From allostasis to addiction: Cortisol dysregulation, daily stress and relations with 9-year alcohol and substance use disorder severity in community adults.

Background

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Aims

Diurnal cortisol dysregulation and daily stressor severity may jointly forecast long-term alcohol use disorder (AUD) and substance use disorder (SUD) severity, yet most evidence is cross-sectional and relies on single cortisol indices. This study examined whether three cortisol indices nonlinearly interacted with daily stressor severity to predict 9-year AUD and SUD severity.

Design

Longitudinal observational study with a 9-year follow-up. Analyses were not pre-registered.

Setting

Community-based sample in the United States of America.

Participants

1617 community-dwelling adults aged 33-83 years at baseline.

Measurements

Ecological momentary assessments of salivary cortisol and daily stressor severity were collected at baseline. AUD and SUD severity were self-reported at baseline and 9-year follow-up. Cortisol indices included diurnal cortisol slope, cortisol awakening response and area under the curve (AUC).

Findings

Parametric hurdle Poisson models yielded null main effects and interactions (all P > 0.050). Generalized additive models with negative binomial family revealed three statistically significant nonlinear interactions: diurnal cortisol slope × stress predicting AUD severity [effective degrees of freedom (edf) = 2.09, χ2 = 12.56, P = 0.005], cortisol awakening response × stress predicting SUD severity (edf = 2.88, χ2 = 11.60, P = 0.019) and AUC × stress predicting AUD severity (edf = 4.08, χ2 = 16.34, P = 0.006). Adjusting for age, sex, education, income and race nullified all three interactions; however, AUC × stress interaction → AUD remained statistically significant after controlling for anxiety and depression.

Conclusions

Nonlinear interactions between cortisol indices and daily stressor severity appear to predict 9-year alcohol use disorder and substance use disorder severity, with cortisol area under the curve emerging as the most robust indicator. Findings are predictive rather than causal. Cognitive-behaviorally based prevention programs targeting stress and cortisol regulation may mitigate substance use risk.