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

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% & 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.

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

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% & 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.

Preprint: Alcohol Stress Response Dampening during imminent vs. distal, uncertain threat

Research indicates that fear and anxiety are distinct processes with separable neurobiological substrates. Predictable vs. unpredictable shock administration has been used to elicit fear vs. anxiety, respectively. Recent research has demonstrated that alcohol may reduce anxiety but not fear. However, previous manipulations of predictability have varied both probability and temporal uncertainty of shock threat, leaving unresolved questions regarding which stimulus characteristics elicit anxiety and are sensitive to alcohol stress response dampening (SRD). We developed a novel paradigm to closely parallel basic research in animals that systematically varied temporal uncertainty of threat while holding threat probability constant. Intoxicated (0.08% target BAC), placebo, and no-alcohol control participants viewed a series of visual threat cues. Certain cue duration (5 seconds) blocks were equivalent to predictable shock blocks eliciting fear in earlier research. Uncertain cue duration (5, 20, 50 or 80 second, intermixed) blocks introduced temporal uncertainty regarding impending shock to elicit anxiety. Startle potentiation relative to matched cue periods in no-shock blocks provided the primary measure of affective response. All threat cues produced robust startle potentiation. Alcohol reduced startle potentiation during the first 5 seconds of threat cue presentation in uncertain but not certain duration blocks. Alcohol also reduced startle potentiation at later times among longer uncertain duration cues, suggesting that alcohol SRD persisted. Trait negative emotionality and binge drinking status moderated alcohol SRD magnitude during uncertain threat. These translational findings corroborate previous reports regarding distinct substrates of fear vs. anxiety, and have implications for both alcoholism etiology and comorbidity with anxiety disorders.

Preprint: How bad could it be? Alcohol dampens stress responses to uncertain intensity threat

Stress response dampening (SRD) is an important motive for alcohol use. However, alcohol SRD is observed inconsistently in and out of the laboratory. This has raised questions about precise mechanisms and boundary conditions required for stress reduction from alcohol. Emerging evidence indicates that alcohol SRD may be observed selectively during uncertain but not certain threats. We measured stress response via potentiation of participants’ defensive startle reflex to threat of shock in blocks of certain (low and high) intensity and uncertain intensity shock. We manipulated 92 participants’ blood alcohol concentrations (BACs) across a broad range (0.00%-0.12%). Increasing BACs were associated with linearly decreasing startle potentiation and self-reported anxiety. This alcohol SRD effect was greater during uncertain than certain threat. Furthermore, we identified binge drinking as a moderator of alcohol SRD. More broadly, these results suggest that distinct mechanisms are involved in response to uncertain vs. certain intensity threats.