Validating an animal model of female veteran risk factors for postpartum depression

Veterans Health Administration, Decatur PA

Investigators

Abstract

Postpartum depression (PPD) is a major depressive episode following childbirth that affects 10-15% of women in the general population but nearly 20-40% of female veterans. Current preclinical models of PPD focus solely on civilian risk factors, incorporating single exposures to either gestational or postpartum stress, postpartum hormone withdrawal, or genetic manipulations to investigate underlying mechanisms of PPD. Female veterans have increased exposure to traumatic stressors during their compared to civilian counterparts and face unique stressors upon leaving the military, including significantly increased divorce rate, homelessness, and social isolation. This multitude of exposures represents a key difference from civilian women and may explain the increased PPD rate, as chronic stress exposure is a major risk factor for PPD. This project proposes to validate a new rodent model of PPD (multi-CUS) that mimics the traumatic stress exposures experienced by female veterans. Female rats will be exposed to three weeks of chronic unpredictable stress, followed by mating. On gestational day 10, females will undergo an additional 10 days of stress. During the postpartum period, depressive-, anxiety-like, and maternal behaviors will be assessed and compared to single, gestational CUS-exposed females as well as non-stress postpartum, and non-pregnant stressed females. Multi- CUS will also be validated at the cellular and molecular levels via examination of plasma corticosterone, hormone, and cytokine levels, brain mitochondrial function, and changes in hippocampal spine density. These are all measures that have been demonstrated in validated models of PPD. The lack of preclinical PPD models based on female veteran exposures means that the consequences of these exposures to veteran health are unknown, posing a health risk to a growing VA healthcare population. This has potentially devastating consequences as PPD in civilians can lead to lifelong recurring depression, negative outcomes for offspring, and even suicide. As female veterans have higher reports of suicide ideation and mental health disorders, they are at an increased risk for negative outcomes from PPD. Successful validation of the multi-CUS model will allow for future use of this model to identify how female veteran exposures may alter PPD symptoms, duration, and treatments.