Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University of Würzburg, Würzburg, Germany.
Int J Neuropsychopharmacol. 2020 May 27;23(5):319-323. doi: 10.1093/ijnp/pyaa016.
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 in these disorders. The present study for the first time, to our knowledge, investigated MAOA methylation in patients with obsessive-compulsive disorder applying a longitudinal psychotherapy-epigenetic approach.
The present sample comprised 14 unmedicated female patients with primary obsessive-compulsive disorder 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- to 10-week semi-standardized, obsessive-compulsive disorder-specific cognitive behavioral therapy. Clinical response was assessed by means of the Yale-Brown Obsessive Compulsive Scale.
Significantly lower MAOA promoter methylation was discerned in obsessive-compulsive disorder patients relative to healthy controls. Data were available for 12 patients with obsessive-compulsive disorder and 14 controls. Furthermore, following cognitive behavioral therapy, clinical improvement, i.e., decreases in obsessive-compulsive disorder symptoms as indicated by lower scores on the Yale-Brown Obsessive Compulsive Scale was found to be significantly correlated with increases in MAOA methylation levels in patients (data available for n = 7).
The present pilot data suggest MAOA hypomethylation as a potential risk marker of obsessive-compulsive disorder and an increase in MAOA methylation levels as a possible mechanistic correlate of response to cognitive behavioral therapy in obsessive-compulsive disorder.
先前的研究表明，单胺氧化酶 A（MAOA）基因的 DNA 甲基化等表观遗传标记在焦虑和应激相关障碍中发生改变，并构成认知行为疗法等心理治疗干预在这些疾病中作用的潜在机制。本研究首次采用纵向心理治疗-表观遗传学方法，研究强迫症患者的 MAOA 甲基化。
本样本包括 14 名未经药物治疗的原发性强迫症女性患者和 14 名年龄和性别匹配的健康对照者。采用亚硫酸氢盐处理的全血 DNA 直接测序法分析 MAOA 启动子甲基化，在 8-10 周的半标准化、强迫症特异性认知行为治疗前后进行分析。采用耶鲁-布朗强迫症量表评估临床反应。
与健康对照组相比，强迫症患者的 MAOA 启动子甲基化明显降低。强迫症患者 n=12，健康对照组 n=14。此外，认知行为治疗后，临床改善，即耶鲁-布朗强迫症量表评分降低，提示强迫症症状改善，与患者 MAOA 甲基化水平升高显著相关（数据可用于 n=7）。
本研究初步数据表明 MAOA 低甲基化为强迫症的潜在风险标志物，MAOA 甲基化水平升高可能是强迫症认知行为治疗反应的机制相关因素。
