Medullary serotonergic network deficiency in the sudden infant death syndrome: review of a 15-year study of a single dataset

J Neuropathol Exp Neurol. 2001 Mar;60(3):228-47. doi: 10.1093/jnen/60.3.228.


The sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant mortality in the United States today, despite a dramatic 38% decrease in incidence due to a national risk reduction campaign advocating the supine sleep position. Our research in SIDS brainstems, beginning in 1985 and involving a single, large dataset, has become increasingly focused upon a specific neurotransmitter (serotonin) and specific territories (ventral medulla and regions of the medullary reticular formation that contain secrotonergic neurons). Based on this research, we propose that SIDS, or a subset of SIDS, is due to a developmental abnormality in a medullary network composed of (at least in part) rhombic lip-derived, serotonergic neurons, including in the caudal raphé and arcuate nucleus (putative human homologue of the cat respiratory chemosensitive fields); and this abnormality results in a failure of protective responses to life-threatening stressors (e.g. asphyxia, hypoxia, hypercapnia) during sleep as the infant passes through a critical period in homeostatic control. We call this the medullary serotonergic network deficiency hypothesis. We review the triple-risk model for SIDS, the development of the dataset using tissue autoradiography for analyzing neurotransmitter receptor binding; age-dependent baseline neurochemical findings in the human brainstem during early life; the evidence for serotonergic, rhombic lip, and ventral medullary deficits in at least some SIDS victim; possible mechanisms of sudden infant death related to these deficits; and potential causes of the deficits in the medullary serotonergic network in SIDS victims. We conclude with a summary of future directions in SIDS brainstem research.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Humans
  • Infant
  • Medulla Oblongata / metabolism*
  • Medulla Oblongata / pathology*
  • Nerve Net / metabolism*
  • Serotonin / deficiency*
  • Sudden Infant Death / pathology*


  • Serotonin