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

Anders Lillevik Thorsen; Vilde Brecke; Dag Alnæs; David Mataix-Cols; Damiaan Denys; Dan J Stein; Odile A van den Heuvel; Olga Therese Ousdal

doi:10.1038/s41380-026-03500-y

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

Anders Lillevik Thorsen
, Vilde Brecke
, Dag Alnæs
, David Mataix-Cols
, Damiaan Denys
,
, Dan J Stein
, Odile A van den Heuvel
, Olga Therese Ousdal

Netherlands Institute for Neuroscience (NIN)

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

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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.

Original language	English
Journal	Molecular Psychiatry
DOIs	https://doi.org/10.1038/s41380-026-03500-y
Publication status	E-pub ahead of print - 15 Mar 2026

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@article{28be2d2c2ecf4b14b6ee29aea67338d2,

title = "Altered frontal and occipital cortical microstructure in obsessive-compulsive disorder - a multisite mega-analysis",

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.",

author = "Thorsen, \{Anders Lillevik\} and Vilde Brecke and Dag Aln{\ae}s and David Mataix-Cols and Kwon, \{Jun Soo\} and Menchon, \{Jose M\} and Yoshinari Abe and Yuki Sakai and Phillips, \{Mary L\} and Bjarne Hansen and Marcelo Hoexter and Janardhan Reddy and Francesco Benedetti and Brennan, \{Brian P\} and Yuqi Cheng and Yoshiyuki Hirano and Damiaan Denys and Kathrin Koch and Tomohiro Nakao and Nurmi, \{Erika L\} and Simpson, \{Helen Blair\} and Fabrizio Piras and Tolin, \{David F\} and Stern, \{Emily R\} and Zhen Wang and Jan Buitelaar and Pedro Morgado and Beucke, \{Jan C\} and Christine Lochner and Stein, \{Dan J\} and \{van den Heuvel\}, \{Odile A\} and Ousdal, \{Olga Therese\}",

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day = "15",

doi = "10.1038/s41380-026-03500-y",

language = "English",

journal = "Molecular Psychiatry",

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T1 - Altered frontal and occipital cortical microstructure in obsessive-compulsive disorder - a multisite mega-analysis

AU - Thorsen, Anders Lillevik

AU - Brecke, Vilde

AU - Alnæs, Dag

AU - Mataix-Cols, David

AU - Kwon, Jun Soo

AU - Menchon, Jose M

AU - Abe, Yoshinari

AU - Sakai, Yuki

AU - Phillips, Mary L

AU - Hansen, Bjarne

AU - Hoexter, Marcelo

AU - Reddy, Janardhan

AU - Benedetti, Francesco

AU - Brennan, Brian P

AU - Cheng, Yuqi

AU - Hirano, Yoshiyuki

AU - Denys, Damiaan

AU - Koch, Kathrin

AU - Nakao, Tomohiro

AU - Nurmi, Erika L

AU - Simpson, Helen Blair

AU - Piras, Fabrizio

AU - Tolin, David F

AU - Stern, Emily R

AU - Wang, Zhen

AU - Buitelaar, Jan

AU - Morgado, Pedro

AU - Beucke, Jan C

AU - Lochner, Christine

AU - Stein, Dan J

AU - van den Heuvel, Odile A

AU - Ousdal, Olga Therese

PY - 2026/3/15

Y1 - 2026/3/15

N2 - 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.

AB - 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.

U2 - 10.1038/s41380-026-03500-y

DO - 10.1038/s41380-026-03500-y

M3 - Article

C2 - 41833995

SN - 1359-4184

JO - Molecular Psychiatry

JF - Molecular Psychiatry

ER -

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

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