Defective signalling of serotonin in the brain may be the root cause of sudden infant death syndrome (SIDS). Scientists from the European Molecular Biology Laboratory in Monterotondo, Italy, genetically modified lab mice to produce low levels of the neurotransmitter serotonin. The results showed the mice suffered drops in heart rate and other symptoms of SIDS, and many of the animals died at an early age.
Researchers now believe that low levels of serotonin in the animals' brainstems, which control heartbeat and breathing, may have caused sudden death, researchers said in the July 4, 2008 issue of Science.
If neurons that make serotonin — serotonergic neurons — are abnormal in infants, there is a risk of sudden infant death syndrome (SIDS). Low levels of serotonin may also be associated with intense spiritual experiences.
Recent research conducted at Rockefeller University shows that both in patients who suffer from depression and in mice that model the disorder, levels of the p11 protein are decreased. This protein is related to serotonin transmission within the brain.
Obsessive-compulsive disorder (OCD) can be a debilitating disorder with the following two anxiety-related essential features: obsessions (undesirable, recurrent, disturbing thoughts) and compulsions (repetitive or ritualized behaviors). SSRIs, and other medicines which alter serotonin levels, have been approved to be used to treat symptoms of OCD.
Serotonin syndrome
Extremely high levels of serotonin can have toxic and potentially fatal effects, causing a condition known as serotonin syndrome. In practice, such toxic levels are essentially impossible to reach through an overdose of a single anti-depressant drug, but require a combination of serotonergic agents, such as an SSRI with an MAOI. The intensity of the symptoms of serotonin syndrome vary over a wide spectrum, and the milder forms are seen even at non-toxic levels.
Chronic diseases resulting from serotonin 5-HT2B overstimulation
In blood, serotonin stored in platelets is active wherever platelets bind, as a vasoconstrictor to stop bleeding, and also as a fibrocyte mitotic, to aid healing. Because of these effects, overdoses of serotonin, or serotonin agonist drugs, may cause acute or chronic pulmonary hypertension from pulmonary vasoconstriction, or else syndromes of retroperitoneal fibrosis or cardiac valve fibrosis (endocardial fibrosis) from overstimulation of serotonic growth receptors on fibrocytes.
Serotonin itself may cause a syndrome of cardiac fibrosis when it is eaten in large quantities in the diet (the Matoki banana of East Africa) or when it is over-secreted by certain mid-gut carcinoid tumors. The valvular fibrosis in such cases is typically on the right side of the heart, since excess serotonin in the serum outside platelets is metabolized in the lungs, and does not reach the left circulation.
Serotonergic agonist drugs in overdose in experimental animals not only cause acute (and sometimes fatal) pulmonary hypertension, but there is epidemiologic evidence that chronic use of certain of these drugs produce a chronic pulmonary hypertensive syndrome in humans. Some serotonergic agonist drugs also cause fibrosis anywhere in the body, particularly the syndrome of retroperitoneal fibrosis, as well as cardiac valve fibrosis.
In the past, three groups of serotonergic drugs have been epidemiologically linked with these syndromes. They are the serotonergic vasoconstrictive anti-migraine drugs (ergotamine and methysergide),
As with fenfluramine, some of these drugs have been withdrawn from the market after groups taking them showed a statistical increase of one or more of the side effects described. An example is pergolide. The drug was in decreasing use since reported in 2003 to be associated with cardiac fibrosis.
Two independent studies published in the New England Journal of Medicine in January 2007, implicated pergolide along with cabergoline in causing valvular heart disease. As a result of this, the FDA removed pergolide from the U.S. market in March, 2007. (Since cabergoline is not approved in the U.S. for Parkinson's Disease, but for hyperprolactinemia, the drug remains on the market. Treatment for hyperprolactinemia requires lower doses than that for Parkinson's Disease, diminishing the risk of valvular heart disease).
Because neither the amino acid L-tryptophan nor the SSRI-class antidepressants raise blood serotonin levels , they are not under suspicion to cause the syndromes described. However, since 5-hydroxytryptophan (5-HTP) does raise blood serotonin levels, it is under some of the same scrutiny as actively serotonergic drugs.
Further Reading
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