Serotonin and Behaviorby Viatcheslav Wlassoff, PhD | June 11, 2014
Serotonin is a common neuromediator in the brain. It belongs to the group of so-called biogenic amines, relatively simple chemicals that facilitate the transfer of signals between the cells of the body. Although nerve cells that use serotonin for communicating with other cells have been intensively studied, they still remain a bit of a mystery.
There is only small number, around 300,000 or so, of serotonergic neurons in the brain. They are distributed in several nuclei at different brain locations such as hindbrain and midbrain. Although their number is small by brain standards, they have an extensive network of connections with huge number of collateral branches. As a result, serotonergic system reaches almost all areas of central nervous system.
The serotonin system is very complex
Serotonergic neurons are involved in a very broad range of physiological and behavioral processes such as cardiovascular regulation, appetite, pain sensitivity, sexual behavior, mood, respiration, cognition, learning etc. They also play important part in a variety of psychiatric conditions (from anxiety disorders to schizophrenia) as well as behavioral impulse-related disorders (violence, attention deficit disorder, substance abuse, obsessive control, etc.)
In evolutionary terms, the serotonergic system is one of the oldest, and seems to be involved in various inhibitory responses throughout the central nervous system. It opposes most of other neuromediator systems and seems to counterbalance neurological reactions controlled by other neurons. As a results, deficiencies in serotonin production, utilization or sensing can lead to serious changes in the brain functioning in general, and its behavioral aspects in particular.
The outcome of the serotonin release by the neuron depends on the type of receptor it binds to on the corresponding target cell. To date, at least 17 types of receptors responding to serotonin have been discovered. In addition, lots of proteins and enzymes are involved in the biosynthesis and metabolism of serotonin and can directly change its level. Various alterations in corresponding genes affect the levels of serotonin or sensitivity to serotonin and may cause behavioral changes.
Changes in serotonin level can affect behavior
The level of serotonin is controlled by multiple mechanisms. Any changes in the genes involved may lead to serious consequences.
Defects in one of the serotonin receptors, 5-HT 1A, are known to lead to the increased anxiety. The decrease of the level of serotonin generated by the action of enzyme monoaminooxidase A is associated with violent behavior and antisocial personality disorder. Increased level of serotonin during early life, caused by decreased activity of this enzyme, seems to be linked with the higher risk of violent behavior and aggression in the adulthood.
Abnormalities in serotonin signalling are important in development of schizophrenia. Observations of serotonin abnormalities in patients with this condition led to the formulation of serotonin hypothesis of schizophrenia.
Many natural and pharmaceutical compounds acting on serotonin receptors cause a variety of behavioral responses. One serotonin receptor seems to be involved in the mechanism of LSD, one of the strongest hallucinogenic compounds known. Binding with LSD causes general decrease in inhibitory action of serotonergic system. Some similarities between mystical experience and the effects of LSD even made scientists to speculate that changes in serotonin are involved in our perception of religion.
Connections between serotonin level and suicidal behavior
Low levels of serotonin are associated with depression and suicidal behavior. There are many genetic factors leading to decreased level of serotonergic activity in certain areas of the brain. They contribute to the development of various disorders. Researchers think that suicidal behavior can correlate with other characteristics such as aggression and impulsiveness, and some individuals are more vulnerable due to their genetic makeup. Some estimates suggest that genetic factors play a role in 30–50% of suicides.
Several genetic alterations in the gene for tryptophan hydroxylase were reported to be associated with suicidal behavior. This enzyme is involved in biosynthesis of serotonin, and therefore its genetic alterations can easily affect the level of this mediator. The enzyme exists in two different forms. The higher level of one of them was observed in depressed patients who attempted suicide.
Serotonin transporter is another protein which genetic alterations may cause problems. One of the commonly observed versions of the corresponding gene lacks a significant portion involved in its regulation. Decreased level of serotonin transporter results also correlates with suicidal behavior, although this correlation is not easy to interpret.
The human genome does not have a “suicide gene”. Some genetic changes, however, create conditions for higher likelihood of deep depressions and suicides. It seems that many of these changes take place in the genes involved in regulation of serotonin in the brain. Like other psychological disorders, suicidal behavior is linked to complex interaction between genes. It cannot be explained by just one factor. Now we have clear evidences that suicidal tendencies can be passed from one generation to the next. But this only means that individuals with higher genetic predisposition would have a slightly higher probability of committing suicide in the face of adverse life events.
What makes the serotonergic system particularly fascinating for scientists is that it does not seem to have direct control over anything, yet at the same time it is involved in a vast range of behaviors, many of which are basic biological responses to the changes and challenges of the environment.
This complexity presents a serious challenge for developing any drugs targeting psychopathologies linked to altered behavior: by targeting one part of the system we can often inadvertently change lots of other things. This reflects the fact that various aspects of our behavior are closely linked on the basic level of brain structure.
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Brent DA, & Mann JJ (2005). Family genetic studies, suicide, and suicidal behavior. American journal of medical genetics. Part C, Seminars in medical genetics, 133C (1), 13-24 PMID: 15648081
Goodman N (2002). The serotonergic system and mysticism: could LSD and the nondrug-induced mystical experience share common neural mechanisms? Journal of psychoactive drugs, 34 (3), 263-72 PMID: 12422936
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Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM, Dwork AJ, & Arango V (2000). A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Archives of general psychiatry, 57 (8), 729-38 PMID: 10920459
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