Since the landmark study by Brown et al (1979) found that the levels of the serotonin metabolite 5-hydroxy indole acetic acid (5-HIAA) correlated with aggression scores, scientists have thought that serotonin deficiency was responsible for such behavior – the serotonin deficiency hypothesis, as it is called.

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Serotonin is a brain neurochemical that is synthesized directly within the brain from its precursor, a monoamine amino acid called tryptophan. It modulates neural function, playing a vital role in a host of essential processes that are involved in the development of neurons and microglia within the brain.

These include neural cell proliferation, differentiation into a different type of cell, travel to another site, migration, synapse production and apoptosis.

It has since been tested hundreds of times in the past 40 years but remains the watchword of the role of serotonin in abnormal aggression. Some have termed this negative relationship the most reliable finding in the history of psychiatry – people with low serotonin levels have an impulsive personality.

Another model, called irritable aggression, says that impaired functioning of serotonin-secreting nerve cells produces greater irritability and a higher level of reactivity to triggers and situations. Impulsive aggression is also said to be characterized by low cerebrospinal fluid levels of serotonin.

Lower serotonin levels in the brain are also thought to be linked to poor orbitofrontal cortex function, which is in turn seen to be present in people with antisocial behavior.

Another hypothesis is that the presence of a connection between serotonin-secreting and dopaminergic neurons causes higher levels of activity of dopamine neurons when the serotonin levels are low.

This could underlie the observed increase in addictive as well as depressive conditions in persons with low serotonin levels.

What is aggression?

Impulsive aggression is a psychological construct in which the individual is not able to control mood or aggressive impulses. It is closely linked to depression, suicidal tendencies, and substance abuse. In other words, such people show impulsive aggression towards oneself and others and become depressed under the stressful situations of life.

Impulsive aggression is also key in criminal and violent behavior and is at the heart of borderline and antisocial personality disorders.  Low serotonin has been linked to impulsive aggression.

Aggression, unlike impulsivity, is not a personality trait, but a behavior wherein one injures or harms others. It is thought by some to be oriented towards survival, but when it is constant and excessive, it injures both at individual and community levels.

The issue with the serotonin-aggression link

However, an objective look at these studies shows that the relationship is not so strong as assumed. For one, the average levels of 5-HIAA in normal and affected groups overlap so much as to leave the definition of ‘normal’ or ‘low’ in doubt.

In contrast to the earlier hypothesis that assigned 80% of the variance in the aggression of a group of soldiers to serotonin levels, a meta-analysis of 175 samples shows that it accounts for a little over 1% of the variance in aggression, hostility, and anger. And the 5-HIAA levels show almost no correlation at all.

The reasons lie not only in the use of flawed methods but also in the increased understanding of serotonin’s role in regulating human behavior. There are known to be multiple different serotoninergic pathways, with over 12 distinct receptor types for serotonin.

Many of these receptors have completely different functions in the living organism, or even opposing functions. Serotonin may act on the nerve cell before or after the synapse, may have tonic vs phasic effects on the brain cell, and may interact with other neurotransmitters to produce its effects.

Thus, a selective or specific serotonin deficiency may be responsible for some aspects of aggression but not all. Personality and environment, such as a hostile personality, also closely interact with serotonin levels and deeply influence the responses to different situations.

Low serotonin levels are also linked to a host of psychiatric afflictions other than impulsive aggression. Some of these include migraines, pathological shyness, obsessive-compulsive disorder, anxiety, restless leg syndrome, gambling, and depression, besides several addictions (food, sex, and drugs).

Selective serotonin reuptake inhibitors are among the most widely prescribed drugs, being consumed by millions upon millions, most commonly for depression, but also many of these other disorders. Unless the data is deeply misleading, the alternative explanation is that serotonin shortage is linked to a plethora of behavioral-emotional problems, and not merely aggression.

This is plausible, given that serotonin-producing neuron in the brainstem network with many different parts of the brain, including a broad range of functions.

Therefore, rather than linking serotonin to aggression specifically, it is wiser to assume that this neurotransmitter underlies many psychiatric conditions and neurobiological processes.

And even more important, it shows that neurobiology cannot explain the steep rise in violent and aggressive behavior in the US, for instance, but this can be imputed with far more justice to social, cultural and economic causes that promote violent behavior.

Perhaps serotonin levels may be one of the genetic causes that predispose to the adoption of aggressive behavior, but nothing more.

Sources

• Duke, A. A., Bègue, L., Bell, R., & Eisenlohr-Moul, T. (2013). Revisiting the serotonin-aggression relation in humans: a meta-analysis. Psychological bulletin, 139(5), 1148–1172. doi:10.1037/a0031544
• Fatih Hilmi Çetin, Yasemin Taş Torun and Esra Güney (2017). The role of serotonin in aggression and impulsiveness, serotonin – a chemical messenger between all types of living cells. IntechOpen, DOI: 10.5772/intechopen.68918. Available from: https://www.intechopen.com/books/serotonin-a-chemical-messenger-between-all-types-of-living-cells/the-role-of-serotonin-in-aggression-and-impulsiveness
• Klasen M, Wolf D, Eisner PD, Eggermann T, Zerres K, Zepf FD, Weber R and Mathiak K (2019) Serotonergic contributions to human brain aggression networks. Frontiers in Neuroscience 13:42. doi: 10.3389/fnins.2019.00042. https://www.frontiersin.org/articles/10.3389/fnins.2019.00042/full
• Wallman, J. (2011). Serotonin and impulse aggression: not so fast. The Biology of Aggression vot. 3 Spring 1999. http://www.hfg.org/hfg_review/3/wallman.htm
• Reddy K. J., Menon K. R., and Hunhan U. G. Neurobiological aspects of violent and criminal behavior. International Journal of Criminal Justice Sciences 2018. Vol. 13 ( 1):  44–54 .  DOI:     10.5281/zenodo.1403384 / http://www.sascv.org/ijcjs/pdfs/ReddyetalVol13Issue1IJCJS.pdf

Further Reading

• All Serotonin Content
• What is Serotonin?
• Serotonin Function
• Serotonin Biosynthesis
• Drugs Targeting the 5-HT System

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.