Our main goal in this study was to evaluate direct biological effects of the mineralocorticoid receptor iso/val polymorphism at the level of threat-related amygdala reactivity and to explore potential interactions between the mineralocorticoid receptor iso/val polymorphism and childhood emotional neglect in mediating variability in amygdala reactivity. To this end, 279 individuals in late childhood or early adolescence completed a widely used and well-characterizedblood-oxygen-level-dependent(BOLD) functional magnetic resonance imaging (fMRI) challenge paradigm that reliably elicits amygdala reactivity in both children and adults in normative and clinical populations (27, 28). Additionally, participants completed a questionnaire assessing childhood trauma exposure. From these data, we tested three primary hypotheses. First, based on evidence that emotional neglect and caregiver deprivation are associated with heightened amygdala reactivity to threat (6), we hypothesized that childhood emotional neglect would predict elevated threat-related amygdala reactivity. Second, because the val allele has been associated with lower cortisol-related mineralocorticoid receptor function and heightened HPA axis activity (22), we hypothesized that the val allele would be associated with elevated amygdala reactivity regardless of past emotional neglect history. Third, we predicted a genotype-by-emotional neglect
