Study Suggests Serotonin Plays a Role in SIDS

Brain chemical implicated in sporadic changes and death in mice

by Tom Valeo

July 7, 2008

A new report that dysfunctional neurons in the serotonin system of mice causes most of them to die has created a stir among researchers into sudden infant death syndrome, or SIDS. The team of researchers who conducted the study reports that defective serotonin neurons periodically depressed the heart rate and temperature in the mice in a way reminiscent of findings in babies who died of SIDS. In many of those infants, doctors have found problems with neurons that produce serotonin, a neurotransmitter vital to respiration, heart rate, temperature regulation and other autonomic (normally unconscious) functions. 

Researchers at the European Molecular Biology Laboratory (EMBL) in Italy used genetic engineering to create mice that possess more serotonin receptors than normal, which apparently over-inhibits serotonin production.

“The majority died suddenly,” said Cornelius Gross, the lead author of the paper, which appears in the July 4 issue of Science. “When we looked closely at what happened before death, we found there was a dramatic drop in heart rate and body temperature,” just as appears to happen in babies diagnosed with SIDS.

The serotonin neurons, located in the medulla (the lower part of the brain stem), are involved in a sensitive regulator system that keeps autonomic functions at appropriate levels. Receptors on these cells detect when they have produced too much serotonin and shut off production in the same way a thermostat shuts off the furnace when the air reaches the right temperature.

These new results coincide with the findings of Hannah Kinney of Children’s Hospital Boston and other researchers who study SIDS. Kinney has found that a majority of babies who died of SIDS had deficits in the serotonin system—a problem not found in babies who died of other causes.

“However, until now, no serotonin deficits capable of causing a catastrophic dysregulation of autonomic circuits have been identified,” Gross writes in the Science paper.

Some researchers who study SIDS suspect that babies who have such a deficient serotonin system may fail to respond adequately to the carbon dioxide they exhale. That would explain why SIDS occurs less often among babies who sleep on their backs—a position that allows exhaled carbon dioxide to disperse into the air more easily. Gross and his colleagues plan to expose their genetically engineered mice to carbon dioxide to see how it affects their heart rate and respiration.

Marian Willinger, a SIDS expert at the National Institutes of Health, said that the findings of the EMBL group coincide with research conducted by Eugene E. Nattie and Aihua Li of Dartmouth Medical School, who found that serotonin dysfunction in mice results in faulty sensitivity to carbon dioxide, especially in males.

“Studies of babies who die of SIDS show that the regulation of lung and heart function are impaired during sleep,” said Willinger, who was not involved in the research reported in Science. “They also have arousal deficits. All of these functions are controlled by serotonin. Once we can identify the pathway to death, we can come up with more strategies for intervention by the caregiver.”

Nattie himself was enthusiastic about the EMBL findings, despite one perplexing discrepancy—the mice studied were genetically engineered to have too many serotonin receptors, while SIDS babies apparently have too few. Nevertheless, he considers the paper a major breakthrough.

“I think the major impact of the paper is that it shows us, in an animal model, that if you disrupt the serotonin system, you can get a disastrous result,” he said. “It’s a very exciting finding.”

SIDS is the leading cause of death in infants between 1 and 12 months old, according to the National Institutes of Health. Willinger added that these findings should show parents who have lost a baby to SIDS that they could not have prevented the death.

“Their baby had a developmental disorder,” she said. “Dr. Kinney has shown that the serotonin neurons [in babies who died of SIDS] looked very immature, suggesting this is a developmental abnormality that occurs during pregnancy. This should supply parents with some sense of comfort that there was nothing they could have done to prevent it.”