Heterogeneity in HPA axis dysregulation and serotonergic vulnerability to depression
Heterogeneity in HPA axis dysregulation and serotonergic vulnerability to depression
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DOI：
10.1016/j.psyneuen.2016.11.016
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发表时间：
2017-03-01
影响因子：
3.7
通讯作者：
Ryan, Joanne
中科院分区：
文献类型：
--
作者：
Ancelin, Marie-Laure;Scali, Jacqueline;Ryan, Joanne
血清素转运蛋白 (5-HTTLPR) 基因的变异可能会影响与逆境相关的抑郁症风险以及皮质醇应激反应性，尽管效果并不总是一致。尚无研究探讨压力环境和促皮质轴功能障碍对抑郁症的影响（作为 5-HTTLPR 的函数）。这项基于人群的研究包括 334 名 65 岁及以上的受试者。除了 5-HTTLPR 和 rs25531 基因分型以及每日皮质醇测量之外，还测量了诊断（根据 DSM-IV 的重性抑郁）和症状（阈下抑郁）水平的抑郁程度。对于具有 SS 基因型的参与者来说，早晨皮质醇水平较高与抑郁症风险增加 4 倍相关。在 LL 参与者中，夜间皮质醇水平和最近的压力事件都会增加抑郁风险，尽管在多变量调整后只有后者仍然显着。相反，SL 个体在皮质醇和近期压力方面似乎对抑郁症有一定的抵抗力。这些发现表明，5-HTTLPR 遗传变异似乎影响压力相关因素与晚年抑郁症之间的关联，尽管基因-环境相互作用未能达到统计显着水平。短等位基因纯合子的参与者似乎具有与皮质醇相关的神经内分泌对抑郁症的脆弱性，而长等位基因纯合子在抑郁风险方面对压力事件反应更强烈。 (C) 2016 年作者。由 Elsevier Ltd 出版。这是一篇遵循 CC BY-NC-ND 许可证 (http://creativecommons.org/licenses/by-nc-nd/4.0/) 的开放获取文章。
Variability in the serotonin transporter (5-HTTLPR) gene can influence the risk of depression associated with adversity, as well as cortisol stress reactivity, although not consistently. No study has examined the impact of both a stressful environment and corticotropic-axis dysfunction on depression, as a function of 5-HTTLPR. This population-based study included 334 subjects aged 65 and older. Depression was measured at both diagnostic (major depression according to DSM-IV) and symptomatic (subthreshold depression) levels of caseness, in addition to 5-HTTLPR and rs25531 genotyping and diurnal cortisol measures. For participants with the SS genotype, higher morning cortisol levels were associated with a 4-fold increased risk of depression. Among LL participants, both evening cortisol levels and recent stressful events increased depression risk, although only the latter remained significant after multivariable adjustment. Conversely, SL individuals appeared somewhat resilient to depression in terms of cortisol and recent stress. These findings indicate that 5-HTTLPR genetic variability appears to influence the association between stress-related factors and late-life depression, although the gene-environment interactions failed to reach statistical significance levels. Participants homozygous for the short allele appeared to have a cortisol-related neuroendocrine vulnerability to depression, while long allele homozygotes were more reactive to stressful events in terms of depression risk. (C) 2016 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).