Although the etiology of OCD remains unknown, convergent evidence suggests disruptions in critical components of cortico-striatal glutamatergic synapses7,21,22,36,37,45. However, no comprehensive analysis of the OCD transcriptome has been performed simultaneously in tissue from OFC and striatum, the most commonly identified regions with functional and structural alterations in neuroimaging studies31,46–50. We therefore examined the transcriptome in two orbitofrontal (medial, lateral) and two striatal (caudate, nucleus accumbens) brain regions in subjects with OCD and unaffected comparison subjects. We first looked at global differential expression in all regions jointly and identified 904 transcripts that were differentially expressed as a function of OCD diagnosis (Fig. 1A, left). Interestingly, most DEG were found in the caudate and nucleus accumbens (Fig. 1A, right) and not in OFC (Fig. S3). Gene set enrichment and hierarchical clustering of all differentially expressed transcripts identified a hub of pathways involved in synaptic neurotransmission and associated with the glutamatergic synapse (Fig. 2). Together, these data further support the involvement of cortical and striatal glutamatergic synaptic dysfunction in OCD pathogenesis. Using our global DEG data, we also estimated broad cell type representation
