Abnormalities of the Brainstem Serotonergic System in the Sudden Infant Death Syndrome: A Review

Abstract

INTRODUCTION Sudden infant death syndrome (SIDS) is the sudden death of an infant younger than 1 year that remains unexplained by a complete autopsy, death scene investigation, and review of the clinical record [1]. There has been an almost 50% decrease in the incidence of SIDS in the United States after a 1992 national recommendation for the supine sleep position. Nevertheless, SIDS remains a leading cause of postneonatal infant mortality. Its overall incidence is 0.6 per 1,000 live births [2]; approximately 6 infants die per day from SIDS in this country alone. Risk factors for SIDS other than the prone sleeping position are well recognized. Environmental risk factors include maternal cigarette smoking and alcohol intake during pregnancy [3–5]. Genetic risk factors include polymorphisms in the serotonin transporter (SERT) [6–8] and cytokine interleukin-10 [9]. Such risk factors appear to be independent of the prone sleeping position and are certainly more difficult to modify. Thus, SIDS remains a major public health problem, thus mandating further research into the underlying cause(s) and mechanism(s) to develop specific strategies to eradicate all SIDS deaths. Moreover, risk reduction messages are likely to be more compelling to families and health care workers and, hence, more successful when they are based on biologically established or plausible mechanisms. This report presents a review of findings related to brainstem serotonergic (5-HT) abnormalities in a subset of SIDS cases. From 1990 to 2003, my colleagues and I published a series of reports concerning 6 neurotransmitter systems in step tissue sections of the same SIDS and control brainstems [5,10–15]. Our overall conclusion was that the 5-HT system in the medulla oblongata, i.e., the so-called medullary 5-HT system, is abnormal in at least 50% of SIDS cases [16]. We focused on brainstem systems involved in the control of respiration, autonomic function, sleep, and arousal because of an increasing body of prospective studies involving infants who subsequently died of SIDS that indicate subtle abnormalities in respiratory and/or autonomic control during sleep and arousal patterns before death [17–19]. Moreover, studies in normal preterm and term infants have indicated that the period of *Corresponding author, e-mail: hannah.kinney@childrens.harvard.edu Pediatric and Developmental Pathology 8, 507–524, 2005 DOI: 10.1007/s10024-005-0067-y a 2005 Society for Pediatric Pathology