Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome

Paterson, David S.; Trachtenberg, Felicia; Thompson, Eric G.; Belliveau, Richard A.; Beggs, Alan H.; Darnall, Ryan; Chadwick, Amy E.; Krous, Henry F.; Kinney, Hannah C.

doi:10.1001/jama.296.17.2124

Cited by 459 publications

(447 citation statements)

References 38 publications

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“…Thus, the 5-HT system may be very important for responding to these exogenous stressors, so that a defect in this system could compromise a vulnerable individual. These observations may be relevant to sudden infant death syndrome, which has previously been linked to abnormalities in the 5-HT system (Paterson et al, 2006), and has been associated with defects in control of body temperature and breathing (Shannon et al, 1977;Hunt et al, 1981;Dunne and Matthews, 1988).…”

Section: Relevance To Physiology and Diseasementioning

confidence: 85%

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

Hodges¹,

Tattersall²,

Harris³

et al. 2008

J. Neurosci.

294

348

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f/f/p mice was decreased by 50% compared with wild-type mice, whereas baseline ventilation and the hypoxic ventilatory response were normal. In addition, Lmx1b f/f/p mice rapidly became hypothermic when exposed to an ambient temperature of 4°C, decreasing core temperature to 30°C within 120 min. This failure of thermoregulation was caused by impaired shivering and nonshivering thermogenesis, whereas thermosensory perception and heat conservation were normal. Finally, intracerebroventricular infusion of 5-HT stimulated baseline ventilation, and rescued the blunted hypercapnic ventilatory response. These data identify a previously unrecognized role of 5-HT neurons in the CO 2 chemoreflex, whereby they enhance the response of the rest of the respiratory network to CO 2 . We conclude that the proper function of the 5-HT system is particularly important under conditions of environmental stress and contributes significantly to the hypercapnic ventilatory response and thermoregulatory cold defense.

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Section: Relevance To Physiology and Diseasementioning

confidence: 85%

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

Hodges¹,

Tattersall²,

Harris³

et al. 2008

J. Neurosci.

294

348

View full text Add to dashboard Cite

show abstract

“…Failure to inhibit the dorsal motor complex may be underlying QT syndromes identified as contributing to some cases of SIDS (7). Reduced 5-HT(1A) receptor binding density is one of several specific features seen only in SIDS cases, not in controls (69), and is implicated in the failure of autonomic regulation of respiration, blood pressure, and arousal. Though protective to the heart, the hypoxia is lethal to the brain.…”

Section: Hypothesized Mechanism For Sids Protection By Supine Sleepmentioning

confidence: 99%

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

Bergman

2014

Pediatr Res

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Supine sleep decreases sudden infant death syndrome (SIDS) incidence, however the mechanisms for this are unclear. The triple risk model for SIDS requires that one or more underlying abnormalities of breathing or autonomic control are present; these are rare, but brainstem defects are found in most SIDS cases. Supine sleep increases sympathetic nervous system tone, and level of state organization, and may therefore act as a stressor. This is evidenced by physiological arousal, and by delayed neurodevelopment in supine compared to prone sleepers. It is argued here that prone sleep position is the biological normative standard in healthy infants, supporting autonomic regulation. During rapid eye movement (REM) sleep (and other circumstances), a parasympathetic-mediated adverse autonomic event (AAE) may be spontaneously triggered. In healthy infants, gasping initiates autoresuscitation and recovery. Hypothesis: the underlying vulnerability to SIDS is specific to autoresuscitation from an AAE, the initial serotonin-dependent gasp is commonly compromised. Serotonin metabolism defects also influence sleep architecture, increasing the likelihood of AAE. The mechanism whereby supine sleep decreases SIDS may therefore be a stressor effect, disturbing sleep architecture to decrease REM and AAEs, and increasing sympathetic tone, which may prevent and counteract the purely parasympathetic-mediated AAE, thereby decreasing the risk of SIDS.

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“…4 SIDS peaks in incidence at 2 to 4 months of age 5,6 and is believed to involve an uncompensated cardiovascular event presumed to occur during sleep, in conjunction with failure of the life-saving arousal response. [7][8][9][10][11] Preterm infants exhibit immature cardio-respiratory control, which persists past term-equivalent age, 12 is related to gestational age (GA) at birth, 13,14 and may contribute to their heightened risk for SIDS. 15 Prone sleeping is a major risk factor for SIDS, particularly among infants born preterm.…”

mentioning

confidence: 99%

Cerebral Oxygenation in Preterm Infants

et al. 2014

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BACKGROUND AND OBJECTIVE: Prone sleeping is a major risk factor for sudden infant death syndrome (SIDS) and preterm infants are at significantly increased risk. In term infants, prone sleeping is associated with reduced mean arterial pressure (MAP) and cerebral tissue oxygenation index (TOI). However, little is known about the effects of sleeping position on TOI and MAP in preterm infants. We aimed to examine TOI and MAP in preterm infants after term-equivalent age, during the period of greatest SIDS risk. METHODS: Thirty-five preterm and 17 term infants underwent daytime polysomnography, including measurement of TOI (NIRO-200 spectrophotometer, Hamamatsu Photonics KK, Japan) and MAP (Finapress Medical Systems, Amsterdam, Netherlands) at 2 to 4 weeks, 2 to 3 months, and 5 to 6 months postterm age. Infants slept prone and supine in active and quiet sleep. The effects of sleep state and position were determined by using 2-way repeated measures analysis of variance and of preterm birth by using 2-way analysis of variance. RESULTS: In preterm infants, TOI was significantly lower when prone compared with supine in both sleep states at all ages (P < .05). Notably, TOI was significantly lower in preterm compared with term infants at 2 to 4 weeks, in both positions (P < .05), and at 2 to 3 months when prone (P < .001), in both sleep states. MAP was also lower in preterm infants in the prone position at 2 to 3 months (P < .01). CONCLUSIONS: Cerebral oxygenation is reduced in the prone position in preterm infants and is lower compared with age-matched term infants, predominantly in the prone position when MAP is also reduced. This may contribute to their increased SIDS risk.

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Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome

Cited by 459 publications

References 38 publications

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons

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

Cerebral Oxygenation in Preterm Infants

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