Epigenome-wide analysis identifies methylome profiles linked to obsessive-compulsive disorder, disease severity, and treatment response

Obsessive-compulsive disorder (OCD) is a mental disorder affecting 2-3% of the general population. The dynamic nature of epigenetics provides a unique opportunity to find biomarkers of OCD symptoms, clinical progression, and treatment response. Consequently, we analyzed a case-control study on Illumina Methylation EPIC BeadChip from 185 OCD patients and 199 controls. Patients and controls were assessed by trained therapists using the Structured Clinical Interview for DSM-IV. We identified 12 CpGs capable of classifying OCD patients and predicting symptom severity. These CpGs are enriched withthe sweet-compulsive brain hypothesis, which proposes that OCD patients may have impaired insulin signaling sensitivity due to abnormal dopaminergic transmission in the striatum. Three of the twelve CpG signals were replicated in an independent study reported in the Han Chinese population. Our findings support the role of epigenetic mechanisms in OCD and may help pave the way for biologically-informed and individualized treatment options.