Cortisol responses to psychosocial stress predict depression trajectories: social-evaluative threat and prior depressive episodes as moderators

Abstract

Background: Alterations of hypothalamic-pituitary-adrenal (HPA) function are well-established in adults with current depression. HPA alterations may persist into remission and confer increased risk for recurrence.

Methods: A modified version of the Trier Social Stress Test (TSST) was administered at baseline to 32 young adults with remitted major depressive disorder and 36 never-depressed controls. Participants were randomly assigned to either a 'high-stress' condition involving social evaluation or a 'low-stress' control condition. Cortisol concentrations were measured in saliva samples throughout the TSST. Participants were assessed again after 6 months for the occurrence of stressful life events and depressive symptoms/disorders during the follow-up period.

Results: Participants who exhibited enhanced cortisol reactivity in the low-stress condition showed increases in depressive symptoms over follow-up, after controlling for stressful life events during the follow-up period. Anticipatory stress cortisol and cortisol reactivity each interacted with history of depressive episodes to predict depression trajectories.

Limitations: The single TSST administration limits conclusions about whether alterations of cortisol reactivity represent trait-like vulnerability factors or consequences ("scars') of past depression.

Conclusions: These results extend previous findings on stress sensitivity in depression and suggest that altered HPA function during remission could reflect an endophenotype for vulnerability to depression recurrence. Findings support interactive models of risk for depression recurrence implicating HPA function, depression history, and sensitivity to minor stressors. Results may have implications for interventions that match treatment approaches to profiles of HPA function.

Figure 1

Interaction of anticipatory stress cortisol, number of previous MDEs, and time predicting depressive symptom ratings (DSRs). Relations among number of previous MDEs and DSR trajectories are shown separately for individuals with higher anticipatory stress cortisol levels (Panel A) and lower anticipatory stress cortisol levels (Panel B). ***p < .001

Figure 2

Risk of incident depression during follow-up stratified on anticipatory stress cortisol levels during the initial evaluation and number of previous MDEs. Note: blue = lower cortisol and fewer MDEs; green = higher cortisol and fewer MDEs; gold = lower cortisol and more MDEs; purple = higher cortisol and more MDEs.