Acute stress modulates genotype effects on amygdala processing in humans

Probing gene-environment interactions that affect neural processing is crucial for understanding individual differences in behavior and disease vulnerability. Here, we tested whether the current environmental context, which affects the acute brain state, modulates genotype effects on brain function in humans. We manipulated the context by inducing acute psychological stress, which increases nor-adrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala using two MRI techniques: conventional blood oxygen level-dependent functional MRI and arterial spin labeling. We showed that only carriers of a common functional deletion in ADRA2B, the gene coding for the alpha 2b-adrenoreceptor, displayed increased phasic amygdala responses under stress. Tonic activity, reflecting the perfusion of the amygdala, increased independently of genotype after stress induction. Thus, when tonic activity was heightened by stress, only deletion carriers showed increased amygdala responses. Our results demonstrate that genetic effects on brain operations can be state dependent, such that they only become apparent under specific, often environmentally controlled, conditions.