The mediating effect of stress reactivity in the 18-year bidirectional relationship between generalized anxiety and depression severity

Background: Generalized anxiety disorder (GAD) and major depressive disorder (MDD) often precede and predict one another. Heightened stress reactivity may be a mediation mechanism underlying the long-term connections between GAD and MDD. However, cross-sectional studies on this topic have hindered directional inferences.

Method: The present study examined stress reactivity as a potential mediator of the sequential associations between GAD and MDD symptoms in a sample of 3,294 community-dwelling adults (M age = 45.6, range = 20-74). Participants completed three waves of measurement (T1, T2, and T3) spaced nine years apart. GAD and MDD symptom severity were assessed at T1, T2, and T3 (Composite International Diagnostic Interview-Short Form). Stress reactivity (Multidimensional Personality Questionnaire) was measured at T2.

Results: Structural equation mediation modeling demonstrated that higher T1 GAD symptoms positively predicted more severe T3 MDD symptoms via T2 stress reactivity, controlling for T1 MDD (d = 0.45-0.50). However, T2 stress reactivity was not a significant mediator in the relationship between T1 MDD severity and T3 GAD symptoms after controlling for T1 GAD. Direct effects indicated that T1 GAD positively predicted T3 MDD 18 years later and vice versa (d = 1.29-1.65).

Limitations: Stress reactivity was assessed using a self-report measure, limiting conclusions to perceived (vs. physiologically indexed) stress reactivity.

Conclusions: These findings indicate that stress reactivity may be one mechanism through which GAD leads to later MDD over prolonged durations. Overall, results suggest that targeting stress reactivity in treatments for GAD may reduce the risk of developing subsequent MDD.