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Study: Weakened serotonin signaling may trigger SIDs
By David Liu, Ph.D.
Jul 5, 2008 - 11:19:17 AM

Editor's note: High levels of serotonin 1a receptor likely means low levels of free serotonin, a substance that is important in cell-firing to send chemical messages regulating heart rate, body temperature and breathing.  It seems in the editor's opinion that maintaining an adequate level of serotonin can be critical in preventing sudden infant death syndrome or SIDS.  Epidemiologic studies have associated increased risk of SIDS with use of infant formulas some of which contain low levels of tryptophan, an amino acid that serve as a precursor for serotonin, which would result in low levels of serotonin.

SUNDAY July 5, 2008 (foodconsumer.org) -- Weakened serotonin signaling in the brain may at least partially be responsible for sudden infant death syndrome (SIDS), according to a study published in the July 5 issue of Science.

SIDS is a lethal and unpredictable affliction that kills about 2500 seemingly healthy infant each year in the United States.   Sleeping stomach-down and overheating during sleep are believed to be risk factors for SIDS.  But biological risk factors remain unknown except that low serotonin has been long suspected as a risk factor.

Dr. Enrica Audero at the European Molecular Biology Laboratory in Monterotondo, Italy and colleagues used a mouse model of SIDS to examine how over-expression of a serotonin receptor triggers serotonin dysfunction and frequently results in death in the animals, a phenomenon similar to SIDS.

The researchers focused in their study on the serotonin 1a receptor, a protein on nerve cells that works with serotonin to signal chemical messages.   When serotonin 1a receptor is overproduced, the serotonin activity would be shut off. Nerve cells that produce serotonin are located in the brainstem regulating basic body functions including heart rate and breathing.

Early studies have demonstrated that activating serotonin 1a receptors causes less firing of serotonin-containing nerve cells and decreases heart rate, body temperature and respiration, which are some of physiological factors for SIDS.

The mice used in the study were genetically modified in a way that they produced about 10 times more serotonin 1a receptor protein than their normal littermates.

When brain tissue from the transgenic mice was sprayed with tryptophan, a precursor for serotonin, less cell-firing was observed compared to the control mice, according to the study.

When a drug blocked the serotonin 1a receptor, cell-firing was restored to the level seen in the tissue from the control mice, suggesting that the high levels of serotonin 1a receptor blocks the serotonin functions.

Cornelius Gross, senior author of the report and researcher at the European Molecular Biology Laboratory said they also looked at what's happening in the serotonin 1a over producing animals and found a "dramatic drop" in heart rate and body temperature.

Among the transgenic mice that over expressed serotonin 1a receptor, 73 percent experienced at least one drip in heart rate and body temperature called "sporadic autonomic crisis" and it took hours or even days for them to recover.   The crisis was so severe that 37 percent of the mice died.

"The events that precipitated crises in our animals are not known, and thus far we have not been able to identify environmental stressors that induce crises," wrote Audero and colleagues. "However, we speculate that crises may occur preferentially after rapid changes in serotonin neuron activity." Such activities could occur during sleep-wake cycles.

The researchers cautioned that the results may not directly explain SIDS because infants who suffer SIDS do not show greater amounts of serotonin 1a receptors. But they said other "functionally equivalent deficits in serotonin signaling may play a role in SIDS.

American Association for the Advancement of Science, the publisher of the journal Science, released an article on its website regarding the study quoting Marian Willinger, SIDS expert at the Eunice Kennedy Shriver National Institute of Child Health and Human Development as saying during a AAAS/Science teleconference on July 3 that "I think it (the study results) says to parents that their babies had a developmental disorder that they were born with."

Willinger was cited as saying that having an infant die of SIDS is a "devastating event" for a family and the study "should provide them with some sense of comfort that there was nothing they could have done to prevent it—it is a real disease."

A foodconsumer.org health observer did not completely agree. He said although those who suffered SIDS may likely have some disorder in the brain or some deficit in certain physiological functionality involving serotonin, environmental factors may also play a significant role in SIDS.

He also said the study could have yielded more important information if the researchers tested tryptophan supplementation to see whether increased intake of tryptophan could prevent the transgenic mice from dying from SIDS.

Early studies suggested decreased intake of tryptophan, the precursor of serotonin, resulting for instance from consumption of soy-based infant formulas, may attribute to increased risk of SIDS.   Low tryptophan means the body may produce low serotonin, an effect similar to what is caused by high levels of serotonin 1a receptor as demonstrated in the current study.

A meta-analysis of 19 previous studies conducted by Kristine L.S.P. McVea, MD, MPH at Nebraska Medical Center in Omaha, Nebraska and colleagues showed infants who were bottle-fed were 2.11 times more likely to suffer SIDS than those who were breastfed.   Soy-based infant formulas are one of common types.

The authors said the results showed there is an association between bottle-feeding and SIDS. But they also said confounding variables may also contribute to the association.   The study was published in Journal of Human Lactation, Vol. 16, No. 1, 13-20 (2000).

Sarwar G. from Nutrition Research Division, Health Protection Branch, Health Canada published a study in Plant Foods for Human Nutrition 2001, vol. 56, no3, pp. 275-284 reporting that tryptophan were 40 percent lower in soy-based formulas than human milk, 10.0-12.3 mg/g protein versus 17 - 19 mg/g protein.  

Sarwar also found that supplementation of tryptophan in an animal model increased serotonin and 5-HIAA (5-hydroxyindole-3-acetic acid), a metabolite of serotonin, in the brains of mice fed soy-based formula.

Many studies have suggested that low serotonin may be a major risk factor for SIDS.  

Okado N. from the University of Tsukuba in Japan and colleagues said in their study report published in 2002 in the March issue of Med Hypotheses that "alone with the genetic factors, environmental temporal factors appear additively to lower the excitatory   function of 5-HT (serotonin) to the respiratory center, and finally SIDS might occur. Now the pathophysiological mechanisms and symptoms of SIDS are explained by decreased levels of 5-HT."