White matter microstructure and its relation to clinical features of obsessive-compulsive disorder: findings from the ENIGMA OCD Working Group.
Journal: Translational psychiatry
Volume: 11
Issue: 1
Year of Publication: 2021
Affiliated Institutions:
Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy. f.piras@hsantalucia.it.
Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy.
Department of Psychiatry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Obsessive-Compulsive Disorder (OCD) Clinic, Department of Psychiatry, National Institute of Mental Health & Neurosciences, Bangalore, India.
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Child, Youth and Emerging Adult Program, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Magnetic Resonance Image Core Facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Instituto e Departamento de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Psychiatry and Clinical Psychobiology, Division of Neuroscience, Scientific Institute Ospedale San Raffaele, Milano, Italy.
Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
Amsterdam University Medical Centers, Vrije Universiteit, Department of Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland.
Institute of Human Behavioral Medicine, SNU-MRC, Seoul, Republic of Korea.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada.
Department of Neuroscience and Graduate School, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Amsterdam university medical centers, Vrije Universiteit, Department of Anatomy & Neurosciences, Amsterdam Neuroscience, Amsterdam, The Netherlands.
SAMRC Unit on Anxiety & Stress Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Department of Neuroradiology, Klinikum rechts der Isar, Technische Universität München, München, Germany.
Research Center for Child Mental Development, Chiba University, Chiba, Japan.
Department of Psychiatry, Oxford University, Oxford, UK.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Child and Adolescent Psychiatry and Psychology, Institute of Neurosciences, Hospital Clínic Universitari, Barcelona, Spain.
Columbia University Irving Medical Center, Columbia University, New York, NY, USA.
Pediatric OCD Consultation Clinic, Anxiety Treatment and Research Center, McMaster University, Hamilton, Ontario, Canada.
MR-Center of the Department of Psychiatry, Psychotherapy and Psychosomatics and the Department of Child and Adolescent Psychiatry, Psychiatric Hospital of the University of Zurich, Zurich, Switzerland.
Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, USA.
Laboratory of Neuropsychiatry, Department of Clinical and Behavioral Neurology, IRCCS Santa Lucia Foundation, Rome, Italy. g.spalletta@hsantalucia.it.
Abstract summary
Microstructural alterations in cortico-subcortical connections are thought to be present in obsessive-compulsive disorder (OCD). However, prior studies have yielded inconsistent findings, perhaps because small sample sizes provided insufficient power to detect subtle abnormalities. Here we investigated microstructural white matter alterations and their relation to clinical features in the largest dataset of adult and pediatric OCD to date. We analyzed diffusion tensor imaging metrics from 700 adult patients and 645 adult controls, as well as 174 pediatric patients and 144 pediatric controls across 19 sites participating in the ENIGMA OCD Working Group, in a cross-sectional case-control magnetic resonance study. We extracted measures of fractional anisotropy (FA) as main outcome, and mean diffusivity, radial diffusivity, and axial diffusivity as secondary outcomes for 25 white matter regions. We meta-analyzed patient-control group differences (Cohen's d) across sites, after adjusting for age and sex, and investigated associations with clinical characteristics. Adult OCD patients showed significant FA reduction in the sagittal stratum (d = -0.21, z = -3.21, p = 0.001) and posterior thalamic radiation (d = -0.26, z = -4.57, p < 0.0001). In the sagittal stratum, lower FA was associated with a younger age of onset (z = 2.71, p = 0.006), longer duration of illness (z = -2.086, p = 0.036), and a higher percentage of medicated patients in the cohorts studied (z = -1.98, p = 0.047). No significant association with symptom severity was found. Pediatric OCD patients did not show any detectable microstructural abnormalities compared to controls. Our findings of microstructural alterations in projection and association fibers to posterior brain regions in OCD are consistent with models emphasizing deficits in connectivity as an important feature of this disorder.
Authors & Co-authors:
Piras Fabrizio F
Piras Federica F
Abe Yoshinari Y
Agarwal Sri Mahavir SM
Anticevic Alan A
Ameis Stephanie S
Arnold Paul P
Banaj Nerisa N
Bargalló Núria N
Batistuzzo Marcelo C MC
Benedetti Francesco F
Beucke Jan-Carl JC
Boedhoe Premika S W PSW
Bollettini Irene I
Brem Silvia S
Calvo Anna A
Cho Kang Ik Kevin KIK
Ciullo Valentina V
Dallaspezia Sara S
Dickie Erin E
Ely Benjamin Adam BA
Fan Siyan S
Fouche Jean-Paul JP
Gruner Patricia P
Gürsel Deniz A DA
Hauser Tobias T
Hirano Yoshiyuki Y
Hoexter Marcelo Q MQ
Iorio Mariangela M
James Anthony A
Reddy Y C Janardhan YCJ
Kaufmann Christian C
Koch Kathrin K
Kochunov Peter P
Kwon Jun Soo JS
Lazaro Luisa L
Lochner Christine C
Marsh Rachel R
Nakagawa Akiko A
Nakamae Takashi T
Narayanaswamy Janardhanan C JC
Sakai Yuki Y
Shimizu Eiji E
Simon Daniela D
Simpson Helen Blair HB
Soreni Noam N
Stämpfli Philipp P
Stern Emily R ER
Szeszko Philip P
Takahashi Jumpei J
Venkatasubramanian Ganesan G
Wang Zhen Z
Yun Je-Yeon JY
Stein Dan J DJ
Jahanshad Neda N
Thompson Paul M PM
van den Heuvel Odile A OA
Spalletta Gianfranco G
Study Outcome
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