Physiological responses to acute psychological stress as a biomarker for depression: A systematic review and meta-analysis.

Abstract

Exposure to psychological stress, as well as individual differences in stress responses, has consistently been implicated in the onset and prognosis of depression. Although stress and depression are closely linked, their underlying physiological mechanisms remain unclear. Given the heterogeneity of depressive symptoms, identifying physiological biomarkers may improve diagnosis and treatment. Prior reviews and meta-analyses suggest a connection between depression and physiological stress reactivity, but inconsistent findings across depression measures and physiological outcomes have limited comprehensive understanding. As such, the purpose of the present meta-analysis was to extend prior work investigating the relationship between depression and physiological responses (both the autonomic nervous system and hypothalamic-pituitary-adrenal axis) to standardized acute psychological stress tasks. A total of 126 studies were identified through PubMed, Embase, APA PsycInfo, and ProQuest. Included studies examined either clinically diagnosed depression (vs. healthy controls) or depressive symptomatology (i.e., continuous scores, high vs. low depression). Depression was associated with blunted overall physiological responses to active mental stress (Hg = -0.09, 95% CI [-0.14, -0.03]) driven primarily by cardiac (Hg = -0.17, 95% CI [-0.26, -0.07]) and hemodynamic (Hg = -0.08, 95% CI [-0.15, -0.02]) parameters. No statistically significant associations were found for heart rate variability or neuroendocrine reactivity. Depression was not associated with physiological reactivity to the cold pressor task. There was no significant association between remitted depression and physiological stress reactivity. These findings suggest that blunted cardiac and hemodynamic reactivity to active mental stress is a state-dependent systems marker and may serve as a treatment response indicator. (PsycInfo Database Record (c) 2026 APA, all rights reserved).