Mineralocorticoid receptor val carriers had heightened amygdala reactivity relative to iso homozygotes. Previous studies have linked the val allele to the loss of cortisol-related mineralocorticoid receptor function and heightened stress reactivity (20, 21, 24; but also see 25). Endogenous cortisol is associated with elevated amygdala reactivity (9, 10), and overexpression of the mineralocorticoid receptor in the amygdala reduces corticosterone release in rodents (19). The relatively potentiated amygdala reactivity in val carriers observed in our study may reflect reduced cortisol-related mineralocorticoid receptor function and heightened basal cortisol levels. The val allele may confer a constitutional profile similar to that observed in maltreated individuals (e.g., heightened basal HPA axis function, blunted cortisol upon awakening, and heightened stress-related endocrine and autonomic responses), and thus similar stress system mechanisms may underlie the relationship between the val allele and heightened amygdala reactivity to threat.
