The Role of Stress, Trauma, and Negative Affect in Alcohol Misuse and Alcohol Use Disorder in Women

Abstract

Recent evidence indicates that the United States is facing a public health crisis of alcohol misuse and alcohol use disorder (AUD), which has been fueled in part by dramatic rises in binge and heavy drinking and prevalence of AUD in women. Historically, alcohol misuse and AUD have been more prevalent in men than in women. However, recent evidence on data from the past decade shows increases in AUD prevalence rates that are associated with substantially higher binge and heavy drinking and AUD prevalence in women compared to men. This paper first addresses the key roles of stress, trauma, childhood maltreatment, negative affect, and mood and anxiety disorders; sex differences in the presentation of these psychosocial and psychological factors; and their contributions to alcohol misuse, escalation to binge and heavy drinking, and transition to AUD in women. Also examined are potential central and peripheral biological mechanisms by which stressors and traumatic experiences, as well as chronic stress states-including depression and anxiety-may facilitate differential pathways to alcohol misuse, escalation, and transition to AUD in women. Finally, this paper discusses major gaps in the literature on sex differences in these areas as well as the need for greater research on sex-specific pathways to alcohol misuse and transition to AUD, so as to support a more comprehensive understanding of AUD etiology and for the development of new strategies for prevention and treatment of alcohol misuse and AUD in women.

Keywords: alcohol craving; child maltreatment; early trauma; girls and women; sex differences.

Figure 1

Gender differences in socially drinking volunteers’ average subjective responses to individually calibrated exposure to stress, alcohol cue, and neutral-relaxing control provocation conditions, assessed repeatedly over time in an experimental study. Figure 1a: Average subjective sadness response over time to neutral, stress, and alcohol cue conditions by gender (in stress: women > men, p = .01). Figure 1b: Average subjective anxiety response over time to neutral, stress, and alcohol cue conditions by gender (in stress: women > men, p < .0001). Figure 1c: Average observed nonverbal behavioral and body responses to neutral, stress, and alcohol cue conditions by gender (in stress: women > men, p = .04). Source: Reproduced with permission from Chaplin et al. 2008. Copyright © 2008 Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Published by Wiley-Blackwell. All rights reserved.

Figure 2

Gender differences in ACTH and NE in men and women with alcohol use disorder (AUD) participating in a laboratory experiment with exposure to individually calibrated stress, alcohol cue, and neutral relaxing imagery on 3 separate days, one condition per day. Figure 2a and Figure 2b: ACTH differences between males and females with AUD at baseline (a) and following stress exposure (b) relative to their neutral response. Attenuation of the diurnal drop is shown in females (Stress > Neutral, p = .0009) but not in males. Figure 2c and Figure 2d: NE differences between males and females with AUD at baseline (a) and following stress exposure (b) relative to their neutral response. Attenuation of the diurnal drop is shown in males, but not in females (Neutral > Stress, p < .0001). Note: ACTH, adrenocorticotropic hormone; NE, norepinephrine. All rights reserved.

Figure 3

Whole-brain voxel-based functional magnetic resonance imaging (fMRI) showing a sex × condition interaction and corresponding activations in the stress-neutral and alcohol cue-neutral contrasts for males (M) and females (F) who drink socially. A: The sex × condition interaction effect was significant in regions of the superior and middle frontal gyrus (SFG/MFG), medial prefrontal cortex (mPFC, dorsomedial and ventromedial), rostral anterior cingulate cortex, emotion limbic regions (posterior insula, putamen, amygdala, hippocampus, and parahippocampal gyrus), temporal lobe, and visuomotor perception areas (parietal lobe, occipital lobe, and cerebellum) (p < 0.01 whole-brain familywise error [FWE] rate corrected). To elucidate the source of the interaction, male versus female contrasts were conducted for (B) stress relative to neutral, and (C) alcohol cue relative to neutral brain responses at the p < .05 whole-brain FWE corrected. Significantly, greater M > F stress-induced activity in the mPFC and limbic regions was observed. Alcohol cue-induced activity in the SFG/MFG was significantly higher in women than in men. No differences in F > M for the stress-neutral and in M > F contrast for the alcohol cue-neutral survived whole-brain correction. Coordinates are given in Montreal Neurological Institute space. Note: F, female; L, left; M, male; mPFC, medial prefrontal cortex; R, right. Source: Reproduced with permission from Seo et al., 2011. Copyright © 2010 Wiley-Liss, Inc. All rights reserved.

Figure 4

In men and women who drink socially, whole brain voxel-based correlation and corresponding scatter plots for (A) alcohol cue-induced craving ratings with neural responses during alcohol cue versus neutral cue exposure in males as well as (B) stress-induced anxiety ratings with neural response during stress versus neutral cue exposure in males and females (p < .05, whole-brain familywise error rate [FWE] corrected). A: In males, elevated alcohol craving ratings were associated with increased activity in the striatum cluster (r = .74) that encompassed ventral and dorsal striatum, including the left nucleus accumbens (X = −13, Y = 12, Z = −12). B1: In males, enhanced stress-induced anxiety ratings were associated with increased brain activity in a medial prefrontal cortex cluster that included the ACC, ventromedial PFC, and medial PFC (r = .59). B2: In females, stress-induced anxiety ratings were positively correlated with bilateral brain activity in superior/middle frontal gyrus (winsorized r = 0.62). Coordinates are given in Montreal Neurological Institute space. Note: ACC, anterior cingulated cortex; L, left; MFG, middle frontal gyrus; PFC, prefrontal cortex; R, right; SFG, superior frontal gyrus. Source: Reproduced with permission from Seo et al., 2011. Copyright © 2010 Wiley-Liss, Inc. All rights reserved.

Figure 5

Scatter plots and regression lines for stress-induced anxiety ratings with neural responses during stress relative to neutral-relaxing exposure for specific regions of interest (ROIs). Simple effects in ROIs from whole-brain regression of significant regions from the gender-by-anxiety interaction effects analyses are shown separately in men and women. Stress-induced anxiety predicted brain responses to stress differentially by gender. The plots show (A) positive (women [W]) and negative (men [M]) associations between stress-induced anxiety ratings and activity in the dorsomedial prefrontal cortex (PFC) (W: β = .38; M: β = −.33), precuneus and inferior parietal lobe (W: β = .33; M: β = −.40), middle/inferior temporal gyrus (W: β = .44; M: β = −.30), and occipital lobe and cerebellum (W: β = .40; M: β = −.36). Beta (β) indicates the standardized coefficient. There were no outliers in any of these brain regions for both men and women. Note: DmPFC, dorsomedial prefrontal cortex; IPL, inferior parietal lobe; Occipital L., occipital lobe. Source: Reproduced with permission from Seo et al., 2017. Copyright © 1999–2020 Wiley-Liss, Inc. All rights reserved.