Gray matter volume abnormalities in obsessive-compulsive disorder correlate with molecular and transcriptional profiles

Abstract

Neuroimaging studies have consistently established altered brain structure in obsessive-compulsive disorder (OCD). However, the molecular and genetic mechanisms underlying structural brain abnormalities remain unclear. In this study, we aimed to investigate altered gray matter volume and its underlying molecular and genetic mechanisms in patients with OCD. Gray matter morphological abnormalities measured with voxel based morphometry analysis were identified in patients with OCD in comparison to sex- and age-matched healthy controls (HCs). Spatial correlations between gray matter morphological abnormalities and neurotransmitter maps were calculated to identify neurotransmitters relating to structural abnormalities. Structural abnormalities related genes were identified by conducting transcriptome-neuroimaging spatial correlations. Compared with HCs, patients with OCD demonstrated significant morphological abnormalities in distributed brain areas, including gray matter atrophy in the anterior cingulate and increased gray matter volume in the thalamus, caudate and precentral and postcentral gyrus. The morphological abnormalities were significantly associated with dopamine synthesis capacity and expression profiles of 1110 genes enriched for trans-synaptic signaling, regulation of membrane potential, modulation of chemical synaptic transmission, brain development, synapse organization and regulation of neurotransmitter levels. These results elucidate the molecular and transcriptional basis of altered gray matter morphology and build linking between molecular, transcriptional and neuroimaging information facilitating an integrative understanding of OCD.