A genetic variation of the noradrenergic system is related to differential amygdala activation during encoding of emotional memories

Abstract

Emotionally arousing events are typically well remembered, but there is a large interindividual variability for this phenomenon. We have recently shown that a functional deletion variant of ADRA2B, the gene encoding the ␣2b-adrenergic receptor, is related to enhanced emotional memory in healthy humans and enhanced traumatic memory in war victims. Here, we investigated the neural mechanisms of this effect in healthy participants by using fMRI. Carriers of the ADRA2B deletion variant exhibited increased activation of the amygdala during encoding of photographs with negative emotional valence compared with noncarriers of the deletion. Additionally, functional connectivity between amygdala and insula was significantly stronger in deletion carriers. The present findings indicate that the ADRA2B deletion variant is related to increased responsivity and connectivity of brain regions implicated in emotional memory.ADRA2B ͉ fMRI ͉ polymorphism ͉ imaging genetics E nhanced memory for emotionally arousing events is a highly adaptive phenomenon, which helps us to remember both dangerous and favorable situations (1). Under certain conditions, however, this mechanism can also lead to intrusive and persistent traumatic memories of an extremely aversive event, thereby contributing to the development and symptoms of posttraumatic stress disorder (PTSD) (2, 3). Elucidating the mechanisms of emotional memory formation thus represents an important aim of modern neuroscience not only in terms of better understanding basic mnemonic processes, but also with regard to the clinical relevance (4, 5).Studies in rodents have indicated that the amygdala is critically involved in mediating the memory-enhancing effect of emotional arousal (6-8). Specifically, emotional arousal leads to a release of norepinephrine (NE) within the amygdala (9), and it has been shown that such amygdala activation strengthens the storage of many different kinds of information via its widespread network of efferent projections to other brain regions (10). Several human studies support this notion by showing that a pharmacologically induced increase of central noradrenergic transmission enhances memory performance (11-13), whereas a pharmacological blockade of noradrenergic transmission abolishes the enhancement of memory for emotional information and prevents enhanced amygdala activation in response to emotional stimuli (14,15).Recently, we reported that carriers of a functionally relevant deletion variant of ADRA2B, the gene encoding the ␣2b-adrenoreceptor, exhibit enhanced memory for emotional vs. neutral pictures compared with noncarriers (16). In that study, 435 participants were presented with neutral and emotional pictures taken from the international affective picture system (IAPS) (17). Delayed free recall was tested after 10 min, during which participants performed on a working memory task. The finding of increased emotional memory in deletion carriers of ADRA2B was followed up in 202 survivors of the Rwandan civil war who had experienced highly aversive ...

Acute stress modulates genotype effects on amygdala processing in humans

“…Furthermore, this finding indicates that carriers of this deletion are more strongly affected by stressful events. It has been shown that carriers of the ADRA2B deletion display increased amygdala activity while encoding arousing negative pictures, but not when encoding less-arousing positive pictures (25). This suggests that the neural effects of this genotype are dependent on arousal.…”

The neurogenetics of remembering emotions past

“…Moreover, trauma survivors with the ADRA2B deletion variant are more likely to reexperience traumatic events (6). Following up on these findings, the results reported by Rasch et al (2) are the first to tie the deletion variant of the gene to patterns of amygdala activation during the encoding of emotional memories. Across all participants, the most arousing images were most remembered 10 min later in a subsequent free recall task.…”

“…Further, why are some of us more likely to remember emotional memories with Proustian vividness than others or more likely to relive traumatic events? Echoing Proust's thesis that one's emotional memories are closer to the heart than to the mind, a study in this issue of PNAS by Rasch et al (2) suggests that individual differences in the ADRA2B gene that codes the ␣2B adrenoreceptor, which plays an important role in vasoconstriction and blood pressure regulation, is also related to brain activation patterns underlying heightened emotional recall.…”

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

“…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).…”