ABSTRACT
Depressive and anxiety disorders are among the leading contributors to the global disease burden and are
more common in women compared to men. Among women in low-resource contexts, such as low- and middle-
income countries (LMICs), exposure to adversities (e.g., poverty, intimate partner violence, negative life events
such as illness or loss) is a powerful risk factor for developing internalizing symptoms (i.e., depressive and
anxiety symptoms). Dysregulated activity in the hypothalamic pituitary adrenal (HPA) axis may be a
mechanism underlying the onset of internalizing disorders and a novel adjunct target for mental health
interventions in addition to psychological symptoms. However, there is little evidence of the long-term effects of
mental health interventions on either psychological symptoms or HPA axis dysregulation. In addition, more
research is needed to characterize the dynamic role of adverse experiences in shaping women’s internalizing
symptoms and HPA axis activity over time, especially in South Asia, where women may have unique familial
social contexts compared to western counterparts. This work is essential for establishing and improving the
long-term effectiveness of mental health interventions globally. In this R21, we propose leveraging multi-year
experimental and observational data from the Bachpan study, an ongoing longitudinal birth cohort with an
embedded cluster randomized control trial of a maternal depression intervention delivered in rural Pakistan.
Specifically, we will test the effects the intervention on HPA axis regulation and internalizing symptoms 6 years
after intervention onset, as well as whether HPA axis activity mediates the effect of the intervention on
internalizing symptoms. We will also examine how adversity exposure, including chronic adversity experienced
over a six-year period, retrospectively reported childhood adversity, and recent adversity, relate to HPA axis
activity and internalizing symptoms. As part of this analysis, we will also examine how within-person changes in
adversity relate to within-person changes in HPA axis activity and internalizing symptoms over time. The rich,
multi-year dataset includes information on multiple domains of women’s mental health and adverse
experiences, as well as hair-derived HPA axis hormones (cortisol and DHEA). The major public health
contribution of this project is that it will generate knowledge on the longitudinal predictors of stress system
dysregulation and internalizing symptoms among women in a low resource context, as well as the potential
ameliorating role of psychosocial intervention.
