Meta-Analysis

. 2022 Feb 21;12(1):70.

doi: 10.1038/s41398-022-01823-2.

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

Cees J Weeland¹, Selina Kasprzak², Niels T de Joode², Yoshinari Abe³, Pino Alonso^{4

5

6}, Stephanie H Ameis^{7

8

9}, Alan Anticevic¹⁰, Paul D Arnold^{11

12}, Srinivas Balachander¹³, Nerisa Banaj¹⁴, Nuria Bargallo^{15

16}, Marcelo C Batistuzzo^{17

18}, Francesco Benedetti^{19

20}, Jan C Beucke^{21

22

23

24}, Irene Bollettini²⁵, Vilde Brecke²⁶, Silvia Brem^{27

28}, Carolina Cappi²⁹, Yuqi Cheng³⁰, Kang Ik K Cho^{31

32}, Daniel L C Costa³³, Sara Dallaspezia³⁴, Damiaan Denys³⁵, Goi Khia Eng^{36

37}, Sónia Ferreira^{38

39

40}, Jamie D Feusner^{41

42}, Martine Fontaine⁴³, Jean-Paul Fouche⁴⁴, Rachael G Grazioplene⁴⁵, Patricia Gruner⁴⁵, Mengxin He³⁰, Yoshiyuki Hirano^{46

47}, Marcelo Q Hoexter¹⁷, Chaim Huyser^{48

49}, Hao Hu⁵⁰, Fern Jaspers-Fayer^{51

52}, Norbert Kathmann²¹, Christian Kaufmann²¹, Minah Kim^{53

54}, Kathrin Koch^{55

56}, Yoo Bin Kwak³², Jun Soo Kwon^{32

54

57

58}, Luisa Lazaro^{59

60}, Chiang-Shan R Li⁵, Christine Lochner⁶¹, Rachel Marsh⁴³, Ignacio Martínez-Zalacaín^{4

6}, David Mataix-Cols^{22

62}, Jose M Menchón^{4

5

6}, Luciano Minnuzi^{63

64}, Pedro Silva Moreira^{38

39

65}, Pedro Morgado^{38

39

66

67}, Akiko Nakagawa⁴⁶, Takashi Nakamae⁶⁸, Janardhanan C Narayanaswamy¹³, Erika L Nurmi⁶⁹, Ana E Ortiz^{70

71}, Jose C Pariente¹⁵, John Piacentini⁷², Maria Picó-Pérez^{38

39

40}, Fabrizio Piras¹⁴, Federica Piras¹⁴, Christopher Pittenger⁷³, Y C Janardhan Reddy¹³, Daniela Rodriguez-Manrique^{56

74

75}, Yuki Sakai^{3

76}, Eiji Shimizu⁴⁶, Venkataram Shivakumar⁷⁷, Helen Blair Simpson^{78

79}, Noam Soreni^{63

80}, Carles Soriano-Mas^{4

5

81}, Nuno Sousa^{38

39

40}, Gianfranco Spalletta^{82

83}, Emily R Stern^{36

37}, Michael C Stevens^{84

85}, S Evelyn Stewart^{51

52

86}, Philip R Szeszko^{87

88}, Jumpei Takahashi⁸⁹, Tais Tanamatis¹⁷, Jinsong Tang^{90

91}, Anders Lillevik Thorsen^{26

92}, David Tolin^{85

93}, Ysbrand D van der Werf², Hein van Marle², Guido A van Wingen³⁵, Daniela Vecchio¹⁴, G Venkatasubramanian⁹⁴, Susanne Walitza^{27

28}, Jicai Wang³⁰, Zhen Wang⁵⁰, Anri Watanabe³, Lidewij H Wolters^{49

95}, Xiufeng Xu³⁰, Je-Yeon Yun^{96

97}, Qing Zhao⁵⁰; ENIGMA OCD Working Group; Tonya White^{98

99}, Paul M Thompson¹⁰⁰, Dan J Stein¹⁰¹, Odile A van den Heuvel^#², Chris Vriend^#²

Affiliations

¹ Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands. c.j.weeland@amsterdamumc.nl.
² Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands.
³ Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ Bellvitge Biomedical Research Insitute-IDIBELL, Bellvitge University Hospital, Barcelona, Spain.
⁵ CIBERSAM, Barcelona, Spain.
⁶ Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
⁷ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
⁸ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁹ Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁰ Departments of Psychiatry and Neuroscience, Yale University, New Haven, CT, USA.
¹¹ The Mathison Centre for Mental Health Research & Education, Departments of Psychiatry and Medical Genetics, Calgary, Canada.
¹² Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹³ OCD clinic, Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India.
¹⁴ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
¹⁵ Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
¹⁶ Image Diagnostic Center, Hospital Clinic, Barcelona, Spain.
¹⁷ Departamento de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
¹⁸ Department of Methods and Techniques in Psychology, Pontificial Catholic University of Sao Paulo, Sao Paulo, SP, Brazil.
¹⁹ Vita-Salute San Raffaele University, Milano, Italy.
²⁰ Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy.
²¹ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
²² Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden.
²³ Department of Medical Psychology, Medical School Hamburg, Hamburg, Germany.
²⁴ Institute for Systems Medicine and Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg, Germany.
²⁵ Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy.
²⁶ Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
²⁷ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
²⁸ Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
²⁹ Icahn School of Medicine at Mount Sinai Department of Psychiatry, New York, NY, USA.
³⁰ Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
³¹ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³² Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, Republic of Korea.
³³ Obsessive-Compulsive Spectrum Disorders Program, Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
³⁴ IRCCS Ospedale San Raffaele, Milano Italy Psychiatry, Milano, Italy.
³⁵ Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
³⁶ Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
³⁷ Clinical Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
³⁸ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
³⁹ ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
⁴⁰ Clinical Academic Center - Braga, Braga, Portugal.
⁴¹ Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada.
⁴² Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
⁴³ Columbia University Medical College, Columbia University, New York, NY, USA.
⁴⁴ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
⁴⁵ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁴⁶ Research Center for Child Mental Development, Chiba University, Chiba, Japan.
⁴⁷ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan.
⁴⁸ Levvel, Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
⁴⁹ Amsterdam UMC, Department of Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
⁵⁰ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵¹ Department of Psychiatry, University of British Columbia, Vancouver, Canada.
⁵² British Columbia Children's Hospital Research Institute, Vancouver, Canada.
⁵³ Seoul National University Hospital, Department of Neuropsychiatry, Seoul, Republic of Korea.
⁵⁴ Seoul National University College of Medicine, Department of Psychiatry, Seoul, Republic of Korea.
⁵⁵ Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität, München, Germany.
⁵⁶ TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universität München, München, Germany.
⁵⁷ Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
⁵⁸ Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea.
⁵⁹ Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic, IDIBAPS, Barcelona, Spain.
⁶⁰ Department of Medicine, University of Barcelona, Barcelona, Spain.
⁶¹ Stellenbosch University, SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch, South Africa.
⁶² Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
⁶³ Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
⁶⁴ Offord Centre for Child Studies, Hamilton, Ontario, Canada.
⁶⁵ Psychological Neuroscience Lab, CIPsi, School of Psychology, University of Minho, Braga, Portugal.
⁶⁶ Clinical Academic Center-Braga (2CA), Braga, Portugal.
⁶⁷ Hospital de Braga, Braga, Portugal.
⁶⁸ Graduate School of Medical Science Kyoto Prefectural University of Medicine, Department of Psychiatry, Kyoto, Japan.
⁶⁹ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
⁷⁰ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic, Barcelona, Spain.
⁷¹ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁷² UCLA Semel Institute, Division of Child and Adolescent Psychiatry, Los Angeles, CA, USA.
⁷³ Department of Psychiatry and Yale Child Study Center, Yale University, New Haven, CT, USA.
⁷⁴ Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany.
⁷⁵ Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians-Universität, Munich, Germany.
⁷⁶ Department of Neural Computation for Decision-Making, Advanced Telecommunications Research Institute International Brain Information Communication Research Laboratory Group, Kyoto, Japan.
⁷⁷ Department of Integrative Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
⁷⁸ Columbia University Irving Medical College, Columbia University, New York, NY, USA.
⁷⁹ New York State Psychiatric Institute, New York, NY, USA.
⁸⁰ Pediatric OCD Consultation Team, Anxiety Treatment and Research Center, Hamilton, Ontario, Canada.
⁸¹ Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁸² IRCCS Santa Lucia Foundation, Laboratory of Neuropsychiatry, Rome, Italy.
⁸³ Baylor College of Medicine, Department of Psychiatry and Behavioral Sciences, Houston, TX, USA.
⁸⁴ Institute of Living, Hartford, CT, USA.
⁸⁵ Yale University School of Medicine, New Haven, CT, USA.
⁸⁶ BC Mental Health and Substance Use Services Research Institute, Vancouver, Canada.
⁸⁷ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸⁸ James J. Peters VA Medical Center, Mental Illness Research, Education and Clinical Center, Bronx, NY, USA.
⁸⁹ Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
⁹⁰ Department of Psychiatry, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁹¹ Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
⁹² Centre for Crisis Psychology, University of Bergen, Bergen, Norway.
⁹³ Institute of Living/Hartford Hospital, Hartford, CT, USA.
⁹⁴ National Institute of Mental Health And Neurosciences, Department of Psychiatry, Bengaluru, India.
⁹⁵ Levvel, Academic Center for Child and Adolescent Psychiatry, Post Box 303, 1115 ZG, Duivendrecht, the Netherlands.
⁹⁶ Seoul National University Hospital, Seoul, Republic of Korea.
⁹⁷ Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁹⁸ Erasmus Medical Center, Department of Child and Adolescent Psychiatry/Psychology, Wytemaweg 8, 3015 GD, Rotterdam, the Netherlands.
⁹⁹ Department of Radiology and Nuclear Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁰⁰ Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁰¹ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

^# Contributed equally.

PMID: 35190533
PMCID: PMC8861046
DOI: 10.1038/s41398-022-01823-2

Meta-Analysis

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

Cees J Weeland et al. Transl Psychiatry. 2022.

. 2022 Feb 21;12(1):70.

doi: 10.1038/s41398-022-01823-2.

Authors

Affiliations

¹ Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands. c.j.weeland@amsterdamumc.nl.
² Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Psychiatry, Department of Anatomy & Neurosciences, Amsterdam, The Netherlands.
³ Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
⁴ Bellvitge Biomedical Research Insitute-IDIBELL, Bellvitge University Hospital, Barcelona, Spain.
⁵ CIBERSAM, Barcelona, Spain.
⁶ Department of Clinical Sciences, University of Barcelona, Barcelona, Spain.
⁷ Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada.
⁸ Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁹ Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, ON, Canada.
¹⁰ Departments of Psychiatry and Neuroscience, Yale University, New Haven, CT, USA.
¹¹ The Mathison Centre for Mental Health Research & Education, Departments of Psychiatry and Medical Genetics, Calgary, Canada.
¹² Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹³ OCD clinic, Department of Psychiatry, National Institute of Mental Health And Neurosciences (NIMHANS), Bangalore, India.
¹⁴ Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
¹⁵ Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
¹⁶ Image Diagnostic Center, Hospital Clinic, Barcelona, Spain.
¹⁷ Departamento de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
¹⁸ Department of Methods and Techniques in Psychology, Pontificial Catholic University of Sao Paulo, Sao Paulo, SP, Brazil.
¹⁹ Vita-Salute San Raffaele University, Milano, Italy.
²⁰ Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy.
²¹ Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
²² Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden.
²³ Department of Medical Psychology, Medical School Hamburg, Hamburg, Germany.
²⁴ Institute for Systems Medicine and Faculty of Human Medicine, MSH Medical School Hamburg, Hamburg, Germany.
²⁵ Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy.
²⁶ Bergen Center for Brain Plasticity, Haukeland University Hospital, Bergen, Norway.
²⁷ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
²⁸ Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
²⁹ Icahn School of Medicine at Mount Sinai Department of Psychiatry, New York, NY, USA.
³⁰ Department of Psychiatry, First Affiliated Hospital of Kunming Medical University, Kunming, China.
³¹ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
³² Department of Brain and Cognitive Sciences, Seoul National University College of Natural Science, Seoul, Republic of Korea.
³³ Obsessive-Compulsive Spectrum Disorders Program, Departamento e Instituto de Psiquiatria, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
³⁴ IRCCS Ospedale San Raffaele, Milano Italy Psychiatry, Milano, Italy.
³⁵ Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
³⁶ Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
³⁷ Clinical Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
³⁸ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
³⁹ ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
⁴⁰ Clinical Academic Center - Braga, Braga, Portugal.
⁴¹ Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada.
⁴² Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.
⁴³ Columbia University Medical College, Columbia University, New York, NY, USA.
⁴⁴ Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
⁴⁵ Department of Psychiatry, Yale University, New Haven, CT, USA.
⁴⁶ Research Center for Child Mental Development, Chiba University, Chiba, Japan.
⁴⁷ United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and University of Fukui, Suita, Japan.
⁴⁸ Levvel, Academic Center for Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
⁴⁹ Amsterdam UMC, Department of Child and Adolescent Psychiatry, Amsterdam, the Netherlands.
⁵⁰ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵¹ Department of Psychiatry, University of British Columbia, Vancouver, Canada.
⁵² British Columbia Children's Hospital Research Institute, Vancouver, Canada.
⁵³ Seoul National University Hospital, Department of Neuropsychiatry, Seoul, Republic of Korea.
⁵⁴ Seoul National University College of Medicine, Department of Psychiatry, Seoul, Republic of Korea.
⁵⁵ Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität, München, Germany.
⁵⁶ TUM-Neuroimaging Center (TUM-NIC) of Klinikum rechts der Isar, Technische Universität München, München, Germany.
⁵⁷ Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
⁵⁸ Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea.
⁵⁹ Department of Child and Adolescent Psychiatry and Psychology, Hospital Clinic, IDIBAPS, Barcelona, Spain.
⁶⁰ Department of Medicine, University of Barcelona, Barcelona, Spain.
⁶¹ Stellenbosch University, SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, Stellenbosch, South Africa.
⁶² Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
⁶³ Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, Canada.
⁶⁴ Offord Centre for Child Studies, Hamilton, Ontario, Canada.
⁶⁵ Psychological Neuroscience Lab, CIPsi, School of Psychology, University of Minho, Braga, Portugal.
⁶⁶ Clinical Academic Center-Braga (2CA), Braga, Portugal.
⁶⁷ Hospital de Braga, Braga, Portugal.
⁶⁸ Graduate School of Medical Science Kyoto Prefectural University of Medicine, Department of Psychiatry, Kyoto, Japan.
⁶⁹ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, USA.
⁷⁰ Department of Child and Adolescent Psychiatry and Psychology, Institute of Neuroscience, Hospital Clinic, Barcelona, Spain.
⁷¹ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
⁷² UCLA Semel Institute, Division of Child and Adolescent Psychiatry, Los Angeles, CA, USA.
⁷³ Department of Psychiatry and Yale Child Study Center, Yale University, New Haven, CT, USA.
⁷⁴ Department of Diagnostic and Interventional Neuroradiology, School of Medicine, Technical University of Munich, Munich, Germany.
⁷⁵ Graduate School of Systemic Neurosciences (GSN), Ludwig-Maximilians-Universität, Munich, Germany.
⁷⁶ Department of Neural Computation for Decision-Making, Advanced Telecommunications Research Institute International Brain Information Communication Research Laboratory Group, Kyoto, Japan.
⁷⁷ Department of Integrative Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India.
⁷⁸ Columbia University Irving Medical College, Columbia University, New York, NY, USA.
⁷⁹ New York State Psychiatric Institute, New York, NY, USA.
⁸⁰ Pediatric OCD Consultation Team, Anxiety Treatment and Research Center, Hamilton, Ontario, Canada.
⁸¹ Department of Psychobiology and Methodology of Health Sciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
⁸² IRCCS Santa Lucia Foundation, Laboratory of Neuropsychiatry, Rome, Italy.
⁸³ Baylor College of Medicine, Department of Psychiatry and Behavioral Sciences, Houston, TX, USA.
⁸⁴ Institute of Living, Hartford, CT, USA.
⁸⁵ Yale University School of Medicine, New Haven, CT, USA.
⁸⁶ BC Mental Health and Substance Use Services Research Institute, Vancouver, Canada.
⁸⁷ Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁸⁸ James J. Peters VA Medical Center, Mental Illness Research, Education and Clinical Center, Bronx, NY, USA.
⁸⁹ Department of Child Psychiatry, Chiba University Hospital, Chiba, Japan.
⁹⁰ Department of Psychiatry, Sir Run-Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
⁹¹ Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, China.
⁹² Centre for Crisis Psychology, University of Bergen, Bergen, Norway.
⁹³ Institute of Living/Hartford Hospital, Hartford, CT, USA.
⁹⁴ National Institute of Mental Health And Neurosciences, Department of Psychiatry, Bengaluru, India.
⁹⁵ Levvel, Academic Center for Child and Adolescent Psychiatry, Post Box 303, 1115 ZG, Duivendrecht, the Netherlands.
⁹⁶ Seoul National University Hospital, Seoul, Republic of Korea.
⁹⁷ Yeongeon Student Support Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
⁹⁸ Erasmus Medical Center, Department of Child and Adolescent Psychiatry/Psychology, Wytemaweg 8, 3015 GD, Rotterdam, the Netherlands.
⁹⁹ Department of Radiology and Nuclear Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁰⁰ Imaging Genetics Center, Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
¹⁰¹ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.

^# Contributed equally.

PMID: 35190533
PMCID: PMC8861046
DOI: 10.1038/s41398-022-01823-2

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 (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest 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.

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Conflict of interest statement

Alan Anticevic is a shareholder and member of the technology advisory board for RBNC Therapeutics. Jamie D. Feusner is affiliated with NOCD, LLC; Prof. Mataix-Cols receives personal fees from UpToDate, Inc and Elsevier, both outside the current work; Pedro Morgado has received in the past 3 years grants, CME-related honoraria, or consulting fees from Angelini, AstraZeneca, Bial Foundation, Biogen, DGS-Portugal, FCT, FLAD, Janssen-Cilag, Gulbenkian Foundation, Lundbeck, Springer Healthcare, Tecnimede and 2CA-Braga; Erika L. Nurmi served on the Scientific Advisory Board of Myriad Genetics and Medical Advisory Board of Tourette Association of America and Teva Pharmaceuticals; Christopher Pittenger is a consultant for Biohaven, CH-TAC, Lundbeck (not relevant to this work); in the last 3 years, Dr. Simpson has received research support from Biohaven for a multi-site clinical trial, royalties from Cambridge University Press and UpToDate, Inc, and a stipend from the American Medical Association for serving as Associate Editor of JAMA-Psychiatry; Susanne Walitza received no funds of Industry Outside professional activities and interests are declared under the link of the University of Zurich www.uzh.ch/prof/ssl-dir/interessenbindungen/client/web/. Her work was supported in the last 5 years by the Swiss National Science Foundation (SNF), diverse EU FP7s, Gesundheitsförderung Schweiz, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz Fonds. Paul M. Thompson received partial research support from Biogen, Inc., for research unrelated to this manuscript; Chris Vriend is listed as an inventor on a patent licensed to General Electronic (WO2018115148A1). Odile A. van den Heuvel received a consultation honorarium from Lundbeck. All other authors from the ENIGMA OCD working group have no conflicts of interest related to this study.

Figures

**Fig. 1. Schematic representation of thalamic nuclei grouping.**
Figure adapted from Thalamic Subregions and Obsessive-Compulsive Symptoms in 2500 Children From the General Population by Weeland et al., 2021, *Journal of the American Academy of Child and Adolescent Psychiatry*.

**Fig. 2. Volumetric differences between obsessive-compulsive patients and healthy controls by age group.**
*p_uncorrected < 0.05; **p_FDR < 0.05; volumetric differences are adjusted for age, sex and intracranial volume. Thal Thalamus.

**Fig. 3. Age trajectory of thalamus subregion volume for medicated obsessive-compulsive patients, unmedicated patients and healthy controls, split by sex and diagnosis.**
Adjusted for intracranial volume. Shading represents error margins. OCD obsessive-compulsive disorder.

See this image and copyright information in PMC

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

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

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