Transcriptome alterations are enriched for synapse-associated genes in the striatum of subjects with obsessive-compulsive disorder

Abstract Obsessive-compulsive disorder (OCD) is a chronic and severe psychiatric for which effective treatment options are limited. Structural functional neuroimaging studies have consistently implicated the orbitofrontal cortex (OFC) striatum in pathophysiology of disorder. Recent genetic evidence points to involvement components excitatory synapse etiology OCD. However, transcriptional alterations that could link risk known structural abnormalities remain mostly unknown. To assess potential changes OFC two striatal regions (caudate nucleus accumbens) OCD subjects relative unaffected comparison subjects, we sequenced messenger RNA transcripts from these brain regions. In joint analysis all three regions, 904 were differentially expressed between 7 versus 8 subjects. Region-specific analyses highlighted smaller number differences, concentrated caudate accumbens. Pathway showed enrichment genes involved synaptic signaling, with synapse-associated displaying lower expression Finally, estimated cell type fractions medium spiny neurons whereas vascular cells astrocyte higher tissue Together, data provide first unbiased examination both These encoded proteins more often than expected by chance, thus implicate as vulnerable molecular compartment