Prospective associations of cortisol dynamics and daily stress with depression, generalized anxiety, and panic...

Flatter diurnal cortisol decline indicates hypothalamic-pituitary-adrenal (HPA) axis dysregulation and has been longitudinally related to major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) symptoms. However, given high heterogeneity in the relationship between diurnal cortisol and future common mental health symptoms, the moderators of these long-term prospective associations remain unclear.

This secondary data analysis of the Midlife Development in the United States (MIDUS) used a longitudinal nine-year sample of community-dwelling adults (N = 1617; M_AGE=56.29 years). Participants completed baseline assessments of diurnal cortisol slopes and stressor severity (Daily Inventory of Stressful Events). Psychiatric symptoms (Composite International Diagnostic Interview-Short Form) were assessed at baseline and nine-year follow-up. Cortisol was sampled four times a day over four days. Day-level diurnal cortisol slope (DCS) was computed as ordinary least squares regression coefficients of log-cortisol on observed collection time, averaged across days. Generalized additive mixed models evaluated nonlinear moderator effects of stressor severity on the relations between DCS and common mental health symptoms.

Between persons, flatter DCS significantly interacted with greater daily stressor severity to predict higher nine-year MDD (d = 0.346), GAD (d = 0.116), and PD (d = 0.046) symptom counts (all p ≤ .002). Participants with both flatter DCS and greater daily stressor severity had notably higher long-term MDD, GAD, and PD symptom counts. Complex, nonlinear associations were observed across all outcomes.

Consistent with the dual-risk stress-sensitization hypothesis, the prognostic value of flatter cortisol slopes is context-specific and contingent on stressor exposures. Findings merit precision medicine investigations into targeting HPA axis dysregulation.