Little is known about what triggers sudden infant death syndrome (SIDS), the leading cause of death in the US in babies aged 1–12 months. Though various environmental risk factors have been identified, including sleep position, insufficient prenatal care and maternal substance abuse, the molecular mechanisms of the syndrome are poorly understood. Recent postmortem studies in SIDS victims have indicated that serotonin dysfunction may be involved, but attempts to develop disease models relying on serotonin deficits have so far been unsuccessful.

A new study led by Cornelius Gross of the European Molecular Biology Laboratory (Monterotondo, Italy) may begin to shed light on the relationship between SIDS and serotonin. The team used mice that were genetically modified to overexpress the serotonin receptor 1A in the brainstem (Science 321, 130–133; 2008). In mammals, this receptor regulates serotonin expression through a negative feedback mechanism. Increasing expression of this receptor reduces serotonin neuron firing and decreases heart rate, body temperature and respiration.

Like human SIDS victims, mutant mice seemed healthy at first, and their baseline heart rates and body temperatures were normal. When researchers used telemetric devices to monitor mice continuously, however, they found that mice sporadically suffered autonomic 'crises' in which their heart rates and body temperatures dropped abruptly. Data from infants who happened to have been monitored during SIDS events indicate that similar symptoms occur in humans, as well. Most mice died from such crises, and death occurred early in life, well before mice were 3 months old. The similarities between modified mice and human SIDS victims suggest that the mice would be an appropriate model for the condition.

The sudden death in mice came as a surprise to researchers, as this effect does not occur in mice lacking serotonin neurons entirely. This would suggest that an imbalanced serotonin system is more lethal than a nonexistent one. Additionally, the team's findings show that sudden death can be caused by an animal's predisposition alone and is not necessarily triggered by environmental stressors that parents, for example, might be able to control.

It is not clear what caused mice to enter crises, but the scientists speculate that the effects may be related to rapid changes in serotonin neuron activity, such as those that occur during the transition from sleep to wakefulness. The group intends to continue exploring the connection between sleep and sudden death.