title: Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome.
abstract: 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.
authors.affiliation: Department of Pathology, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. Hannah.Kinney@tch.harvard.edu
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Randall
authors.forename: Lynn A
authors.initials: LA
authors.lastname: Sleeper
authors.forename: Marian
authors.initials: M
authors.lastname: Willinger
authors.forename: Richard A
authors.initials: RA
authors.lastname: Belliveau
authors.forename: Natasa
authors.initials: N
authors.lastname: Zec
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Rava
authors.forename: Laura
authors.initials: L
authors.lastname: Dominici
authors.forename: Solomon
authors.initials: S
authors.lastname: Iyasu
authors.forename: Bradley
authors.initials: B
authors.lastname: Randall
authors.forename: Donald
authors.initials: D
authors.lastname: Habbe
authors.forename: Harry
authors.initials: H
authors.lastname: Wilson
authors.forename: Frederick
authors.initials: F
authors.lastname: Mandell
authors.forename: Mary
authors.initials: M
authors.lastname: McClain
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Welty
mesh_terms: D000367:Age Factors; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism / Q000473:pathology; D001345:Autoradiography; D001665:Binding Sites; D001933:Brain Stem / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D000431:Ethanol / Q000009:adverse effects; D005260:Female; D006801:Humans; D007198:Indians, North American / Q000208:ethnology; D007223:Infant; D007231:Infant, Newborn; D007407:Interviews as Topic; D008238:Lysergic Acid Diethylamide / Q000493:pharmacokinetics; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects; D013398:Sudden Infant Death / Q000453:epidemiology / Q000473:pathology*
chemical_list: D011985:Receptors, Serotonin; D012906:Smoke; D012701:Serotonin; D000431:Ethanol; D008238:Lysergic Acid Diethylamide