The brainstem serotonin system is thought to help coordinate breathing, blood pressure, sensitivity to carbon dioxide, and temperature during waking and sleep. When babies sleep face down or have their faces covered by bedding, they are thought to re-breathe exhaled carbon dioxide, therefore breathing in less oxygen. Normally, the rise in carbon dioxide activates nerve cells in the brainstem, which in turn stimulate respiratory and arousal centers in the brain so that the baby doesn't asphyxiate.

"A normal baby will wake up, turn his or her head, and start breathing faster when carbon dioxide levels rise," explains Kinney.

But in babies who die from SIDS, defects in the serotonin system may impair these reflexes, the researchers believe.

Kinney previously documented serotonin receptor abnormalities in two other populations of SIDS infants, including American Indian infants in the Northern Plains, whose SIDS rate is among the highest in the world. The current study confirms those findings in a third population and, for the first time, pinpoints multiple defects in the serotonin system other than those in serotonin receptors: deficiencies in a particular type of serotonin receptor (called 5HT1A), an abnormally high number of serotonergic neurons (neurons that make and release serotonin), a preponderance of immature serotonergic neurons, and evidence for insufficient amounts of the serotonin transporter protein, which "recycles" serotonin so that nerve cells can reuse it.

"We provide strong evidence that SIDS is a biological problem, and that the brainstem serotonin system is a good place to focus continued research efforts," says Paterson.

He and Kinney believe that the abnormalities they observed begin during early fetal development, and that prenatal insults like maternal smoking and alcohol use may adversely affect development of the brainstem serotonin system during this time. More research is needed to explain what causes the abnormalities and how they can be prevented.

The findings also provide a biological explanation for why SIDS occurs twice as often in males than females -- male SIDS infants had significantly fewer 5-HT1A receptors than female SIDS infants.

In addition, serotonin abnormalities help explain why infants under 6 months are most vulnerable to SIDS. At birth, babies must adjust from being totally dependent on their mother to breathing on their own and maintaining their own blood pressure. If the brainstem serotonin system is defective or still immature, this transition to total independence in the control of vital functions may be impaired during the crucial first six months of life.

"We think that the control systems for vital or homeostatic functions reach full maturity only towards the end of the first year of life," Kinney says.

The researchers note that despite the national Back to Sleep campaign, which urges caregivers to put babies to bed on their backs, 65 percent of the SIDS infants in this study were found sleeping on their stomach or side.

The study was funded by the National Institute of Child Health and Human Development. Additional funding came from private SIDS foundations such as the CJ Foundation for SIDS, the First Candle/SIDS Alliance, the CJ Murphy Foundation, the Barrett Fellowship for SIDS Research and the Scottish Cot Death Foundation.