Mineralocorticoid Receptor Iso/Val (rs5522) Genotype Moderates the Association Between Previous Childhood Emotional Neglect and Amygdala Reactivity
Mineralocorticoid Receptor Iso/Val (rs5522) Genotype Moderates the Association Between Previous Childhood Emotional Neglect and Amygdala Reactivity
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DOI：
10.1176/appi.ajp.2011.11060855
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发表时间：
2012-05-01
影响因子：
17.7
通讯作者：
Hariri, Ahmad R.
中科院分区：
文献类型：
--
作者：
Bogdan, Ryan;Williamson, Douglas E.;Hariri, Ahmad R.
目的：杏仁核对威胁性刺激的反应尤其强烈，其反应程度预示着抑郁和焦虑情绪的个体差异。新的研究表明，童年时期的情绪疏忽以及高皮质醇血症可能会导致与威胁相关的杏仁核反应性增强。这增加了影响下丘脑-垂体-肾上腺(HPA)轴功能的基因变异导致杏仁核反应性个体差异的可能性，这既是独立的，也是儿童情绪忽视的函数。方法：本研究评估了影响HPA轴功能的功能性遗传变异--盐皮质激素受体等位基因/Val多态(Rs5522)是否影响儿童后期和青春期早期279人的威胁相关杏仁核反应性。这项研究还探索了该基因对杏仁核反应性的影响程度取决于儿童既往的情感忽视。结果：儿童以前的情感忽视和Val等位基因与杏仁核更强的反应性相关。此外，还观察到了显著的情感忽视交互作用，Val等位基因携带者杏仁核更强的反应性与儿童既往的情感忽视无关，而同基因纯合子的更大反应性仅在情感忽视增加的历史背景下才被揭示。在先前相对较低的情绪忽视水平下，Val携带者的杏仁核反应性相对同基因纯合子更高。结论：这些结果表明，相对较高的Mygdala反应性可能代表了一种生物学机制，通过这种机制，童年逆境和HPA轴对应激的功能遗传变异可能介导了精神病理的风险。
Objective: The amygdala is especially reactive to threatening stimuli, and the degree of reactivity predicts individual differences in the expression of depression and anxiety. Emerging research suggests that emotional neglect during childhood as well as hypercortisolemia may lead to heightened threat-related amygdala reactivity. This raises the possibility that genetic variation affecting hypothalamic-pituitary-adrenal (HPA) axis function contributes to individual differences in amygdala reactivity, both independently and as a function of childhood emotional neglect.Method: This study assessed whether the mineralocorticoid receptor iso/val polymorphism (rs5522), a functional genetic variant affecting HPA axis function, influenced threat-related amygdala reactivity in 279 individuals in late childhood and early adolescence. The study also explored the extent to which any effects of the genotype on amygdala reactivity were contingent upon previous childhood emotional neglect.Results: Prior childhood emotional neglect and the val allele were associated with greater amygdala reactivity. Moreover, a significant genotype-by-emotional neglect interaction was observed whereby greater amygdala reactivity in val allele carriers was independent of previous childhood emotional neglect, while greater reactivity in iso homozygotes was revealed only in the context of a history of elevated emotional neglect. At relatively low levels of previous emotional neglect, val carriers had heightened amygdala reactivity relative to iso homozygotes.Conclusions: These results suggest that relatively greater a mygdala reactivity may represent a biological mechanism through which childhood adversity and functional genetic variation in HPA axis responsiveness to stress may mediate risk for psychopathology.