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Comparison of pharmacological and non-pharmacological antidepressants in postpartum depression: outcomes of mother and male and female offspring

University of British Columbia

Postpartum depression (PPD) is a psychiatric illness that affects approximately 15% of mothers, negatively impacting mental health during the postpartum as well as increasing risk for future depression. For the developing child, untreated PPD is associated with several adverse outcomes including increased risk for depression, anxiety, and poor cognition particularly in boys. However, treating PPD is complicated because pharmacological antidepressants like fluoxetine (FLX) may function differently within the physiological conditions of the postpartum period. Additionally, these drugs are active in breast milk, directly reaching the infant and potentially influencing neurodevelopment. The long-term effects of neonatal antidepressant exposure are unclear. Alternatively, non-pharmacological antidepressants such as exercise are generally beneficial for maternal and fetal health; however, its potential as an antidepressant in the postpartum and its long-term effects on offspring are unclear. To investigate this, this thesis used a rat model of PPD in which dams are treated with high levels of corticosterone (CORT; primary rat glucocorticoid) and compared how different types of antidepressants affected dams and adult male and female offspring. In chapter 2, maternal postpartum FLX prevented CORT-induced disruptions in maternal care but was unable to prevent CORT-induced depressive-like behaviour or reductions in hippocampal neurogenesis. In chapter 3, maternal postpartum FLX increased anxiety-like behaviour, impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback, and increased hippocampal neurogenesis in adult male but not female offspring. In chapter 4, maternal exercise did not prevent CORT-induced disruptions in maternal care but it prevented CORT-induced depressive-like behaviour and increased hippocampal neurogenesis. While neither antidepressant alone increased maternal neurogenesis, the combination of both treatments increased neurogenesis. In chapter 5, maternal exercise increased hippocampal neurogenesis in dorsal hippocampus but maternal postpartum FLX reduced it. However, exposure to maternal postpartum FLX prevented the neurogenic effect of maternal exercise. Maternal exercise facilitated HPA axis negative feedback in males but impaired in females. Collectively, these data indicate that antidepressants can have dynamic effects on endophenotypes of PPD, emphasizing the need for further research in PPD. Furthermore, male and female offspring development is differentially sensitive to these maternal antidepressant interventions, highlighting the importance of studying sex differences in neurodevelopment.

Text

2018-04-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/63362

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/