Early life stress and HPA axis function independently predict adult depressive symptoms in metropolitan Cebu, Philippines

Abstract

Objectives: Alterations in adult hypothalamic-pituitary-adrenal (HPA) axis activity have increasingly been linked with early life stress and adult depression, but a limited number of studies have used longitudinal data to explore HPA axis dysregulation as an underlying mechanism driving the long-term depressive impacts of early stressors. Here we address potential long-term impacts of early life, family-based stress on depressive symptoms among young adults in a longitudinal birth cohort study begun in 1983 in the Philippines.

Materials and methods: We relate a composite measure of family-based stressors experienced between birth and adolescence to circadian dynamics in adult salivary cortisol and depressive risk measured at 21-22 years of age. Multiple regression analyses were conducted to examine the relationship between early life stress levels and risk of adult depressive symptoms, as well as the role of adult diurnal cortisol activity in this relationship.

Results: Greater levels of early life familial stress predicted more severe depressive symptomatology at age 21-22 in a dose-response fashion (p < .0001) independent of adult diurnal cortisol patterns. Flatter diurnal cortisol slopes are directly associated with higher adult depressive symptoms, an effect mostly driven by evening cortisol levels (p = .004). When considering the cumulative effects of early life stress measures, however, exposure to more of these stressors during development is associated with even higher depressive symptoms.

Discussion: The long-term depressive effects of early life familial stress extend to this large sample of Cebuano young adults, and early life stress and HPA axis function may shape adult depressive symptoms through independent pathways in this sample. Our findings provide further evidence that HPA axis activity is shaped by early life conditions and is associated with depressive symptoms.

Keywords: HPA axis; Philippines; depression; developmental origins of health and disease; early life stress; family stress; global mental health; low- and middle-income countries.

FIGURE 1

Effect size of early life stress groups on depressive symptom scores (p < .0001)

FIGURE 2

Mean values of depressive symptom scores stratified by past history of witnessing domestic violence (p < .0001)

FIGURE 3

Partial regression plot of CES-D residual values on natural logged and standardized residuals of bedtime cortisol (nmol/L). Residuals derived from separate regressions adjusting for times of saliva collections and smoking status (p = .004)