High serum serotonin in sudden infant death syndrome

Robin L. Haynes; Andrew L. Frelinger; Emma K. Giles; Richard D. Goldstein; Hoa Tran; Harry P. Kozakewich; Elisabeth A. Haas; Anja J. Gerrits; Othon J. Mena; Felicia L. Trachtenberg; David S. Paterson; Gerard T. Berry; Khosrow Adeli; Hannah C. Kinney; Alan D. Michelson

doi:10.1073/pnas.1617374114

New Research In

Edited by Barry S. Coller, The Rockefeller University, New York, NY, and approved June 8, 2017 (received for review October 21, 2016)

Significance

Sudden infant death syndrome (SIDS), the leading cause of postneonatal infant mortality, is defined as the sudden death of an infant less than 1 y of age that remains unexplained after a complete autopsy and death scene investigation. Although SIDS has been associated with deficiencies in central (brainstem) serotonin (5-hydroxytryptamine, 5-HT), there are no known peripheral biomarkers for SIDS. Here we demonstrate increased serum serotonin levels in a subset (31%) of SIDS infants compared with control infants. These findings suggest the potential of a high serum serotonin level as a forensic biomarker at autopsy to differentiate SIDS deaths with serotonergic defects from other causes of sudden death and, importantly, as evidence of a peripheral 5-HT abnormality in SIDS.

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.

Footnotes

↵¹To whom correspondence should be addressed. Email: robin.haynes{at}childrens.harvard.edu.

Author contributions: R.L.H., A.L.F., R.D.G., H.C.K., and A.D.M. designed research; R.L.H., E.K.G., H.T., A.J.G., and D.S.P. performed research; R.L.H., A.L.F., E.K.G., and F.L.T. analyzed data; R.L.H., A.L.F., R.D.G., H.P.K., E.A.H., O.J.M., F.L.T., G.T.B., H.C.K., and A.D.M. wrote the paper; E.A.H. collected autopsy SIDS and control samples; O.J.M. collected SIDS and control autopsy samples; and K.A. provided healthy subject samples.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1617374114/-/DCSupplemental.

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