ArticleBiological psychiatry. Cognitive neuroscience and neuroimaging2026
Regional Cerebellar Volumetrics in Obsessive-Compulsive Disorder: An ENIGMA-OCD Study.
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Srinivas BalachanderOCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Janardhanan C NarayanaswamyOCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India; Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Victoria, Australia; Mental Health, Drugs & Alcohol Services, Barwon Health, Geelong, Victoria, Australia.
Venkataram ShivakumarDepartment of Integrative Medicine, National Institute of Mental Health and Neurosciences, Bangalore, India.
Yoshinari AbeDepartment of Psychiatry, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan; Sugimoto Psychiatric Clinic, Kyoto, Japan.
Pino AlonsoBellvitge Biomedical Research Institute-Institut d'Investigació Biomèdica de Bellvitge, Bellvitge University Hospital, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
Lea L BackhausenCentro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Barcelona, Spain; Department of Child and Adolescent Psychiatry, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany.
Nerisa BanajLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
Marcelo C BatistuzzoDepartamento e Instituto de Psiquiatria do Hospital das Clínicas, Instituto da Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paul, Faculdade de Medicina, Universidade de São Paulo, Brazil; Department of Methods and Techniques in Psychology, Pontifical Catholic University, São Paulo, Brazil.
Francesco BenedettiVita-Salute San Raffaele University, Milano, Italy; Department of Psychiatry and Clinical Psychobiology, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Scientific Institute Ospedale San Raffaele, Milano, Italy.
Irene BollettiniDepartment of Psychiatry and Clinical Psychobiology, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Scientific Institute Ospedale San Raffaele, Milano, Italy.
Beatrice BraviDepartment of Psychiatry and Clinical Psychobiology, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Scientific Institute Ospedale San Raffaele, Milano, Italy.
Silvia BremDepartment of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and Eidgenössische Technische Hochschule Zürich, Zurich, Switzerland.
Carolina CappiDepartamento e Instituto de Psiquiatria do Hospital das Clínicas, Instituto da Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paul, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Ritu Bhusal ChhatkuliResearch Center for Child Mental Development, Chiba University, Chiba, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University, Chiba University, and University of Fukui, Suita, Japan.
Sunah ChoiDepartment of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
Patrícia CoelhoLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
Ana Daniela CostaLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
Sara DallaspeziaLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
Damiaan DenysDepartment of Psychiatry, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands.
Juliana B DinizDepartamento e Instituto de Psiquiatria do Hospital das Clínicas, Instituto da Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paul, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Nadza DzinalijaDepartment of Anatomy & Neurosciences, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, the Netherlands.
Goi Khia EngDepartment of Psychiatry, New York University School of Medicine, New York, New York; Clinical Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York.
Jamie D FeusnerDivision of Neurosciences and Clinical Translation, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Simone FiedlerDepartment of Child and Adolescent Psychiatry, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany.
Minji HaDepartment of Brain and Cognitive Sciences, Seoul National University College of Natural Sciences, Seoul, South Korea.
Yoshiyuki HiranoResearch Center for Child Mental Development, Chiba University, Chiba, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University, Chiba University, and University of Fukui, Suita, Japan.
Marcelo Q HoexterDepartamento e Instituto de Psiquiatria do Hospital das Clínicas, Instituto da Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paul, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Hao HuDepartment of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chaim HuijserLevvel, Specialist in Youth and Family, Amsterdam, the Netherlands; Department of Child and Adolescent Psychiatry, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Jonathan IpserSouth African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Neda JahanshadImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
Jiseon JangDepartment of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea.
Minah KimDepartment of Neuropsychiatry, Seoul National University Hospital, Seoul, South Korea; Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
Kathrin KochDepartment of Diagnostic and Interventional Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany.
Kohei KuritaResearch Center for Child Mental Development, Chiba University, Chiba, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University, Chiba University, and University of Fukui, Suita, Japan.
Jun Soo KwonDepartment of Psychiatry, Hanyang University College of Medicine, Seoul, South Korea; Department of Psychiatry, Hanyang University Hospital, Seoul, South Korea; Institute of Human Behavioral Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea.
Luisa LazaroDepartment of Child and Adolescent Psychiatry and Psychology, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi | Sunyer, Barcelona, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain.
Christine LochnerSouth African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch University, Stellenbosch, South Africa.
Mafalda Machado-SousaLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
Daniela Rodriguez ManriqueDepartment of Diagnostic and Interventional Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany.
Hein van MarleDepartment of Anatomy & Neurosciences, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Ignacio Martínez-ZalacaínBellvitge Biomedical Research Institute-Institut d'Investigació Biomèdica de Bellvitge, Bellvitge University Hospital, Barcelona, Spain; Department of Radiology, Bellvitge University Hospital, Barcelona, Spain.
David Mataix-ColsDepartment of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
Jose M MenchónBellvitge Biomedical Research Institute-Institut d'Investigació Biomèdica de Bellvitge, Bellvitge University Hospital, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
Pedro MorgadoLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
Laurens van de MortelDepartment of Psychiatry, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Emma Muñoz-MorenoMRI Core Facility, Institut d'Investigacions Biomèdiques August Pi | Sunye, Barcelona, Spain.
Tomohiro NakaoDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
Erika NurmiDivision of Child and Adolescent Psychiatry, Jane and Terry Semel Institute for Neurosciences, University of California, Los Angeles, California.
Joseph O'NeillDivision of Child and Adolescent Psychiatry, Jane and Terry Semel Institute for Neurosciences, University of California, Los Angeles, California; University of California, Los Angeles, Brain Research Institute, Los Angeles, California.
Ana E OrtizDepartment of Child and Adolescent Psychiatry and Psychology, Hospital Clínic, Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi | Sunyer, Barcelona, Spain.
Olga Therese OusdalBergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway; Department of Radiology, Haukeland University Hospital, Bergen, Norway; Department of Biomedicine, University of Bergen, Bergen, Norway.
Saül Pascual-DiazMRI Core Facility, Institut d'Investigacions Biomèdiques August Pi | Sunye, Barcelona, Spain.
Clelia PellicanoLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
Mary L PhillipsDepartment of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
John PiacentiniDivision of Child and Adolescent Psychiatry, Jane and Terry Semel Institute for Neurosciences, University of California, Los Angeles, California.
Maria Picó-PérezLife and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal; Departamento de Psicología Básica, Clínica y Psicobiología, Universitat Jaume I, Castellón de la Plana, Spain.
Fabrizio PirasLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
Federica PirasLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
Yuki SakaiDepartment of Neural Computation for Decision Making, Advanced Telecommunication Research Institute International Brain Information Communication Research Laboratory Group, Kyoto, Japan.
Roseli G ShavittDepartamento e Instituto de Psiquiatria do Hospital das Clínicas, Instituto da Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paul, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Eiji ShimizuResearch Center for Child Mental Development, Chiba University, Chiba, Japan; United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University, Chiba University, and University of Fukui, Suita, Japan; Department of Cognitive Behavioral Physiology, Chiba University, Chiba, Japan.
Carles Soriano-MasBellvitge Biomedical Research Institute-Institut d'Investigació Biomèdica de Bellvitge, Bellvitge University Hospital, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental, Carlos III Health Institute, Barcelona, Spain; Department of Social Psychology and Quantitative Psychology, Institute of Neurosciences, University of Barcelona, Barcelona, Spain.
Emily R SternDepartment of Psychiatry, New York University School of Medicine, New York, New York; Clinical Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York; Neuroscience Institute, New York University School of Medicine, New York, New York.
Anders Lillevik ThorsenBergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway; Centre for Crisis Psychology, University of Bergen, Bergen, Norway.
Hirofumi TomiyamaDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
Daniela VecchioLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome, Italy.
Dick J VeltmanDepartment of Anatomy & Neurosciences, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, the Netherlands.
Nora C VetterDepartment of Child and Adolescent Psychiatry, Faculty of Medicine, TUD Dresden University of Technology, Dresden, Germany; Department of Psychology, MSB Medical School Berlin, Berlin, Germany.
Chris VriendDepartment of Anatomy & Neurosciences, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, the Netherlands.
Susanne WalitzaDepartment of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich, University of Zurich and Eidgenössische Technische Hochschule Zürich, Zurich, Switzerland.
Zhen WangDepartment of Clinical Psychology, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ysbrand D van der WerfDepartment of Anatomy & Neurosciences, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, the Netherlands.
Guido van WingenDepartment of Psychiatry, Amsterdam University Medical Center, location University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Amsterdam University Medical Center, Amsterdam, the Netherlands.
Qing ZhaoDepartment of Clinical Psychology, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
ENIGMA-OCD Working Group
Sophia ThomopoulosImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, California.
Dan J SteinSouth African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Odile A van den HeuvelDepartment of Anatomy & Neurosciences, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Neuroscience, Compulsivity Impulsivity and Attention, Amsterdam, the Netherlands.
Ganesan VenkatasubramanianOCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Y C Janardhan ReddyOCD Clinic, Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India. Electronic address: ycjreddy@gmail.com.
Funding
Training U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MBrain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCDR01MH116038 · NIMH · YALE UNIVERSITY · PI ANTICEVIC, ALAN, PITTENGER, CHRISTOPHER JOHN · 2019 to 2023
$3.7MCognitive-Behavioral Therapy & Glutametergic Neurometabolites in Pediatric OCDR01MH081864 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI O'NEILL, JOSEPH, PIACENTINI, JOHN C. · 2008 to 2012
$3.0MCognitive-Behavioral Therapy and Glutamate in Cingulate Gyrus in OCDR01MH085900 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI FEUSNER, JAMIE, O'NEILL, JOSEPH · 2011 to 2014
$1.8MNIBIB NIH HHS U54 EB020403NIMH NIH HHS R01 MH081864NIMH NIH HHS R01 MH085900NIMH NIH HHS R01 MH116038
Abstract
backgroundAlthough subtle differences in cortico-striato-thalamo-cortical circuit structure and function are critical to the current understanding of the neurocircuitry in obsessive-compulsive disorder (OCD), emerging evidence suggests that the cerebellum may also be involved. However, much of this evidence comes from studies with small samples and notable methodological heterogeneity.
methodsWe conducted a mega-analysis of individual-participant data on cerebellar subregional volumes, comparing individuals with OCD and healthy controls (HCs) from the ENIGMA-OCD Working Group. Three-dimensional T1-weighted volumetric structural brain magnetic resonance imaging (MRI) scans from 1954 individuals with OCD and 2091 HCs across 22 sites (40 datasets) were processed using the ACAPULCO (Automatic Cerebellum Anatomical parcellation using U-Net Locally Constrained Optimization) pipeline to extract cerebellar parcellations. We harmonized the volume measures across sites using the ComBat algorithm. Multiple linear regression models were fitted to estimate group differences separately within the pediatric (<12 years), adolescent (12-17 years), and adult (from 18 years) samples, adjusting for age, gender, and intracranial volume.
resultsIn adults with OCD (vs. HCs), we found significantly smaller volumes of the corpus medullare (d = -0.093, false discovery rate (FDR)-corrected p = .036), left VIIb (d = -0.085, p
conclusionsWe report novel findings implicating specific cerebellar subregions across developmental stages of OCD and the key impact of medication status. Additional research on the functional significance of these findings may offer new translational leads.
Indexed as
CerebellumObsessive-Compulsive DisorderAdolescentAdultChildFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedOrgan SizeYoung AdultCerebellumMega-analysisObsessive-compulsive disorderOCDStructural MRI
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