Alcohol stress response dampening: selective reduction of anxiety in the face of uncertain threat

Abstract

Problematic alcohol use and stress response dampening (SRD) are intimately interconnected. Recent evidence suggests that alcohol produces selective SRD during uncertain but not certain threat. We systematically varied shock probability in a novel task assessing alcohol SRD during low probable/uncertain threat, while holding temporal precision of threat constant. Intoxicated (0.08% target blood alcohol concentration) and placebo participants completed a cued shock threat task in which probability of shock administration at the offset of brief visual cues varied parametrically. High probability (100%) shock cues represented certain threat as used in earlier research, while lower probability (20% and 60%) shock cues provided novel uncertain threat conditions. Startle potentiation during cues and inter-trial intervals (ITIs) served as the measure of affective response. General linear model analysis indicated that alcohol SRD magnitude increased monotonically as threat uncertainty increased. Alcohol SRD was significantly greater during 20% and 60% shock threat relative to 100% shock threat. Alcohol also significantly reduced startle potentiation during distal threat in shock-free ITIs. Alcohol SRD magnitude during distal/uncertain threat was meaningfully moderated by individual differences in negative affectivity and weekly alcohol consumption. This work advances understanding of which properties of uncertainty are relevant to anxiety and anxiolytic effects of alcohol.

Figure 1. Task Design Schematic

The task involved presentation of blocks of colored square cues presented for 5 s each, separated by a variable duration inter-trial interval (ITI; range = 15 – 20 s). Cues were blocked into three Threat Probability conditions (100% vs. 60% vs. 20%) that indicated the probability of shock administration (at 4.5s post-cue onset) during any discrete cue in that block. Blocks of no-shock cues were also presented to calculate startle potentiation associated with shock threat. Unique colors (indicated by grayscale in figure) were associated with each cue type. The startle response was elicited by white noise probes presented during cues (at 4 s post-cue onset) and ITI periods between cues (at 13 or 15 s post-cue offset).

Figure 2. Beverage Group and Threat Probability Effects on Startle Potentiation during Cues

Left Panel Startle potentiation scores during threat cues are displayed by Threat Probability. The Beverage Group X Threat Probability interaction was significant (p= .022). Follow-up tests revealed a significant Beverage Group simple effect during 20% threat (p= .023) and a marginal Beverage Group simple effect during 60% threat (p= .097). The Beverage Group simple effect was not significant during 100% threat (p= .719). Error bars represent the standard errors for the startle potentiation point estimates from the General Linear Model. Significant and marginal simple Beverage Group effects are indicated (+ p ≤ .10, * p ≤ .05). Right Panel: General Linear Model (GLM) Beverage Group Coefficients are displayed by Threat Probability. The Beverage Group GLM coefficients indicate the magnitude by which startle potentiation during threat cues was reduced in the alcohol group relative to the placebo group. The magnitude of this Beverage Group effect monotonically increased with decreasing threat probability. Single degree of freedom coefficient contrasts indicated that the Beverage Group effects during 20% threat and 60% threat were both significantly greater than the Beverage group effect during 100% threat (ps ≤ .013 & .030, respectively). Error bars represent the standard errors for the Beverage Group coefficients. Significant and marginal Beverage Group coefficient contrasts are indicated (* p ≤ .05).

Figure 3. Beverage Group and Threat Probability Effects on Startle Potentiation during Shock-free Inter-Trial-Intervals

Left Panel: Startle potentiation scores during the inter-trial intervals (ITIs) between threat cues are displayed by Threat Probability. No shocks were administered during the ITIs. The Beverage Group effect was significant (p= .002) indicating that alcohol reduced startle potentiation across all threat probability blocks. In addition, significant or marginal Beverage Group simple effects were observed for all threat probability blocks (ps = .015, .001, & .078 for 100%, 60% and 20% respectively). Error bars represent the standard errors for the startle potentiation point estimates from the General Linear Model. Significant and marginal simple Beverage Group effects are indicated (+ p ≤ .10, * p ≤ .05, *** p ≤ .001). Right Panel: General Linear Model (GLM) Beverage Group Coefficients are displayed by Threat Probability. The Beverage Group GLM coefficients indicate the magnitude by which startle potentiation during the inter-trial-intervals was reduced in the alcohol group relative to the placebo group. None of the single degree of freedom coefficient contrasts across threat probabilities were significant, indicating that Beverage Group effects were comparable across threat probabilities. Error bars represent the standard errors for the Beverage Group coefficients.

Figure 4. Individual Difference Moderators of Beverage Group Effects on Inter-Trial Interval Startle Potentiation

Left Panel: Mean ITI startle potentiation scores are displayed by Beverage Group and typical weekly alcohol consumption (drinks per week). The Beverage Group X Drinks/week interaction was significant (p= .019), with Beverage Group effects decreasing with increasing weekly alcohol consumption. Standard error confidence bands for ITI startle potentiation point estimates are displayed in gray. Right Panel: Mean ITI startle potentiation scores are displayed by Beverage Group and Negative Emotionality. The Beverage Group × Negative Emotionality interaction was significant (p= .037), with Beverage Group effects increasing with increasing Negative Emotionality. Standard error confidence bands for ITI startle potentiation point estimates are displayed in gray.