Commentary: Interaction of the ADRB2 Gene Polymorphism with Childhood Trauma in Predicting Adult Symptoms of Posttraumatic Stress Disorder

While posttraumatic stress disorder (PTSD) is relatively common among psychiatric conditions, it only emerges in a subpopulation of persons exposed to environmental trauma (1). Brain noradrenergic system dysfunction has been implicated in development of PTSD (2). However, unknown is the extent to which polymorphisms in brain noradrenergic system genes interact with childhood environmental trauma to alter resilience or vulnerability to developing PTSD in adulthood. Using a cohort of predominantly male military veterans and another with predominantly female civilians, Liberzon et al. found that individuals with a beta2-adrenergic receptor (ADRB2) gene variant and childhood trauma are at heightened risk for adult PTSD (3). Interestingly, ADRB2 polymorphism has also been associated with a risk for the development of chronic pain (4). Another ADRB2 gene variant was associated with resilience to adult PTSD symptoms (3). Collectively, these findings suggest that ADRB2 gene variants affecting brain noradrenergic system function interact with childhood adversity to alter vulnerability or resilience to development of PTSD. Replication of this research in large cohorts is needed as well as physiological confirmation of abnormal noradrenergic system function (3). Noradrenergic system dysfunction has also been implicated in increased susceptibility to stressinduced opioid use and craving in individuals with opioid use disorders (OUD) (5). Furthermore, PTSD frequently co-occurs with OUD (6, 7). Thus, research should prospectively investigate whether similar gene by childhood-adversity interactions heighten vulnerability to developing co-occurring PTSD and OUD. One limitation of this study is insufficient information to determine whether it accounts for epigenetic and associated brain vulnerability factors from such childhood trauma that may also predispose to developing PTSD. It is difficult to determine whether this study controlled for pertinent non-specific neurobiological factors indirectly impacting response to trauma in a particular person, independent of this gene by environmental-adversity interaction. It is also unclear whether altered expression of this gene is tangential/incidental to co-occurring critical brain development changes altering PTSD vulnerability.