MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.
MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy.
复制标题
DOI：
10.1038/tp.2016.41
复制
发表时间：
2016-04-05
影响因子：
6.8
通讯作者：
Domschke K
中科院分区：
文献类型：
--
作者：
Ziegler C;Richter J;Mahr M;Gajewska A;Schiele MA;Gehrmann A;Schmidt B;Lesch KP;Lang T;Helbig-Lang S;Pauli P;Kircher T;Reif A;Rief W;Vossbeck-Elsebusch AN;Arolt V;Wittchen HU;Hamm AO;Deckert J;Domschke K
研究发现，惊恐障碍 (PD) 中单胺氧化酶 A (MAOA) 基因的甲基化等表观遗传特征会发生改变。假设表观遗传过程的时间可塑性是成功消除恐惧的机制，我们认为目前的心理治疗-表观遗传学研究首次研究了 PD 中基于暴露的认知行为治疗 (CBT) 过程中 MAOA 甲基化的变化。通过对从血细胞中提取的经亚硫酸氢钠处理的 DNA 进行直接测序，比较了 N=28 名女性白人 PD 患者（发现样本）和 N=28 名年龄和性别匹配的健康对照之间的 MAOA 甲基化。此外，在基线 (T0) 和 6 周 CBT (T1) 后，对发现样本中的 MAOA 甲基化进行了进一步分析，并与健康对照的等待时间平行，以及女性 PD 患者的独立样本 (N=20) 中的 MAOA 甲基化。患者的 MAOA 甲基化水平低于健康对照 (P<0.001)，基线 PD 严重程度与 MAOA 甲基化水平呈负相关 (P=0.01)。在发现样本中，随着 CBT 反应（恐慌发作次数；T0-T1：+3.37±2.17%），MAOA 甲基化增加至健康对照的水平，而无反应者的甲基化进一步下降（-2.00±1.28% P=0.001）。在复制样本中，MAOA 甲基化的增加与 CBT 后广场恐惧症状的减少相关（P=0.02-0.03）。目前的结果支持先前的证据，表明 MAOA 低甲基化作为 PD 风险标志物，并表明 MAOA 低甲基化作为 CBT 反应的潜在表观遗传相关性的可逆性。表观遗传特征作为心理治疗干预作用机制的新兴概念可能会促进表观遗传模式作为持久灭绝效应的生物标志物。
Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0–T1: +3.37±2.17%), while non-responders further decreased in methylation (−2.00±1.28% P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02–0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.