Monoamine oxidase A hypomethylation in obsessive-compulsive disorder - reversibility by successful psychotherapy?

BACKGROUND: Epigenetic markers such as DNA methylation of the monoamine oxidase A (MAOA) gene have previously been shown to be altered in anxiety- and stress-related disorders and to constitute a potential mechanism of action of psychotherapeutic interventions such as cognitive-behavioral therapy (CBT) in these disorders. The present study for the first time investigated MAOA methylation in patients with obsessive-compulsive disorder (OCD) applying a longitudinal psychotherapy-epigenetic approach. METHODS: The present sample comprised 14 unmedicated female patients with primary OCD and 14 age- and sex-matched healthy controls. MAOA promoter methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from whole blood before and after an 8-10-week semi-standardized, OCD-specific CBT. Clinical response was assessed by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). RESULTS: Significantly lower MAOA promoter methylation was discerned in OCD patients relative to healthy controls. Data was available for 12 OCD patients and 14 controls. Furthermore, following CBT clinical improvement, i.e. decreases in OCD symptoms as indicated by lower Y-BOCS scores, was found to be significantly correlated with increases in MAOA methylation levels in OCD patients (data available for N=7). CONCLUSIONS: The present pilot data suggest MAOA hypomethylation as a potential risk marker of OCD, and an increase in MAOA methylation levels as a possible mechanistic correlate of CBT response in OCD.