Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans.

Moberg, Christine A.; Bradford, Daniel E.; Kaye, Jesse T.; Curtin, John J.

doi:10.1037/abn0000265

Cited by 33 publications

(34 citation statements)

References 87 publications

(149 reference statements)

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“…In two independent samples, our lab found that greater levels of current problematic alcohol use (e.g., binge drinking) were associated with greater aversive reactivity to U-threat, measured via startle eyeblink potentiation (Gorka et al, 2016a). Recently, Moberg et al (2017) replicated and extended the findings in Gorka et al (2016a) by demonstrating that individuals with current alcohol dependence displayed greater startle potentiation to U-threat, but not P-threat, compared with controls. In a separate sample of panic disorder patients, it was similarly shown that individuals with remitted alcohol dependence displayed greater startle potentiation to U-threat, but not P-threat, compared with individuals with no lifetime diagnosis of alcohol use disorder (AUD; Gorka et al, 2013).…”

Section: Introductionmentioning

confidence: 64%

Preliminary evidence that reactivity to uncertain threat is an endophenotype for alcohol use disorder

Gorka

Shankman

2017

Drug and Alcohol Dependence

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Background Having an exaggerated reactivity to threats that are uncertain (U-threat) may facil00itate the initiation and maintenance of excessive alcohol use in some individuals. This abnormality may not just be a concomitant for alcohol use disorder (AUD), but also an endophenotype for AUD. Method The aim of the current study was therefore to provide a preliminary test of whether U-threat is an endophenotype for AUD using several of the endophenotype criteria outlined by Gottesman and Gould (2003). Specifically, the study examined whether heightened U-threat reactivity is evidenced in those with: 1) current AUD; 2) remitted AUD (early and sustained remission examined separately); and 3) at-risk for AUD by virtue of having a positive family history of AUD. Participants (N=147) completed a well-validated threat-of-shock task and startle eyeblink potentiation was collected as an index of aversive responding. Individuals and all available first-degree family members were diagnosed using structured clinical interviews. Results Individuals at-risk for AUD, with current AUD, and AUD in remission (both early and sustained) all displayed exaggerated reactivity to U-threat, but not predictable threat, compared with non-AUD controls. Moreover, there were no significant differences between the at-risk and any of the AUD groups indicating that exaggerated reactivity to U-threat is relatively state-independent and present regardless of current AUD disease status. Conclusions The findings together highlight that exaggerated reactivity to U-threat may be a promising endophenotype for AUD that can aid in the refinement of mechanistic AUD disease models.

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Section: Introductionmentioning

confidence: 64%

Preliminary evidence that reactivity to uncertain threat is an endophenotype for alcohol use disorder

Gorka

Shankman

2017

Drug and Alcohol Dependence

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“…However, neuroadaptation following chronic anxiety may change the nature of these responses and underlying neurocircuits over time. Consistent with this view, while studies generally show increased defensive reactivity and increased amygdala activity in pathological anxiety (66,118), instances of hypo-reactivity in patients are not infrequent (119,120). The current interpretation of these opposing effects is that they reflect distinct symptoms.…”

Section: Step 4: Mechanisms Of Pathophysiologymentioning

confidence: 82%

Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences

Grillon

Robinson

Cornwell

et al. 2019

Neuropsychopharmacol.

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“…The current startle findings are consistent with prior studies examining reactivity to U‐threat in relation to AUD and drinking behaviors. In four separate samples, it has been shown that heavy drinkers and individuals with AUD display increased startle to U‐threat compared with healthy controls and individuals with anxiety disorders. It has also been previously demonstrated that startle magnitude to U‐threat correlates with AUDIT scores and self‐reported drinking problems .…”

Section: Discussionmentioning

confidence: 99%

“…More specifically, it is important to understand whether behavioral and brain measures of U‐threat reactivity actually map onto the severity of AUD illness as well as negative reinforcement processes such as drinking to cope with negative affect. To date, two studies have shown that greater self‐reported alcohol problems were related to greater startle potentiation to U‐threat . It is important to extend this line of work to include U‐threat measures beyond just startle.…”

Section: Introductionmentioning

confidence: 99%

Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives

et al. 2019

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A developing theory is that individuals with alcohol use disorder (AUD) display exaggerated reactivity to threats that are uncertain (U-threat), which facilitates excessive drinking as a means of avoidance-based coping. There is a promising initial behavioral evidence supporting this theory; however, the neural bases of reactivity to U-threat in individuals with AUD have not been examined. The extent to which biomarkers of U-threat reactivity map onto drinking behaviors and coping motives for alcohol use is also unknown. The current study therefore examined group differences in behavioral and neural reactivity to U-threat in adults with and without AUD. The study also tested whether behavior and brain responses to U-threat correlate with problematic drinking and coping motivated drinking. Volunteers (n = 65) with and without a history of AUD (38 AUD, 27 controls) were included and completed a well-validated threat-of-shock task to probe responses to U-threat and predictable threat (P-threat) while startle eyeblink potentiation was collected. Individuals also completed a newly designed, analogous version of the task during functional magnetic resonance imaging (fMRI). Results indicated that individuals with AUD displayed greater startle magnitude during U-threat, but not P-threat, and greater right insula and dorsal anterior cingulate cortex (dACC) activation during both forms of threat compared with controls. Startle magnitude and insula activation during U-threat positively correlated with self-reported problem drinking and coping motives for alcohol use. Findings demonstrate that individuals with AUD display exaggerated sensitivity to U-threat at the behavioral and neural level and that these multimethod biomarkers tap into negative reinforcement processes of alcohol abuse.

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Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans.

Cited by 33 publications

References 87 publications

Preliminary evidence that reactivity to uncertain threat is an endophenotype for alcohol use disorder

Preliminary evidence that reactivity to uncertain threat is an endophenotype for alcohol use disorder

Modeling anxiety in healthy humans: a key intermediate bridge between basic and clinical sciences

Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives

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