Abstract
Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Different striatal subregions belonging to the cortico-striato-thalamic circuitry (CSTC) play an important role in the pathophysiology of OCD. The transcriptomes of 3 separate striatal areas (putamen (PT), caudate nucleus (CN) and accumbens nucleus (NAC)) from postmortem brain tissue were compared between 6 OCD and 8 control cases. In addition to network connectivity deregulation, different biological processes are specific to each striatum region according to the tripartite model of the striatum and contribute in various ways to OCD pathophysiology. Specifically, regulation of neurotransmitter levels and presynaptic processes involved in chemical synaptic transmission were shared between NAC and PT. The Gene Ontology terms cellular response to chemical stimulus, response to external stimulus, response to organic substance, regulation of synaptic plasticity, and modulation of synaptic transmission were shared between CN and PT. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study also suggest striatum subregion specificity. At the transcriptional level, our study supports differences in the 3 circuit CSTC model associated with OCD.
Highlights
Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions
We showed that different differentially expressed genes (DEGs) as well as network connectivity deregulation were specific for each striatum region (CN, NAC and PT) by comparing OCD cases and controls
Comparisons between areas showed that Caudate Nucleus (CN) has a larger number of DEGs and that they have a greater overlap with DEGs from PT
Summary
Obsessive-compulsive disorder (OCD) is a psychiatric disorder characterized by obsessions and/or compulsions. Most genes harboring common and/or rare variants previously associated with OCD that were differentially expressed or part of a least preserved coexpression module in our study suggest striatum subregion specificity. Based on Gene Ontology (GO) enrichment analysis and gene network analysis performed in the majority of the above studies, glutamate signaling, synaptic connectivity, and cortico-striato-thalamic circuitry (CSTC) are important in OCD pathophysiology. In addition to symptomatic evidence involving different striatum areas associated with OCD, the striatum tripartite model and connectivity were defined by gene expression[18]. This validation of these small circuits has been demonstrated by delineating distinct striatum subregions based on connectivity using diffusion-weighted imaging (DWI) data. In differentially expressed genes (DEGs) and coexpression module analyses, the authors found enrichment for interneuron signaling, neuronal catabolism, microglia signaling and astrocyte metabolism, but they analyzed the CN and PT together[19]
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