We examined how a functional genetic polymorphism affecting HPA axis function and a history of childhood emotional neglect independently and interactively influence amygdala reactivity to threatening stimuli. Three primary findings emerged. First, extending recent research linking extreme forms of emotional neglect (e.g., institutional rearing) to heightened threat-related amygdala reactivity (4, 6), we observed a similar pattern with self-reported emotional neglect in a community sample. Second, we found that the val allele was associated with heightened threat-related amygdala reactivity (however, this effect fell short of significance when we included ancestry-informative principal components but remained significant in the Caucasian-only subsample; see the online data supplement). This effect is consistent with evidence that the val allele of a common mineralocorticoid receptor iso/val polymorphism confers heightened neuroendocrine and autonomic responses to stressors (20, 22, 24). Third, we observed an interaction between the mineralocorticoid receptor genotype and a history of childhood emotional neglect such that a positive association between emotional neglect and threat-related amygdala reactivity was observed only in iso homozygotes, and val carriers had heightened amygdala reactivity relative to iso homozygotes only at relatively low levels of previous childhood emotional neglect.
