A Caudate Pathway-level Transcriptomic Signature of Translational, Bioenergetic, and Proteostatic Programs in...

Obsessive-compulsive disorder (OCD) is linked to cortico-striato-thalamo-cortical circuit dysfunction, but molecular programs within striatal circuit nodes remain incompletely characterized. We tested whether translation, mitochondrial bioenergetics, and proteostasis show a coordinated transcriptomic signature in the OCD caudate. We reanalyzed postmortem caudate RNA-sequencing data from GSE262138 after retaining OCD cases and unaffected controls (OCD n = 27; control n = 85). Gene-level models adjusted for RNA integrity number and sex. Ranked gene statistics were used for pathway enrichment, module testing, expression-matched random-gene comparisons, sensitivity analyses, marker-score adjustment, and comparison with published OCD striatal literature. The caudate gene-level landscape showed a broad ranked-expression pattern. Pathway analysis identified recurrent lower expression of translation/ribosome, mitochondrial oxidative phosphorylation, electron-transport, and proteostasis-related terms across annotation systems. Translation/ribosome, mitochondrial/OXPHOS, and proteostasis modules showed lower average shifts relative to expression-matched random gene sets, and the direction remained consistent across sensitivity analyses. OCD caudate transcriptomic variation shows a pathway-level signature centered on translational, bioenergetic, and proteostatic programs. The results connect public postmortem caudate expression data with CSTC circuit biology and provide a focused molecular view of OCD-associated caudate dysfunction.