Hpa Axis Genetic Variation and Life Stress Influences on Functional Connectivity in Resting State Networks

Abstract

Stressful or traumatic experiences are a key risk factor for developing psychopathology, primarily through the impact that chronic stress has on hypothalamic-pituitary-adrenal (HPA) axis functioning. The HPA axis regulates the stress response but can become dysregulated with chronic activation and impact brain functioning. In addition to environmental stressors, genetic variation in genes in the HPA axis appear to influence HPA axis functioning and is also related to disruption in brain functioning, particularly in the context of high life stress. The current study focused on examining potential mechanisms through which trauma and stress interacts with HPA axis genes to impact key networks involved in emotional processing and regulation that are disrupted in stress-related psychopathology (i.e. depression and anxiety). I found that individuals with high cumulative genetic risk in the HPA axis showed weaker functional coupling between the amygdala and visual cortices as number of traumatic experiences increased. I found no evidence that genetic variance in HPA axis-related genes was associated with altered connectivity in the default mode network or salience network in the context of environmental stress. The current findings provide evidence that environmental factors interact with genetic variation in the HPA axis to influence fear-related circuitry in the brain of emerging adults, possibly elucidating mechanism through which these factors confer risk for stress-related psychopathology.