Altered frontal and occipital cortical microstructure in obsessive-compulsive disorder - a multisite mega-analysis

Alterations in cortical morphology have consistently been reported in obsessive-compulsive disorder (OCD). However, the microstructural properties of the cortex in OCD, including intracortical myelination, remain far less explored. The contrast between signal intensity in gray and subjacent white matter from T1-weighted magnetic resonance imaging (MRI), i.e. the gray/white matter contrast (GWC), is linked to intracortical myelination and may offer novel insights into the cortical microstructure of OCD. Here, we compared multivariate patterns of GWC defined from an independent component analysis between 454 adults with OCD and 394 healthy controls from eight international sites. To contextualize GWC results with the macrostructure of gray matter in OCD, we also investigated the association between GWC and each individual's similarity with the pattern of gray matter morphology derived from ENIGMA-OCD using the Regional Vulnerability Index (RVI). Finally, we investigated the association of GWC with demographic and clinical characteristics of participants with OCD. Individuals with OCD showed significantly higher GWC in occipital and frontal regions relative to healthy controls. Moreover, OCD individuals had elevated OCD RVI, and individuals with a higher OCD RVI showed widespread higher GWC across the cortex. Finally, sexual/religious symptoms in OCD individuals were associated with higher GWC in frontal regions. In conclusion, we present new evidence of cortical microstructural alterations in OCD, with microstructural alterations relating to both the gray matter macrostructure and the clinical presentation of the disorder.

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Journal
Molecular Psychiatry
Published
2026-03-15
DOI
https://doi.org/10.1038/s41380-026-03500-y
Primary Topic
Obsessive-Compulsive Spectrum Disorders
Type
article
Field-Weighted Citation Impact
0.00

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article

Altered frontal and occipital cortical microstructure in obsessive-compulsive disorder - a multisite mega-analysis

David F. Tolin, Damiaan Denys, Z. Wang, Dag Alnæs et al.
Molecular Psychiatry
Obsessive-Compulsive Spectrum Disorders
article

Altered frontal and occipital cortical microstructure in obsessive-compulsive disorder - a multisite mega-analysis

David F. Tolin, Damiaan Denys, Z. Wang, Dag Alnæs, Jan C. Beucke, Jun Soo Kwon, Konrad Koch, Vilde Brecke, M. Phillips, Olga Therese Ousdal, Estee Stern, T. Mitsuhiro Nakao, Yuqi Cheng, Brian Brennan, Anders Lillevik Thorsen, David Mataix-Cols, Yoshiyuki Hirano, Bjarne Hansen, Fabrizio Piras, Helen Blair Simpson, Yuki Sakai, on behalf of the ENIGMA-OCD Working Group, Francesco Benedetti, Odile A. van den Heuvel, Yoshinari Abe, Janardhan Reddy, Christine Lochner, Pedro Morgado, Dan J. Stein, Erika L. Nurmi, Jose M. Menchon, Marcelo Hoexter, Jan Buitelaar
article en

Abstract

Alterations in cortical morphology have consistently been reported in obsessive-compulsive disorder (OCD). However, the microstructural properties of the cortex in OCD, including intracortical myelination, remain far less explored. The contrast between signal intensity in gray and subjacent white matter from T1-weighted magnetic resonance imaging (MRI), i.e. the gray/white matter contrast (GWC), is linked to intracortical myelination and may offer novel insights into the cortical microstructure of OCD. Here, we compared multivariate patterns of GWC defined from an independent component analysis between 454 adults with OCD and 394 healthy controls from eight international sites. To contextualize GWC results with the macrostructure of gray matter in OCD, we also investigated the association between GWC and each individual's similarity with the pattern of gray matter morphology derived from ENIGMA-OCD using the Regional Vulnerability Index (RVI). Finally, we investigated the association of GWC with demographic and clinical characteristics of participants with OCD. Individuals with OCD showed significantly higher GWC in occipital and frontal regions relative to healthy controls. Moreover, OCD individuals had elevated OCD RVI, and individuals with a higher OCD RVI showed widespread higher GWC across the cortex. Finally, sexual/religious symptoms in OCD individuals were associated with higher GWC in frontal regions. In conclusion, we present new evidence of cortical microstructural alterations in OCD, with microstructural alterations relating to both the gray matter macrostructure and the clinical presentation of the disorder.

Molecular Psychiatry
South African Medical Research Council (ZA), Nathan Kline Institute for Psychiatric Research (US), Oslo University Hospital (NO), Netherlands Institute for Neuroscience (NL), Hartford Hospital (US), RELX Group (Netherlands) (NL), Royal Netherlands Academy of Arts and Sciences (NL), Kyushu University (JP), Harvard University (US), Seoul National University (KR), Radboud University Nijmegen (NL), University of Cape Town (ZA), University of California, Los Angeles (US), University of Pittsburgh (US), University of Oslo (NO), Lund University (SE), Kunming Medical University (CN), Stellenbosch University (ZA), Columbia University Irving Medical Center (US), Høyskolen Kristiania (NO), Haukeland University Hospital (NO), McLean Hospital (US), Bellvitge University Hospital (ES), TUM Klinikum (DE), Shanghai Mental Health Center (CN), Karolinska Institutet (SE), Yale University (US), Humboldt-Universität zu Berlin (DE), Kyoto Prefectural University of Medicine (JP), Institut d'Investigació Biomédica de Bellvitge (ES), MSH Medical School Hamburg – University of Applied Sciences and Medical University (DE), Neurobehavioral Systems (US), Advanced Telecommunications Research Institute International (JP), Amsterdam Neuroscience (NL), Dutch Expert Centre for Screening (NL), First Affiliated Hospital of Kunming Medical University (CN), Stockholm Health Care Services (SE), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR), Karakter (NL), Fondazione Santa Lucia (IT), Amsterdam University Medical Centers (NL), Clinical Academic Center of Braga (PT), Center for Forensic Mental Health, Chiba University (JP), New York State Psychiatric Institute, University of Bergen (NO), New York University (US), Technical University of Munich (DE), National Institute of Mental Health and Neurosciences (IN), Vrije Universiteit Amsterdam (NL), University of Amsterdam (NL), University of Minho (PT)
Wellcome Trust, Trond Mohn stiftelse, National Research Foundation, Fundação de Amparo à Pesquisa do Estado de São Paulo, Ministero della Salute, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Research Foundation of Korea, Helse Vest, Universitetet i Bergen, Amsterdam Neuroscience, Agència de Gestió d'Ajuts Universitaris i de Recerca, Instituto de Salud Carlos III
Openalex Percentile: Top 25%
Obsessive-Compulsive Spectrum Disorders
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