UBC Theses and Dissertations
Perinatal depression and treatment implications for mother and offspring : lessons from an animal model Qiu, Wansu
Perinatal depression (PND) is a heterogenous disease where risk factors, symptoms, severity, treatment efficacy, and effects on children can differ depending on timing of onset. The majority of new cases occur with depression onset in the postpartum (postpartum depression; PPD). Very few people with PPD are adequately treated and even in these individuals only ~50% will reach remission with current front-line treatments of selective serotonin reuptake inhibitors (SSRIs). Inflammatory signalling has been related to antidepressant efficacy outside of the postpartum, and I investigated inflammatory mechanisms that may modulate the efficacy of fluoxetine (FLX) in the postpartum. In children, maternal SSRI treatment alters neurodevelopment, including an increased risk for autism spectrum disorder. In Chapter 4, I investigate oxytocin (OT) as a therapeutic in preadolescent offspring to ameliorate maternal treatment effects of CORT and FLX. In Chapter 2, postpartum FLX did not reduce passive coping behaviour in the dams and was commensurate with FLX induced elevations in hippocampal IL-1β levels, peripheral CXCL1 levels, and reduced plasma tryptophan concentrations. In Chapter 3, postpartum CORT treatment increased putative neurotoxic and neuroprotective metabolites within the tryptophan-metabolic pathway in dams. Maternal postpartum FLX did not reverse any postpartum CORT effects, and together with CORT, shifted the tryptophan metabolism towards neurotoxicity. In Chapter 4, maternal FLX reduced neurogenesis and IL-10, IL-13, IFN-γ expression in the hippocampus of offspring. Maternal CORT increased hippocampal neurogenesis and hippocampal IL-6:IL-10 ratio in both sexes, while periadolescent OT treatment reversed these and increased social behaviour in offspring of maternal CORT-treated dams. OT increased neurogenesis in the hippocampus of adult male offspring but not adult female offspring. Collectively, these data suggest the inefficacy of FLX long-term during the postpartum may be due to increased proinflammatory signalling in the hippocampus and reduced tryptophan, and future studies should investigate these pathways to improve long-term efficacy of SSRIs. Moreover, PPD and postpartum antidepressant treatments can have long-term consequences in offspring, which may be ameliorated with OT treatment prior to adolescence. Together, these data can facilitate a better understanding of the consequences of untreated and treated maternal PPD for better outcomes in mothers and children.
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