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 α2b-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. ADRA2B | gene-environment interactions | fMRI | imaging genetics

Genetic variation of the α2b‐adrenoceptor affects neural correlates of successful emotional memory formation

“…Given that the propranolol reaches the brain and blocks the subsequent memory effect for emotional stimuli in the amygdala, presumably via a reduction of noradrenergic signaling [Liang et al, 1986], our results are in line with the idea that deletion carriers have higher noradrenaline availability compared to nondeletion carriers [Cousijn et al, 2010;de Quervain et al, 2007]. In this study, we observed a larger contribution of the amygdala to successful memory formation in deletion carriers.…”

“…Additionally, Cousijn and colleagues [2010] used acute psychological stress, which increases noradrenergic activity, and probed its effect on tonic activity and phasic responses in the amygdala. The authors found that only deletion carriers displayed increased phasic amygdala responses under stress while amygdala perfusion, reflecting tonic activity, increased independently of genotype after stress induction [Cousijn et al, 2010]. Hence, there is initial neural evidence that the deletion variant in the ADRA2B gene may influence emotional memory via altered amygdala functioning.…”

Genetic Variations of α2-Adrenergic Receptors Illuminate the Diversity of Receptor Functions

“…Both of these studies collapsed heterozygous and homozygous carriers of the deletion into a single group, suggesting that just one mutant allele can result in a phenotype. An additional independent study, also using an fMRI approach in health volunteers, discovered that deletion carriers exhibited enhanced amygdala activity during an emotional memory task specifically following exposure to acute stress (Cousjin et al, 2010). This last piece 8.…”

The ‘affect tagging and consolidation’ (ATaC) model of depression vulnerability

“…Finally, as previously mentioned this review has focused primarily on the influence of the 5-HT system and the 5-HTTLPR on functional amygdala activity and depression vulnerability. However, we acknowledge the importance of genes which influence other monoamine systems such as ADRA2B and COMT in modulating affective amygdala function, emotional memory, and potentially depression vulnerability (Cousijn et al, 2010;Lonsdorf et al, 2011;Naudts, Azevedo, David, van Heeringen, & Gibbs, 2012;Shen et al, 2014;Todd, Palombo, Levine, & Anderson, 2011).…”

“…Evidence suggests that affective reactivity in the amygdala may be influenced by several monoamine systems, including serotonin (5-HT), norepinephrine (NE), and dopamine (DA; Costafreda et al, 2013;Cousijn et al, 2010;Dannlowski et al, 2010;Delaveau et al, 2009;Rasch et al, 2009). Initially, a simple lack of monoamines was thought to cause depressive symptoms, however the role of monoamines in MDD has been shown to be much more complex than this (Delgado, 2000;Hirschfeld, 2000).…”