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

Mol Psychiatry. 2026 Mar 15. doi: 10.1038/s41380-026-03500-y. Online ahead of print.

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.

PMID:41833995 | DOI:10.1038/s41380-026-03500-y