Laboratory of NeuroGenetics, Department of Psychology and Neuroscience, and Institute for Genome Sciences and Policy, Duke University, Durham, NC, USA.
Am J Psychiatry. 2012 May;169(5):515-22. doi: 10.1176/appi.ajp.2011.11060855.
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.
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.
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.
These results suggest that relatively greater amygdala 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.
杏仁核对威胁性刺激特别敏感，其反应程度可预测抑郁和焦虑症状的个体差异。新兴研究表明，儿童时期的情感忽视以及皮质醇过多可能导致与威胁相关的杏仁核反应性增强。这就提出了一种可能性，即影响下丘脑-垂体-肾上腺（HPA）轴功能的遗传变异可能导致杏仁核反应性的个体差异，无论是独立的还是作为儿童时期情感忽视的一种功能。
本研究评估了矿物质皮质激素受体同工酶/变体多态性（rs5522），这是一种影响 HPA 轴功能的功能性遗传变异，是否会影响 279 名处于童年后期和青春期早期的个体与威胁相关的杏仁核反应性。该研究还探讨了基因型对杏仁核反应性的影响在多大程度上取决于先前的儿童期情感忽视。
先前的儿童期情感忽视和变体等位基因与更大的杏仁核反应性相关。此外，观察到基因型与情感忽视的显著交互作用，即变体等位基因携带者的杏仁核反应性增加与先前的儿童期情感忽视无关，而同工酶纯合子的反应性增加仅在经历过情感忽视升高的情况下才会显现。在先前情感忽视程度相对较低的情况下，变体携带者的杏仁核反应性相对于同工酶纯合子升高。
这些结果表明，相对较大的杏仁核反应性可能代表了一种生物学机制，通过该机制，儿童时期的逆境和 HPA 轴对压力的反应性的功能性遗传变异可能会影响精神病理学的风险。
