Serotonin is a neurotransmitter that plays a role in mood, learning, and memory. It is also involved in various other brain functions. Serotonin is found in the gastrointestinal tract, blood platelets, and throughout the central nervous system (CNS). Serotonin’s main function is to modulate mood and affect. Low levels of serotonin are associated with depression while higher levels are linked to happiness and well-being.
Serotonin affects nearly every organ in the body and has diverse functions ranging from regulating sleep and appetite to moderating stress responses. In the brain, serotonin helps regulate anxiety, impulsivity, aggression, appetite, temperature, sexual behavior, pain perception/sensitivity as well as many other functions. Research suggests that serotonin plays an important role in social behaviors such as trustworthiness/cooperation.
The vast majority of serotonin (~ 95%) is produced by enterochromaffin cells in the gut where it regulates intestinal movements. The remainder is produced by neurons in the CNS where it carries out its various neurotransmitter roles. Serotonin is synthesized from tryptophan via two different biochemical pathways: 1) tryptophan hydroxylase pathway which involves one enzyme (tryptophan hydroxylase); 2) 5-hydroxyindoleacetic acid pathway which involves three enzymes (aromatic amino acid decarboxylase [AADC], monoamine oxidase [MAO], and hydroxyindole-O-methyltransferase).
Both pathways require BH4 (tetrahydrobiopterin) as a cofactor which serves to recycle BH4 back to its active form after it has been used up during conversion of tryptophan to serotonin or dopamine respectively. BH4 can become depleted due to genetic defects (e.g., GTP cyclohydrolase I deficiency), certain medications (e.g., methotrexate), or inflammation/infection . When this occurs not enough serotonin or dopamine can be produced leading to problems with mood regulation , cognitive function , and other neuropsychiatric symptoms .
Although most people think of serotonin as being primarily a brain neurotransmitter , over 90% of our body’s total supply actually resides outside of the CNS – mainly in the gastrointestinal tract (GI) where it regulates peristalsis and bowel movements but also present in blood vessels where it acts a vasoconstrictor . While most GI effects are mediated indirectly through activation of local enteric nerves that innervate enteric smooth muscle cells , recent evidence suggests that some effects may be direct . For example , administration of SSRIs leads to an increase in intestinal permeability likely due directly to changes in gut epithelial cell tight junctions mediated by locally released serotonin . This finding could have important implications for understanding how SSRIs might influence susceptibility to GI infections or development of food allergies/intolerances .
In platelets , serotonin promotes clotting by causing vascular smooth muscle contraction and aggregation of platelets . Platelet-derived serum containing high levels of free tryptophan decreases clotting time while additionof exogenous free tryptophan shortens clotting time further suggesting that plasma concentrationsof free tryptophan influence whole blood clotting time independentofplatelet contentandfunction . Because both 5HTP(5-hydroxytryptophan)andL -tryptophansuppressappetite , theseaminoacidshavebeenproposedasa treatmentfor obesitybut theiruseislimitedbysideeffects includingnauseaandvomiting causedbyincreasedgastricacidsecretionaswellasheartburn causedbygastroesophagealreflux disease(GERD)( heartburn ).