Psychobiological Stress Response Profiles in Current and Remitted Depression: A Person-Centered, Multisystem Approach

Biol Psychiatry Glob Open Sci. 2024 Oct 9;5(1):100400. doi: 10.1016/j.bpsgos.2024.100400. eCollection 2025 Jan.

Abstract

Background: A dysregulated stress response, including exaggerated affective reactivity and abnormal hypothalamic-pituitary-adrenal axis responsivity, has been implicated in the etiology, maintenance, and relapse of major depressive disorder (MDD). Among adolescents, discordant affective and physiological stress response profiles have been linked to negative affective outcomes and increased risk for psychopathology. Whether these findings extend to adults with varying degree of MDD risk is unclear, as are possible links to various risk factors.

Methods: We used a person-centered, multisystem approach in a sample of 119 unmedicated adults with current or remitted MDD and individuals without past MDD to evaluate psychobiological stress response profiles. Multitrajectory modeling was applied to positive affect, negative affect, and salivary cortisol (CORT) levels in response to the Maastricht Acute Stress Test.

Results: Analyses identified 4 within-person profiles, 1 typical, termed normative (n = 32, 26.9%) and 3 atypical: CORT hyperreactivity affective stability (n = 17, 14.3%), CORT hyporeactivity affective reactivity 1 (n = 45, 37.8%), and CORT hyporeactivity affective reactivity 2 (n = 25, 21.0%). While validating the assumption of a normative profile and increased risk for psychopathology in non-normative stress response profiles, coherent associations emerged between stress response profiles and clinical status, depression severity, anhedonia, perceived stress, childhood adversity, and reports of well-being, suggesting increased risk for psychopathology for individuals with a hyperreactive or discordant hyporeactive stress response profile.

Conclusions: This work advances our understanding of stress response mechanisms in MDD and underscores the potential of targeted interventions to enhance resilience and reduce psychopathology based on individual stress response profiles.

Keywords: Affective responding; Cortisol reactivity; Major depressive disorder; Multitrajectory modeling; Stress concordance; Stress response.

Plain language summary

Depression has been characterized by dysregulated stress responses, including exaggerated affective reactivity and abnormal stress hormone levels. In adolescents, discordant affective and physiological stress responses have been linked to negative outcomes and higher psychopathology risk, but this has not been explored in adults. Using person-centered, multitrajectory modeling, we found that hyperreactive or discordant hyporeactive stress response profiles were associated with more psychopathology.