Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome

J Neuropathol Exp Neurol. 2003 Nov;62(11):1178-91. doi: 10.1093/jnen/62.11.1178.


The rate of the sudden infant death syndrome (SIDS) among American Indian infants in the Northern Plains is almost 6 times higher than in U.S. white infants. In a study of infant mortality among Northern Plains Indians, we tested the hypothesis that receptor binding abnormalities to the neurotransmitter serotonin (5-HT) in SIDS cases, compared with autopsied controls, occur in regions of the medulla oblongata that contain 5-HT neurons and that are critical for the regulation of cardiorespiration and central chemosensitivity during sleep, i.e. the medullary 5-HT system. Tritiated-lysergic acid diethylamide binding to 5-HT(1A-D) and 5-HT2 receptors was measured in 19 brainstem nuclei in 23 SIDS and 6 control infants using tissue receptor autoradiography. Binding in the arcuate nucleus, a part of the medullary 5-HT system along the ventral surface, in the SIDS infants (mean age-adjusted binding 7.1 +/- 0.8 fmol/mg tissue, n = 23) was significantly lower than in controls (mean age-adjusted binding 13.1 +/- 1.6 fmol/mg tissue, n = 5) (p = 0.003). Binding also demonstrated significant diagnosis x age interactions (p < 0.04) in 4 other nuclei that are components of the 5-HT system. These data suggest that medullary 5-HT dysfunction can lead to sleep-related, sudden death in affected SIDS infants, and confirm the same binding abnormalities reported by us in a larger dataset of non-American Indian SIDS and control infants. This study also links 5-HT abnormalities in the arcuate nucleus with exposure to adverse prenatal exposures, i.e. cigarette smoking (p = 0.011) and alcohol (p = 0.075), during the periconceptional period or throughout pregnancy. Prenatal exposure to cigarette smoke and/or alcohol may contribute to abnormal fetal medullary 5-HT development in SIDS infants.

Publication types

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

MeSH terms

  • Age Factors
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Arcuate Nucleus of Hypothalamus / pathology
  • Autoradiography
  • Binding Sites
  • Brain Stem / abnormalities*
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Case-Control Studies
  • Ethanol / adverse effects
  • Female
  • Humans
  • Indians, North American / ethnology
  • Infant
  • Infant, Newborn
  • Interviews as Topic
  • Lysergic Acid Diethylamide / pharmacokinetics
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism*
  • Smoke / adverse effects
  • Sudden Infant Death / epidemiology
  • Sudden Infant Death / pathology*


  • Receptors, Serotonin
  • Smoke
  • Serotonin
  • Ethanol
  • Lysergic Acid Diethylamide