Exploring genetic and epigenetic markers for predicting or monitoring response to cognitive-behavioral therapy in obsessive-compulsive disorder: A systematic review

Growing evidence has identified potential biomarkers of cognitive-behavioural therapy (CBT) efficacy in obsessive-compulsive disorder (OCD). Genetic and epigenetic mechanisms (e.g., polymorphisms, DNA methylation) contribute to OCD pathogenesis and CBT response variability, establishing them as a key research focus. To evaluate their associations with CBT outcomes in OCD, we conducted a systematic review of PubMed, Web of Science, CNKI, and Cochrane Library (from inception to January 2025), identifying eight studies that met rigorous inclusion criteria. The identified predictors included: (1) Genetic polymorphisms (BDNF); (2) Epigenetic modifications (DNA methylation of MAOA, SLC6A4, OXTR, PIWIL1, MIR886, PLEKHA1, KCNQ1, TRPM8, HEBP1, HTR7P1, MAPK8IP3, ENAH, RABGGTB (SNORD45C), MYEF2, GALK2, CEP192, and UIMC1). These markers may influence neural plasticity, neurotransmitter regulation, and related processes, providing molecular substrates for the observed treatment effects. Converging evidence suggests that distinct neurocognitive mechanisms may mediate CBT efficacy in OCD, particularly fear extinction learning and goal-directed behaviors (GDBs), which we analyze mechanistically. Future studies should integrate polygenic risk scores (PRS) with functional neuroimaging to dissect individual variability in CBT response, mainly through cortico-striato-thalamo-cortical (CSTC) circuit profiling. To our knowledge, this is the first systematic review synthesizing genetic and epigenetic predictors of CBT response in OCD; these findings provide compelling evidence for biomarkers for CBT personalization in OCD, advancing a novel precision psychiatry framework.