Examining the daily reciprocal relations between alcohol abstinence self-efficacy and drinking among non-treatment seeking individuals with alcohol use disorder (AUD).

Theoretical and empirical models of alcohol use and misuse indicate that abstinence self-efficacy (ASE) predicts improvements in treatment outcomes among individuals with alcohol use disorder (AUD). More recently, studies have begun examining daily fluctuations in ASE to better understand in-the-moment determinants of drinking behaviors. With the goal of assessing how ASE is implicated in maintenance (rather than changing) of hazardous drinking patterns, the current study examined daily reciprocal relations between ASE and drinking among individuals with AUD. Non-treatment seeking adults (n = 63) with AUD were recruited and completed daily surveys assessing ASE and drinking behaviors for 14 days. Data were analyzed using time-lagged multilevel modeling. Results indicated that both within- and between-person elevations in ASE predicted decreased likelihood of drinking, but only within-person ASE predicted fewer drinks consumed on drinking days. Previous-day drinking behavior was unrelated to next-day ASE; however, higher percentage of drinking days during the monitoring period (between-person) was associated with lower daily ASE. These results demonstrate that confidence in one's ability to abstain from drinking varies considerably across days, and that fluctuations may be implicated in daily drinking decisions. The lack of effect of previous-day drinking on ASE (combined with the significant effect of average drinking frequency) may suggest that sustained periods of reduced drinking or abstinence are necessary to impact ASE. This study points to ASE's role in the maintenance of daily drinking behavior among non-treatment-seeking individuals with AUD and reiterates the importance of self-efficacy in behavioral control and decision-making at the daily level.

Impact of handgun ownership and biological sex on startle reactivity to predictable and unpredictable threats.

Extant literature suggests that many individuals obtain firearms because they perceive the world as unsafe and believe that firearm ownership increases physical protection. Converging evidence suggests that firearm owners are vulnerable to uncertainty and experience chronic anticipatory anxiety in daily life; however, biological sex is thought to potentially moderate this association. Studies have yet to examine this hypothesis using objective markers of anticipatory anxiety. The present study therefore examined the impact of handgun ownership and biological sex on psychophysiological reactivity to predictable (P-) and unpredictable (U-) threat (N = 133). Male and female adult participants were classified into two groups: a) individuals who do not currently own any handguns (n = 52), and b) individuals who currently own one or more handguns (n = 81). Startle eyeblink potentiation was recorded as an index of aversive reactivity during a well-validated threat-of-shock paradigm designed to probe anticipatory anxiety (during U-threat) and fear (during P-threat). Results revealed no main effect of group on startle reactivity to P- or U-threat. Females displayed greater startle reactivity to threat (P- and U-) compared with males. The main effect was qualified by a significant group x biological sex interaction. Male handgun owners exhibited greater startle to U-threat, but not P-threat, relative to non-handgun owners. There was no effect of group on startle reactivity in females. Findings revealed that biological sex and threat type influenced threat reactivity. Male handgun owners displayed increased sensitivity to stressors that are uncertain, which may reflect an objective mechanism related to firearm ownership.

Reward-related neural dysfunction in youth with a history of suicidal ideation: The importance of temporal predictability.

Abnormal reward processing is an important yet understudied risk factor for suicide. Recent neuroimaging studies have found that suicidality is associated with abnormal reward-related neural reactivity and connectivity across a wide range of brain regions and circuits. The varying, and oftentimes discrepant, findings have hindered progress in elucidating the neurobiological link between reward processing dysfunction and suicide risk. Some of this variability is likely related to different reward-related paradigms that are utilized across studies. The primary aim of the current study was to address these issues by comparing neural reactivity between youth with and without a history of suicidal ideation during direct manipulation of reward parameters. A total of 108 unmedicated youth, ages 17-19, were classified into two groups: 1) history of suicidal ideation (n = 39) and 2) no history of suicidal ideation (n = 69). All participants completed a novel reward anticipation task probing anticipation of predictable (P-reward) and unpredictable (U-reward) monetary reward. Results revealed that compared with controls, youth with a history of suicidal ideation exhibited increased neural activation in the dorsal anterior cingulate cortex (dACC) and right anterior insula (aINS) during anticipation of U-reward. There were no group differences during anticipation of P-reward. These findings suggest that propensity for suicidal ideation may be related to specific abnormalities during anticipation of U-reward, but not P-reward.

Acute orexin antagonism selectively modulates anticipatory anxiety in humans: implications for addiction and anxiety.

Research indicates that heightened anticipatory anxiety underlies several forms of psychopathology. Anticipatory anxiety can be reliably and objectively measured in the laboratory using the No-Predictable-Unpredictable (NPU) threat paradigm. The NPU paradigm is an ideal research tool for the NIH 'Fast-Fail' approach of screening promising compounds and testing human target engagement. Evidence from preclinical studies suggests that the hypocretin/orexin (ORX) hypothalamic neuropeptide system is a potential means for modulating anticipatory anxiety and disrupting stress-related alcohol use. The current study tested this question using a psychophysiological probe of the ORX system in humans. We examined whether a single dose of suvorexant (SUV; 10 mg; dual ORX receptor antagonist) can effectively and selectively target a well-validated human laboratory index of exaggerated anticipatory anxiety using a within-subjects placebo-controlled design. A total of twenty-one volunteers completed two laboratory sessions during acute administration of 10 mg SUV or placebo. Across sessions, we administered the NPU paradigm probing sustained anticipatory anxiety and fear while startle eyeblink was recorded as an index of aversive reactivity. Questionnaires assessing mood states and subjective drug effects were also collected. Results indicated SUV was well-tolerated. Compared with placebo, SUV was associated with decreased startle reactivity during anticipatory anxiety but not fear or no-threat conditions. Therefore, SUV selectively and effectively reduced objective indicators of anticipatory anxiety in humans and engaged our laboratory target of psychopathology. ORX antagonism may be a promising strategy for modulating human anxiety and potentially, stress-related alcohol use.

Association between startle reactivity to uncertain threats and structural brain volume.

Sensitivity to uncertain threat (U-threat) is a clinically important individual difference factor in multiple psychopathologies. Recent studies have implicated a specific frontolimbic circuit as a key network involved in the anticipation of aversive stimuli. In particular, the insula, thalamus, and dorsal anterior cingulate cortex (dACC) have recently been found to be robustly activated by anticipation of U-threat. However, no study to date has examined the association between U-threat reactivity and structural brain volume. In the present study, we utilized a pooled sample of 186 young adult volunteers who completed a structural MRI scan and the well-validated No-Predictable-Unpredictable (NPU) threat of electric shock task. Startle eyeblink potentiation was collected during the NPU task as an objective index of aversive reactivity. ROI-based analyses revealed that increased startle reactivity to U-threat was associated with reduced gray matter volume in the right insula and bilateral thalamus, but not the dACC. These results add to a growing literature implicating the insula and thalamus as core nodes involved in individual differences in U-threat reactivity.

Neural and self-report indices of cognitive reappraisal moderate the association between sensitivity to uncertain threat and problem alcohol use.

Exaggerated reactivity to threats that are uncertain (U-threat) is a risk factor for problem alcohol use. Data suggest that exaggerated reactivity to U-threat is associated with chronic anxiety and motivation for coping-oriented drinking. Not all individuals with high U-threat reactivity engage in excessive drinking and theory and research suggest that individual differences in emotion regulation, particularly frequency and effectiveness of cognitive reappraisal, are potential moderators of this well-established link. The aim of the current study was to test this hypothesis using a multimodal laboratory design. A total of 83 volunteers with depression and/or anxiety completed a well-validated threat sensitivity task and two complimentary assessments of cognitive reappraisal. Threat sensitivity was measured using startle eyeblink potentiation during threat-of-electric shock. Cognitive reappraisal was measured using self-report and estimates of prefrontal cortex activation (PFC; i.e., ventrolateral, dorsolateral and dorsomedial) during instructed reappraisal during functional magnetic resonance imaging. Results revealed self-reported and PFC indices of reappraisal were correlated within-subjects. Additionally, self-reported and ventrolateral (vlPFC) activation during reappraisal moderated the association between reactivity to U-threat and problem alcohol use. Across both measures, at low engagement in reappraisal, greater startle reactivity to U-threat was associated with greater problem alcohol use. At high engagement in reappraisal, there was no association between U-threat reactivity and problem alcohol use. Together, the findings reveal that exaggerated reactivity to U-threat may be a particularly robust risk factor for problem alcohol use in the context of impaired or ineffective emotion regulation.

Neural and Self-report Measures of Sensitivity to Uncertainty as Predictors of COVID-Related Negative Affect.

The COVID-19 pandemic has been a period of unprecedented uncertainty. Research indicates individuals differ in their response to uncertainty and these differences are mediated by anterior insula (aINS) function. Those most sensitive to uncertainty are likely vulnerable to negative affect in the context of the pandemic. The current study was designed to directly test this question using both neural and self-reported measures of sensitivity to uncertainty. Fifty-nine volunteers completed a task designed to probe neural response to anticipation of predictable (P-) and unpredictable (U-) threat-of-electric-shock during functional magnetic resonance imaging and a self-report measure of intolerance of uncertainty (IU). Approximately two years later, during the peak of the pandemic, participants reported their emotional reactions to the COVID-19 crisis. Multilevel mixed models revealed that greater aINS activation to U-threat and greater self-reported IU were independent predictors of increased COVID-related negative affect. These findings were significant when adjusting for biological sex and depression and anxiety symptom severity. The results add to a growing literature demonstrating that individual differences in response to uncertainty have a robust impact on mood and functioning. Results also highlight that individuals highly sensitive to uncertainty may be at increased risk for poor mental health during the ongoing pandemic.