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. 2017 Jul 18;114(29):7695-7700.
doi: 10.1073/pnas.1617374114. Epub 2017 Jul 3.

High serum serotonin in sudden infant death syndrome

Robin L Haynes  1 , Andrew L Frelinger 3rd  2 , Emma K Giles  3 , Richard D Goldstein  4 , Hoa Tran  3 , Harry P Kozakewich  3 , Elisabeth A Haas  5 , Anja J Gerrits  2 , Othon J Mena  6 , Felicia L Trachtenberg  7 , David S Paterson  3 , Gerard T Berry  8 , Khosrow Adeli  9 , Hannah C Kinney  3 , Alan D Michelson  2
Affiliations

High serum serotonin in sudden infant death syndrome

Robin L Haynes et al. Proc Natl Acad Sci U S A. .

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.

Keywords: asphyxia; brainstem; high-performance liquid chromatography; platelets; pulmonary neuroepithelial bodies.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Serum 5-HT values determined by ELISA and HPLC. (A) There was a significant elevation (average of 95%) in SIDS infants [177.2 ± 15.1 (SE) ng/mL] compared with controls [91.1 ± 30.6 (SE) ng/mL], P = 0.014, by ELISA. HPLC confirmed this finding in a subset of cases. The bars in the graph represent SD. (B) Serum 5-HT levels obtained with two different methods, ELISA and HPLC, showed significant correlation in SIDS cases [Spearman correlation of 0.84 (P < 0.001)] and controls [Spearman correlation of 0.87 (P < 0.001)]. There is no significant effect of (C) postmortem interval or (D) storage length at −80 °C on the levels of serum 5-HT in control or SIDS infants.
Fig. S1.
Fig. S1.
Effect of breastfeeding on serum 5-HT in control and SIDS cases. Data are mean ± SD.
See this image and copyright information in PMC

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