Risks and benefits of prenatal exposure to antidepressants: Neurobiological mechanisms and clinical evidence.

Abstract

This review summarizes current evidence on how maternal stress, depression, and antidepressant treatment during pregnancy influence offspring neurodevelopment. We focus on neurobiological mechanisms linking maternal and fetal brains, particularly interactions between monoaminergic systems and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signaling axis. Preclinical studies demonstrate that maternal stress during gestation alters the activity of offspring monoaminergic neurons and associated neuroplasticity pathways. Prenatal stress typically reduces serotonergic neuronal firing while enhancing catecholaminergic transmission, whereas pregestational stress may produce opposite neurophysiological effects. These changes are accompanied by behavioral alterations, including increased anxiety- and depression-like behavior. Clinical studies indicate that maternal stress and depression are associated with structural and functional brain alterations in offspring, particularly within the amygdala-hippocampal network involved in emotional regulation. Prenatal antidepressant exposure may modify these outcomes, with effects varying according to drug class, timing of exposure, and maternal clinical status. Although some studies report mild perinatal effects such as earlier delivery or lower birth weight, many associations between prenatal antidepressant exposure and neurodevelopmental disorders appear to be largely explained by underlying maternal psychiatric conditions. The available evidence highlights the complex interaction between maternal mental health, neurotrophic signalling, and monoaminergic neurophysiology in offspring brain development.