Initial findings of striatum tripartite model in OCD brain samples based on transcriptome analysis

Area of Science:

• Neuroscience
• Psychiatry
• Genomics

Background:

• Obsessive-compulsive disorder (OCD) is a complex psychiatric condition.
• The cortico-striato-thalamic circuitry (CSTC) is implicated in OCD pathophysiology.
• Striatal subregions (putamen, caudate nucleus, accumbens nucleus) exhibit distinct roles.

Purpose of the Study:

• To compare transcriptomes of striatal subregions in OCD versus control cases.
• To identify region-specific biological processes contributing to OCD.
• To investigate the role of gene variants in OCD pathophysiology within specific striatal areas.

Main Methods:

• Postmortem brain tissue analysis of 3 striatal areas (putamen, caudate nucleus, accumbens nucleus).
• Transcriptome comparison between 6 OCD cases and 8 control cases.
• Analysis of gene expression and coexpression modules, considering known OCD-associated variants.

Main Results:

• Differential gene expression and biological processes identified across striatal subregions in OCD.
• Shared processes like neurotransmitter regulation and synaptic transmission between accumbens nucleus and putamen.
• Specific Gene Ontology terms related to cellular and synaptic responses identified between caudate nucleus and putamen.
• Striatal subregion specificity observed for differentially expressed genes and variants associated with OCD.

Conclusions:

• Transcriptional differences in striatal subregions contribute to OCD pathophysiology.
• The tripartite model of the striatum offers insights into OCD mechanisms.
• Findings support distinct roles for CSTC circuits in OCD at the transcriptional level.