The Pathophysiological Mechanisms and Biomarkers Associated with Postpartum Depression - A Literature Review

Abstract

INTRODUCTION: Known as Postpartum Depression (PPD), Major Depressive Episode with peripartum onset is defined in DSM-5 by depressive symptoms during or after pregnancy, associated with anxiety, panic attacks, and psychosis. Although underdiagnosed, it affects up to 20% of pregnant women. Risk factors include previous depression and anxiety, impaired mother-infant bonding, disrupted family dynamics, and low socioeconomic status. OBJECTIVE: To analyze the pathophysiological mechanisms and biomarkers related to PPD. METHODS: A literature review was conducted. On August 31, 2024, a PubMed search was performed using the descriptors (DeCS): Postpartum Depression, Pathophysiology, Mechanism, Causes. Sixty-three results were obtained; articles not freely available or not addressing PPD pathophysiology were excluded, resulting in n = 8. RESULTS: Multiple biological and pathophysiological factors are linked to PPD. Hormonal impact during pregnancy and puerperium is evident, marked by changes in estrogen and progesterone levels with well-established effects. Reduced oxytocin is also related. Thyroid disorders, particularly hypothyroidism, are associated with late PPD through cortisol interaction. The hypothalamic-pituitary-adrenal (HPA) axis influences depressive symptoms from early pregnancy via maternal and placental glucocorticoid interaction. Increased risk was also observed with antihypertensives such as Methyldopa, due to neutrophilic mechanisms, reduced cerebral flow, neurotoxicity, and elevated prolactin. Genetic factors involve eight main genes associated with PPD (HNRNPA2B1, IL10, RAD51, UBA52, NHP2, RPL13A, FBL, SPI1) and possible methylation changes through epigenetics. Finally, decreased GABAergic system activity brings promising perspectives for new therapies, especially allopregnanolone. CONCLUSION: PPD is a multifaceted condition requiring further research on hormonal fluctuations, HPA axis dysfunction, thyroid aspects, genetic and epigenetic factors, biological markers, and drug impacts. Advancing knowledge in these areas is crucial to improve diagnosis, screening, prevention, and treatment, ensuring adequate maternal and family mental health.