Peripheral Blood Biomarkers Reveal Dysregulated Monoaminergic Pathways in Obsessive–Compulsive Disorder: A Transcriptional and Epigenetic Analysis

This study investigated the complexity of neurotransmitter-related gene regulation in peripheral blood mononuclear cells (PBMCs) of patients with obsessive-compulsive disorder (OCD), aiming to identify clinically relevant molecular markers. We analyzed three key genes: <i>SLC6A4</i> (serotonin transporter), <i>MAOB</i> (monoamine oxidase B, a dopamine-degrading enzyme), and <i>COMT</i> (catechol-O-methyltransferase, a dopamine/norepinephrine metabolizing enzyme). OCD patients exhibited significant downregulation of <i>SLC6A4</i> and <i>MAOB</i>, accompanied by upregulation of <i>MB-COMT</i>. The contrasting expression of <i>MAOB</i> and <i>MB-COMT</i> suggests a dysregulated compensatory mechanism in dopamine homeostasis, which contributes to clinical heterogeneity and variability in treatment for OCD. Epigenetic analysis revealed that downregulation of <i>SLC6A4</i> was associated with hypermethylation of the gene promoter, demonstrating the critical role of epigenetic mechanisms in neurotransmitter system dysregulation. Moreover, gene-gene correlations identified distinctive molecular expression patterns that reliably discriminated OCD patients from healthy individuals, proposing their potential as peripheral biomarkers. In conclusion, serotonergic and dopaminergic abnormalities characterize OCD, where epigenetic regulation contributes to gene dysregulation. The identified molecular signatures may explain the inefficiency of treatments and support biomarker-guided clinical approaches. Given that peripheral gene regulation and core neurotransmitter systems are similar, this study contributes to the biological picture of OCD, indicating the accuracy of diagnoses and treatments.