Serotonin (5-hydroxytryptamine, 5-HT) is a chemical found in the human body.
It carries signals along and between nerves - a neurotransmitter. It is mainly found in the brain, bowels and blood platelets.
Serotonin is thought to be especially active in constricting smooth muscles, transmitting impulses between nerve cells, regulating cyclic body processes and contributing to wellbeing and happiness.
Serotonin is regarded by some researchers as a chemical that is responsible for maintaining mood balance, and that a deficit of serotonin leads to depression.
The word serotonin comes from its discovery when it was isolated in 1948 by Maurice M. Rapport and initially classified as a serum agent that affected vascular tone.
Contents of this article:
You will also see introductions at the end of some sections to any recent developments that have been covered by MNT's news stories. Also look out for links to information about related conditions.
Fast facts on serotonin
Here are some key points about serotonin. More detail and supporting information is in the main article.
- Serotonin is an important chemical neurotransmitter in the human body.
- It is commonly regarded as a chemical that is responsible for maintaining mood balance.
- Serotonin is created by a biochemical conversion process.
- Serotonin is manufactured in the brain and the intestines. The majority of the body's serotonin, between 80-90%, can be found in the gastrointestinal tract.
- Serotonin that is used inside the brain must be produced within it.
- It is thought that serotonin can affect mood and social behavior, appetite and digestion, sleep, memory and sexual desire and function.
- An association has been made between depression and serotonin. Scientists remain unsure whether decreased levels of serotonin contribute to depression or depression causes a decrease in serotonin levels.
- Drugs that alter serotonin levels have important clinical uses such as in the treatment of depression, nausea and migraine.
- Medical research continues to evaluate the role of serotonin in obesity and Parkinson's disease.
- Other ways to increase body serotonin levels include mood induction, light, exercise and diet.
What is serotonin?
Serotonin is created by a biochemical conversion process which combines tryptophan, a component of proteins, with tryptophan hydroxylase, a chemical reactor. Together, they form 5-hydroxyltryptamine (5-HT), also referred to as serotonin.
Serotonin is most commonly believed to be a neurotransmitter, although some consider the chemical to be a hormone.
Where does serotonin come from?
Serotonin is manufactured in the brain and the intestines. The majority of the body's serotonin, between 80-90%, can be found in the gastrointestinal (GI) tract. It can also be found in the blood platelets and the central nervous system (CNS).
As serotonin can be found widely across the body, it is believed that the chemical plays a role in influencing a variety of body and psychological functions.
Serotonin cannot cross the blood-brain barrier, therefore, serotonin that is used inside the brain must be produced within it.
What does serotonin do?
As a neurotransmitter, serotonin relays signals between nerve cells (neurons), regulating their intensity.
Serotonin is a neurotransmitter, regulating signals between neurons.
Serotonin is widely believed to play a key role in the central nervous system, as well as in the general functioning of the body and in particular the GI tract. Studies have found links between serotonin and bone metabolism, breast milk production, liver regeneration and cell division.
Functions of serotonin
As a neurotransmitter, serotonin influences both directly and indirectly the majority of brain cells. The following is a list of things that it is thought that serotonin could affect:
- Bowel function. Most of the body's serotonin is found in the gastrointestinal tract where it regulates bowel function and movements. It also plays a part in reducing the appetite while consuming a meal.
- Mood. It is most well know for its role in the brain where it plays a major part in mood, anxiety and happiness. Illicit mood-altering drugs such as Ecstasy and LSD cause a massive rise in serotonin levels.
- Clotting. Its third major role is in the formation of blood clots. Serotonin is released by platelets when there is a wound, and the resulting vasoconstriction (narrowing of the tiny arteries - arterioles) reduces blood flow and aids the formation of blood clots.
- Nausea. If you eat something that is toxic or irritating, more serotonin is produced in the gut to increase transit time and expel the irritant in diarrhea. This increase in blood serotonin levels also causes nausea by stimulating the nausea area in the brain.
- Bone density. Studies have shown that a persistent high level of serotonin in the bones can lead to an increase in osteoporosis.
- Sexual function. Low serotonin levels in the intoxicated state are thought to contribute to the associated increase in libido, while those taking medication that increase serotonin levels are seen to have a reduction in libido and sexual function.
Serotonin and depression
It is unknown precisely what causes depression. It is thought to be likely that an imbalance of neurotransmitters or hormones in the body can lead to the disorder.
An association has been made between depression and serotonin, although scientists are unsure whether decreased levels of serotonin contribute to depression or depression causes a decrease in serotonin levels.
Although it is possible to measure the level of serotonin in the bloodstream, via a serum serotonin level test, it is currently not possible to measure serotonin levels within the brain. Researchers do not know whether serotonin levels in the bloodstream reflect the serotonin levels in the brain.
Serotonin levels are heavily associated with depression, although some studies have contradicted this.
It is believed that medication such as selective serotonin reuptake inhibitors (SSRIs) that can affect the levels of serotonin in the body work as antidepressants and are able to relieve the symptoms of depression. It is unknown precisely how they work, however.
A study published in 2014 may offer evidence contrary to these widely-held theories. Scientists ran mice without the capacity to create serotonin through a series of behavioral tests.The mice did not show any signs of depression, suggesting that factors other than serotonin could be involved with the development of depression. A similar conclusion was drawn by a professor of psychiatry writing an editorial piece for The BMJ in April 2015. He suggested that low serotonin is a mythical cause of depression.
Recent developments on the link between serotonin and depression from MNT news
A study from researchers at Duke University in Durham, NC (published in February 2015) found that mice deficient in serotonin were more vulnerable to social stressors than a group of healthy control mice.
A study in mice suggested that serotonin deficiency may not play as influential a role in depression as has previously been thought.
SSRIs and serotonin levels4
SSRIs are approved by the Food and Drug Administration (FDA) to treat depression and are the most commonly prescribed antidepressants. Common examples of SSRIs are fluoxetine (Prozac), citalopram (Celexa) and sertraline (Zoloft). The less commonly used MAOI (monoamine oxidase inhibitors) such isocarboxazid (Marplan) prevent serotonin breakdown.
Probably the most famous medical use of serotonin alteration is in the role of anti-depressants with selective serotonin (SSRIs) and norepinephrine (SNRIs) reuptake inhibitors.
Normally once a neurotransmitter has transmitted its neural impulse it is generally reabsorbed. SSRIs inhibit the re-absorption of serotonin (and norepinephrine) neurotransmitters and thus increase the levels in the synapse of the nerves in the brain, and thus elevate mood.
They are also effective in the treatment of anxiety, panic disorders and obsessive-compulsive disorders.
Recreational drugs such as MDMA and cocaine also inhibit the re-absorption of serotonin in order to create their highs.
Minor side effects of SSRIs and SNRIs that typically decrease after the first or second week of use include:
- Nausea
- Diarrhea
- Weight loss or gain
- Increased sweating
- Dizziness
- Sleepiness or insomnia
- Tremor
- Dry mouth
- Headache
- Restlessness
- Suicidal thoughts
- Sexual dysfunction.
SSRIs and suicide
Zoloft causes some younger users of the drug to report being suicidal. The FDA requires all antidepressants to carry a black-box warning about the danger of suicide during the initial stages of treatment, especially in children.
Antiemetics - preventing and treating nausea
The antiserotonergic drugs that act on the 5-HT3 receptors e.g. ondansetron (Zofran) are extremely important drugs used in nausea from chemical toxins such as chemotherapy drugs and drugs used in general anesthesia.
They act centrally on the area in the brain involved with nausea.
Migraine - the treatment of migraine headaches
Migraine is the most frequent neurological disorder in the adult population worldwide, affecting up to 12% of the general population.
Serotonergic vasoconstrictive antimigraine drugs - the Triptans - e.g. almotriptan (Axert), Rizatriptan (Maxalt), sumatriptan (Alsuma) and zolmitriptan (Zomig) are effective in reducing migraine symptoms and are well tolerated.
Appetite suppressants - to help reduce obesity
Serotonergic appetite suppressants such as fenfluramine (Pondimin) and chlorphentermine - are no longer licensed for this use.
Parkinson's disease
Several functions have been attributed to the serotonergic system including cognition, emotion and motor behavior; thus altered serotonergic neurotransmission may contribute to the motor and non-motor features commonly associated with Parkinson's disease.
Serotonergic anti-Parkinsonian drugs (pergolide, cabergoline) have been used in the treatment of Parkinson's disease and are no longer licensed, but research continues in this area.
Premenstrual syndrome
The cause of premenstrual syndrome (PMS) is unknown, but an over sensitivity to one of the female hormones, progesterone, seems to reduce the level of serotonin in the brain.
Some SSRIs are licensed to help women through difficult physical and emotional symptoms around the changes in their monthly menstrual cycle, even if the woman is not clinically depressed. The drug need not be taken throughout the whole cycle, and women may find relief within a few days of starting to take it.
Obesity
New research is examining the role of serotonin inhibition in treating obesity.
Irritable bowel syndrome
Work continues to evaluate the evidence of the value and safety of serotonin receptor modulation in irritable bowel syndrome. Alosetron and cilansetron are currently in use in the US.
The FDA have issued a warning about taking SSRIs or SNRIs (used for depression, anxiety, pain, and many other conditions) with triptans. Taking these medicines together can cause a very rare but serious condition called serotonin syndrome.
What is 'serotonin syndrome'?
Serotonin syndrome is the consequence of excessive stimulation of the central nervous system and peripheral serotonin receptors. It can arise due to taking medication, illegal drugs or dietary supplements, and normally occurs when two drugs that affect serotonin levels are taken at the same time i.e. taking migraine medicine alongside antidepressants.
Carcinoid tumors can cause excessive levels of serotonin. These are cancerous and are commonly found in the GI tract. The tumors cause too much serotonin to be released. Most carcinoid tumors have no symptoms, and so they are often found when tests or procedures are carried out for other conditions.
Serotonin syndrome leads to excessive nerve activity. Symptoms can occur within a few hours of the substance, inducing the condition, being taken. It is potentially life-threatening, and signs and symptoms include:7
Excessive levels of serotonin can occur through taking two different kinds of serotonin-boosting medication, such as antidepressants and migraine medicine.
- Agitation and restlessness
- Confusion
- Increased heart rate and blood pressure
- Pupil dilation
- Diarrhea
- Headaches
- Shivering
- Sweating
- Loss of muscle co-ordination
- Goosebumps
- Muscle rigidity.
If the case is severe then serotonin syndrome can be life threatening. It can lead to high fever, irregular heartbeat, seizures and unconsciousness.
Treatment
Serotonin syndrome cannot be diagnosed by a single test, and as many other conditions share similar symptoms, a health care provider will attempt to rule these out before diagnosing serotonin syndrome.
If diagnosed, treatment will focus on attempting to restore normal serotonin levels. If symptoms are minor then stopping the medication that began the problem could be enough to make the symptoms go away after a few days.
More extreme forms of serotonin syndrome may require treatment in hospital. Depending on the degree of the symptoms, various medications can be given to relax or paralyze the muscles, control heart rate and blood pressure and in some cases block the production of serotonin.
Oxygen can also be given as can fluids intravenously, in order to maintain normal levels of oxygen in the bloodstream and to treat fever and dehydration.
Natural ways to boost serotonin levels
As well as SSRIs and illegal drugs, there are believed to be other ways to increase the levels of serotonin in the body.
Legumes such as chickpeas may have rich amount of trytophan, the key component of serotonin.
- Mood induction: alterations in thought, either through psychotherapy or self-induction, could increase levels of serotonin if the interaction between serotonin synthesis and mood is a two-way relationship.
- Light: already used as a treatment for seasonal affective disorder, a few studies have suggested that it can be used to treat depression as well.
- Exercise: exercise has an antidepressant effect, and some research has suggested that it can increase brain serotonin function.
- Diet: foods that have higher levels of tryptophan than others could be linked to improved mood and cognition, possibly due to increased serotonin levels.
These are all areas that require further study, as current knowledge remains speculative.
There is a lot that is still unknown about serotonin. The difficulties surrounding the study of brain functions means that it will be some time before a full knowledge of serotonin can be acquired.
Recent developments related to serotonin from MNT news
Taking certain medications prescribed to treat depression, anxiety and other mental-health problems during pregnancy has been linked to a higher risk of autism and developmental delays in male children, according to a study published in Pediatrics.
New research from the Washington University School of Medicine in St. Louis, MO, and the University of Pennsylvania finds that a commonly prescribed antidepressant may be effective at slowing onset of Alzheimer's disease.
Researchers from the Geisel School of Medicine at Dartmouth, NH, recently investigated the role of serotonin on breathing responses in sleeping infants. The findings, published in Experimental Physiology, offer a new avenue of research into sudden infant death syndrome.
