HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS.
HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS.
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DOI：
10.1002/da.22430
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发表时间：
2015-12
影响因子：
7.4
通讯作者：
Wong CC
中科院分区：
文献类型：
--
作者：
Roberts S;Keers R;Lester KJ;Coleman JR;Breen G;Arendt K;Blatter-Meunier J;Cooper P;Creswell C;Fjermestad K;Havik OE;Herren C;Hogendoorn SM;Hudson JL;Krause K;Lyneham HJ;Morris T;Nauta M;Rapee RM;Rey Y;Schneider S;Schneider SC;Silverman WK;Thastum M;Thirlwall K;Waite P;Eley TC;Wong CC
下丘脑-垂体-肾上腺（HPA）轴功能与应激相关精神病诊断的发展和对不良生活经历的反应有关。本研究旨在探讨HPA轴的遗传学和表观遗传学与认知行为治疗（CBT）反应的关系。患有焦虑症的儿童被招募到基因治疗项目（GxT，N = 1，152）。分析FKBP 5和GR的多态性与CBT反应的相关性。在CBT之前和之后，在一个子集（n = 98）中测量FKBP 5和GR启动子区域的DNA甲基化百分比。采用线性混合效应模型研究基因型、DNA甲基化和原发性焦虑症严重程度变化（治疗反应）之间的关系。治疗反应与FKBP 5和GR多态性或治疗前DNA甲基化百分比无关。然而，FKBP 5 DNA甲基化的变化名义上与治疗反应显著相关。严重程度降低最多的参与者在治疗期间DNA甲基化百分比降低，而严重程度降低很少/没有降低的参与者DNA甲基化百分比增加。这种效应是由具有一个或多个FKBP 5风险等位基因的人驱动的，在没有FKBP 5风险等位基因的人中没有观察到相关性。GR甲基化和反应之间没有显著的关联。FKBP 5甲基化的等位基因特异性变化与治疗反应相关。这是迄今为止调查HPA轴相关基因在心理治疗中的作用的最大研究。此外，这是第一项证明DNA甲基化变化可能以基因型依赖性方式与心理治疗反应相关的研究。
Hypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress‐related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Allele‐specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype‐dependent manner.