bob Oranje, Anouk Schrantee, Leyla Namazova-Baranova, Joseph A. King, Beatriz Luna, Silvia Brem, Eric Earl, Alasdair Vance, Michela Tosetti, Christine Deruelle, Ramona Baur-Streubel, Jackie Fitzgerald, Kirsten O'Hearn, Michael C. Stevens, Yoshiyuki Hirano, J. Antoni Ramos-Quiroga, Erika L. Nurmi, Kaylita Chantiluke, Joseph O'Neill, Kerstin Kohls, Olga Puig, Devon Shook, Clodagh M. Murphy, Gustavo Sudre, Marlene Behrmann, Jaap Oosterlaan, Tinatin Gogberashvili, Lianne Schmaal, Carles Soriano-Mas, Liesbeth Hoekstra, Ignacio Martínez-Zalacaín, Noam Soreni, Marcel P. Zwiers, Paulo Mattos, Gregor Kohls, Andreas J. Fallgatter, Tiffany M. Chaim-Avancini, Alexander Baranov, S. Evelyn Stewart, Sara Dallaspezia, Gianfranco Spalletta, Jonna Kuntsi, Lizanne J. S. Schweren, Joel T. Nigg, Leanne Tamm, Premika S.W. Boedhoe, Adriana Di Martino, Jane McGrath, Marcelo C. Batistuzzo, Norbert Skokauskas, Filippo Muratori, John Piacentini, Jean-Paul Fouche, Sarah Baumeister, Alan Anticevic, Neil A. Harrison, Christine M. Freitag, Pedro G.P. Rosa, Stephen V. Faraone, Ana Cubillo, David Mataix-Cols, Yuki Sakai, Stefan Ehrlich, Eileen Oberwelland Weiss, Fabrizio Piras, Dirk J. Heslenfeld, Je-Yeon Yun, Paul Pauli, Catharina A. Hartman, Ganesan Venkatasubramanian, Janardhanan C. Narayanaswamy, Charles B Malpas, Jan C. Beucke, José M. Menchón, Egill A. Fridgeirsson, Margot J. Taylor, Mauricio Moller Martinho, H. Blair Simpson, Jan K. Buitelaar, Gerd Kvale, Ivanei E. Bramati, Aki Tsuchiyagaito, Susanne Walitza, Irene Bollettini, Jeffery N. Epstein, Anders M. Dale, Thomas Ethofer, Terry L. Jernigan, David Coghill, Rachel Marsh, Andreas Reif, Astri J. Lundervold, Pieter J. Hoekstra, Oana Georgiana Rus, Damiaan Denys, Gregory L. Wallace, Matt C. Gabel, Hazel McCarthy, Sarah Hohmann, Rosa Nicolau, Stephanie H. Ameis, Neda Jahanshad, Takashi Nakamae, Xin Feng, Emily R. Stern, Georg G. von Polier, Yanni Liu, Paulo Marques, Anushree Bose, Hao Hu, Sara Lera-Miguel, Deniz A. Gürsel, Jochen Seitz, Jos W. R. Twisk, Mario Rodrigues Louzã, Clare Kelly, Annette Conzelmann, Alysa E. Doyle, Odile A. van den Heuvel, Anthony A. James, Chris Perriello, Joost Janssen, Damien A. Fair, Norbert Kathmann, Francisco X. Castellanos, Paul D. Arnold, Oscar Vilarroya, Geraldo F. Busatto, Federica Piras, Pino Alonso, Akiko Nakagawa, Sarah Durston, Lena Schwarz, Mitul A. Mehta, Dan J. Stein, Celso Arango, Daan van Rooij, Ilan Dinstein, Anastasia Christakou, Klaus-Peter Lesch, Kerstin J. Plessen, Jennifer Fedor, Yolanda Vives-Gilabert, Ilaria Gori, Louise Gallagher, Brian P. Brennan, Yuqi Cheng, Barbara Franke, Sabin Khadka, Stephanie E. Novotny, Martine Hoogman, Georgii Karkashadze, Georg C. Ziegler, Yuliya N. Yoncheva, Rosa Calvo, Thomas Wolfers, Marcelo Q. Hoexter, Benjamin A. Ely, Masaru Kuno, Alessandra Retico, Yoshinari Abe, Geoffrey B. Hall, Tobias Banaschewski, Anatoly Anikin, Christine Lochner, Astrid Morer, Guido van Wingen, Jan Haavik, Joseph Biederman, Luisa Lázaro, Francesco Benedetti, Fengfeng Zhou, Guillaume Auzias, Daniel Brandeis, Dmitry Kapilushniy, Katya Rubia, Philip Shaw, Christian Kaufmann, Sara Calderoni, Marcus V. Zanetti, Anastasia Solovieva, Zhen Wang, Francesca Assogna, Jamie D. Feusner, Chaim Huyser, Fernanda Tovar-Moll, Theo G.M. van Erp, Y.C. Janardhan Reddy, Jun Soo Kwon, Yannis Paloyelis, Anna Calvo, Patricia Gruner, Kathrin C. Zierhut, Liesbeth Reneman, Tomohiro Nakao, Janita Bralten, Marie F. Høvik, Mark A. Bellgrove, Maarten Mennes, Paul M. Thompson, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Epidemiology and Data Science, Pediatric surgery, Radiology and nuclear medicine, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Psychiatry, APH - Methodology, APH - Health Behaviors & Chronic Diseases, Boedhoe, Premika S W, van Rooij, Daan, Hoogman, Martine, Twisk, Jos W R, 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, Tobia, 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, Thoma, 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, Thoma, 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, Kardatzki, Bernd, Karkashadze, Georgii, Kathmann, Norbert, Kaufmann, Christian, Kelly, Clare, Khadka, Sabin, King, Joseph A, Koch, Kathrin, Kohls, Gregor, Konrad, Kerstin, Kuno, Masaru, Kuntsi, Jonna, Kvale, Gerd, Kwon, Jun Soo, Lázaro, Luisa, Lera-Miguel, Sara, Lesch, Klaus-Peter, Hoekstra, Liesbeth, Liu, Yanni, Lochner, Christine, Louza, Mario R, Luna, Beatriz, Lundervold, Astri J, Malpas, Charles B, Marques, Paulo, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Mattos, Paulo, Mccarthy, Hazel, Mcgrath, Jane, Mehta, Mitul A, Menchón, José M, Mennes, Maarten, Martinho, Mauricio Moller, Moreira, Pedro S, Morer, Astrid, Morgado, Pedro, Muratori, Filippo, Murphy, Clodagh M, Murphy, Declan G M, Nakagawa, Akiko, Nakamae, Takashi, Nakao, Tomohiro, Namazova-Baranova, Leyla, Narayanaswamy, Janardhanan C, Nicolau, Rosa, Nigg, Joel T, Novotny, Stephanie E, Nurmi, Erika L, Weiss, Eileen Oberwelland, O'Gorman Tuura, Ruth L, O'Hearn, Kirsten, O'Neill, Joseph, Oosterlaan, Jaap, Oranje, Bob, Paloyelis, Yanni, Parellada, Mara, Pauli, Paul, Perriello, Chri, Piacentini, John, Piras, Fabrizio, Piras, Federica, Plessen, Kerstin J, Puig, Olga, Ramos-Quiroga, J Antoni, Reddy, Y C Janardhan, Reif, Andrea, Reneman, Liesbeth, Retico, Alessandra, Rosa, Pedro G P, Rubia, Katya, Rus, Oana Georgiana, Sakai, Yuki, Schrantee, Anouk, Schwarz, Lena, Schweren, Lizanne J S, Seitz, Jochen, Shaw, Philip, Shook, Devon, Silk, Tim J, Simpson, H Blair, Skokauskas, Norbert, Soliva Vila, Juan Carlo, Solovieva, Anastasia, Soreni, Noam, Soriano-Mas, Carle, Spalletta, Gianfranco, Stern, Emily R, Stevens, Michael C, Stewart, S Evelyn, Sudre, Gustavo, Szeszko, Philip R, Tamm, Leanne, Taylor, Margot J, Tolin, David F, Tosetti, Michela, Tovar-Moll, Fernanda, Tsuchiyagaito, Aki, van Erp, Theo G M, van Wingen, Guido A, Vance, Alasdair, Venkatasubramanian, Ganesan, Vilarroya, Oscar, Vives-Gilabert, Yolanda, von Polier, Georg G, Walitza, Susanne, Wallace, Gregory L, Wang, Zhen, Wolfers, Thoma, Yoncheva, Yuliya N, Yun, Je-Yeon, Zanetti, Marcus V, Zhou, Fengfeng, Ziegler, Georg C, Zierhut, Kathrin C, Zwiers, Marcel P, Thompson, Paul M, Stein, Dan J, Buitelaar, Jan, Franke, Barbara, van den Heuvel, Odile A, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, General Paediatrics, ARD - Amsterdam Reproduction and Development, Radiology and Nuclear Medicine, APH - Personalized Medicine, and APH - Mental Health
Subjects: Male, Research Report, Obsessive-Compulsive Disorder, Frontal cortex, Systems Analysis, Attention Deficit Hyperactivity Disorder, Autism Spectrum Disorder, [SDV]Life Sciences [q-bio], Hippocampal formation, Audiology, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, Child, Obsessive-compulsive disorder (OCD), ComputingMilieux_MISCELLANEOUS, Intelligence quotient, Psychopathology, ATTENTION-DEFICIT/HYPERACTIVITY DISORDER, ABNORMALITIES, ENIGMA, Organ Size, 3. Good health, Psychiatry and Mental health, Autism spectrum disorder, Brain size, Cohort, Female, MRI, Adult, medicine.medical_specialty, CORTEX, Adolescent, DEFICIT HYPERACTIVITY DISORDER, Human Development, Neuroimaging, behavioral disciplines and activities, Article, 03 medical and health sciences, FIELD-STRENGTH, mental disorders, medicine, MEGA-ANALYSIS, Attention deficit hyperactivity disorder, Humans, Cortical surface, Structural MRI, Attention Deficit Disorder with Hyperactivity, Cerebrum, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], business.industry, medicine.disease, 030227 psychiatry, VOXEL, Autism, business, 030217 neurology & neurosurgery
Abstract: ObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and 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. We examined subcortical volume, cortical thickness and 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 ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.
Published: 2020
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34. Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium

Author: Xiang-Zhen Kong, Premika S.W. Boedhoe, Yoshinari Abe, Pino Alonso, Stephanie H. Ameis, Paul D. Arnold, Francesca Assogna, Justin T. Baker, Marcelo C. Batistuzzo, Francesco Benedetti, Jan C. Beucke, Irene Bollettini, Anushree Bose, Silvia Brem, Brian P. Brennan, Jan Buitelaar, Rosa Calvo, Yuqi Cheng, Kang Ik K. Cho, Sara Dallaspezia, Damiaan Denys, Benjamin A. Ely, Jamie Feusner, Kate D. Fitzgerald, Jean-Paul Fouche, Egill A. Fridgeirsson, David C. Glahn, Patricia Gruner, Deniz A. Gürsel, Tobias U. Hauser, Yoshiyuki Hirano, Marcelo Q. Hoexter, Hao Hu, Chaim Huyser, Anthony James, Fern Jaspers-Fayer, Norbert Kathmann, Christian Kaufmann, Kathrin Koch, Masaru Kuno, Gerd Kvale, Jun Soo Kwon, Luisa Lazaro, Yanni Liu, Christine Lochner, Paulo Marques, Rachel Marsh, Ignacio Martínez-Zalacaín, David Mataix-Cols, Sarah E. Medland, José M. Menchón, Luciano Minuzzi, Pedro S. Moreira, Astrid Morer, Pedro Morgado, Akiko Nakagawa, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswamy, Erika L. Nurmi, Joseph O'Neill, Jose C. Pariente, Chris Perriello, John Piacentini, Fabrizio Piras, Federica Piras, Christopher Pittenger, Y.C. Janardhan Reddy, Oana Georgiana Rus-Oswald, Yuki Sakai, Joao R. Sato, Lianne Schmaal, H. Blair Simpson, Noam Soreni, Carles Soriano-Mas, Gianfranco Spalletta, Emily R. Stern, Michael C. Stevens, S. Evelyn Stewart, Philip R. Szeszko, David F. Tolin, Aki Tsuchiyagaito, Daan van Rooij, Guido A. van Wingen, Ganesan Venkatasubramanian, Zhen Wang, Je-Yeon Yun, Paul M. Thompson, Dan J. Stein, Odile A. van den Heuvel, Clyde Francks, Alan Anticevic, Nerisa Banaj, Nuria Bargalló, Daniel Brandeis, Geraldo F. Busatto, Anna Calvo, Valentina Ciullo, Froukje E. de Vries, Stella J. de Wit, Erin Dickie, Renate Drechsler, Madalena Esteves, Andrea Falini, Yu Fang, Martijn Figee, Martine Fontaine, Geoff Hall, Sayo Hamatani, Gregory L. Hanna, Bjarne Hansen, Keisuke Ikari, Neda Jahanshad, Ricardo Magalhães, Yasutaka Masuda, Koji Matsumoto, James T. McCracken, Euripedes C. Miguel, Jin Narumoto, Seiji Nishida, Sara Poletti, Tim Reess, Eiji Shimizu, Nuno Sousa, Jumpei Takahashi, Jinsong Tang, Anders Lillevik Thorsen, Ysbrand D. van der Werf, Dick J. Veltman, Daniela Vecchio, Susanne Walitza, Anri Watanabe, Jian Xu, Xiufeng Xu, Kei Yamada, Tokiko Yoshida, Mojtaba Zarei, Qing Zhao, Cong Zhou, ENIGMA-OCD Working Group, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, Graduate School, Child Psychiatry, Kong, X. -Z., Boedhoe, P. S. W., Abe, Y., Alonso, P., Ameis, S. H., Arnold, P. D., Assogna, F., Baker, J. T., Batistuzzo, M. C., Benedetti, F., Beucke, J. C., Bollettini, I., Bose, A., Brem, S., Brennan, B. P., Buitelaar, J., Calvo, R., Cheng, Y., Cho, K. I. K., Dallaspezia, S., Denys, D., Ely, B. A., Feusner, J., Fitzgerald, K. D., Fouche, J. -P., Fridgeirsson, E. A., Glahn, D. C., Gruner, P., Gursel, D. A., Hauser, T. U., Hirano, Y., Hoexter, M. Q., Hu, H., Huyser, C., James, A., Jaspers-Fayer, F., Kathmann, N., Kaufmann, C., Koch, K., Kuno, M., Kvale, G., Kwon, J. S., Lazaro, L., Liu, Y., Lochner, C., Marques, P., Marsh, R., Martinez-Zalacain, I., Mataix-Cols, D., Medland, S. E., Menchon, J. M., Minuzzi, L., Moreira, P. S., Morer, A., Morgado, P., Nakagawa, A., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E. L., O'Neill, J., Pariente, J. C., Perriello, C., Piacentini, J., Piras, F., Pittenger, C., Reddy, Y. C. J., Rus-Oswald, O. G., Sakai, Y., Sato, J. R., Schmaal, L., Simpson, H. B., Soreni, N., Soriano-Mas, C., Spalletta, G., Stern, E. R., Stevens, M. C., Stewart, S. E., Szeszko, P. R., Tolin, D. F., Tsuchiyagaito, A., van Rooij, D., van Wingen, G. A., Venkatasubramanian, G., Wang, Z., Yun, J. -Y., Anticevic, A., Banaj, N., Bargallo, N., Brandeis, D., Busatto, G. F., Calvo, A., Ciullo, V., de Vries, F. E., de Wit, S. J., Dickie, E., Drechsler, R., Esteves, M., Falini, A., Fang, Y., Figee, M., Fontaine, M., Hall, G., Hamatani, S., Hanna, G. L., Hansen, B., Ikari, K., Jahanshad, N., Magalhaes, R., Masuda, Y., Matsumoto, K., Mccracken, J. T., Miguel, E. C., Narumoto, J., Nishida, S., Poletti, S., Reess, T., Shimizu, E., Sousa, N., Takahashi, J., Tang, J., Thorsen, A. L., van der Werf, Y. D., Veltman, D. J., Vecchio, D., Walitza, S., Watanabe, A., Xu, J., Xu, X., Yamada, K., Yoshida, T., Zarei, M., Zhao, Q., Zhou, C., Thompson, P. M., Stein, D. J., van den Heuvel, O. A., Francks, C., Netherlands Institute for Neuroscience (NIN), Universidade do Minho, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Psychiatry
Subjects: 0301 basic medicine, Adult, medicine.medical_specialty, Obsessive-Compulsive Disorder, Mega-analysis, Mega-analysi, media_common.quotation_subject, Thalamus, Medicina Básica [Ciências Médicas], Audiology, Asymmetry, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, mental disorders, medicine, Image Processing, Computer-Assisted, Obsessive-compulsive disorder, Brain asymmetry, Humans, Child, Biological Psychiatry, Depression (differential diagnoses), media_common, Brain Mapping, Science & Technology, medicine.diagnostic_test, business.industry, Laterality, Neurosi obsessiva, Brain, Magnetic resonance imaging, Cerebral cortex, Magnetic Resonance Imaging, humanities, Escorça cerebral, 030104 developmental biology, Meta-analysis, Ciências Médicas::Medicina Básica, Pallidum, Anxiety, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Accepted Manuscript, BACKGROUND: Lateralized 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.METHODS: We 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.RESULTS: In 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 = -20.21). 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.CONCLUSIONS: The 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., This research was funded by the Max Planck Society (Germany). Additional funding was from the Japan Society for the Promotion of Science (KAKENHI Grant No. 18K15523 [to YA], KAKENHI Grant No. 16K04344 [to YH], KAKENHI Grant Nos. 16K19778 and 18K07608 [to TNakam], and KAKENHI Grant No. 26461762 [to AN]); the Carlos III Health Institute (Grant No. PI14/00419 [to PA], Grant No. PI040829 cofunded by European Regional Development Fund [to LL], Grant No. FI17/00294 [to IM-Z], Grant No. PI16/00950 [to JMM], and Grant Nos. CPII16/00048, PI13/01958, and PI16/00889 cofunded by European Regional Development Funds [to CS-M]); the Ontario Mental Health Foundation (Research Training Fellowship [to SHA]); Alberta Innovates Translational Health Chair in Child and Youth Mental Health (to PDA), the Ontario Brain Institute (to PDA); the National Institute of Mental Health (Grant No. K23MH104515 [to JTB], Grant No. K23-MH092397 [to BPB], Grant No. K23MH082176 [to KDF), Grant No. R21MH101441 [to RM], Grant No. R01MH081864 [to JO and JP], and Grant No. R01MH085900 [to JO and JF], Grant No. R21MH093889 [to HBS]); Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant No. 2011/21357–9 [to MCB], Grant No. 2011/21357–9 [to GFB], Grant No. 2011/21357–9 [to MQH], and Grant No. 2011/21357–9 [to ECM]); the Swiss National Science Foundation (Grant No. 320030_130237 [to SB; principal investigator, Susanne Walitza]); the Hartmann Müller Foundation (Grant No. 1460 [to SB]); the David Judah Fund at the Massachusetts General Hospital (to BPB); EU FP7 Project TACTICS (Grant No. 278948 [to JB]); the National Natural Science Foundation of China (Grant No. 81560233 [to YC] and Grant No. 81371340 [to ZW]); the International OCD Foundation (Grant No. K23 MH115206 [to PG]); the Wellcome Sir Henry Dale Fellowship (Grant No. 211155/Z/18/Z [to TUH]); the Jacobs Foundation (to TUH); the Brain and Behavior Research Foundation (2018 NARSAD Young Investigator Grant No. 27023 [to TUH]); the Agency for Medical Research and Development (Grant No. JP18dm0307002 [to YH]); the Michael Smith Foundation for Health Research (to FJ-F); the Federal Ministry of Education and Research of Germany (Grant No. BMBF-01GW0724 [to NK]); the Deutsche Forschungsgemeinschaft (Grant No. KO 3744/7–1 [to KK]); the Helse Vest Health Authority (Grant Nos. 911754 and 911880 [to GK]); the Norwegian Research Council (Grant No. HELSEFORSK 243675 [to GK]); the Marató TV3 Foundation (Grant Nos. 01/2010 and 091710 [to LL]); the Agency for Management of University and Research Grants (Grant No. 2017 SGR 881 [to LL] and 2017 SGR 1247 from the Generalitat de Catalunya [to JMM]); Fundação para a Ciência e a Tecnologia (Grant No. PDE/BDE/113604/2015 from the PhD-iHES Program [to RM], Grant No. PDE/BDE/113601/2015 from the PhD-iHES Program [to PSM]); the Japanese Ministry of Education, Culture, Sports, Science and Technology (Grant-in-Aid for Scientific Research (Grant Nos. 22591262, 25461732, and 16K10253 [to TNakao]); the Government of India Department of Science and Technology (DST INSPIRE Faculty Grant No. -IFA12-LSBM-26 [to JCN] and Grant No. SR/S0/HS/0016/2011 [to YCJR]); the Government of India Department of Biotechnology (Grant No. BT/06/IYBA/2012 [to JCN] and Grant No. BT/PR13334/Med/30/259/2009 [to YCJR]); the New York State Office of Mental Health (to HBS); the Italian Ministry of Health (Grant No. RC13-14-15-16A [to GS]); the National Center for Advancing Translational Sciences (Grant No. UL1TR000067/KL2TR00069 [to ERS]); the Canadian Institutes of Health Research (to SES); the Michael Smith Foundation for Health Research (to SES); the British Columbia Provincial Health Services Authority (to SES); the Netherlands Organization for Scientific Research (Grant No. NWO/ZonMW Vidi 917.15.318 [to GAvW]); the Wellcome-DBT India Alliance (Grant No. 500236/Z/11/Z [to GV]); the Shanghai Key Laboratory of Psychotic Disorders (Grant No. 13dz2260500 [to ZW]).
Published: 2020
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35. Cortical Thickness Trajectories across the Lifespan: Data from 17,075 healthy individuals aged 3-90 years

Author: Stefan Ehrlich, Danai Dima, Nhat Trung Doan, Simon E. Fisher, Dominik Grotegerd, Nicholas G. Martin, Tiffany M. Chaim-Avancini, Sophie Maingault, Sean N. Hatton, Derrek P. Hibar, Vincent P. Clark, Anders M. Dale, Iris E. C. Sommer, Ben J. Harrison, Annabella Di Giorgio, Benedicto Crespo-Facorro, Ian H. Gotlib, Andrew J. Kalnin, Andreas Reif, Edith Pomarol-Clotet, Thomas Espeseth, Theodore D. Satterthwaite, Pieter J. Hoekstra, René S. Kahn, Margaret J. Wright, Núria Bargalló, Maria J. Portella, Thomas Frodl, Lianne Schmaal, Chaim Huyser, Sophia I. Thomopoulos, Odille A van den Heuvel, Rachel M. Brouwer, Rachel E. Gur, Stefan Borgwardt, Marise W. J. Machielsen, Kathryn I. Alpert, Dick J. Veltman, Sim Kang, Irina V. Lebedeva, Marcus V. Zanetti, Anne Uhlmann, Christopher R.K. Ching, John D. West, Paul Pauli, Susanne Erk, Xavier Caseras, Kun Yang, Randy L. Buckner, Julian N. Trollor, Katharina Wittfeld, Fabrice Crivello, Theo G.M. van Erp, Luisa Lázaro, Jan Egil Nordvik, Sarah Baumeister, Steven G. Potkin, Calhoun Vd, Ian B. Hickie, Giulio Pergola, Henrik Walter, Katie L. McMahon, Theophilus N. Akudjedu, Patricia J. Conrod, Nic J.A. van der Wee, Won Hee Lee, Dennis van 't Ent, Barbara Franke, Knut Schnell, Josiane Bourque, Matthew D. Sacchet, Perminder S. Sachdev, Esther Walton, Raymond Salvador, Colm McDonald, Gunter Schumann, Paul M. Thompson, Georg C. Ziegler, Erin W. Dickie, Christine Lochner, Andreas Meyer-Lindenberg, Eco J. C. de Geus, Ole A. Andreassen, Joshua L. Roffman, Oliver Grimm, Andrew M. McIntosh, Ryota Kanai, Mauricio H. Serpa, Dennis van den Meer, Jessica A. Turner, Simon Cervenka, Alexander Tomyshev, Lara M. Wierenga, Francisco X. Castellanos, Bernd Kramer, Erlend S. Dørum, Alessandro Bertolino, P. G. P. Rosa, Avram J. Holmes, Klaus-Peter Lesch, Norbert Hosten, Hilleke E. Hulshoff Pol, Jean-Paul Fouche, Neda Jahanshad, Daniel Brandeis, José M. Menchón, Jiyang Jiang, Jan K. Buitelaar, Andrew J. Saykin, Genevieve McPhilemy, Efstathios Papachristou, Hans-Jörgen Grabe, Bernd Weber, Beng-Choon Ho, Pablo Najt, Fleur M. Howells, Yannis Paloyelis, Lieuwe de Haan, Lachlan T. Strike, Dag Alnæs, David Mataix-Cols, Henry Völzke, Daniel H. Wolf, Suzanne C. Swagerman, Paola Fuentes-Claramonte, Marieke Klein, Patricia Gruner, Anthony A. James, Ingrid Agartz, Dara M. Cannon, Jim Lagopoulos, Geraldo F. Busatto, Tomohiro Nakao, Dan J. Stein, Gaelle E Doucet, Erick J. Canales-Rodríguez, Cristopher Davey, Tatyana P Klushnik, Jaap Oosterlaan, Ilya M. Veer, Steven Williams, Bernard Mazoyer, Helena Fatouros-Bergman, Yulyia Yoncheva, Ramona Baur-Streubel, Anouk den Braber, Nynke A. Groenewold, Salvador Sarró, Ignacio Martínez-Zalacaín, Sanne Koops, M. Aghajani, Lei Wang, Sarah E. Medland, C.A. Hartman, Aurora Bonvino, Pascual Sánchez-Juan, Andreas Heinz, Tobias Banaschewski, Amirhossein Modabbernia, Jilly Naaijen, Yang Wang, Sophia Frangou, Henry Brodaty, Henk Temmingh, Greig I. de Zubicaray, Nancy C. Andreasen, Carles Soriano-Mas, Neeltje E.M. van Haren, Brenna C. McDonald, Ruben C. Gur, Micael Andersson, Dorret I. Boomsma, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Víctor Ortiz-García de la Foz, Anton Albajes-Eizagirre, David C. Glahn, Alan Breier, Heather C. Whalley, Jordan W. Smoller, Joaquim Radua, Christian K. Tamnes, Eveline A. Crone, Philip Asherson, John A. Joska, Wei Wen, Jonna Kuntsi, Lars Nyberg, Thomas H. Wassink, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lars T. Westlye, Annette Conzelmann, Sarah Hohmann, and Laura Koenders
Subjects: 0303 health sciences, medicine.medical_specialty, Fractional polynomial, Cognition, Audiology, Biology, Regression, Pooling data, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging genetics, Healthy individuals, medicine, General pattern, Analysis of variance, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: Delineating age-related cortical trajectories in healthy individuals is critical given the association of cortical thickness with cognition and behaviour. Previous research has shown that deriving robust estimates of age-related brain morphometric changes requires large-scale studies. In response, we conducted a large-scale analysis of cortical thickness in 17,075 individuals aged 3-90 years by pooling data through the Lifespan Working group of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium. We used fractional polynomial (FP) regression to characterize age-related trajectories in cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma (LMS) method. Inter-individual variability was estimated using meta-analysis and one-way analysis of variance. Overall, cortical thickness peaked in childhood and had a steep decrease during the first 2-3 decades of life; thereafter, it showed a gradual monotonic decrease which was steeper in men than in women particularly in middle-life. Notable exceptions to this general pattern were entorhinal, temporopolar and anterior cingulate cortices. Inter-individual 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 reconcile uncertainties about age-related trajectories of cortical thickness; the centile values provide estimates of normative variance in cortical thickness, and may assist in detecting abnormal deviations in cortical thickness, and associated behavioural, cognitive and clinical outcomes.
Published: 2020
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36. Subcortical Volume Trajectories across the Lifespan: Data from 18,605 healthy individuals aged 3-90 years

Author: Lara M. Wierenga, Iris E. C. Sommer, Edith Pomarol-Clotet, Erick J. Canales-Rodríguez, van Erp Tg, Lars T. Westlye, van Haren Ne, Francisco X. Castellanos, P. G. P. Rosa, Kang S, van der Wee Nj, Joaquim Radua, Jim Lagopoulos, José M. Menchón, Helena Fatouros-Bergman, Jan K. Buitelaar, Bernd Weber, Annette Conzelmann, Núria Bargalló, S. E. Medland, Maria J. Portella, Patricia J. Conrod, Amanda Worker, Klaus-Peter Lesch, Jonna Kuntsi, S.G. Potkin, R. Salvador, Knut Schnell, Stefan Borgwardt, Katharina Wittfeld, Kathryn I. Alpert, Dick J. Veltman, de Geus Ej, Ole A. Andreassen, Sophia Frangou, Di Giorgio A, Avram J. Holmes, Rachel M. Brouwer, Thomas Frodl, Lachlan T. Strike, Anton Albajes-Eizagirre, Giulio Pergola, van den Heuvel Oa, Perminder S. Sachdev, Esther Walton, Josiane Bourque, Dag Alnæs, David C. Glahn, Ramona Baur-Streubel, Laura Koenders, Christian K. Tamnes, Alan Breier, Jordan W. Smoller, Yulyia Yoncheva, Marise W. J. Machielsen, Sarah Hohmann, Magnus Andersson, Paola Fuentes-Claramonte, David Mataix-Cols, Salvador Sarró, Stefan Ehrlich, John A. Joska, Marieke Klein, Mauricio H. Serpa, den Braber A, Henry Völzke, Jilly Naaijen, de Haan L, Thomas H. Wassink, Daniel H. Wolf, Thomas Espeseth, Yang Wang, Henrik Walter, Wei Wen, Calhoun, Dan J. Stein, Simon E. Fisher, Eveline A. Crone, Ingrid Agartz, Susanne Erk, Oliver Grimm, Andrew M. McIntosh, Dominik Grotegerd, Henry Brodaty, Katie L. McMahon, Jaap Oosterlaan, Danai Dima, Aurora Bonvino, Anders M. Dale, Alexander Tomyshev, Ignacio Martínez-Zalacaín, Anthony A. James, Andrew J. Kalnin, Barbara Franke, Theophilus N. Akudjedu, Andreas Reif, Pieter J. Hoekstra, Nordvik Je, Lars Nyberg, Bernard Mazoyer, Paul M. Thompson, Andrew J. Saykin, Genevieve McPhilemy, Nhat Trung Doan, Geraldo F. Busatto, Colm McDonald, van ’t Ent D, Sophia I. Thomopoulos, Derrek P. Hibar, Neda Jahanshad, Norbert Hosten, Ryota Kanai, Ruben C. Gur, D.I. Boomsma, Lianne Schmaal, Jean-Paul Fouche, Anne Uhlmann, Jessica A. Turner, Fabrice Crivello, P. Asherson, de la Foz Vo, Heather C. Whalley, C.A. Hartman, Ching Cr, Dirk J. Heslenfeld, Jiyang Jiang, Pascual Sánchez-Juan, Andreas Heinz, Simon Cervenka, Irina V. Lebedeva, Nancy C. Andreasen, Erik G. Jönsson, Oliver Gruber, Ben J. Harrison, Tiffany M. Chaim-Avancini, Sophie Maingault, Efstathios Papachristou, Beng-Choon Ho, Marcus V. Zanetti, Doucet Ge, Nynke A. Groenewold, Sacchet, Andreas Meyer-Lindenberg, Bernhard K. Krämer, M. Aghajani, Diana Tordesillas-Gutiérrez, Martine Hoogman, Lu Wang, Pablo Najt, van den Meer D, Christopher G. Davey, Theodore D. Satterthwaite, René S. Kahn, Margaret J. Wright, N. G. Martin, G. Schumann, Tobias Banaschewski, Amirhossein Modabbernia, Benedicto Crespo-Facorro, Ian B. Hickie, Alessandro Bertolino, Sanne Koops, Sean N. Hatton, Georg C. Ziegler, Carles Soriano-Mas, Kun Yang, Brenna C. McDonald, Sarah Baumeister, Scr Williams, Julian N. Trollor, Paul Pauli, Joshua L. Roffman, Xavier Caseras, Won Hee Lee, Henk Temmingh, Rachel E. Gur, Randy L. Buckner, Vincent P. Clark, Daniel Brandeis, Ian H. Gotlib, Hulshoff Pol He, Hans-Jörgen Grabe, Fleur M. Howells, Christine Lochner, Yannis Paloyelis, Erlend S. Dørum, Suzanne C. Swagerman, Patricia Gruner, Dara M. Cannon, Tomohiro Nakao, Tatyana P Klushnik, Ilya M. Veer, de Zubicaray Gi, Chaim Huyser, John D. West, Luisa Lázaro, and Erin W. Dickie
Subjects: 0303 health sciences, Putamen, Thalamus, Brain morphometry, Hippocampus, Nucleus accumbens, Biology, 03 medical and health sciences, Lateral ventricles, 0302 clinical medicine, nervous system, Brain size, Basal ganglia, Neuroscience, 030217 neurology & neurosurgery, 030304 developmental biology
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 capitalised on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine the age-related morphometric trajectories 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 early in life; the volume of the basal ganglia showed a gradual monotonic decline thereafter while the volumes of the thalamus, amygdala and the hippocampus remained largely stable (with some degree of decline in thalamus) until the sixth decade of life followed by a steep decline thereafter. The lateral ventricles showed a trajectory of continuous enlargement throughout the lifespan. Significant age-related increase in inter-individual variability was found for the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to derive risk predictions for the early identification of diverse clinical phenotypes.
Published: 2020
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37. European Multicentre Tics in Children Studies (EMTICS)

Author: Schrag, A, Martino, D, Apter, A, Ball, J, Bartolini, E, Benaroya-Milshtein, N, Buttiglione, M, Cardona, F, Creti, R, Efstratiou, A, Gariup, M, Georgitsi, M, Hedderly, T, Heyman, I, Margarit, I, Mir, P, Moll, N, Morer, A, Müller, N, Müller-Vahl, K, Münchau, A, Orefici, G, Plessen, Kj, Porcelli, C, Paschou, P, Rizzo, R, Roessner, V, Schwarz, Mj, Steinberg, T, Tagwerker Gloor, F, Tarnok, Z, Walitza, S, Dietrich, A, Hoekstra, Pj, Zacharias, Anastasiou, Isobel, Heyman, Chaim, Huyser, Marcos, Madruga, Pablo, Mir, Astrid, Morer, Nanette Mol Debes, Natalie, Moll, Norbert Mu ̈ller, Peter, Nagy, Kerstin Jessica Plessen, Cesare, Porcelli, Renata, Rizzo, Veit, Roessner, Jaana, Schnell, Liselotte, Skov, Zsanett, Tarnok, Susanne, Walitza, Andrea, Dietrich, Baglioni, Valentina, Juliane, Ball, Emese, Bognar, Bianka, Burger, Judith, Buse, Marta Correa Vela, Maria Cristina Ferro, Carolin, Fremer, Mariangela, Gulisano, Annelieke, Hagen, Julie, Hagstrøm, Anna, Marotta, Neri, Valeria, Thaïra J, C Openneer, Pellico, Alessandra, Kerstin, J Plessen, Daphna, Ruhrman, Jaana M, L Schnell, Silvestri, PAOLA ROSARIA, Tamar, Steinberg, Friederike Tagwerker Gloor, Elif, Weidinger, EMTICS Collaborative Group, Anastasiou, Z., Apter, A., Baglioni, V., Ball, J., Bartolini, E., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Buttiglione, M., Cardona, F., Correa Vela, M., Creti, R., Dietrich, A., Debes, N.M., Efstratiou, A., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gariup, M., Georgitsi, M., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Imperi, M., Karagiannidis, I., Laviola, G., Macri, S., Madruga-Garrido, M., Margarit, I., Marotta, A., Martino, D., Meier, U.C., Mir, P., Moll, N., Morer, A., Müller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Orefici, G., Paschou, P., Pellico, A., Petruzzelli, O., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roazzi, P., Roessner, V., Ruhrman, D., Schnell, JML, Schrag, A., Schütze, G.A., Schwarz, M.J., Silvestri, P.R., Skov, L., Steinberg, T., Stöber, S., Gloor, F.T., Tallon, M., Tarnok, Z., Turner, V.L., Walitza, S., Weidinger, E., Woods, M.L., European Commission, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), University College London, NHS Foundation Trust, GlaxoSmithKline, German Research Foundation, Instituto de Biomedicina de Sevilla (IBIS), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: Male, Pediatrics, Tic disorder, BLOOD, Tourette syndrome, Obsessive–compulsive disorder, Cohort Studies, 0302 clinical medicine, Risk Factors, QUALITY-OF-LIFE, Obsessive-compulsive disorder, Developmental and Educational Psychology, Genetics, Longitudinal, Streptococcal infection, Stress, Prospective cohort study, Child, GENE-EXPRESSION, education.field_of_study, HAIR CORTISOL, 05 social sciences, A STREPTOCOCCAL INFECTIONS, Original Contribution, General Medicine, 3. Good health, Europe, Psychiatry and Mental health, LA-TOURETTE SYNDROME, Child, Preschool, NEUROPSYCHIATRIC DISORDERS, Cohort, Female, 050104 developmental & child psychology, Cohort study, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Tics, Adolescent, PSYCHOSOCIAL STRESS, Population, 03 medical and health sciences, mental disorders, medicine, Humans, 0501 psychology and cognitive sciences, Genetic Predisposition to Disease, education, Tic Disorders/complications, Tic Disorders/diagnosis, Tic Disorders/pathology, business.industry, OBSESSIVE-COMPULSIVE DISORDER, medicine.disease, 030227 psychiatry, nervous system diseases, body regions, PSYCHOMETRIC PROPERTIES, Tic Disorders, Pediatrics, Perinatology and Child Health, Chronic Tic Disorder, business, human activities
Abstract: EMTICS Collaborative Group., Genetic predisposition, autoimmunity and environmental factors [e.g. pre- and perinatal difficulties, Group A Streptococcal (GAS) and other infections, stress-inducing events] might interact to create a neurobiological vulnerability to the development of tics and associated behaviours. However, the existing evidence for this relies primarily on small prospective or larger retrospective population-based studies, and is therefore still inconclusive. This article describes the design and methodology of the EMTICS study, a longitudinal observational European multicentre study involving 16 clinical centres, with the following objectives: (1) to investigate the association of environmental factors (GAS exposure and psychosocial stress, primarily) with the onset and course of tics and/or obsessive–compulsive symptoms through the prospective observation of at-risk individuals (ONSET cohort: 260 children aged 3–10 years who are tic-free at study entry and have a first-degree relative with a chronic tic disorder) and affected individuals (COURSE cohort: 715 youth aged 3–16 years with a tic disorder); (2) to characterise the immune response to microbial antigens and the host’s immune response regulation in association with onset and exacerbations of tics; (3) to increase knowledge of the human gene pathways influencing the pathogenesis of tic disorders; and (4) to develop prediction models for the risk of onset and exacerbations of tic disorders. The EMTICS study is, to our knowledge, the largest prospective cohort assessment of the contribution of different genetic and environmental factors to the risk of developing tics in putatively predisposed individuals and to the risk of exacerbating tics in young individuals with chronic tic disorders., This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under Grant agreement no. 278367. Schrag was supported by the National Institute for Health Research UCLH Biomedical Research Centre, and Müller, Burger, Schnell and Weidinger by Stiftung Immunität und Seele. This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (Heyman); partially sponsored by GSK Vaccines (Margarit, Bartolini); and Deutsche Forschungsgemeinschaft (DFG): projects 1692/3-1, 4-1 (Münchau).
Published: 2019
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38. An overview of the first 5 years of the ENIGMA obsessive-compulsive disorder working group: The power of worldwide collaboration

Author: Edna Grünblatt, Noam Soreni, Takashi Nakamae, Susanne Walitza, Anthony A. James, Paul D. Arnold, Iliyan Ivanov, Patricia Gruner, Janardhanan C. Narayanaswamy, Dick J. Veltman, Gianfranco Spalletta, Sara Bertolín, H. Blair Simpson, Tomohiro Nakao, Je-Yeon Yun, David Mataix-Cols, Gerd Kvale, Carles Soriano-Mas, Guido van Wingen, Ganesan Venkatasubramanian, Luisa Lázaro, Francesco Benedetti, Chris Vriend, Xiangzhen Kong, Jan C. Beucke, Kate D. Fitzgerald, Martine Hoogman, Y. C.Janardhan Reddy, Kathrin Koch, Daan van Rooij, Jun Soo Kwon, David F. Tolin, Rachel Marsh, Jan K. Buitelaar, Neda Jahanshad, Christopher Pittenger, Stephan F. Taylor, Tomáš Paus, Willem B Bruin, Clyde Francks, Anushree Bose, Chaim Huyser, Christine Lochner, Erika L. Nurmi, Dan J. Stein, Joseph O'Neill, S. Evelyn Stewart, Yash Patel, João Ricardo Sato, Zhen Wang, Irene Bollettini, Lianne Schmaal, Alessandro S. De Nadai, Fabrizio Piras, Yoshiyuki Hirano, Brian P. Brennan, Odile A. van den Heuvel, Pedro Morgado, Sophia I. Thomopoulos, Marcelo Q. Hoexter, Premika S.W. Boedhoe, Paul M. Thompson, van den Heuvel, O. A., Boedhoe, P. S. W., Bertolin, S., Bruin, W. B., Francks, C., Ivanov, I., Jahanshad, N., Kong, X. -Z., Kwon, J. S., O'Neill, J., Paus, T., Patel, Y., Piras, F., Schmaal, L., Soriano-Mas, C., Spalletta, G., van Wingen, G. A., Yun, J. -Y., Vriend, C., Simpson, H. B., van Rooij, D., Hoexter, M. Q., Hoogman, M., Buitelaar, J. K., Arnold, P., Beucke, J. C., Benedetti, F., Bollettini, I., Bose, A., Brennan, B. P., De Nadai, A. S., Fitzgerald, K., Gruner, P., Grunblatt, E., Hirano, Y., Huyser, C., James, A., Koch, K., Kvale, G., Lazaro, L., Lochner, C., Marsh, R., Mataix-Cols, D., Morgado, P., Nakamae, T., Nakao, T., Narayanaswamy, J. C., Nurmi, E., Pittenger, C., Reddy, Y. C. J., Sato, J. R., Soreni, N., Stewart, S. E., Taylor, S. F., Tolin, D., Thomopoulos, S. I., Veltman, D. J., Venkatasubramanian, G., Walitza, S., Wang, Z., Thompson, P. M., and Stein, D. J.
Subjects: mega-analysis, Obsessive-Compulsive Disorder, Review Article, Machine Learning, 0302 clinical medicine, Neurobiology, Obsessive-compulsive disorder, Multicenter Studies as Topic, Disease process, Cervell, Review Articles, Pediatric, Psychiatry, Cerebral Cortex, Collaborative community, Radiological and Ultrasound Technology, 05 social sciences, ENIGMA, Brain, Experimental Psychology, Serious Mental Illness, humanities, 3. Good health, Mental Health, Neurology, Meta-analysis, Neurological, Cognitive Sciences, Mega analysis, Anatomy, Psychology, Neurobiologia, Clinical psychology, MRI, ENIGMA-OCD working group, Neuroimaging, behavioral disciplines and activities, 050105 experimental psychology, Lateralization of brain function, Power (social and political), 03 medical and health sciences, obsessive–compulsive disorder, Obsessive compulsive, Clinical Research, mental disorders, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Psiquiatria, mega‐analysis, volume, Neurosi obsessiva, Neurosciences, surface area, cortical thickness, Brain Disorders, meta-analysis, meta‐analysis, Neurology (clinical), 030217 neurology & neurosurgery
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
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39. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author: Sheng Wang, Jeffrey D. Mandell, Yogesh Kumar, Nawei Sun, Montana T. Morris, Juan Arbelaez, Cara Nasello, Shan Dong, Clif Duhn, Xin Zhao, Zhiyu Yang, Shanmukha S. Padmanabhuni, Dongmei Yu, Robert A. King, Andrea Dietrich, Najah Khalifa, Niklas Dahl, Alden Y. Huang, Benjamin M. Neale, Giovanni Coppola, Carol A. Mathews, Jeremiah M. Scharf, Thomas V. Fernandez, Joseph D. Buxbaum, Silvia De Rubeis, Dorothy E. Grice, Jinchuan Xing, Gary A. Heiman, Jay A. Tischfield, Peristera Paschou, A. Jeremy Willsey, Matthew W. State, Mohamed Abdulkadir, Benjamin Bodmer, Yana Bromberg, Lawrence W. Brown, Keun-Ah Cheon, Barbara J. Coffey, Li Deng, Lonneke Elzerman, Carolin Fremer, Blanca Garcia-Delgar, Donald L. Gilbert, Julie Hagstrøm, Tammy Hedderly, Isobel Heyman, Pieter J. Hoekstra, Hyun Ju Hong, Chaim Huyser, Eun-Joo Kim, Young Key Kim, Young-Shin Kim, Yun-Joo Koh, Sodahm Kook, Samuel Kuperman, Bennett L Leventhal, Andrea G. Ludolph, Marcos Madruga-Garrido, Athanasios Maras, Pablo Mir, Astrid Morer, Montana T Morris, Kirsten Müller-Vahl, Alexander Münchau, Tara L. Murphy, Kerstin J. Plessen, Hannah Poisner, Veit Roessner, Stephan J. Sanders, Eun-Young Shin, Dong-Ho Song, Jungeun Song, Joshua K. Thackray, Jennifer Tübing, Frank Visscher, Sina Wanderer, A Jeremy Willsey, Martin Woods, Yeting Zhang, Samuel H. Zinner, Christos Androutsos, Csaba Barta, Luca Farkas, Jakub Fichna, Marianthi Georgitsi, Piotr Janik, Iordanis Karagiannidis, Anastasia Koumoula, Peter Nagy, Joanna Puchala, Renata Rizzo, Natalia Szejko, Urszula Szymanska, Zsanett Tarnok, Vaia Tsironi, Tomasz Wolanczyk, Cezary Zekanowski, Cathy L. Barr, James R. Batterson, Cheston Berlin, Ruth D. Bruun, Cathy L. Budman, Danielle C. Cath, Sylvain Chouinard, Nancy J. Cox, Sabrina Darrow, Lea K. Davis, Yves Dion, Nelson B. Freimer, Marco A. Grados, Matthew E. Hirschtritt, Cornelia Illmann, Roger Kurlan, James F. Leckman, Gholson J. Lyon, Irene A. Malaty, William M. MacMahon, Michael S. Okun, Lisa Osiecki, David L. Pauls, Danielle Posthuma, Vasily Ramensky, Mary M. Robertson, Guy A. Rouleau, Paul Sandor, Harvey S. Singer, Jan Smit, Jae-Hoon Sul, Tourette International Collaborative Genetics Study (TIC Genetics), Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE), Tourette Association of America International Consortium for Genetics (TAAICG), Abdulkadir, M., Arbelaez, J., Bodmer, B., Bromberg, Y., Brown, L.W., Cheon, K.A., Coffey, B.J., Deng, L., Dietrich, A., Dong, S., Duhn, C., Elzerman, L., Fernandez, T.V., Fremer, C., Garcia-Delgar, B., Gilbert, D.L., Grice, D.E., Hagstrøm, J., Hedderly, T., Heiman, G.A., Heyman, I., Hoekstra, P.J., Hong, H.J., Huyser, C., Kim, E.J., Kim, Y.K., Kim, Y.S., King, R.A., Koh, Y.J., Kook, S., Kuperman, S., Leventhal, B.L., Ludolph, A.G., Madruga-Garrido, M., Mandell, J.D., Maras, A., Mir, P., Morer, A., Morris, M.T., Müller-Vahl, K., Münchau, A., Murphy, T.L., Nasello, C., Plessen, K.J., Poisner, H., Roessner, V., Sanders, S.J., Shin, E.Y., Song, D.H., Song, J., State, M.W., Sun, N., Thackray, J.K., Tischfield, J.A., Tübing, J., Visscher, F., Wanderer, S., Wang, S., Willsey, A.J., Woods, M., Xing, J., Zhang, Y., Zhao, X., Zinner, S.H., Androutsos, C., Barta, C., Farkas, L., Fichna, J., Georgitsi, M., Janik, P., Karagiannidis, I., Koumoula, A., Nagy, P., Paschou, P., Puchala, J., Rizzo, R., Szejko, N., Szymanska, U., Tarnok, Z., Tsironi, V., Wolanczyk, T., Zekanowski, C., Barr, C.L., Batterson, J.R., Berlin, C., Bruun, R.D., Budman, C.L., Cath, D.C., Chouinard, S., Coppola, G., Cox, N.J., Darrow, S., Davis, L.K., Dion, Y., Freimer, N.B., Grados, M.A., Hirschtritt, M.E., Huang, A.Y., Illmann, C., Kurlan, R., Leckman, J.F., Lyon, G.J., Malaty, I.A., Mathews, C.A., MacMahon, W.M., Neale, B.M., Okun, M.S., Osiecki, L., Pauls, D.L., Posthuma, D., Ramensky, V., Robertson, M.M., Rouleau, G.A., Sandor, P., Scharf, J.M., Singer, H.S., Smit, J., Sul, J.H., and Yu, D.
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, DNA Copy Number Variations, Receptors, Cell Surface, Biology, Genome, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, RARE, SCHIZOPHRENIA, medicine, Humans, Copy-number variation, Child, NEURODEVELOPMENTAL DISORDERS, Gene, lcsh:QH301-705.5, Exome sequencing, 030304 developmental biology, Medicinsk genetik, Sequence (medicine), Genetics, 0303 health sciences, SEVERE INTELLECTUAL DISABILITY, Cadherin, MUTATIONS, AUTISM SPECTRUM DISORDER, Cell Polarity, OBSESSIVE-COMPULSIVE DISORDER, Cadherins, medicine.disease, Pedigree, PREVALENCE, CONGENITAL HEART-DISEASE, GENOME, 030104 developmental biology, lcsh:Biology (General), Schizophrenia, Medical genetics, Female, Cadherins/genetics, Receptors, Cell Surface/genetics, Tourette Syndrome/genetics, Tourette Syndrome/pathology, TIC Genetics, Tourette disorder, cell polarity, copy number variants, de novo variants, gene discovery, microarray genotyping, multiplex, simplex, whole exome sequencing, Medical Genetics, 030217 neurology & neurosurgery, Tourette Syndrome
Abstract: SUMMARY We previously established the contribution of de novo damaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novo damaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3 (cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk., In Brief Wang et al. expand their earlier exome-sequencing work in TD, adding 291 trios and conducting combined analyses suggesting de novo variants carry more risk in individuals with unaffected parents, establishing de novo structural variants as risk factors, identifying CELSR3 as a risk gene, and implicating cell polarity in pathogenesis., Graphical Abstract
Published: 2018

40. Investigation of previously implicated genetic variants in chronic tic disorders

Author: Samuel Kuperman, Frank Visscher, Kirsten R. Müller-Vahl, Eun-Young Shin, Jennifer Tübing, Els van den Ban, Sina Wanderer, Hyun Ju Hong, Yun-Joo Koh, Jungeun Song, Gary A. Heiman, Lonneke Elzerman, Donald L. Gilbert, Derek Gordon, Laura Ibanez-Gomez, Keun-Ah Cheon, Douglas Londono, Young Key Kim, Bennett L. Leventhal, Alexander Münchau, Odette Fründt, Andrea G. Ludolph, Astrid Morer, Sodahm Kook, Thomas V. Fernandez, Lawrence W. Brown, Marcos Madruga-Garrido, Ewgeni Jakubovski, Jay A. Tischfield, Mohamed Abdulkadir, Blanca Garcia-Delgar, Carolin Fremer, Samuel H. Zinner, Pablo Mir, Robert A. King, Martin Woods, Veit Roessner, Young Shin Kim, Isobel Heyman, Tara Murphy, Athanasios Maras, Dong-Ho Song, Pieter J. Hoekstra, Tammy Hedderly, Barbara J. Coffey, Andrea Dietrich, Chaim Huyser, Dorothy E. Grice, Kerstin J. Plessen, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Child Psychiatry, and Child and Adolescent Psychiatry / Psychology
Subjects: 0301 basic medicine, Male, Candidate gene, Genome-wide association study, Tryptophan Hydroxylase, Obsessive–compulsive disorder, Severity of Illness Index, Linkage Disequilibrium, PICALM, 0302 clinical medicine, Candidate gene study, Obsessive-compulsive disorder, Pharmacology (medical), Child, POPULATION, Psychiatry, Genetics, LA-TOURETTE-SYNDROME, education.field_of_study, SLITRK1 GENE, Single Nucleotide, General Medicine, Transmission disequilibrium test, Middle Aged, 3. Good health, Psychiatry and Mental health, COMPREHENSIVE METAANALYSIS, Child, Preschool, HISTIDINE-DECARBOXYLASE, Cognitive Sciences, Female, Microtubule-Associated Proteins, Adult, Adolescent, Genotype, Clinical Sciences, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, SNP, Humans, Polymorphism, GENOME-WIDE ASSOCIATION, AUTISM, Preschool, education, Biological Psychiatry, FAMILY-BASED ASSOCIATION, Genetic association, Family Health, Original Paper, Tourette syndrome, Neurosciences, OBSESSIVE-COMPULSIVE DISORDER, Transmission Disequilibrium Test, CROSS-DISORDER, 030104 developmental biology, Attention-deficit/hyperactivity disorder, Tic Disorders, 030217 neurology & neurosurgery, Genome-Wide Association Study
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. Electronic supplementary material The online version of this article (doi:10.1007/s00406-017-0808-8) contains supplementary material, which is available to authorized users.
Published: 2018
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41. Antibodies to neuronal surface proteins in Tourette Syndrome: Lack of evidence in a European paediatric cohort

Author: V. Baglioni, E. Coutinho, D.A. Menassa, M.P. Giannoccaro, L. Jacobson, M. Buttiglione, O. Petruzzelli, F. Cardona, A. Vincent, Zacharias Anastasiou, Alan Apter, Erika Bartolini, Noa Benaroya-Milshtein, Benjamin Bodmer, Emese Bognar, Bianka Burger, Marta Correa Vela, Roberta Creti, Andrea Dietrich, Nanette M. Debes, Androulla Efstratiou, Maria Cristina Ferro, Carolin Fremer, Blanca Garcia-Delgar, Maria Gariup, Marianthi Georgitsi, Mariangela Gulisano, Annelieke Hagen, Julie Hagstrøm, Tammy J. Hedderly, Isobel Heyman, Pieter J. Hoekstra, Chaim Huyser, Monica Imperi, Iordanis Karagiannidis, Giovanni Laviola, Simone Macri, Marcos Madruga-Garrido, Immaculada Margarit, Anna Marotta, Davide Martino, Ute C. Meier, Pablo Mir, Natalie Moll, Astrid Morer, Kirsten Müller-Vahl, Alexander Münchau, Peter Nagy, Valeria Neri, Thaïra J.C. Openneer, Graziella Orefici, Peristera Paschou, Alessandra Pellico, Cesare Porcelli, Marina Redondo, Renata Rizzo, Paolo Roazzi, Veit Roessner, Daphna Ruhrman, Jaana M.L. Schnell, Anette Schrag, Gregor A. Schütze, Markus J. Schwarz, Paola Rosaria Silvestri, Liselotte Skov, Tamar Steinberg, Sara Stöber, Marco Tallon, Zsanett Tarnok, Baglioni V., Coutinho E., Menassa D.A., Giannoccaro M.P., Jacobson L., Buttiglione M., Petruzzelli O., Cardona F., Vincent A., and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: 0301 basic medicine, Male, Tics, Adolescent, DISORDERS, CNTNAP2, Immunology, Primary Cell Culture, CHILDREN, Hippocampal formation, Tourette syndrome, Hippocampus, Receptors, N-Methyl-D-Aspartate, Epitope, White People, Cohort Studies, 03 medical and health sciences, Behavioral Neuroscience, 0302 clinical medicine, Antigen, medicine, Animals, Humans, Child, Autoantibodies, Neurons, antibodies to neuronal antigens, movement disorders, biology, RECEPTOR, Endocrine and Autonomic Systems, business.industry, Dentate gyrus, Autoantibody, Brain, Membrane Proteins, medicine.disease, Rats, Tourette Syndrome, Tic Disorders, Neurodevelopmental Disorders, Neuronal- Surface Antibodies, Antineuronal Antibodies, Voltage-Gated Potassium Channels Antibodies, CASPR2, NMDAR, 030104 developmental biology, nervous system, Child, Preschool, Dentate Gyrus, biology.protein, Female, Antibody, business, 030217 neurology & neurosurgery
Abstract: The EMTICS collaborative group: Anastasiou, Zacharias; Apter, Alan; Baglioni, Valentina; Bartolini, Erika; Benaroya-Milshtein, Noa; Bodmer, Benjamin; Bognar, Emese; Burger', Bianka; Buttiglione, Maura; Cardona, Francesco; Vela, Marta Correa; Creti, Roberta; Dietrich, Andrea; Debes, Nanette M.; Efstratiou, Androulla; Ferro, Maria Cristina; Fremer, Carolin; Garcia-Delgar, Blanca; Gariup, Maria; Georgitsi, Marianthi; Gulisano, Mariangela; Hagen, Annelieke; Hagstrom, Julie; Hedderly, Tammy J.; Heyman, Isobel; Hoekstra, Pieter J.; Huyser, Chaim; Imperi, Monica; Karagiannidis, Iordanis; Laviola, Giovanni; Macri, Simone; Madruga-Garrido, Marcos; Margarit, Immaculada; Marotta, Anna; Martino, Davide; Meier, Ute C.; Mir, Pablo; Mo, Natalie; More, Astrid; Mueller-Vahl, Kirsten; Muenchau, Alexander; Nagy, Peter; Neri, Valeria; Openneer, Thafra J. C.; Orefici, Graziella; Paschou, Peristera; Pellico, Alessandra; Petruzzelli, Onofrio; Porcelli, Cesare; Redondo, Marina; Rizzo, Renata; Roazzi, Paolo; Roessner, Veit; Ruhrman, Daphna; Schnell, Jaana M. L.; Schrag, Anette; Schutze, Gregor A.; Schwarz, Markus J.; Silvestri, Paola Rosaria; Skov, Liselotte; Steinberg, Tamar; Stober, Sara; Tallon, Marco; Tarnok, Zsanett, In Tourette Syndrome (TS) a role for autoantibodies directed against neuronal proteins has long been suspected, but so far results are still inconsistent. The aim of this study was to look for antibodies to specific or undefined neuronal proteins that could be involved in the aetiology of the disease. Sera from children with Tourette Syndrome or another chronic tic disorder (TS/TD), collected as part of the longitudinal European Multicenter Tics in Children Study, were investigated. Participants included 30 siblings of patients with TS/TD prior to developing tics (preclinical stage) and the same children after the first tic onset (onset), and 158 patients in the chronic phase undergoing an acute relapse (exacerbation). Presence of antibodies binding to rodent brain tissue was assessed by immunohistology on rat brain sections and by immunofluorescent staining of live hippocampal neurons. Live cell-based assays were used to screen for antibodies to NMDAR, CASPR2, LGI1, AMPAR and GABAAR. Immunohistology indicated evidence of antibodies reactive with brain tissue, binding mainly to the hippocampus, the basal ganglia or the cerebellum in 26/218 (12%), with 8% of the preclinical or onset sera binding to the dentate gyrus/CA3 region or cerebellum. Only two individuals (one pre-clinical, one chronic) had antibodies binding the NMDAR and the binding was only weakly positive. No other specific antibodies were detected. Despite some immunoreactivity towards neuronal antigens on brain tissue, this was not mirrored by antibodies binding to live neurons, suggesting the presence of non-specific antibodies or those that bind non-pathogenic intracellular epitopes. NMDAR or the other neuronal surface antibodies tested were very infrequent in these patients. The evidence for pathogenic antibodies that could be causative of TS is weak.
Published: 2019

42. Error processing and inhibitory control in Obsessive-Compulsive Disorder: A meta-analysis using statistical parametric maps

Author: Joaquim Radua, Murat Yücel, F. Isik Karahanoglu, Tracy Luks, Yann Chye, Yanni Liu, Stella J. De Wit, Stephan F. Taylor, Chao Suo, Dara S. Manoach, Katya Rubia, Chaim Huyser, Kate D. Fitzgerald, Odile A. van den Heuvel, Carol A. Mathews, Luke Norman, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Anatomy and neurosciences, Child Psychiatry, and ANS - Compulsivity, Impulsivity & Attention
Subjects: 0301 basic medicine, Male, Obsessive-Compulsive Disorder, Audiology, Medical and Health Sciences, 0302 clinical medicine, Supramarginal gyrus, Neural Pathways, Medicine, Error processing, Inhibition, Psychiatry, Brain Mapping, Supplementary motor area, medicine.diagnostic_test, fMRI, Brain, Biological Sciences, Serious Mental Illness, Magnetic Resonance Imaging, Inhibition, Psychological, medicine.anatomical_structure, Mental Health, Meta-analysis, Female, Adult, medicine.medical_specialty, Adolescent, Thalamus, behavioral disciplines and activities, Article, 03 medical and health sciences, Young Adult, Clinical Research, Humans, Inhibitory control, Biological Psychiatry, Anterior cingulate cortex, OCD, business.industry, Psychology and Cognitive Sciences, Neurosciences, Brain Disorders, 030104 developmental biology, Psychological, Orbitofrontal cortex, Performance monitoring, business, Functional magnetic resonance imaging, Insula, 030217 neurology & neurosurgery
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
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43. Distinct Subcortical Volume Alterations in Pediatric and Adult OCD

Author: Federica Piras, Christine Lochner, Jan C. Beucke, José M. Menchón, Philip R. Szeszko, Hao Hu, Janardhanan C. Narayanaswamy, Damiaan Denys, Guido van Wingen, Yanni Liu, Luisa Lazaro, Jean Paul Fouche, Marcelo Queiroz Hoexter, Y. C.Janardhan Reddy, Silvia Brem, Paul D. Arnold, Sara Dallaspezia, Keisuke Ikari, Neda Jahanshad, Qing Zhao, Kang Ik Cho, Norbert Kathmann, Gianfranco Spalletta, Yuqi Cheng, Susanne Walitza, Derrek P. Hibar, Dan J. Stein, Christopher Pittenger, Odile A. van den Heuvel, Yoshinari Abe, Anushree Bose, David Mataix-Cols, Ganesan Venkatasubramanian, Je Yeon Yun, Ignacio Martínez-Zalacaín, Xiufeng Xu, João Ricardo Sato, Noam Soreni, Premika S.W. Boedhoe, Luciano Minuzzi, Carles Soriano-Mas, David F. Tolin, Kate D. Fitzgerald, Christian Kaufmann, Rachel Marsh, H. Blair Simpson, Fabrizio Piras, Zhen Wang, Michael C. Stevens, Lianne Schmaal, Marcelo C. Batistuzzo, Takashi Nakamae, Paul M. Thompson, Stephanie H. Ameis, Gregory L. Hanna, Irene Bollettini, Chaim Huyser, Kathrin Koch, Jun Soo Kwon, Mónica Giménez, Anna Calvo, Francesco Benedetti, Patricia Gruner, Jian Xu, Tomohiro Nakao, Universitat de Barcelona, Other departments, ANS - Amsterdam Neuroscience, Adult Psychiatry, Boedhoe, Premika S. W., Schmaal, Lianne, Abe, Yoshinari, Ameis, Stephanie H., Arnold, Paul D., Batistuzzo, Marcelo C., Benedetti, Francesco, Beucke, Jan C., Bollettini, Irene, Bose, Anushree, Brem, Silvia, Calvo, Anna, Cheng, Yuqi, Cho, Kang Ik, Dallaspezia, Sara, Denys, Damiaan, Fitzgerald, Kate D., Fouche, Jean-Paul, Giménez, Mònica, Gruner, Patricia, Hanna, Gregory L., Hibar, Derrek P., Hoexter, Marcelo Q., Hu, Hao, Huyser, Chaim, Ikari, Keisuke, Jahanshad, Neda, Kathmann, Norbert, Kaufmann, Christian, Koch, Kathrin, Kwon, Jun Soo, Lazaro, Luisa, Liu, Yanni, Lochner, Christine, Marsh, Rachel, Martínez-Zalacaín, Ignacio, Mataix-Cols, David, Menchón, José M., Minuzzi, Luciano, Nakamae, Takashi, Nakao, Tomohiro, Narayanaswamy, Janardhanan C., Piras, Fabrizio, Piras, Federica, Pittenger, Christopher, Reddy, Y. C. Janardhan, Sato, Joao R., Simpson, H. Blair, Soreni, Noam, Soriano-Mas, Carle, 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, Yun, Je-Yeon, Zhao, Qing, Thompson, Paul M., Stein, Dan J., Van Den Heuvel, Odile A., Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Netherlands Institute for Neuroscience (NIN)
Subjects: Obsessive-Compulsive Disorder, FreeSurfer, Audiology, Pediatrics, Hippocampus, 0302 clinical medicine, Neurodevelopmental disorder, Thalamus, Obsessive-compulsive disorder, Young adult, Child, Psychiatry, Pediatria, medicine.diagnostic_test, Healthy subjects, Organ Size, Middle Aged, Control subjects, Magnetic Resonance Imaging, Psychiatry and Mental health, Psychiatry and Mental Health, Mega analysis, Psychology, Human, Adult, medicine.medical_specialty, Adolescent, Neuroimaging, Globus Pallidus, behavioral disciplines and activities, Article, Malalts, 03 medical and health sciences, Young Adult, Hippocampu, mental disorders, medicine, Humans, Thalamu, Sick, Neurosi obsessiva, Globus Pallidu, Magnetic resonance imaging, Voxel-based morphometry, medicine.disease, 030227 psychiatry, Structural MRI, 030217 neurology & neurosurgery
Abstract: Objective: structural brain imaging studies in obsessive compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta and mega-analyses of data from OCD sites worldwide. Method: T-1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. Results: the meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. Conclusions: the results indicate different patterns of sub cortical abnormalities in pediatric and adult OCD patients. The patlidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.
Published: 2017
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44. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author: Laura M. Thornton, Paul Lichtenstein, Verneri Anttila, Diego Albani, Josep Antoni Ramos-Quiroga, Roger A.H. Adan, Monika Schlögelhofer, Stephen Sanders, Enrique Castelao, Klaus Berger, Nina Dalkner, Urs Heilbronner, Engilbert Sigurdsson, Pablo Mir, Fuquan Zhang, James T.R. Walters, Patrick F. Sullivan, Fragiskos Gonidakis, F. Kyle Satterstrom, Sara Marsal, Per Hoffmann, Amy Perry, Valentina Ciullo, Beate Herpertz-Dahlmann, Catharina Lavebratt, Kieran C. Murphy, Tammy Hedderly, Hyun Ju Hong, Evald Saemundsen, Sascha B. Fischer, Hailiang Huang, Andrew D. Grotzinger, Nienke Vulink, Murray B. Stein, Mark A. Frye, Laura J. Scott, David Curtis, Todd Lencz, Janiece E. DeSocio, Richard A. Belliveau, Eduard Vieta, Andrea Dietrich, Wade H. Berrettini, Kenneth S. Kendler, Marquis P. Vawter, Paul S. Nestadt, Michael E. Talkowski, Manuel Mattheisen, Ingrid Agartz, Elisa Docampo, Bernhard T. Baune, Stefan Ehrlich, Jolanta Lissowska, Felecia Cerrato, Terje Nærland, Robin M. Murray, Jennifer Reichert, Annette M. Hartmann, Hannelore Ehrenreich, Howard J. Edenberg, Katherine A. Halmi, Qingqin S. Li, Peristera Paschou, Marie Bækvad-Hansen, Esther Walton, Alessio Maria Monteleone, Ted Reichborn-Kjennerud, Frank Bellivier, Jungeun Song, D. Blake Woodside, Young Shin Kim, Jochen Seitz, Jacques Pantel, Palmiero Monteleone, Erika L. Nurmi, Rodney J. Scott, Kang Sim, Ekaterina A. Khramtsova, Udo Dannlowski, Rolf Adolfsson, Danielle Posthuma, Melissa J. Green, Laura Ibanez-Gomez, Jakob Grove, Elvira Bramon, Gregory L. Hanna, Cynthia M. Bulik, Yiran Guo, Stephan Ripke, Mary M. Robertson, Harald N. Aschauer, Adebayo Anjorin, Joanna Martin, Bertram Müller-Myhsok, Deborah Kaminská, Jose Guzman-Parra, Benedetta Nacmias, Erik G. Jönsson, Jonathan R. I. Coleman, Douglas F. Levinson, Hamdi Mbarek, Gun Peggy Knudsen, Karin Egberts, Mette Nyegaard, Patrik K. E. Magnusson, Mark Adams, Douglas Blackwood, Elisabeth B. Binder, Marcus Ising, Anna R. Docherty, Jim van Os, Nese Direk, Lina Martinsson, Maria Arranz, Christel M. Middeldorp, Stefan Kloiber, Sintia Iole Belangero, Eske M. Derks, Ingrid Melle, Erlend Bøen, Jan Haavik, Federica Piras, Unna N. Danner, Anil K. Malhotra, Gerome Breen, Stephen V. Faraone, Amanda B Zheutlin, Timothy Poterba, Stephan Ruhrmann, Inge Joa, Ulrik Fredrik Malt, Sarah E. Bergen, Federica Tozzi, Lauren A. Weiss, Hana Papezova, Dominic Holland, Elliot S. Gershon, Jaakko Kaprio, Merete Nordentoft, Scott D. Gordon, Christopher Pittenger, Keun-Ah Cheon, Jennifer Jordan, Philip Gorwood, Myrna M. Weissman, Preben Bo Mortensen, Melissa A. Munn-Chernoff, Isobel Heyman, Eun-Young Shin, Christie L. Burton, Katherine Gordon-Smith, Sietske G. Helder, Peter Nagy, Till F. M. Andlauer, Yunpeng Wang, Young Key Kim, Kate Langley, Søren Dalsgaard, Richard Delorme, Torbjørn Elvsåshagen, Bennett L. Leventhal, Giovanni Gambaro, Christos Androutsos, Jennifer Tübing, Marion Roberts, Annelie Nordin Adolfsson, Hakon Hakonarson, Dorothy E. Grice, Vaughan J. Carr, Konstantinos Tziouvas, Stephanie Zerwas, Cathy L. Barr, Michael Conlon O'Donovan, Per Qvist, Beate St Pourcain, Samuel Kuperman, Leila Karhunen, Jack Samuels, Markus M. Nöthen, Martien J H Kas, Alfonso Tortorella, Mikael Landén, Jennifer Crosbie, Marco A. Grados, Joanna M. Biernacka, Paul D. Arnold, Irene A. Malaty, Jurjen J. Luykx, Nicholas Bass, Naomi R. Wray, Catharina A. Hartman, Christina M. Hultman, Michael S. Okun, Brandon Wormley, Michael Bauer, Daniel J. Smith, Ian Jones, Kathryn Roeder, Brien P. Riley, Caroline M. Nievergelt, Katrin Gade, Sarah Kittel-Schneider, Roy H. Perlis, James R. Mitchell, Ziarih Hawi, James Lee, Liz Forty, William E. Bunney, Thomas Damm Als, Catherine Schaefer, Digby Quested, Matteo Cassina, Anna C. Koller, Patrick Turley, Agnes A. Steixner, Anu Raevuori, Assen Jablensky, Peter Holmans, Dong-Ho Song, S. Evelyn Stewart, Jan K. Buitelaar, Fernando S. Goes, Alexander Münchau, Ayman H. Fanous, Nicolas Ramoz, James B. Potash, Monica Gratacos Mayora, Tobias Banaschewski, Céline S. Reinbold, Renata Rizzo, Arianna Di Florio, Lenka Foretova, Gianfranco Spalletta, Aarno Palotie, Eleftheria Zeggini, Lawrence W. Brown, Julie K. O'Toole, Lynn E. DeLisi, Ulrich Schall, Mary Roberson, Barbara J. Coffey, Bryan J. Mowry, Murray J. Cairns, Dan J. Stein, Glyn Lewis, Marta Ribasés, C. Robert Cloninger, Bettina Konte, John B. Vincent, Duncan S. Palmer, Radhika Kandaswamy, Christine Ladd-Acosta, Lars Alfredsson, Frank Visscher, Ulrike Schmidt, Aiden Corvin, Susan L. Santangelo, Brenda W.J.H. Penninx, David J. Porteous, Tetsuya Ando, Arne E. Vaaler, Bru Cormand, Laura Carlberg, Claire Churchhouse, Manfred Stuhrmann, Niamh Mullins, Christine Søholm Hansen, Cathy L. Budman, Hartmut Imgart, Dan E. Arking, James J. McGough, Michael Gill, Christel Depienne, Roland Burghardt, Antonio Julià, Anders M. Dale, Sven Sandin, Katharina Domschke, Maria Grigoroiu-Serbanescu, Susana Jiménez-Murcia, Marianne Giørtz Pedersen, Zsanett Tarnok, Gisli Baldursson, Michele T. Pato, David M. Hougaard, Thorgeir E. Thorgeirsson, Katharina Bey, Kerstin J. Plessen, Margaret A. Richter, Ole A. Andreassen, Claudine Laurent-Levinson, Leonid Padyukov, Jacques Mallet, Daniela Degortes, John R. Kelsoe, Robert D. Levitan, Andreas Reif, Chaim Huyser, Derek W. Morris, Sina Wanderer, William Byerley, Edna Grünblatt, E.J.C. de Geus, Hyejung Won, Josephine Elia, Rudolf Uher, Jay A. Tischfield, Andreas Karwautz, Gustavo Turecki, Pieter J. Hoekstra, Dorret I. Boomsma, Jacob Rosenthal, Daniele Cusi, Michael C. Neale, Sara Mostafavi, Gwyneth Zai, F. Anthony O'Neill, Gary Donohoe, Karola Rehnström, Harry Brandt, Helena Gaspar, Francis J. McMahon, H-Erich Wichmann, Andrew W. Bergen, Giovanni Coppola, Lea K. Davis, Lenka Slachtova, Olav B. Smeland, Erin C. Dunn, Nicholas G. Martin, Allan L. Naarden, Jo Knight, Cristina Sánchez-Mora, Masashi Ikeda, Lorraine Southam, Sandro Sorbi, Barbara Franke, Martin Schalling, Russell Schachar, Yen-Chen Anne Feng, Kirsten R. Müller-Vahl, André Scherag, Zhaozhong Zhu, Eric A. Storch, Páll Magnússon, David Cohen, Olafur O Gudmundsson, Harvey S. Singer, Brian Kelly, Jonas Bybjerg-Grauholm, Blanca Garcia-Delgar, Thomas Hansen, Carmel M. Loughland, Christine Lochner, Stacy Steinberg, Martin Woods, Jorge A. Quiroz, Raquel Rabionet, Alden Y. Huang, Janice M. Fullerton, María Soler Artigas, Hans J. Grabe, Philip Asherson, Margit Burmeister, Alicia R. Martin, Martin A. Kennedy, Janet Treasure, Anders D. Børglum, Eva C. Schulte, Andreas Hartmann, Frans Henskens, Youl-Ri Kim, Jens Treutlein, Joanna Hauser, Manfred M. Fichter, Damiaan Denys, Ann E. Pulver, Kelly L. Klump, Paul Sandor, Michael Wagner, Philippe Courtet, Sandra Van der Auwera, Susanne Lucae, Eystein Stordal, Michel G. Nivard, Maurizio Clementi, Astrid Morer, Philip B. Mitchell, Huda Akil, Edwin H. Cook, Jennifer L. Moran, Donald W. Black, Jeremiah M. Scharf, Jana Strohmaier, Colm McDonald, Meg M.-J. Wang, Richard M. Myers, Stephanie Godard, Pablo V. Gejman, Athanasios Maras, Marcella Rietschel, Nancy G. Buccola, Konstantinos Hatzikotoulas, Dalila Pinto, Jouke-Jan Hottenga, Kari Stefansson, James S. Sutcliffe, Andres Metspalu, Amaia Hervás, Joel Gelernter, Wolfgang Herzog, Paula Rovira, Gunnar Morken, Tara Murphy, Mark Weiser, Vincent Millischer, Frank Dudbridge, Dan Rujescu, Vladimir Bencko, Valdo Ricca, Kimberly Chambert, Guy A. Rouleau, James J. Crowley, Thomas G. Schulze, Toni-Kim Clarke, Triinu Peters, Gudrun Wagner, Daniel A. Geller, Henry R. Kranzler, G. Bragi Walters, Vera Golimbet, Clement C. Zai, Nigel Williams, Andreas Birgegård, Joseph D. Buxbaum, Elliot M. Tucker-Drob, Jerome C. Foo, Tracey L. Petryshen, Daniel P. Howrigan, Hunna J. Watson, Franziska Degenhardt, Peter R. Schofield, Jesper Buchhave Poulsen, Stefan Herms, Johannes Hebebrand, Mario Maj, George Kirov, Fabrizio Piras, Sara McDevitt, James T. McCracken, Carol A. Mathews, Michael John Owen, Peter Falkai, Donald L. Gilbert, Enda M. Byrne, Fernando Fernández-Aranda, Csaba Barta, Stéphane Jamain, Jubao Duan, Dongmei Yu, Danielle C. Cath, Ole Mors, Sigrun Hope, Laramie E. Duncan, Alan R. Sanders, Sang-Yun Oh, Carsten Bøcker Pedersen, Henning Tiemeier, Roseann E. Peterson, Raymond K. Walters, Margarita C T Slof-Op 't Landt, Madeline Alexander, Stephanie Le Hellard, Ina Giegling, Annemarie A. van Elburg, Steven P. Hamilton, Vesna Boraska Perica, Thomas V. Fernandez, Danielle M. Dick, Francesco Bettella, Roel A. Ophoff, Grant W. Montgomery, Gerald Nestadt, Nakao Iwata, Jessica H. Baker, Walter H. Kaye, Jeremy M. Silverman, Mark J. Daly, Robert A. King, Sarah E. Medland, Anastasios Konstantinidis, Robert D. Oades, Samuel H. Zinner, Steven Crawford, Daniel H. Geschwind, Patrick W. L. Leung, Martin Alda, Marie Navratilova, Pak C. Sham, Paul A. Tooney, Tian Ge, Veit Roessner, Martin Preisig, Thomas Werge, Eli A. Stahl, David A. Collier, Stephanie H. Witt, Dermot Walsh, Miquel Casas, Anna Keski-Rahkonen, Jane H. Christensen, Silvia De Rubeis, Giorgio Pistis, Sven Cichon, Bruno Etain, Dominique Campion, O. Joseph Bienvenu, Christian Dina, Manolis Kogevinas, Thomas Espeseth, Benjamin M. Neale, Ditte Demontis, Klaus-Peter Lesch, Marina Mitjans, Tiffany A. Greenwood, Marcos Madruga-Garrido, Sibylle G. Schwab, Oedegaard Ketil Joachim, Hreinn Stefansson, Sara A. Paciga, Monica Forzan, Dieter B. Wildenauer, Lena Backlund, A. Jeremy Willsey, Carlos N. Pato, Nicholas John Craddock, Inge A. Meijer, Sandra K. Loo, Filip Rybakowski, Tracey D. Wade, Scott J. Crow, Bernard Lerer, Valsamma Eapen, Esben Agerbo, Andrew M. McIntosh, Luis Augusto Rohde, Susan L. McElroy, Stephan Zipfel, Peter P. Zandi, Cathryn M. Lewis, Lars Klareskog, Martin Begemann, Phil Lee, Richard Anney, Mark A. Bellgrove, Lisa Jones, Andreas J. Forstner, Agnieszka Słopień, Hilary Coon, Dong Li, Alessandro Serretti, Carsten Horn, Christos Pantelis, Ryan L. Collins, David M. Howard, Lucía Colodro-Conde, Pippa A. Thomson, Martin Hautzinger, Alysa E. Doyle, Julie Hagstrøm, Oliver S. P. Davis, Karen S. Mitchell, Jordan W. Smoller, Michael Strober, John I. Nurnberger, Andrea G. Ludolph, Monika Budde, Anna Maaser, Lambertus Klei, Aribert Rothenberger, Yulia Worbe, Fabian Streit, James L. Kennedy, Barbara E. Stranger, Ashley Dumont, Jianxin Shi, Dale R. Nyholt, Craig Johnson, Jonna Kuntsi, Yun-Joo Koh, Loes M. Olde Loohuis, Robert B. Freedman, Anke Hinney, Susanne Walitza, Enrico Domenici, Margarita Rivera, Sodahm Kook, Erica Greenberg, Tetyana Zayats, Josef Frank, Gary A. Heiman, Andrew McQuillin, Abraham Reichenberg, Piotr M. Czerski, Humberto Nicolini, Lee P.H., Anttila V., Won H., Feng Y.-C.A., Rosenthal J., Zhu Z., Tucker-Drob E.M., Nivard M.G., Grotzinger A.D., Posthuma D., Wang M.M.-J., Yu D., Stahl E.A., Walters R.K., Anney R.J.L., Duncan L.E., Ge T., Adolfsson R., Banaschewski T., Belangero S., Cook E.H., Coppola G., Derks E.M., Hoekstra P.J., Kaprio J., Keski-Rahkonen A., Kirov G., Kranzler H.R., Luykx J.J., Rohde L.A., Zai C.C., Agerbo E., Arranz M.J., Asherson P., Baekvad-Hansen M., Baldursson G., Bellgrove M., Belliveau R.A., Buitelaar J., Burton C.L., Bybjerg-Grauholm J., Casas M., Cerrato F., Chambert K., Churchhouse C., Cormand B., Crosbie J., Dalsgaard S., Demontis D., Doyle A.E., Dumont A., Elia J., Grove J., Gudmundsson O.O., Haavik J., Hakonarson H., Hansen C.S., Hartman C.A., Hawi Z., Hervas A., Hougaard D.M., Howrigan D.P., Huang H., Kuntsi J., Langley K., Lesch K.-P., Leung P.W.L., Loo S.K., Martin J., Martin A.R., McGough J.J., Medland S.E., Moran J.L., Mors O., Mortensen P.B., Oades R.D., Palmer D.S., Pedersen C.B., Pedersen M.G., Peters T., Poterba T., Poulsen J.B., Ramos-Quiroga J.A., Reif A., Ribases M., Rothenberger A., Rovira P., Sanchez-Mora C., Satterstrom F.K., Schachar R., Artigas M.S., Steinberg S., Stefansson H., Turley P., Walters G.B., Werge T., Zayats T., Arking D.E., Bettella F., Buxbaum J.D., Christensen J.H., Collins R.L., Coon H., De Rubeis S., Delorme R., Grice D.E., Hansen T.F., Holmans P.A., Hope S., Hultman C.M., Klei L., Ladd-Acosta C., Magnusson P., Naerland T., Nyegaard M., Pinto D., Qvist P., Rehnstrom K., Reichenberg A., Reichert J., Roeder K., Rouleau G.A., Saemundsen E., Sanders S.J., Sandin S., St Pourcain B., Stefansson K., Sutcliffe J.S., Talkowski M.E., Weiss L.A., Willsey A.J., Agartz I., Akil H., Albani D., Alda M., Als T.D., Anjorin A., Backlund L., Bass N., Bauer M., Baune B.T., Bellivier F., Bergen S.E., Berrettini W.H., Biernacka J.M., Blackwood D.H.R., Boen E., Budde M., Bunney W., Burmeister M., Byerley W., Byrne E.M., Cichon S., Clarke T.-K., Coleman J.R.I., Craddock N., Curtis D., Czerski P.M., Dale A.M., Dalkner N., Dannlowski U., Degenhardt F., Di Florio A., Elvsashagen T., Etain B., Fischer S.B., Forstner A.J., Forty L., Frank J., Frye M., Fullerton J.M., Gade K., Gaspar H.A., Gershon E.S., Gill M., Goes F.S., Gordon S.D., Gordon-Smith K., Green M.J., Greenwood T.A., Grigoroiu-Serbanescu M., Guzman-Parra J., Hauser J., Hautzinger M., Heilbronner U., Herms S., Hoffmann P., Holland D., Jamain S., Jones I., Jones L.A., Kandaswamy R., Kelsoe J.R., Kennedy J.L., Joachim O.K., Kittel-Schneider S., Kogevinas M., Koller A.C., Lavebratt C., Lewis C.M., Li Q.S., Lissowska J., Loohuis L.M.O., Lucae S., Maaser A., Malt U.F., Martin N.G., Martinsson L., McElroy S.L., McMahon F.J., McQuillin A., Melle I., Metspalu A., Millischer V., Mitchell P.B., Montgomery G.W., Morken G., Morris D.W., Muller-Myhsok B., Mullins N., Myers R.M., Nievergelt C.M., Nordentoft M., Adolfsson A.N., Nothen M.M., Ophoff R.A., Owen M.J., Paciga S.A., Pato C.N., Pato M.T., Perlis R.H., Perry A., Potash J.B., Reinbold C.S., Rietschel M., Rivera M., Roberson M., Schalling M., Schofield P.R., Schulze T.G., Scott L.J., Serretti A., Sigurdsson E., Smeland O.B., Stordal E., Streit F., Strohmaier J., Thorgeirsson T.E., Treutlein J., Turecki G., Vaaler A.E., Vieta E., Vincent J.B., Wang Y., Witt S.H., Zandi P., Adan R.A.H., Alfredsson L., Ando T., Aschauer H., Baker J.H., Bencko V., Bergen A.W., Birgegard A., Perica V.B., Brandt H., Burghardt R., Carlberg L., Cassina M., Clementi M., Courtet P., Crawford S., Crow S., Crowley J.J., Danner U.N., Davis O.S.P., Degortes D., DeSocio J.E., Dick D.M., Dina C., Docampo E., Egberts K., Ehrlich S., Espeseth T., Fernandez-Aranda F., Fichter M.M., Foretova L., Forzan M., Gambaro G., Giegling I., Gonidakis F., Gorwood P., Mayora M.G., Guo Y., Halmi K.A., Hatzikotoulas K., Hebebrand J., Helder S.G., Herpertz-Dahlmann B., Herzog W., Hinney A., Imgart H., Jimenez-Murcia S., Johnson C., Jordan J., Julia A., Kaminska D., Karhunen L., Karwautz A., Kas M.J.H., Kaye W.H., Kennedy M.A., Kim Y.-R., Klareskog L., Klump K.L., Knudsen G.P.S., Landen M., Le Hellard S., Levitan R.D., Li D., Lichtenstein P., Maj M., Marsal S., McDevitt S., Mitchell J., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., O'Toole J.K., Padyukov L., Pantel J., Papezova H., Rabionet R., Raevuori A., Ramoz N., Reichborn-Kjennerud T., Ricca V., Roberts M., Rujescu D., Rybakowski F., Scherag A., Schmidt U., Seitz J., Slachtova L., Slof-Op't Landt M.C.T., Slopien A., Sorbi S., Southam L., Strober M., Tortorella A., Tozzi F., Treasure J., Tziouvas K., van Elburg A.A., Wade T.D., Wagner G., Walton E., Watson H.J., Wichmann H.-E., Woodside D.B., Zeggini E., Zerwas S., Zipfel S., Adams M.J., Andlauer T.F.M., Berger K., Binder E.B., Boomsma D.I., Castelao E., Colodro-Conde L., Direk N., Docherty A.R., Domenici E., Domschke K., Dunn E.C., Foo J.C., de. 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H., Anttila, V., Won, H., Feng, Y. -C. A., Rosenthal, J., Zhu, Z., Tucker-Drob, E. M., Nivard, M. G., Grotzinger, A. D., Posthuma, D., Wang, M. M. -J., Yu, D., Stahl, E. A., Walters, R. K., Anney, R. J. L., Duncan, L. E., Ge, T., Adolfsson, R., Banaschewski, T., Belangero, S., Cook, E. H., Coppola, G., Derks, E. M., Hoekstra, P. J., Kaprio, J., Keski-Rahkonen, A., Kirov, G., Kranzler, H. R., Luykx, J. J., Rohde, L. A., Zai, C. C., Agerbo, E., Arranz, M. J., Asherson, P., Baekvad-Hansen, M., Baldursson, G., Bellgrove, M., Belliveau, R. A., Buitelaar, J., Burton, C. L., Bybjerg-Grauholm, J., Casas, M., Cerrato, F., Chambert, K., Churchhouse, C., Cormand, B., Crosbie, J., Dalsgaard, S., Demontis, D., Doyle, A. E., Dumont, A., Elia, J., Grove, J., Gudmundsson, O. O., Haavik, J., Hakonarson, H., Hansen, C. S., Hartman, C. A., Hawi, Z., Hervas, A., Hougaard, D. M., Howrigan, D. P., Huang, H., Kuntsi, J., Langley, K., Lesch, K. -P., Leung, P. W. L., Loo, S. K., Martin, J., Martin, A. 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B., Brandt, H., Burghardt, R., Carlberg, L., Cassina, M., Clementi, M., Courtet, P., Crawford, S., Crow, S., Crowley, J. J., Danner, U. N., Davis, O. S. P., Degortes, D., Desocio, J. E., Dick, D. M., Dina, C., Docampo, E., Egberts, K., Ehrlich, S., Espeseth, T., Fernandez-Aranda, F., Fichter, M. M., Foretova, L., Forzan, M., Gambaro, G., Giegling, I., Gonidakis, F., Gorwood, P., Mayora, M. G., Guo, Y., Halmi, K. A., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Imgart, H., Jimenez-Murcia, S., Johnson, C., Jordan, J., Julia, A., Kaminska, D., Karhunen, L., Karwautz, A., Kas, M. J. H., Kaye, W. H., Kennedy, M. A., Kim, Y. -R., Klareskog, L., Klump, K. L., Knudsen, G. P. S., Landen, M., Le Hellard, S., Levitan, R. D., Li, D., Lichtenstein, P., Maj, M., Marsal, S., Mcdevitt, S., Mitchell, J., Monteleone, P., Monteleone, A. M., Munn-Chernoff, M. A., Nacmias, B., Navratilova, M., O'Toole, J. K., Padyukov, L., Pantel, J., Papezova, H., Rabionet, R., Raevuori, A., Ramoz, N., Reichborn-Kjennerud, T., Ricca, V., Roberts, M., Rujescu, D., Rybakowski, F., Scherag, A., Schmidt, U., Seitz, J., Slachtova, L., Slof-Op't Landt, M. C. T., Slopien, A., Sorbi, S., Southam, L., Strober, M., Tortorella, A., Tozzi, F., Treasure, J., Tziouvas, K., van Elburg, A. A., Wade, T. D., Wagner, G., Walton, E., Watson, H. J., Wichmann, H. -E., Woodside, D. B., Zeggini, E., Zerwas, S., Zipfel, S., Adams, M. J., Andlauer, T. F. M., Berger, K., Binder, E. B., Boomsma, D. I., Castelao, E., Colodro-Conde, L., Direk, N., Docherty, A. R., Domenici, E., Domschke, K., Dunn, E. C., Foo, J. C., D, e. Geus E. J. C., Grabe, H. J., Hamilton, S. P., Horn, C., Hottenga, J. -J., Howard, D., Ising, M., Kloiber, S., Levinson, D. F., Lewis, G., Magnusson, P. K. E., Mbarek, H., Middeldorp, C. M., Mostafavi, S., Nyholt, D. R., Penninx, B. W., Peterson, R. E., Pistis, G., Porteous, D. J., Preisig, M., Quiroz, J. A., Schaefer, C., Schulte, E. C., Shi, J., Smith, D. J., Thomson, P. A., Tiemeier, H., Uher, R., van der Auwera, S., Weissman, M. M., Alexander, M., Begemann, M., Bramon, E., Buccola, N. G., Cairns, M. J., Campion, D., Carr, V. J., Cloninger, C. R., Cohen, D., Collier, D. A., Corvin, A., Delisi, L. E., Donohoe, G., Dudbridge, F., Duan, J., Freedman, R., Gejman, P. V., Golimbet, V., Godard, S., Ehrenreich, H., Hartmann, A. M., Henskens, F. A., Ikeda, M., Iwata, N., Jablensky, A. V., Joa, I., Jonsson, E. G., Kelly, B. J., Knight, J., Konte, B., Laurent-Levinson, C., Lee, J., Lencz, T., Lerer, B., Loughland, C. M., Malhotra, A. K., Mallet, J., Mcdonald, C., Mitjans, M., Mowry, B. J., Murphy, K. C., Murray, R. M., O'Neill, F. A., Oh, S. -Y., Palotie, A., Pantelis, C., Pulver, A. E., Petryshen, T. L., Quested, D. J., Riley, B., Sanders, A. R., Schall, U., Schwab, S. G., Scott, R. J., Sham, P. C., Silverman, J. M., Sim, K., Steixner, A. A., Tooney, P. A., van Os, J., Vawter, M. P., Walsh, D., Weiser, M., Wildenauer, D. B., Williams, N. M., Wormley, B. K., Zhang, F., Androutsos, C., Arnold, P. D., Barr, C. L., Barta, C., Bey, K., Bienvenu, O. J., Black, D. W., Brown, L. W., Budman, C., Cath, D., Cheon, K. -A., Ciullo, V., Coffey, B. J., Cusi, D., Davis, L. K., Denys, D., Depienne, C., Dietrich, A., Eapen, V., Falkai, P., Fernandez, T. V., Garcia-Delgar, B., Geller, D. A., Gilbert, D. L., Grados, M. A., Greenberg, E., Grunblatt, E., Hagstrom, J., Hanna, G. L., Hartmann, A., Hedderly, T., Heiman, G. A., Heyman, I., Hong, H. J., Huang, A., Huyser, C., Ibanez-Gomez, L., Khramtsova, E. A., Kim, Y. K., Kim, Y. -S., King, R. A., Koh, Y. -J., Konstantinidis, A., Kook, S., Kuperman, S., Leventhal, B. L., Lochner, C., Ludolph, A. G., Madruga-Garrido, M., Malaty, I., Maras, A., Mccracken, J. T., Meijer, I. A., Mir, P., Morer, A., Muller-Vahl, K. R., Munchau, A., Murphy, T. L., Naarden, A., Nagy, P., Nestadt, G., Nestadt, P. S., Nicolini, H., Nurmi, E. L., Okun, M. S., Paschou, P., Piras, F., Pittenger, C., Plessen, K. J., Richter, M. A., Rizzo, R., Robertson, M., Roessner, V., Ruhrmann, S., Samuels, J. F., Sandor, P., Schlogelhofer, M., Shin, E. -Y., Singer, H., Song, D. -H., Song, J., Spalletta, G., Stein, D. J., Stewart, S. E., Storch, E. A., Stranger, B., Stuhrmann, M., Tarnok, Z., Tischfield, J. A., Tubing, J., Visscher, F., Vulink, N., Wagner, M., Walitza, S., Wanderer, S., Woods, M., Worbe, Y., Zai, G., Zinner, S. H., Sullivan, P. F., Franke, B., Daly, M. J., Bulik, C. M., Mcintosh, A. M., O'Donovan, M. C., Zheutlin, A., Andreassen, O. A., Borglum, A. D., Breen, G., Edenberg, H. J., Fanous, A. H., Faraone, S. V., Gelernter, J., Mathews, C. A., Mattheisen, M., Mitchell, K. S., Neale, M. C., Nurnberger, J. I., Ripke, S., Santangelo, S. L., Scharf, J. M., Stein, M. B., Thornton, L. M., Walters, J. T. R., Wray, N. R., Geschwind, D. H., Neale, B. M., Kendler, K. S., and Smoller, J. W.
Subjects: Netherlands Twin Register (NTR), cross-disorder genetics, Medizin, Genome-wide association study, Tourette syndrome, functional genomics, gene expression, genetic architecture, genetic correlation, GWAS, neurodevelopment, pleiotropy, psychiatric disorders, Psychiatric genetics, 0302 clinical medicine, Pleiotropy, functional genomic, WIDE ASSOCIATION, cross-disorder genetic, 0303 health sciences, Mental Disorders, Genetic Pleiotropy, HUMAN BRAIN, INSIGHTS, Autism spectrum disorder, Schizophrenia, DISEASES, GENETIC CORRELATIONS, medicine.medical_specialty, Neurogenesis, Quantitative Trait Loci, BF, Biology, GENOTYPE IMPUTATION, Psychiatric geneticscross-disorder geneticspsychiatric disorderspleiotropyneurodevelopmentGWASgenetic correlationgene expressiongenetic architecturefunctional genomics, Article, General Biochemistry, Genetics and Molecular Biology, psychiatric disorder, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Bipolar disorder, TRANSCRIPTOME, Psychiatry, 030304 developmental biology, Gwas, Psychiatric Genetics, Cross-disorder Genetics, Functional Genomics, Gene Expression, Genetic Architecture, Genetic Correlation, Neurodevelopment, Psychiatric Disorders, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], IDENTIFICATION, MUTATIONS, medicine.disease, Genetic architecture, DEMETHYLASE, RC0321, 1182 Biochemistry, cell and molecular biology, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.
Published: 2019
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45. Corrigendum

Author: João Ricardo Sato, Susanne Walitza, Fabrizio Piras, Chris Vriend, Carles Soriano-Mas, Damiaan Denys, Irene Bollettini, Chaim Huyser, Francesco Benedetti, Dan Stein, and Odile Van den Heuvel
Subjects: Adult, Cerebral Cortex, Male, Obsessive-Compulsive Disorder, brain structural covariance network, graph theory, illness duration, Brain, Original Articles, behavioral disciplines and activities, Corrigenda, Magnetic Resonance Imaging, humanities, pharmacotherapy, mental disorders, Neural Pathways, Image Processing, Computer-Assisted, Humans, Female, Neurology (clinical)
Abstract: In the largest brain structural covariance study of OCD to date, Yun et al. show a less segregated organization of structural covariance networks and a reorganization of brain hubs, including cingulate and orbitofrontal regions, in OCD. The findings point to altered trajectories of brain development and maturation., 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

46. P.787 Prefrontal cortical thickness is associated with response to cognitive-behavioural therapy in children and adolescents with OCD

Author: Yoshiyuki Hirano, I. Martínez-Zalacaín, Pedro Morgado, Carles Soriano-Mas, Brian P. Brennan, Marcelo Queiroz Hoexter, Dan J. Stein, Susanne Walitza, Erika L. Nurmi, Joseph O'Neill, J.M. Menchón, Kate D. Fitzgerald, O. A. Van den Heuvel, P. Alonso, B. H. Simpson, S. Bertolin Triquell, Rachel Marsh, Gerd Kvale, Premika S.W. Boedhoe, Luisa Lázaro, Evelyn Stewart, Paul M. Thompson, and Chaim Huyser
Subjects: Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Cognition, Neurology (clinical), Psychology, Biological Psychiatry, Clinical psychology
Published: 2019
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47. Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group

Author: Alan Anticevic, Valentina Ciullo, Janardhanan C. Narayanaswamy, Paul D. Arnold, Pino Alonso, Seiji Nishida, Luisa Lázaro, Christine Lochner, Zhen Wang, Joseph O'Neill, Silvia Brem, Guido A. Van Wingen, Jean Paul Fouche, Marcelo Queiroz Hoexter, Y. C.Janardhan Reddy, Michael C. Stevens, Stephanie H. Ameis, Fabrizio Piras, Jun Soo Kwon, Rosa Calvo, Marcelo C. Batistuzzo, Gregory L. Hanna, Yoshinari Abe, Yuki Sakai, David F. Tolin, Irene Bollettini, Kathrin Koch, H. Blair Simpson, Noam Soreni, Erika L. Nurmi, Kang Ik Kevin Cho, Luciano Minuzzi, Jan C. Beucke, Susanne Walitza, Jamie D. Feusner, Derrek P. Hibar, Chaim Huyser, Anna Calvo, Tomohiro Nakao, Ignacio Martínez-Zalacaín, Patricia Gruner, Francesco Benedetti, Je Yeon Yun, David Mataix-Cols, Paul M. Thompson, Odile A. van den Heuvel, Anthony A. James, Premika S.W. Boedhoe, Yuqi Cheng, Hao Hu, Tim Jonas Reess, John Piacentini, Carles Soriano-Mas, Neda Jahanshad, Kate D. Fitzgerald, Astrid Morer, Sara Dallaspezia, Gianfranco Spalletta, Dan J. Stein, Takashi Nakamae, João Ricardo Sato, Egill A. Fridgeirsson, Christian Kaufmann, Ganesan Venkatasubramanian, Philip R. Szeszko, Lianne Schmaal, Rachel Marsh, Norbert Kathmann, Anushree Bose, Federica Piras, José M. Menchón, D. Denys, Anatomy and neurosciences, Psychiatry, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, 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, 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, Y C Janardhan, Reess, Tim J, Sakai, Yuki, Sato, Joao R, Simpson, H Blair, Soreni, Noam, Soriano-Mas, Carle, 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, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, Graduate School, Child Psychiatry, and Netherlands Institute for Neuroscience (NIN)
Subjects: Adult, Obsessive-Compulsive Disorder, medicine.medical_specialty, Adolescent, FreeSurfer, behavioral disciplines and activities, Article, Temporal lobe, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Reference Values, Cortical abnormalities, Parietal Lobe, mental disorders, Journal Article, medicine, Obsessive-compulsive disorder, Humans, Cortical Thickne, Age of Onset, Young adult, Child, Psychiatry, Cerebral Cortex, Neurosi obsessiva, Parietal lobe, Surface Area, Voxel-based morphometry, Magnetic Resonance Imaging, Temporal Lobe, humanities, Frontal Lobe, 030227 psychiatry, Psychiatry and Mental health, Diagnòstic per la imatge, Frontal lobe, Diagnostic imaging, Age of onset, Psychology, 030217 neurology & neurosurgery, MRI
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 cortexand a thinner inferiorparietalcortex.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 showedsignificant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from 20.10 to 20.33. 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
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48. Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

Author: Matthan W.A. Caan, D. van t Ent, B.P. de Kwaasteniet, Maria M. Rive, Maarten W. J. Koeter, Janna Cousijn, Marise W. J. Machielsen, Dick J. Veltman, Carin J. Meijer, L. de Haan, A. den Braber, E. van der Giessen, A.C.M. van Gasselt, W. van den Brink, Chaim Huyser, Aart H. Schene, F. J. van der Meer, Laura Koenders, Erasmus School of Social and Behavioural Sciences, Neurology, Anatomy and neurosciences, Psychiatry, NCA - Neurobiology of mental health, Other departments, Amsterdam Neuroscience, Adult Psychiatry, Graduate School, Amsterdam Public Health, Radiology and Nuclear Medicine, Child Psychiatry, Biological Psychology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Ontwikkelingspsychologie (Psychologie, FMG), and Faculteit der Geneeskunde
Subjects: Male, Marijuana Abuse, medicine.medical_specialty, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], Audiology, Grey matter, Young Adult, SDG 3 - Good Health and Well-being, mental disorders, medicine, Humans, Pharmacology (medical), Gray Matter, Psychiatry, Biological Psychiatry, Anterior cingulate cortex, Fusiform gyrus, Putamen, Smoking, Brain morphometry, Brain, Organ Size, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, nervous system, Schizophrenia, Brain size, Orbitofrontal cortex, Psychology, Antipsychotic Agents, Research Paper
Abstract: Contains fulltext : 154675.pdf (Publisher’s version ) (Open Access) 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.
Published: 2015
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49. The Tourette International Collaborative Genetics (TIC Genetics) study, finding the genes causing Tourette syndrome: objectives and methods

Author: Dong Ho Song, Andrea Dietrich, Jay Tischfield, Julie Hagstrøm, Gary Heiman, Marta Correa Vela, Chaim Huyser, Keun-Ah Cheon, Astrid Morer, Samuel Kuperman, Blanca Garcia-Delgar, Isobel Heyman, Veit Roessner, Dorothy E Grice, Child Psychiatry, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)
Subjects: medicine.medical_specialty, Tics, Genetic Linkage, Trios, CHILDREN, Genomics, VARIANTS, Tourette syndrome, Genetic linkage, Methods, Developmental and Educational Psychology, Child and adolescent psychiatry, medicine, Humans, Genetic Predisposition to Disease, Pediatrics, Perinatology, and Child Health, Cooperative Behavior, AUTISM, Child, Genetics, MAJOR GENE, PSYCHIATRIC-DISORDERS, Repository, Inheritance (genetic algorithm), Rare variants, Original Contribution, OBSESSIVE-COMPULSIVE DISORDER, General Medicine, SEVERITY-SCALE, medicine.disease, Mental health, Pedigree, 3. Good health, Psychiatry and Mental health, Genes, EUROPEAN CLINICAL GUIDELINES, BEHAVIOR-THERAPY, Attention Deficit Disorder with Hyperactivity, Tic Disorders, RELIABILITY, Pediatrics, Perinatology and Child Health, Multiplex families, Autism, Female, Gene-Environment Interaction, Psychology
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder characterized by recurrent motor and vocal tics, often accompanied by obsessive-compulsive disorder and/or attention-deficit/hyperactivity disorder. While the evidence for a genetic contribution is strong, its exact nature has yet to be clarified fully. There is now mounting evidence that the genetic risks for TS include both common and rare variants and may involve complex multigenic inheritance or, in rare cases, a single major gene. Based on recent progress in many other common disorders with apparently similar genetic architectures, it is clear that large patient cohorts and open-access repositories will be essential to further advance the field. To that end, the large multicenter Tourette International Collaborative Genetics (TIC Genetics) study was established. The goal of the TIC Genetics study is to undertake a comprehensive gene discovery effort, focusing both on familial genetic variants with large effects within multiply affected pedigrees and on de novo mutations ascertained through the analysis of apparently simplex parent-child trios with non-familial tics. The clinical data and biomaterials (DNA, transformed cell lines, RNA) are part of a sharing repository located within the National Institute for Mental Health Center for Collaborative Genomics Research on Mental Disorders, USA, and will be made available to the broad scientific community. This resource will ultimately facilitate better understanding of the pathophysiology of TS and related disorders and the development of novel therapies. Here, we describe the objectives and methods of the TIC Genetics study as a reference for future studies from our group and to facilitate collaboration between genetics consortia in the field of TS.
Published: 2015
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50. Association and Causation in Brain Imaging in the Case of OCD:Response to McKay et al

Author: Ignacio Martinez-Zalacain, Susanne Walitza, Ganesan Venkatasubramanian, Carles Soriano-Mas, Jose Menchon, Rosa Calvo-Escalona, Damiaan Denys, Guido Van Wingen, Chaim Huyser, Ysbrand Van der Werf, Lianne Schmaal, Astrid Morer, Luisa Lazaro, Francesco Benedetti, Dan Stein, Odile Van den Heuvel, Other departments, Amsterdam Neuroscience, Adult Psychiatry, Psychiatry, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Boedhoe, Psw, Schmaal, L, Mataix-Cols, D, Jahanshad, N, ENIGMA OCD Working, Group, Benedetti, F, Thompson, Pm, Stein, D, and van den Heuvel, Oa
Subjects: medicine.diagnostic_test, 05 social sciences, Magnetic resonance imaging, medicine.disease, Causality, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, Neurodevelopmental disorder, Neuroimaging, medicine, 0501 psychology and cognitive sciences, Causation, Psychology, Association (psychology), Neuroscience, 030217 neurology & neurosurgery, 050104 developmental & child psychology
Published: 2017
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