Perinatal depression: Heterogeneity of disease and in animal models

Perinatal depression (PND) can have either an antepartum or postpartum onset. Although the greatest risk factor for PND is previous depression history, de novo PND occurs with the majority of cases occurring in the postpartum. Timing of depression can impact etiology, prognosis, and response to treatment. Thus, it is crucial to study the impact of the heterogeneity of PND for better health outcomes. In this review, we outline the differences between antepartum and postpartum depression onset of PND. We discuss maternal physiological changes that differ between pregnancy and postpartum and how these may differentially impact depression susceptibility. We highlight changes in the maternal steroid and peptide hormone levels, immune signalling, serotonergic tone, metabolic factors, brain morphology, and the gut microbiome. Finally, we argue that studying the heterogeneity of PND in clinical and preclinical models can lead to improved knowledge of disease etiopathology and treatment outcomes.