Reduced cortical thickness in obsessive-compulsive disorder and candidate molecular correlates

Associations between obsessive-compulsive disorder (OCD) and cortical thickness (CTh) deficits have been inconsistent, and underlying candidate molecular correlates remain poorly understood. To address this, our study aims to investigate CTh alterations in OCD, evaluate potential clinical and methodological confounding factors, and explore the spatial associations of CTh alterations with molecular profiles. A meta-analysis comparing CTh differences between OCD patients and healthy controls was conducted, followed by subgroup and meta-regression analyses to evaluate the impact of clinical and methodological variables. Spatial associations between CTh differences in OCD and gene transcriptomic and neurotransmitter profiles were assessed. The results of meta-analysis revealed that OCD patients exhibited CTh deficits in left posterior cingulate cortex (PCC), left anterior cingulate cortex (ACC), and right pars opercularis compared with controls, although the left ACC cluster showed significant publication bias. Subgroup analyses demonstrated additional thinning in left inferior parietal lobule and right PCC in medicated and comorbid groups. Correlation analyses indicated that CTh alterations in OCD were associated with genes enriched in synaptic signaling and organization, which were highly expressed in excitatory neurons, inhibitory neurons, and glial cells, implicated in excitatory/inhibitory balance and signaling transmission efficiency. CTh alterations in OCD were also linked to multiple neurotransmitter systems, including mainly glutamate, 5-hydroxytryptamine, dopamine, and gamma-aminobutyric acid. Taken together, these findings suggest that OCD is associated with CTh deficits in regions affiliated with default mode and cingulo-opercular networks, which are influenced by medication and comorbidity, and these CTh alterations show spatial associations with genetic and neurotransmitter profiles primarily involving synaptic/glutamatergic pathways, providing hypothesis-generating insights into the neurobiological correlates of OCD.