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

The sudden infant death syndrome (SIDS) is the leading cause of postneonata l infant mortality in the United States today, despite a dramatic 38% decre ase in incidence due to a national risk reduction campaign advocating the s upine sleep position. Our research in SIDS brainstems, beginning in 1985 an d involving a single, large dataset, has become increasingly focused upon a specific neurotransmitter (serotonin) and specific territories (ventral me dulla and regions of the medullary reticular formation that contain seroton ergic neurons). Based on this research, we propose that SIDS, or a subset o f SIDS, is due to a developmental abnormality in a medullary network compos ed of (at least in part) rhombic lip-derived, serotonergic neurons, includi ng in the caudal raphe 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. asphyxi a, hypoxia, hypercapnia) during sleep as the infant passes through a critic al period in homeostatic control. We call this the medullary serotonergic n etwork deficiency hypothesis. We review the triple-risk model for SIDS, the development of the dataset using tissue autoradiography for analyzing neur otransmitter receptor binding; age-dependent baseline neurochemical finding s in the human brainstem during early life; the evidence for serotonergic, rhombic lip, and ventral medullary deficits in at least some SIDS victims; possible mechanisms of sudden infant death related to these deficits; and p otential causes of the deficits in the medullary serotonergic network in SI DS victims. We conclude with a summary of future directions in SIDS brainst em research.