The findings provide the strongest evidence yet of a specific neurological cause for SIDS, a little-understood condition that kills roughly 2,500 infants each year in the United States.
In the study, autopsy tissue taken from babies who had died of SIDS and other causes showed abnormalities in the lower brain stems of the SIDS babies. Among other things, this region of the brain is thought to help regulate breathing and arousal.
Environmental factors, such as stomach sleeping, overheating, and exposure to cigarette smoke are all believed to increase a baby's risk of death from SIDS.
But the search for a biological link has turned up little, until now.
"This is very good evidence that there definitely is a biological problem that contributes to SIDS," neuroscientist and study co-author David S. Paterson, PhD, tells WebMD.
"There very well may be other biological causes which have not been identified. This gives us a good starting point to keep looking," says Paterson, of Boston Children's Hospital.
The Serotonin System
Boston Children's Hospital neuropathologist Hannah Kinney, MD, has searched for a biological cause for SIDS for the past two decades.
She and Paterson had previously identified defects in the serotonin system of the lower brain stem in babies who had died of SIDS.
The brain stem serotonin system is believed to help coordinate breathing, blood pressure, sensitivity to carbon dioxide, arousal, and temperature. Serotonin works as a chemical messenger in this system.
Kinney and Paterson believe babies who die of SIDS actually suffocate from breathing the carbon dioxide they exhale during sleep.
Normal babies wake up when the air they breathe contains too much carbon dioxide and not enough oxygen, but the thinking is that babies susceptible to SIDS lack this arousal reflex.
In their latest study, which appears in the Nov. 1 issue of The Journal of the American Medical Association, the researchers confirmed their earlier findings and expanded on them.
They examined autopsied tissue from the lower brain stems of 31 infants who had died of SIDS and 10 infants who had died from other causes.
Multiple defects in the serotonin system of the SIDS babies were identified, including abnormally high numbers of neurons that make and release serotonin and deficiencies in certain serotonin receptor binding sites.
"Our hypothesis right now is that we're seeing a compensation mechanism," Paterson says. "If you have more serotonin neurons, it may be because you have less serotonin and more neurons are recruited to produce and use serotonin to correct this deficiency."
Male babies who died of SIDS had less serotonin receptor binding – necessary for serotonin to work -- than either female babies who died of SIDS or the babies who died of other causes. This may help explain why SIDS is twice as common in males as in females.
Identifying At-Risk Infants
The next step, Paterson says, is to confirm that the serotonin system abnormalities reported in this study play a role in SIDS.
The hope is that the discovery of a biological trigger will lead to better ways to identify at-risk infants and intervene to protect them.
Even though much is still unknown, the identification of a specific biological link to SIDS is a huge step forward, says Marian Willinger, PhD.
Willinger is special assistant for SIDS at the National Institute of Child Health and Human Development, which funded the study.
"This research is important because it gives us a specific place to look in our future research," she tells WebMD. "We still don't have the whole story. But it is getting pieced together little by little."
Despite public health efforts to urge parents and caregivers to put infants to sleep on their backs, roughly half the infants in the study who died of SIDS were found sleeping on their stomachs or sides. About one in four were bed sharing, which is another suspected risk factor for SIDS.
Putting babies to sleep on their backs, alone in a crib, with little bedding, can help reduce SIDS risk, but these interventions don't eliminate the risk, Willinger says.
"Back sleeping is an effective intervention, but there are still babies who die of SIDS after being placed on their backs," she says.