A recent study published in Depression and Anxiety demonstrated a direct and interactive association of recent life stress and cumulative hypothalamic-pituitary-adrenal (HPA) axis functioning with depressive symptoms among adolescents.

Benjamin G. Shapero, PhD, from the department of psychiatry, Massachusetts General Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues enrolled a community sample of 58 adolescents (67.2% female; 58.6% white; mean age, 15.07±1.02 years) in the study. Participants completed the Children’s Depression Inventory, Adolescent Life Events Questionnaire, and Life Events Interview. The investigators assessed hair cortisol concentrations to gauge cumulative exposure to HPA axis functioning and collected data on sociodemographic variables and 3 covariates: depression diagnosis, early childhood stress, and pubertal development.

Participants who were female, older, black, and more economically disadvantaged, as well as those who reported early-life stress and longer sleep, had higher hair cortisol levels. Findings indicated a direct association of recent life stress (P =.001) and cumulative HPA axis exposure (P =.025) with increased depressive symptoms in the entire sample. Furthermore, recent life stress, cumulative HPA axis exposure, and their interaction explained 40.8% of variation in depressive symptoms.

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The HPA axis exposure-moderated relationship between recent life stress and depression only remained significant for adolescents who experienced average (P =.004) and high (P <.001) cumulative HPA axis exposure. In addition, the interaction of recent life stress and cumulative HPA axis exposure on depressive symptoms remained significant in multiple sensitivity analyses. This relationship was more potent for chronic than for episodic stress.

According to the authors, this study distinguishes itself from others given its focus on cumulative exposure to cortisol rather than acute circulating levels. They argue that hair cortisol represents a more stable measure of HPA axis functioning than other assessments. However, the authors cautioned that chronic stress may ultimately lead to decreases, rather than increases, in cortisol.

The authors noted that these findings should be considered preliminary, as the study has a number of limitations, including the failure to account for hair washing or the use of hair dyes that could affect cortisol levels. These findings are also limited by the size of the study population. The authors call for further research to “evaluate the synergistic impact of life stress and cumulative HPA axis exposure on the course and onset of depression.”


Shapero BG, Curley EE, Black CL, Alloy LB. The interactive association of proximal life stress and cumulative HPA axis functioning with depressive symptoms [published online October 15, 2019]. Depress Anxiety. doi:10.1002/da.22957