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基于全基因组表达谱分析的焦虑障碍暴露疗法的反应

Genome-wide expression and response to exposure-based psychological therapy for anxiety disorders.

机构信息

King's College London, Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, London, UK.

National Institute for Health Research Biomedical Research Centre, South London and Maudsley National Health Service Trust, London, UK.

出版信息

Transl Psychiatry. 2017 Aug 29;7(8):e1219. doi: 10.1038/tp.2017.177.

Abstract

Exposure-based psychological treatments for anxiety have high efficacy. However, a substantial proportion of patients do not respond to therapy. Research examining the potential biological underpinnings of therapy response is still in its infancy, and most studies have focussed on candidate genes. To our knowledge, this study represents the first investigation of genome-wide expression profiles with respect to treatment outcome. Participants (n=102) with panic disorder or specific phobia received exposure-based cognitive behavioural therapy. Treatment outcome was defined as percentage reduction from baseline in clinician-rated severity of their primary anxiety diagnosis at post treatment and 6 month follow-up. Gene expression was determined from whole blood samples at three time points using the Illumina HT-12v4 BeadChip microarray. Linear regression models tested the association between treatment outcome and changes in gene expression from pre-treatment to post treatment, and pre-treatment to follow-up. Network analysis was conducted using weighted gene co-expression network analysis, and change in the detected modules from pre-treatment to post treatment and follow-up was tested for association with treatment outcome. No changes in gene expression were significantly associated with treatment outcomes when correcting for multiple testing (q<0.05), although a small number of genes showed a suggestive association with treatment outcome (q<0.5, n=20). Network analysis showed no association between treatment outcome and change in gene expression for any module. We report suggestive evidence for the role of a small number of genes in treatment outcome. Although preliminary, these findings contribute to a growing body of research suggesting that response to psychological therapies may be associated with changes at a biological level.

摘要

基于暴露的心理治疗对焦虑症具有很高的疗效。然而,相当一部分患者对治疗没有反应。研究检查治疗反应的潜在生物学基础仍处于起步阶段,大多数研究都集中在候选基因上。据我们所知,这项研究代表了首次针对治疗结果进行的全基因组表达谱研究。参与者(n=102)患有恐慌症或特定恐惧症,接受基于暴露的认知行为治疗。治疗结果定义为治疗后和 6 个月随访时临床医生评定的主要焦虑诊断严重程度相对于基线的百分比降低。使用 Illumina HT-12v4 BeadChip 微阵列,在三个时间点从全血样本中确定基因表达。线性回归模型测试了治疗结果与从治疗前到治疗后以及从治疗前到随访期间基因表达变化之间的关联。使用加权基因共表达网络分析进行网络分析,并测试检测到的模块从治疗前到治疗后和随访期间的变化与治疗结果的关联。尽管有少数基因与治疗结果有提示性关联(q<0.5,n=20),但在进行多次检验校正后,没有基因表达变化与治疗结果显著相关(q<0.05)。网络分析显示,治疗结果与任何模块的基因表达变化之间均无关联。我们报告了少数基因在治疗结果中的作用的初步证据。尽管这些发现还很初步,但它们有助于越来越多的研究表明,对心理治疗的反应可能与生物学水平的变化有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c43a/5611743/3a0cb8bf6c41/tp2017177f1.jpg

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