Take a deep breath and wake up: The protean role of serotonin preventing sudden death in infancy.

Recordings from infants who died suddenly and unexpectedly demonstrate the occurrence of recurring apneas, ineffective gasping, and finally, failure to restore eupnea and arouse prior to death. Immunohistochemical and autoradiographic data demonstrate a constellation of serotonergic defects in the caudal raphe nuclei in infants who died of Sudden Infant Death Syndrome (SIDS). The purpose of this review is to synthesize what is known about adaptive responses of the infant to severely hypoxic conditions, which unleash a flood of neuromodulators that inhibit cardiorespiratory function, thermogenesis, and arousal and the emerging role of serotonin, which combats this cardiorespiratory inhibition to foster autoresuscitation, eupnea, and arousal to ensure survival following an hypoxic episode. The laryngeal and carotid body chemoreflexes are potent in newborns and infants, and both reflexes can induce apnea and bradycardia, which may be adaptive initially, but must be terminated if an infant is to survive. Serotonin has a unique ability to touch on each of the processes that may be required to recover from hypoxic reflex apnea: gasping, the restoration of heart rate and blood pressure, termination of apneas and, eventually, stimulation of eupnea and arousal. Recurrent apneic events, bradycardia, ineffective gasping and a failure to terminate apneas and restore eupnea are observed in animals harboring defects in the caudal serotonergic system models - all of these phenotypes are reminiscent of and compatible with the cardiorespiratory recordings made in infants who subsequently died of SIDS. The caudal serotonergic system provides an organized, multi-pronged defense against reflex cardiorespiratory inhibition and the hypoxia that accompanies prolonged apnea, bradycardia and hypotension, and any deficiency of caudal serotonergic function will increase the propensity for sudden unexplained infant death.