High serum serotonin in sudden infant death syndrome

Abstract

Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, likely comprises heterogeneous disorders with the common phenotype of sudden death without explanation upon postmortem investigation. Previously, we reported that ∼40% of SIDS deaths are associated with abnormalities in serotonin (5-hydroxytryptamine, 5-HT) in regions of the brainstem critical in homeostatic regulation. Here we tested the hypothesis that SIDS is associated with an alteration in serum 5-HT levels. Serum 5-HT, adjusted for postconceptional age, was significantly elevated (95%) in SIDS infants (n = 61) compared with autopsied controls (n = 15) [SIDS, 177.2 ± 15.1 (mean ± SE) ng/mL versus controls, 91.1 ± 30.6 ng/mL] (P = 0.014), as determined by ELISA. This increase was validated using high-performance liquid chromatography. Thirty-one percent (19/61) of SIDS cases had 5-HT levels greater than 2 SDs above the mean of the controls, thus defining a subset of SIDS cases with elevated 5-HT. There was no association between genotypes of the serotonin transporter promoter region polymorphism and serum 5-HT level. This study demonstrates that SIDS is associated with peripheral abnormalities in the 5-HT pathway. High serum 5-HT may serve as a potential forensic biomarker in autopsied infants with SIDS with serotonergic defects.asphyxia | brainstem | pulmonary neuroepithelial bodies | platelets | high-performance liquid chromatography

Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT3receptors

“…An elevated serum levels of 5-HT has been observed in victims of SIDS (18). The present study showed, for the first time, that PNE doubles the 5-HT concentration in BALF (from 1.3 to 2.5 ng/ml) in rat pups, similar to the findings of the 5-HT protein level in blood (;4 ng/ ml), which is doubled by cigarette smoking for 6 wk in rats (53).…”

“…PCFs are critical for the generation of central origin apnea (13,14), and, upon activation, 5-HT receptor 3 (5-HT 3 R) in PCFs is capable of inducing an apneic response (15)(16)(17). Although the elevated serum 5-HT levels have been observed in victims of SIDS (18), whether PNE affects the 5-HT level in bronchoalveolar lavage fluid (BALF) and augments the apnea mediated by 5-HT 3 R in PCFs and the relevant mechanism underlying this augmentation remains unknown.…”

Advances in cellular and integrative control of oxygen homeostasis within the central nervous system

“…Children that die from SIDS breathe normally under normoxic conditions, but fail to gasp during hypoxia (Poets et al 1999;Garcia et al 2013). Various studies also demonstrated dysregulation of 5-HT in SIDS (Broadbelt et al 2012;Massey et al 2013;Rognum et al 2014;Haynes et al 2016Haynes et al , 2017Bright et al 2017). Thus, infants with disturbed 5-HT mechanisms might be protected under normal oxygenated conditions, but become vulnerable to genetic mutations that affect serotonergic neurons when the network transitions into a hypoxic state (Tryba et al 2006;Garcia et al 2013).…”

Central and peripheral chemoreceptors in sudden infant death syndrome

“…Although the above morphometric and neurochemical changes further support a pathogenetic role for central respiratory chemoreceptors, they are still difficult to apply for diagnosis in the forensic context, due to the need for specific methodological experience and proper controls for comparison. Of particular interest is a recent paper which reported higher serum serotonin levels in SIDS victims than in controls, with a subset of 31% SIDS cases with serotonin levels higher than 2 standard deviations above the mean of controls, supporting peripheral anomalies in serotonin metabolism and proposing a simple marker (Haynes et al 2017).…”

“…Of particular interest is a recent paper which reported higher serum serotonin levels in SIDS victims than in controls, with a subset of 31% SIDS cases with serotonin levels higher than 2 standard deviations above the mean of controls, supporting peripheral anomalies in serotonin metabolism and proposing a simple marker (Haynes et al . ).…”