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

Abstract

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol-dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol-dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to nonalcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent premorbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse. (PsycINFO Database Record

Figure 1. Startle Potentiation by Group and Stressor Type

Bars display startle potentiation to predictable (white) and unpredictable (gray) shock within each Group (alcoholic vs. control). Confidence bars represent ± one standard error for point estimates of startle potentiation from the General Linear Model (GLM). This GLM adjusted for all covariates including Task Block Order, Startle Reactivity, Beck Anxiety Inventory, and Beck Depression Inventory (quantitative variables mean-centered). The unpredictable vs. predictable startle potentiation contrast was greater among alcoholics than controls (p=.022). Moreover, this simple effect contrast was significant among alcoholics (p=.021) but not controls (p=.291). * - p < .05. ns - Non-significant. Figure © 2016 John Curtin, Daniel Bradford, Jesse Kaye, and Christine Moberg under Creative Commons Attribution 4.0 International Public License CC-By

Figure 2. Individual Differences for Unpredictable (vs. Predictable) Startle Potentiation among Alcoholics

Black lines display the relationship between the size of the unpredictable minus predictable startle potentiation difference score and each individual difference variable within the alcoholic group. Gray confidence bands (panels A, C, D) and black confidence bars (panel B) represent ± one standard error for point estimates of startle potentiation from the General Linear Model (GLM). This GLM adjusted for all covariates including Task Block Order, Startle Reactivity, Beck Anxiety Inventory, and Beck Depression Inventory (quantitative variables mean-centered). * - p < .05 Figure © 2016 John Curtin, Daniel Bradford, Jesse Kaye, and Christine Moberg under Creative Commons Attribution 4.0 International Public License CC-By