Platelet Serotonin in Newborns and Infants: Ontogeny, Heritability, and Effect of In Utero Exposure to Selective Serotonin Reuptake Inhibitors

Abstract

Ontogeny of platelet serotonin (5-hydroxytryptamine, 5-HT) during the first year of life was examined in newborns and infants. The effects of in utero exposure to selective serotonin reuptake inhibitors (SSRI, including fluoxetine, sertraline, and citalopram) were examined by comparing cord blood 5-HT levels in exposed and unexposed newborns. Heritability was assessed by correlation of the platelet 5-HT values observed for mother-infant pairs. No age effect was observed in 1-49 wk-old infants (r ϭ 0.13, p ϭ 0.49) and mean platelet 5-HT levels in infants (241 Ϯ 102 ng/mL, n ϭ 33; 615 Ϯ 320 ng/10 9 platelets, n ϭ 32) were similar to those reported for older children and adults. However, significantly lower blood 5-HT levels were observed in newborns (81.3 Ϯ 32.5 ng/mL, n ϭ 16, p Ͻ 0.0001; 297 Ϯ 101 ng/10 9 platelets, n ϭ 11, p ϭ 0.0007) compared with the 1-49 wk-old infants. The mean cord blood 5-HT concentrations in newborns exposed in utero to SSRI (n ϭ 8) were substantially lower than that seen in unexposed (n ϭ 16) newborns (20.6 Ϯ 14.4 versus. 81.3 Ϯ 32.5 ng/mL, p ϭ 0.0001; 90.7 Ϯ 55.4 versus. 297 Ϯ 101 ng/10 9 platelets, p ϭ 0.0005). Platelet serotonin levels (ng/10 9 platelets) in mother-child pairs (n ϭ 32) were significantly correlated (r ϭ 0.415, p ϭ 0.018). The results indicate that, although platelet 5-HT is low at birth, values quickly increase and stabilize at near-adult levels by 1 mo of age. Gestational exposure to SSRI appears to substantially reduce platelet 5-HT uptake in the fetus, strongly suggesting that such exposure has important physiologic effects. The observed mother-infant correlation agrees with a previous report of high heritability in a large adult population. There is a continuing interest in platelet serotonin (5-HT) due to its hemostatic, thrombogenic, and cardiovascular effects (1, 2), its utility in assessing the bioeffects of SSRI (3-5), and its alteration in several neuropsychiatric disorders (6 -8). In prior work (9 -11), we carried out a series of studies examining the effects of SSRI exposure on platelet 5-HT in nursing infants and in the present study seek to extend the available data regarding the normal ontogeny of platelet 5-HT in infants. We also wished to establish more firmly prior reports of low platelet 5-HT levels in newborn cord blood and to examine the effects of gestational SSRI exposure on cord blood levels.Finally, our investigations of nursing mother-infant pairs provided the opportunity to contribute to the limited data assessing the heritability of platelet 5-HT.The platelet and neuronal 5-HT transporters are encoded by the same gene and appear identical in terms of pharmacology (12, 13). All platelet 5-HT is accumulated by uptake through the platelet membrane 5-HT transporter and a number of studies have used the decline in platelet 5-HT seen after administration of reuptake inhibitors as an index of central and peripheral transporter blockade (3-5). The impact of central serotonin 5-HT modulation by SSRI during critical periods of brain development is un...

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

“…Whole-blood 5-HT in newborns is correlated with their mothers' (r = 0.42, P = 0.02). This was a short-term effect because infants older than 4 weeks had 5-HT concentrations similar to adult concentrations as predicted based upon the pharmacology and clearance of the drug (Anderson et al, 2004). This effect is isolated to the prenatal period of exposure when fetal exposure is considerable compared with SSRI exposure postpartum in mother-infant breastfeeding pairs that results in no changes in concentrations of 5-HT in newborns (Epperson et al, 2003).…”

Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay

“…In mice, maternal fluoxetine in early development reversed the effects of prenatal maternal stress on depressive-like behaviors and hippocampal neurogenesis in adolescent offspring. 8 In humans, SSRIs cross the placenta, 9 reduce serotonin reuptake in the placenta 10 and fetus, 11 and may reduce uterine blood flow, leading to fetal hypoxemia. 12 Fetal hypoxia can adversely affect birth and developmental outcomes; an association with ASD is plausible.…”

Decreased numbers of dense granules in fetal and neonatal platelets

“…Neonatal platelets have been reported to have low levels of serotonin 10,11 relative to those from older children/adults, and to show decreased re-release of serotonin 13 and mepacrine, 14 despite comparable levels of uptake. The mepacrine observation was interpreted as indicating that neonatal platelets do not have decreased dense granules relative to adults, but rather a defect in an unspecified release mechanism.…”