Serotonin and SIDS 

Serotonin is an increasingly interesting area of research and Professor Haycock, our medical advisor summarises recent findings in this field. 

Brain cells communicate with one another by means of chemicals called neurotransmitters. Release of a neurotransmitter molecule by one cell conveys a message to an adjacent cell, either stimulating or suppressing activity. One neurotransmitter is called serotonin (also known as 5-hydroxytryptamine, 5-HT): cells that use serotonin as a neurotransmitter are serotoninergic. Serotonin is important in the function of the part of the brain, the medulla oblongata, that controls essential functions such as blood pressure, breathing, temperature regulation and arousal from sleep. Evidence has been accumulating for some years that infants who die of SIDS show differences in the medullary serotoninergic system when compared with infants who have died of other, known, causes.(1-5). A report published in 2006 by the group led by Dr Hannah Kinney at the Children’s Hospital, Boston confirmed these differences and demonstrated that they are more extensive than previously reported.(6)

A 2008 study by a group of Italian scientists (7) showed that reproducing the changes in the medullary serotoninergic system seen in SIDS victims by genetic engineering in mice caused the affected animals to have unstable heart function and temperature control, and many of the mice died spontaneously in early life. The model did not reproduce all the features of SIDS, for example the excess of males that is consistently seen in clinical practice, but taken together with the human studies cited above it does offer a plausible explanation of why vulnerable infants fail to arouse when subject to stresses such as infection, thermal stress, hypoxia (low blood oxygen concentrations) among others. It is important to recognise that, although the mouse model was produced by genetic manipulation, it is not established whether the changes seen in human SIDS victims are of genetic origin or acquired in response to some as yet unknown external, environmental factor. For example, one research group in Sweden (8) has shown that antenatal exposure to nicotine causes developmental changes in the medulla of infant mice. These scientists did not specifically investigate the serotoninergic system but the known importance of maternal smoking as a risk factor for SIDS at least raises the possibility that there may be a causal connection. Both the experimental and the clinical observations included in this review are consistent with the triple risk hypothesis of SIDS:9 that in order to be at high risk of death, there must be (1) an inherent vulnerability in the infant not possessed by other infants; (2) an exogenous stressor (some event external to the infant such as infection, prone sleeping or hypoxia); and (3) a critical developmental period (most SIDS cases occur within a particular age range, which was also the case in the genetically engineered mice). According to this hypothesis, abnormalities of the serotoninergic system would fall into the category of an inherent or underlying vulnerability.


1 Panigrahy A, Filiano J, Sleeper LA, et al. Decreased serotonergic receptor binding in rhombic lip-derived regions of the medulla oblongata in the sudden infant death syndrome. J Neuropathol Exp Neurol 2000;59(5):377-84.
2 Weese-Mayer DE, Berry-Kravis EM, Maher BS, et al. Sudden infant death syndrome: association with a promoter polymorphism of the serotonin transporter gene. Am J Med Genet A 2003;117(3):268-74.
3 Weese-Mayer DE, Zhou L, Berry-Kravis EM, et al. Association of the serotonin transporter gene with sudden infant death syndrome: a haplotype analysis. Am J Med Genet A 2003;122(3):238-45.
4 Kinney HC, Myers MM, Belliveau RA, et al. Subtle autonomic and respiratory dysfunction in sudden infant death syndrome associated with serotonergic brainstem abnormalities: a case report. J Neuropathol Exp Neurol 2005;64(8):689-94.
5 Kinney HC, Randall LL, Sleeper LA, et al. Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome. J Neuropathol Exp Neurol 2003;62(11):1178-91.
6 Paterson DS, Trachtenberg FL, Thompson EG, et al. Multiple serotonergic brainstem abnormalities in sudden infant death syndrome. Jama 2006;296(17):2124-32.
7 Audero E, Coppi E, Mlinar B, et al. Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition. Science 2008;321(5885):130-3.
8 Cohen G, Roux JC, Grailhe R, et al. Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function. Proc Natl Acad Sci U S A 2005;102(10):3817-21.
9 Filiano JJ, Kinney HC. A perspective on neuropathologic findings in victims of the sudden infant death syndrome: the triple-risk model. Biol Neonate 1994;65(3-4):194-7.