Newswise — The hypothalamic–pituitary–adrenal (HPA) axis is the body’s key stress response system. By driving production of the stress hormone cortisol, and then ensuring a return to baseline levels, the HPA axis regulates our reaction to stressful events.  Chronic alcohol use, however, can lead to persistently elevated cortisol, reducing the body’s capacity to respond appropriately to stress. Among people in treatment for alcohol use disorder (AUD), the blunted stress response predicts risk of relapse and a return to drinking. Longer-term life stress, including childhood adversity, post-traumatic stress disorder (PTSD), and chronic stress, can also dampen HPA axis function, complicating interpretation of the alterations evident in people with AUD. However, it is not known how stress and trauma intereact with AUD to affect HPA-axis reactivity. A new report in Alcoholism: Clinical and Experimental Research by researchers from the universities of Texas, Florida, and Colorado addresses this issue, using multiple measures of recent and lifetime stress to evaluate the impact on HPA axis responses in people with and without AUD.

The study involved 26 healthy men recruited as controls, and 70 men with AUD recruited from residential treatment programs after abstaining from alcohol for four to six weeks. This timeframe ensured that acute withdrawal symptoms had resolved, but that alcohol-induced changes to the HPA axis would remain. Only males were included because of known differences in alcohol dependence and the HPA-axis response between the sexes.

Participants completed questionnaires to assess childhood abuse, neglect, and adverse events, PTSD symptoms, and lifetime stress. They were then exposed to two stress challenges on consecutive evenings to elicit HPA axis responses via different neuronal pathways: the first, a pharmacological stress challenge, involved intravenous administration of ovine corticotropin releasing hormone (oCRH), while the second, a psychological stress challenge, entailed a public speaking exercise followed by an arithmetic test. Blood samples were collected before and after each challenge and analyzed for levels of cortisol and adrenocorticotrophic hormone (ACTH), which stimulates cortisol production.

Scores for childhood adversity, lifetime trauma, and recent chronic stress were derived for each individual from the questionnaires. Using statistical modeling, the researchers showed that among the control group participants, higher scores (indicating greater adversity, trauma, or stress) were associated with a reduced ACTH response following the pharmacological stressor. In the AUD group, however, there was no association between the scores and ACTH response. In the control (but again not the AUD) group, higher levels of recent chronic stress were also associated with blunted cortisol responses to oCRH, but childhood adversity and lifetime trauma had no effect. Nor was there any effect of the life stress measures on responses to the psychological stressor test, in either the control or AUD group.  

The findings provide further evidence that childhood adversity, lifetime trauma, and chronic stress exert persistent and measurable effects on HPA axis functioning in healthy men. However, this was not evident in people with AUD, as there was no observed additive effect of adversity/trauma/stress on HPA axis reactivity over and above that exerted by AUD. Repeated alcohol intoxication followed by withdrawal has dramatic effects on the HPA axis, and the researchers suggest that this may overwhelm the relatively more subtle effects of past adversity and trauma. Future studies of stress exposure and reactivity in people in early recovery from AUD should account for this.

Childhood Adversity, Lifetime Trauma, and Chronic Stress as Modifiers of Alcohol Use Disorder on Hypothalamic-Pituitary-Adrenal Axis Reactivity. A. Zhang, J.L. Price, D. Leonard, C.S. North, A. Suris, M.A. Javors, B. Adinoff (pages xxx)