Sheikh Haroon I, Kryski Katie R, Kotelnikova Yuliya, Hayden Elizabeth P, Singh Shiva M
Molecular Genetics Unit, Department of Biology, Western University, London, Ontario, Canada.
Department of Psychology, Brain & Mind Institute, Western University, London, Ontario, Canada.
Neurosci Lett. 2017 Oct 17;659:86-91. doi: 10.1016/j.neulet.2017.08.060. Epub 2017 Aug 30.
Individual differences in hypothalamus-pituitary-adrenal (HPA) axis reactivity to stress (measured via salivary cortisol) have been widely implicated in the etiology of internalizing problems such as depression and anxiety. Literature suggests that stress during early childhood is an important source of contextual risk although its effects may be moderated by polymorphisms of neurotransmitter genes. The COMT val158met is one such polymorphism, and literature documents its link to internalizing problems. To extend these findings, and to better understand the role of this polymorphism in developmental risk, we investigated links between the val158met polymorphism and early-age cortisol response. Additionally, we investigated whether cortisol reactivity mediated the link between COMT and emerging internalizing symptoms. The study was conducted in a community sample of 409 preschoolers. Saliva samples were collected pre-stress task (baseline) and every 10min post-stress task for one-hour to asses cortisol response. Child anxious and depressive symptoms were tabulated based on parent-reports. Markers of early childhood stress included marital discord, socio-economic status and the UCLA Life Stress Interview. Findings indicated that the val158met polymorphism is associated with childhood cortisol response (p<0.05). A gene-environment interaction between val158met and life stress also predicted child anxiety symptoms (p<0.01). Finally, cortisol response mediated the main-effect of val158met on child anxiety symptoms (pathway ps<0.05). Analyses suggest that COMT val158met moderates the influence of early life stress on preschool-age symptoms of anxiety. Additionally, cortisol reactivity acts as a mechanistic mediator of the main-effect of COMT genotype on child anxious symptoms.
下丘脑 - 垂体 - 肾上腺（HPA）轴对应激的反应性个体差异（通过唾液皮质醇测量）与诸如抑郁和焦虑等内化问题的病因广泛相关。文献表明，幼儿期的应激是情境风险的重要来源，尽管其影响可能会受到神经递质基因多态性的调节。儿茶酚 - O - 甲基转移酶（COMT）val158met就是这样一种多态性，文献记载了它与内化问题的联系。为了扩展这些发现，并更好地理解这种多态性在发育风险中的作用，我们研究了val158met多态性与早期皮质醇反应之间的联系。此外，我们研究了皮质醇反应性是否介导了COMT与新出现的内化症状之间的联系。该研究在409名学龄前儿童的社区样本中进行。在应激任务前（基线）和应激任务后每10分钟收集一次唾液样本，持续一小时以评估皮质醇反应。根据家长报告统计儿童的焦虑和抑郁症状。幼儿期应激的指标包括婚姻不和、社会经济地位和加州大学洛杉矶分校生活应激访谈。研究结果表明，val158met多态性与儿童皮质醇反应相关（p<0.05）。val158met与生活应激之间的基因 - 环境相互作用也预测了儿童焦虑症状（p<0.01）。最后，皮质醇反应介导了val158met对儿童焦虑症状的主效应（路径p<0.05）。分析表明，COMT val158met调节了早期生活应激对学龄前焦虑症状的影响。此外，皮质醇反应性是COMT基因型对儿童焦虑症状主效应的机制介导因素。
