Fetal serotonin signaling: setting pathways for early childhood development and behavior.
Finely tuning levels of the key neurotransmitter serotonin (5-hydroxytryptamine [5-HT]) during early life is essential for brain development and setting pathways for health and disorder across the early life span. Given the central role of 5-HT in brain development, regulation of mood, stress reactivity, and risk for psychiatric disorders, alterations in 5-HT signaling early in life have critical implications for behavior and mental health in childhood and adolescence. This article reviews the developmental consequences of two key influences that alter fetal 5-HT signaling: (1) in utero exposure to 5-HT reuptake inhibitor antidepressants, and (2) genetic variations in the 5-HT transporter gene (SLC6A4). The consequences of altered prenatal 5-HT signaling vary greatly, and developmental outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations), experiential (prenatal drug or maternal mood exposure), and contextual (postnatal social environment) variables. Emerging evidence suggests both exposure to 5-HT reuptake inhibitors and genetic variations that affect 5-HT signaling may increase sensitivity to negative social contexts for some individuals, whereas for others, they may confer sensitivity to positive life circumstances. In this sense, factors that change central 5-HT levels may function less like influences that predict "vulnerability," but rather act like "plasticity factors." Understanding the impact of early changes in serotonergic programming offers critical insights that might explain patterns of individual differences in developmental risk and resilience.
Department of Pediatrics, Child and Family Research Institute, Vancouver, British Columbia, Canada. toberlander@cw.bc.ca
Tim F
TF
Oberlander
D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D002648:Child; D002652:Child Behavior / Q000187:drug effects* / Q000502:physiology; D002657:Child Development / Q000187:drug effects* / Q000502:physiology; D003866:Depressive Disorder / Q000188:drug therapy; D005260:Female; D006803:Human Development / Q000187:drug effects / Q000502:physiology; D006801:Humans; D018811:Maternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human