Acute stress modulates genotype effects on amygdala processing in humans

Abstract

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 noradrenergic 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 alpha2b-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.

Fig. 1.

Overview and timeline of the experimental design. All participants went through both conditions. For half of the participants the first part of the experiment (Upper) consisted of the stress condition, whereas for the other half the first part consisted of the neutral condition. Preparation took place outside the scanner. Between the second and third movie n-back data were acquired, which are not reported here. The numbers below the movies and tasks indicate the time in minutes. P, PANAS; S, saliva sampling. Acquisition of each PANAS and each saliva sample took 5 min, thereby causing a 20-min gap between conditions.

Fig. 2.

The influence of the common deletion in ADRA2B on amygdala responses is modulated by acute stress. (A) Significant interaction between ADRA2B genotype and acute stress in the right amygdala. (B) Larger conventional fMRI responses in deletion carriers than nondeletion carriers in the acute stress condition. The figures show the statistical comparisons (P < 0.005 uncorrected for visualization purposes) superimposed on a single-subject T1-weighted image (y = 0).

Fig. 3.

The influence of acute stress and the common deletion in ADRA2B on amygdala perfusion and amygdala responses. Shown is the combination of tonic amygdala activity (CASL fMRI) and phasic amygdala responses (BOLD fMRI). (A) Tonic activity: amygdala perfusion was higher in the stress than control condition, and this effect was not significantly different between ADRA2B genotypes. (B) Phasic responses: deletion carriers were able to increase amygdala responses in both the stress and neutral condition despite the differences in perfusion, whereas nondeletion carriers only increased amygdala activity during the neutral condition. a.u., arbitrary units.