Effects of paternal and maternal depression on offspring: Manifestations, mechanisms, and interventions

Parental depression-encompassing both maternal and paternal depressive disorders-represents a significant risk factor for adverse neurodevelopmental and mental health outcomes in offspring. While maternal depression has been extensively characterized, paternal depression remains comparatively understudied, despite meta-analytic evidence indicating that offspring of depressed fathers face a 42% elevated risk of developing depression themselves. This narrative review addresses the specific gap in the literature by integrating human and animal evidence to examine how biological sex and gender-related sociocultural factors differentially shape the intergenerational transmission of depression. We summarize distinct mechanisms underlying maternal versus paternal effects, including placental and epigenetic pathways, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, neurotransmitter alterations, and gut microbiota disturbances. Furthermore, we discuss sex-specific vulnerabilities in offspring and gender-differential symptom expression and parenting behaviors that moderate these associations. Finally, we evaluate evidence-based interventions-ranging from cognitive-behavioral therapy and pharmacotherapy to environmental enrichment and physical activity-and discuss their translational potential for disrupting intergenerational cycles of psychopathology. By adopting a dual-parental and sex/gender-sensitive framework, this review aims to inform holistic, family-centered prevention and intervention strategies.