Stress vulnerability and alcohol use and consequences: From human laboratory studies to clinical outcomes

Abstract

It is well known that vulnerability to stress is a risk factor for alcohol use disorder (AUD). Chronic alcohol use can result in neuroadaptations in cortico-striatal pathways and hypothalamic pituitary adrenal (HPA) axis function that are manifested in altered behavioral and cognitive control functions contributing to alcohol craving, compulsive motivation, consumption, and consequences. This symposium brings together studies utilizing novel approaches to help improve our understanding of stress - past, acute, and chronic - on alcohol seeking and consumption and related outcomes using a combination of human laboratory models, neuroimaging, and clinical measures. Examining factors that determine vulnerability as well as resilience to stress are of particular interest in the study of AUD because, in addition to increasing our understanding of the risk factors for AUD, such knowledge can be used to develop more effective treatments. Dr. Stangl presented a novel human experimental model that demonstrates, for the first time, stress-induced increases in alcohol self-administration in binge drinkers using a guided imagery paradigm combined with intravenous alcohol self-administration (IV-ASA). Dr. Blaine presented data demonstrating that glucocorticoid response to stress drives compulsive alcohol motivation and intake in binge/heavy drinkers. Dr. Plawecki presented data examining sex differences in the effect of two distinct stress paradigms - mood induction and abstinence - on IV-ASA in moderate drinkers. Dr. Schwandt presented clinical data providing a new perspective on the relationship between childhood trauma and AUD by suggesting possible underlying mechanisms that confer resilience, rather than vulnerability, to severe early life stress exposure.

Keywords: Alcohol use disorder; Early life stress; Gender; Intravenous alcohol self-administration; Resilience; fMRI.

Figure 1.

Childhood Trauma and Stress-Cue Exposure

Figure 2.

Alcohol craving in (A) social drinkers and (B) problem drinkers as a function of timepoint. (C) (D) Problem drinkers consumed higher amounts of beer following presentation of beer cues compared to social drinkers in response to all 3 imagery conditions. Values are displayed as mean +/− SEM. Reproduced and modified with permission from Milivojevic V, Ansell E, Simpson C, Siedlarz KM, Sinha R, Fox HC (2017). Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Binge Drinkers. Alcoholism: Clinical and Experimental Research 41:585-595. Copyright © 2017 by the Research Society on Alcoholism.

Figure 3:

Cumulative Work for Alcohol in the Neutral and Negative Mood Sessions by Gender. Women worked less for alcohol in both sessions, compared to men, and the reduction for women was statistically significant in the negative mood session. See Cyders at al 2016 for more details.

Figure 4:

PAR based on Cumulative Work for Alcohol for Men and Women. Women tended to increase, while men decreased, their motivation for alcohol post abstinence. See Plawecki et al 2017 for more details.

Figure 5.

Distribution of the alcohol dependence severity score from the ADS in the high childhood trauma sample (n = 367), showing the three subgroups identified based on high severity (ADS score ≥27 = Vulnerable), low severity (ADS score ≤17 = Moderately Resilient), and absence of alcohol dependence (ADS of 0 = Resilient).