At the cellular level, animal research suggests that stress may potentiate amygdala reactivity to threat by increasing calcium influx in basolateral amygdala neurons, thus increasing excitatory and reducing inhibitory neurotransmission (39). Human studies show that pharmacologically induced elevations of cortisol and norepinephrine together potentiate amygdala reactivity to threatening faces (40). However, pharmacologically administered hydrocortisone alone blunts amygdala reactivity, likely because of glucocorticoid-mediated negative feedback in the context of no other HPA axis activation (40, 41). We speculate that changes in HPA axis function as well as amygdala cytoarchitecture in people with a history of childhood emotional neglect may promote heightened amygdala reactivity to threat. This heightened reactivity may translate to increased vigilance and lay the groundwork for the development of stress-related psychopathologies such as mood and anxiety disorders. Consistent with this speculation, the association between stress and anxiety-related behavior in animals is abolished with the antagonism of excitatory N-methyl-d-aspartic acid neurotransmission in the amygdala (42).
