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.

This study was supported by Sichuan Science and Technology Program (2024NSFSC0653). These authors contributed equally: Yufei Chen, Haoran Li, Fenghua Long. Department of Radiology, Huaxi MR Research Center (HMRRC), Institution of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, P.R.

China Yufei Chen, Haoran Li, Fenghua Long, Youjin Zhao & Fei Li Psychoradiology Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan Province, P.R. China Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, 45219, OH, USA RKM has received research support from Martek Biosciences Inc, Royal DSM Nutritional Products, LLC, Inflammation Research Foundation, Ortho-McNeil Janssen, AstraZeneca, Eli Lilly, NARSAD, and NIH, and previously served on the scientific advisory board of the Inflammation Research Foundation. The remaining authors declare no biomedical financial interests or potential conflicts of interest.

This study was based exclusively on secondary analyses of previously published and publicly available data and did not involve the recruitment of new human or animal participants or the collection of new individual-level data. All methods were performed in accordance with the relevant guidelines and regulations. The original studies included in the meta-analysis had obtained ethics approval from their respective institutional review boards or ethics committees and informed consent from their participants.