Genetic and Molecular Correlates of Cortical Thickness Alterations in Adults with Obsessive-Compulsive Disorder: A Transcription-Neuroimaging Association Analysis

Abstract

Abstract Although numerous neuroimaging studies have shown neural alterations in individuals with obsessive-compulsive disorder (OCD), a psychiatric disorder characterised by intrusive cognitions and repetitive behaviours, the molecular mechanisms linking brain structural changes and gene expression remain poorly understood. By combining the Allen Human Brain Atlas dataset with neuroimaging data from the Meta-Analysis (ENIGMA) consortium and independent cohorts, this study performed partial least squares regression and enrichment analysis to probe the correlation between transcription and cortical thickness variation in adults with OCD. The cortical map of case–control differences in cortical thickness was spatially correlated with cortical expression of a weighted combination of genes enriched for neurobiologically relevant ontology terms, preferentially expressed across different cell types and cortical layers. These genes were specifically expressed in brain tissue, spanning nearly all cortical developmental stages. Protein-protein interaction analysis revealed that these genes coded a network of proteins encompassing several highly interactive hubs. The findings of this study bridge the gap between neural structure and transcriptome data in OCD, fostering an integrative understanding of the potential biological mechanisms.