Serotonin

Serotonin (pronounced /ˌsɛrəˈtoʊnən/) (5-hydroxytryptamine, or 5-HT) is a monoamine neurotransmitter synthesized in serotonergic neurons in the central nervous system (CNS) and enterochromaffin cells in the gastrointestinal tract of animals including humans. Serotonin is also found in many mushrooms and plants, including fruits and vegetables.

Pharmacology

The serotonin receptor, or 5-HT receptors, are found throughout the central nervous system and the peripheral nervous system.

5-HT Receptor System

5-hydroxytryptamine receptors or 5-HT receptors, or serotonin receptors, are a group of G protein-coupled receptor and ligand-gated ion channels found in the central and peripheral nervous systems.[1][2][3] They mediate both excitatory and inhibitory neurotransmission. The serotonin receptors are activated by the neurotransmitter serotonin, which acts as their natural ligand.

The serotonin receptors modulate the release of many neurotransmitters, including glutamate, GABA, dopamine, epinephrine / norepinephrine, and acetylcholine, as well as many hormones, including oxytocin, prolactin, vasopressin, cortisol, corticotropin, and substance P, among others. The serotonin receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, and thermoregulation. The serotonin receptors are the target of a variety of pharmaceutical and recreational drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.[4]

Roles in humans

In the central nervous system, serotonin plays an important role as a neurotransmitter in the modulation of anger, aggression, body temperature, mood, sleep, human sexuality, appetite, and metabolism, as well as stimulating vomiting.[5]

Serotonin has broad activities in the brain, and genetic variation in serotonin receptors and the serotonin transporter, which facilitates reuptake of serotonin into presynapses, have been implicated in neurological diseases. Drugs targeting serotonin-induced pathways are being used in the treatment of many psychiatric disorders, and one focus of clinical research is the influence of genetics on serotonin action and metabolism in psychiatric settings. Such studies have revealed that the variation in the promoter region of the serotonin transporter protein accounts for nearly 10% of total variance in anxiety-related personality, and the effect of this gene on depression was found to interact with the environment.[6]

Levels of serotonin in the brain show association with aggression[7], and a mutation in the gene which codes for the 5-HT2A receptor may double the risk of suicide for those with that genotype.[8] In addition, serotonin is also a peripheral signal mediator. It is found extensively in the human gastrointestinal tract as about 80-90% of the body’s total serotonin is found in the enterochromaffin cells in the gut.[5]In the blood, the major storage site is platelets, which collect serotonin for use in mediating post-injury vasoconstriction. Recent research suggests that serotonin plays an important role in liver regeneration and acts as a mitogen (induces cell division) throughout the body. Recent research also suggests that intestinal serotonin may inhibit bone formation. [9]

Serotonin syndrome

Extremely high levels of serotonin can cause a condition known as serotonin syndrome that has toxic and potentially fatal effects. Serotonin syndrome, also known as serotonin toxicity, can be induced via overdose of particular drugs and some drug combinations where both substances have seretonergic actions. Many drug interactions have been found to cause serotonin syndrome, the most notorious of which being the combination of an SSRI antidepressant and an MAOI antidepressant.

Symptoms can start showing within minutes and can include increased heart rate, sweating, anxiety, hyperthermia, shivering, high blood pressure, agitation, seizures, and rarely death. Symptoms usually resolve after 24 hours, but can last up to several months in some cases.

Serotonin deficiency

Serotonin deficiency is a common contributor to mood problems. Some feel it is an epidemic in the United States. Serotonin is key to our feelings of happiness and very important for our emotions because it helps defend against both anxiety and depression. Many of the current biochemical theories of depression focus on the biogenic amines, which are a group of chemical compounds important in neurotransmission—most importantly norepinephrine, serotonin and, to a lesser extent, dopamine, acetylcholine and epinephrine.

WHAT CAUSES OR CONTRIBUTES TO SEROTONIN DEFICIENCY?

Many life stressors can lead to low serotonin:

• Prolonged periods of stress can deplete serotonin levels. Our fast paced, fast food society greatly contributes to these imbalances.
• Genetic factors, faulty metabolism, and digestive issues can impair absorption and breakdown of our food which reduces are ability to build serotonin.
• Poor Diet. Neurotransmitters are made in the body from proteins. Also required are certain vitamins and minerals called “cofactors”. If your nutrition is poor and you do not take in enough protein, vitamins, or minerals to build the neurotransmitters, a neurotransmitter imbalance develops. We really do think and feel what we eat.
• Toxic substances like heavy metals, pesticides, drug use, and some prescription drugs can cause permanent damage to the nerve cells that make serotonin and other neurotransmitters.
• Certain drugs and substances such as caffeine, alcohol, nicotine, NutraSweet, antidepressants, and some cholesterol lowering medications deplete serotonin and other neurotransmitter levels.
• Hormone changes cause low levels of serotonin and neurotransmitter imbalances.
• Lack of sunlight contributes to low serotonin levels

SYMPTOMS

You may have a shortage of serotonin if you have a sad depressed mood, low energy, negative thoughts, feel tense and irritable, crave sweets, and have a reduced interest in sex. Other serotonin related disorders include:

• Depression
• Anxiety
• Panic Attacks
• Insomnia
• Irritable bowel
• PMS/ Hormone dysfunction
• Fibromyalgia
• Obesity
• Eating disorders
• Obsessions and Compulsions
• Muscle pain
• Chronic Pain
• Alcohol abuse
• Migraine Headaches

 

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Reference:

 

[1]. Hoyer D, Clarke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP (1994). “International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin)”. Pharmacol. Rev. 46 (2): 157–203. PMID 7938165.

[2]. Frazer A, Hensler JG (1999). “Chapter 13: Serotonin Receptors”. In Siegel GJ, Agranoff BW, Albers RW, Fisher SK, Uhler MD (eds.). Basic Neurochemistry: MolecularCellular, and Medical Aspects. Philadelphia: Lippincott-Raven. pp. 263–292. ISBN 978-0-397-51820-3.

[3]. Beliveau, Vincent; Ganz, Melanie; Feng, Ling; Ozenne, Brice; Højgaard, Liselotte; Fisher, Patrick M.; Svarer, Claus; Greve, Douglas N.; Knudsen, Gitte M. (2017-01-04). “A High-Resolution In Vivo Atlas of the Human Brain’s Serotonin System”. Journal of Neuroscience. 37 (1): 120–128. doi:10.1523/jneurosci.2830-16.2016. PMC 5214625. PMID 28053035.

[4]. Nichols DE, Nichols CD (May 2008). “Serotonin receptors”. Chem. Rev. 108 (5): 1614–41. doi:10.1021/cr078224o.

[5].Lesch, K.; Bengel, D.; Heils, A.; Sabol, S. Z.; Greenberg, B. D.; Petri, S.; Clemens, R.; Müller, J. B.; Hamer, D. H.; Murphy, D. L. (1996). Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region. Science 274: 1527–31

[6].Caspi, A.; Sugden, K.; Moffitt, T. E.; Taylor, A.; Craig, I. W.; Harrington, W.; McClay, J.; Mill, J.; Martin, J.; Braithwaite, A.; Poulton, R. (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301: 386–89.

[7].Caspi N, Modai I, Barak P, Waisbourd A, Zbarsky H, Hirschmann S, Ritsner M. (2001 Mar). Pindolol augmentation in aggressive schizophrenic patients: a double-blind crossover randomized study. Int Clin Psychopharmacol. 16(2): 111-5.

[8]. Basky, Greg (May 2000). Suicide linked to serotonin gene. CMAJ 162 (9).

[9].Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes. 2013;20(1):14‐21. doi:10.1097/MED.0b013e32835bc703

[6]. Serotonin Syndrom. Psychonaut Wiki, accessed May 2020.