Alcohol Use Disorder Masks the Effects of Childhood Adversity, Lifetime Trauma, and Chronic Stress on Hypothalamic–Pituitary–Adrenal Axis Reactivity

Abstract

Background: Individuals with alcohol use disorder (AUD) and those who have experienced traumas or chronic stress exhibit dysregulated hypothalamic-pituitary-adrenal (HPA) axis reactivity. Whether and how trauma and stress histories interact with AUD to affect HPA axis reactivity has not been assessed.Methods: In the present study, 26 healthy male controls and 70 abstinent men with AUD were administered a pharmacologic probe [ovine corticotropin-releasing hormone (oCRH)] and psychosocial stressor to assess HPA axis reactivity. Plasma adrenocorticotropin hormone (ACTH) and cortisol were assessed every 10-20 minutes. Hierarchical clustering of multiple measures of trauma and stress identified 3 distinct clusters: childhood adversity, lifetime trauma, and chronic stress. General linear model procedures were used to examine main effects of group (AUD/control) and interaction effects of the 3 clusters upon net-integrated ACTH and cortisol response.Results: We found that higher levels of childhood adversity, lifetime trauma, and chronic stress were each associated with blunted oCRH-induced ACTH reactivity in controls, but not in the AUD group. Recent chronic stress within the prior 6 months had the strongest influence upon ACTH reactivity in the control group, and lifetime trauma, the least.Conclusions: Childhood adversity, lifetime trauma, and chronic stress likely exert persistent, measurable effects upon HPA axis functioning in healthy controls. This association appears to be masked in individuals with AUD, potentially confounding studies examining the effects of stress, adversity, and/or trauma upon the HPA axis in this population during the protracted withdrawal phase of recovery. Future work targeting stress exposure and reactivity should consider the heightened effect of previous alcohol use relative to past adversity and trauma.

Effect of intravenous ghrelin administration, combined with alcohol, on circulating metabolome in heavy drinking individuals with alcohol use disorder

“…Moreover, in the IV-AC experiment, significant differences between the ghrelin and placebo infusions were seen in levels of glycocholic acid (q < 0.0001) and phenylalanine (q = 0.0458). However, these metabolites were not significantly altered in the IV-ASA experiment (glycocholic acid q = 0.3197 and phenylalanine q = 0. exposure increased cortisol levels (Adinoff et al, 2003;Blaine et al, 2019;Blaine & Sinha, 2017;King et al, 2002King et al, , 2011Mennella et al, 2005;Roche et al, 2014;Zhang et al, 2020). Consistent with these studies, we did not observe an increase in cortisol levels after alcohol administration in either of the experiments under the placebo condition.…”

Impact of adverse childhood experiences on the symptom severity of different mental disorders: a cross-diagnostic study

“…The study found58 59 that as many as 68% of women with substance abuse disorders (including addictive drugs and alcohol) experienced childhood sexual trauma, and the rate of substance abuse or dependence was significantly higher among women who experienced childhood sexual trauma than among those who did not. As revealed by pathophysiological studies,60 altered secretion in the hypothalamic-pituitary-adrenocortical system is the possible mechanism by which negative childhood experiences increase the risk of substance abuse. In addition, substance abuse patients often also have post-traumatic stress disorder, and patients with comorbid substance abuse and post-traumatic stress disorder are more difficult to treat with conventional therapies.…”

Treating posttraumatic stress disorder and alcohol use disorder comorbidity: Current pharmacological therapies and the future of MDMA-integrated psychotherapy

“…There are varying hypotheses that attempt to explain the reason behind PTSD and AUD comorbidity. Chronic stress-inducing dysregulation of the hypothalamic–pituitary–adrenal axis has been shown to lead to increased alcohol use (Zhang et al, 2020), with PTSD symptom severity serving as a moderating factor in this process (Goldstein et al, 2023). A self-medication hypothesis is posited to play a role in the development of PTSD and AUD comorbidity, with repeated trauma exposure and further alcohol use perpetuating cyclically.…”