Selective serotonin reuptake inhibitors (SSRIs) and heart defects: potential mechanisms for the observed associations

Abstract

Several epidemiological investigations have shown an association between congenital heart defects and the selective serotonin reuptake inhibitor (SSRI) class of antidepressants. At first glance this association may not seem to make biological sense, especially since, in many cases, serotonin is thought of as a neurotransmitter involved in signaling between neurons. However, serotonin also acts as a signaling molecule during embryogenesis affecting cell proliferation, migration, death, and differentiation. Serotonin may be particularly important for heart development and evidence suggests that from the time that progenitor heart cells are patterned during the establishment of laterality, to formation of the outflow tract, to myocardial cell differentiation, to septation of the heart chambers, the neurotransmitter may act as an important signaling molecule. Thus, numerous investigations have identified potential target sites where serotonin could regulate key cellular processes in cardiac development, thereby providing biological plausibility for the origin of heart defects caused by SSRIs.