Keers Robert, Coleman Jonathan R I, Lester Kathryn J, Roberts Susanna, Breen Gerome, Thastum Mikael, Bögels Susan, Schneider Silvia, Heiervang Einar, Meiser-Stedman Richard, Nauta Maaike, Creswell Cathy, Thirlwall Kerstin, Rapee Ronald M, Hudson Jennifer L, Lewis Cathryn, Plomin Robert, Eley Thalia C
Department of Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
Psychother Psychosom. 2016;85(3):146-58. doi: 10.1159/000444023. Epub 2016 Apr 5.
The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders.
We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders.
The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively).
Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.
差异易感性假说表明，某些基因变异会调节消极和积极环境对心理健康的影响，因此可能是心理治疗反应的重要预测指标。然而，迄今为止，此类变异的识别仅限于预先选定的候选基因。在本研究中，我们将差异易感性假说从候选基因方法扩展到全基因组方法，以检验环境敏感性多基因评分是否能预测焦虑症儿童对认知行为疗法（CBT）的反应。
我们使用一种新方法识别与环境敏感性相关的变异，该方法将1026对同卵双胞胎情感问题的配对内变异性作为配对基因型的函数进行检验。我们基于全基因组研究结果创建了一个环境敏感性多基因评分，并在1406名儿童中测试该评分作为养育方式对情感问题的调节因素，以及在973名焦虑症儿童中测试其作为个体、团体和简短家长主导的CBT治疗反应的调节因素。
多基因评分显著调节了养育方式对情感问题的影响以及治疗效果。高分个体对个体CBT的反应明显优于团体CBT或简短家长主导的CBT（缓解率分别为70.9%、55.5%和41.6%）。
在成功复制之前，我们的结果应被视为探索性的。然而，如果得到复制，结果表明环境敏感性最高的个体在不利环境中更易出现情感问题，但也能从最强化的治疗类型中获益更多。
