Examining the Relationships Between Chronic Stress, HPA Axis Activity, and Depression in a Prospective and Longitudinal Study of Medical Internship

Abstract

OBJECTIVE: Depression is common, and stress plays a causal role in depression onset, perhaps via Hypothalamic-Pituitary-Adrenal (HPA) axis activation. Decades of work documented HPA hyperactivity in depression. Yet, the nature of this relationship is unclear, partly because the HPA axis is a complex system and cortisol measurement over time has been challenging. A recent development of cortisol assessment in hair has now made it possible to quantify cortisol secretions over prolonged periods of time. In this study, we incorporated hair cortisol measurement into an existing prospective and longitudinal study of medical internship, stress, and depression. This gave us a rare opportunity to investigate links between chronic stress, hair cortisol, and depressive symptoms and allowed us to test the impact of psychological factors. Specifically, we examined 1) hair cortisol changes in response to medical internship, 2) associations between hair cortisol levels and depressive symptoms, 3) psychological factors that impact respective associations, and 4) prospective indicators of depression vulnerability. METHODS: Seventy-four medical residents (age 25-33) were recruited. We assessed hair cortisol, depressive symptoms, and psychological variables (perceived stress, mastery/control, social support, loneliness, resilience, compassion, childhood trauma) prior to internship start as well as repeatedly throughout medical internship. RESULTS: Hair cortisol levels changed over time: they increased sharply with the onset of internship stress, decreased as internship continued, and rose again towards the end of internship, prior the start of the second residency year. The initial increase in hair cortisol responses to internship stress was not directly related to depressive symptoms in response to or in the midst of internship. Preliminary findings showed that elevated hair cortisol levels were related to increased depressive symptoms during periods of anticipation, and that both were related to less adaptive psychosocial correlates prior to internship stress. CONCLUSION: The prospective and longitudinal study examined links between chronic stress, HPA axis activity, depressive symptoms, and psychological factors. Our finding supports the validity of hair cortisol as a field-friendly biomarker for chronic stress exposure. Hair cortisol responses to chronic stress may perhaps reflect context-specific psychological processes related to anticipation, novelty/familiarity, and social evaluative threat. Hair cortisol and depressive symptom responses to stress were not directly related, but links between hair cortisol, depressive symptoms, and psychological factors were present prior to stress exposure, perhaps reflecting shared underlying vulnerabilities that were most apparent in the context of stressor anticipation, when stress was moderate and uniquely characterized by high levels of uncertainty. During internship stress, hair cortisol may reflect the impact of stress exposure, perhaps related to contextual features, which may not be mechanistically linked to depression risk; however, in the absence of ongoing stress, it may indicate the impact of underlying vulnerabilities, which may be more directly linked to depressive symptoms. In sum, our results are consistent with a paradigm shift in the literature towards more complex models of how stress context, stress systems, and disorders are linked, suggesting interwoven interactions between neuroendocrine, genetic, environmental, and psychological factors that constitute vulnerability for the development of depression in the context of stress.PHDPsychologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/137074/1/stemayer_1.pd