Stress‐related suppression of peripheral cytokines predicts future relapse in alcohol‐dependent individuals with and without subclinical depression

Abstract

Chronic alcohol abuse and depressive symptoms are both associated with peripheral cytokine changes. Despite this, cytokine adaptations have not been assessed in comorbid populations or prospectively as predictors of relapse. We examine cytokine responses to stress in alcohol-dependent individuals and social drinkers, both with and without subclinical depression. We also examine the potential link between cytokine adaptations in response to stress and prospective alcohol relapse risk. Thirtythree, alcohol-dependent individuals (21 with and 12 without high depressive symptoms) and 37 controls (16 with and 21 without high depressive symptoms) were exposed to two 5-minute personalized guided imagery conditions (stress and neutral) across consecutive days in a randomized and counterbalanced order. Alcohol craving and serum measures of tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and interleukin-1 receptor antagonist (IL-1ra) were collected prior to and following imagery exposure. Following treatment discharge, follow-up interviews were conducted over 90 days to assess relapse. Dampened IL-1ra and IL-6 in response to stress was observed as a function of alcohol dependence and not moderated by depressive symptoms. Lower levels of IL-6 following stress also predicted greater drinking days following treatment. Conversely, high depressive symptomatology was associated solely with pro-inflammatory adaptations. Stress-related suppression of TNFα predicted drinking severity only in alcoholdependent individuals with subclinical depression, and suppressed TNFR1 following stress was only seen in individuals with subclinical depression. Stress-induced suppression of pro-inflammatory TNF markers may indicate a risk factor for alcoholdependent individuals with co-occurring depressive symptoms.

Hypothalamic‐pituitary‐adrenal and autonomic response to psychological stress in abstinent alcohol use disorder individuals with and without depressive symptomatology

“…Thirty‐three recently abstinent individuals with AUD (21 with co‐occurring depressive symptoms and 12 without) and 37 socially drinking controls (16 with co‐occurring depressive symptoms and 21 without) were recruited from the greater New Haven area as part of a larger project (Fox et al., 2019). The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders‐IV (DSM‐IV)‐TR, Axis I Disorders (SCID I (First et al., 2005); was administered to confirm the criteria for alcohol dependence.…”

“…Recent literature has suggested that several alcohol dependence phenotypes, including coexisting depression, may moderate the relationship between stress system pathophysiology and alcohol use (George R Breese et al., 2005; Sinha et al., 2011). Furthermore, both co‐occurring anxiety and depressive symptomatology, respectively, have been shown to moderate the HPA axis and related immune system response to stress during protracted abstinence in individuals with AUD (Araos et al., 2015; Fox et al., 2019; Pascual et al., 2015; Wetherell & Montgomery, 2014).…”

“…A further complicating factor is the pervasive coexistence of depressive symptoms in those with Alcohol Use Disorder (AUD), where the contribution of depressive symptomatology to these processes is not well understood. Individuals with AUD (AD) (21 with and 12 without sub-clinical depressive symptoms) and 37 social drinking controls (16 with and 21 without sub-clinical depressive symptoms) as part of a more extensive study (Fox et al, 2019). All participants were exposed to two 5-min personalized guided imagery conditions (stress and neutral) in a randomized and counterbalanced order across consecutive days.…”