The Brainstem and Serotonin in the Sudden Infant Death Syndrome

Abstract

The sudden infant death syndrome (SIDS) is the sudden death of an infant under one year of age that is typically associated with sleep and that remains unexplained after a complete autopsy and death scene investigation. A leading hypothesis about its pathogenesis is that many cases result from defects in brainstem-mediated protective responses to homeostatic stressors occurring during sleep in a critical developmental period. Here we review the evidence for the brainstem hypothesis in SIDS with a focus upon abnormalities related to the neurotransmitter serotonin in the medulla oblongata, as these are the most robust pathologic findings to date. In this context, we synthesize the human autopsy data with genetic, whole-animal, and cellular data concerning the function and development of the medullary serotonergic system. These emerging data suggest an important underlying mechanism in SIDS that may help lead to identification of infants at risk and specific interventions to prevent death.

Central serotonin neurons are required for arousal to CO 2

“…SIDS is the leading cause of death in children between the ages of 1 mo and 1 y (46). Infants with SIDS are also often found prone (46), and it has been proposed that a defect in the response to CO 2 and an impaired ability to arouse from sleep both contribute to the death of these infants (46,47). Multiple abnormalities in the brainstem 5-HT system have been identified in human infants with SIDS (46,47).…”

“…Infants with SIDS are also often found prone (46), and it has been proposed that a defect in the response to CO 2 and an impaired ability to arouse from sleep both contribute to the death of these infants (46,47). Multiple abnormalities in the brainstem 5-HT system have been identified in human infants with SIDS (46,47). In obstructive sleep apnea, a reduction of 5-HT tone occurs during sleep and has been proposed to contribute to the upper airway collapse that results in apnea (48), although the relative contribution of an effect on motor neurons has been debated (49).…”

Proposal for mechanisms of protection of supine sleep against sudden infant death syndrome: an integrated mechanism review

“…The AAE can arise from many other causes, not least obstructive apnoea and identified intrinsic and extrinsic risk factors (4).…”

“…Kohyama identifies the inhibitory phase of REM sleep as being the key period of risk in SIDS and ALTE (apparent life-threatening event) subjects (60); in polygraphic sleep recordings of future SIDS victims Kahn found that 78% of events with apnoeas and bradycardia occurred during REM sleep (9). A feature of REM sleep is an almost complete absence of medullary 5-HT firing; this may be implicated in failure of autoresuscitation (4,61). Future SIDS victims showed significant alterations in sleep architecture compared to controls (Figure 1, "Prone Sleep, 5-HT defect"), with more REM in early life (62), and increased subcortical arousals during REM sleep and decreased cortical arousals (9,63).…”

Functional single-nucleotide variant of HSPD1 in sudden infant death syndrome

“…SIDS is generally agreed to be a multifactorial disease and according to the frequently encountered "triplerisk hypothesis, " SIDS may occur when an infant left vulnerable by a combination of predisposing and developmental risk factors encounters an environmental trigger event (e.g., sleeping in prone position, overheating) (4,5). Predisposing risk factors include alterations in a plethora of genes, e.g., involved in thermoregulation and catecholamine production, as well as conditions such as abnormal brainstem processes in the regulation of autonomic respiration and/or arousal (6,7).…”