Placental serotonin: implications for the developmental effects of SSRIs and maternal depression

In addition to its role in the pathophysiology of numerous psychiatric disorders, increasing evidence points to serotonin (5-HT) as a crucial molecule for the modulation of neurodevelopmental processes. Recent evidence indicates that the placenta is involved in the synthesis of 5-HT from maternally derived tryptophan (TRP). This gives rise to the possibility that genetic and environmental perturbations directly affecting placental TRP metabolism may lead to abnormal brain circuit wiring in the developing embryo, and therefore contribute to the developmental origin of psychiatric disorders. In this review, we discuss how perturbations of the placental TRP metabolic pathway may lead to abnormal brain development and function throughout life. Of particular interest is prenatal exposure to maternal depression and antidepressants, both known to alter fetal development. We review existing evidence on how antidepressants can alter placental physiology in its key function of maintaining fetal homeostasis and have long-term effects on fetal forebrain development.