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

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.