Genetic Research on Serotonin

What's the science behind anger management? Anger is a normal and healthy emotion – it motivates us to address injustice. While it's healthy to be angry and passionate about an issue, it's also important to be able to regulate this anger and control aggressive impulses that arise as a result. Serotonin is one neurotransmitter that can help us with that process. Genetic research on serotonin explores how genes affect serotonin and aggression.

Genetic Research on Serotonin Genetic Research on Serotonin

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Table of contents
    • First, we will discuss the correlation between serotonin levels and aggression levels.
    • Then, we will look at how the genetic predisposition to low serotonin levels might affect the regulation of anger.
    • Moving along, we will examine the evidence for serotonin gene mutation affecting aggression. Specifically, we will look at the MAOA gene mutation.
    • We will also provide a brief overview of genetical research on serotonin and dopamine.
    • Finally, we will evaluate the serotonin explanation of aggression.

    Genetic research on serotonin, professional woman meditating during work, StudySmarterFig. 1 - Research suggests that serotonin can calm us dow, regulate mood and improve self-control.

    What is the Neurobiology of Impulsive Aggression?

    To understand how serotonin can help regulate aggression, we need first to understand the neurobiology of aggression.

    The brain structure associated with generating aggressive impulses is called the limbic system.

    The limbic system is a complex structure which is involved in emotional responses, it consists of a few other structures, some of which are the hippocampus, the amygdala, and the hypothalamus.

    When we are under threat, the amygdala can produce intense feelings of anger, which often drive aggressive behaviours. The orbitofrontal cortex can regulate these impulses from the limbic system, a structure associated with executive function and emotional regulation.

    The orbitofrontal cortex processes information from other brain structures, including the limbic system, and engages in decision-making regarding this information and inhibits aggressive impulses.

    What's the Correlation Between Serotonin Levels and Aggression Levels?

    Serotonin is considered to be a key neurotransmitter in the communication between the limbic system and the orbitofrontal cortex. It can stabilise our mood, calm our anger and promote self-control.

    Serotonin is a neurotransmitter linked with regulating mood, attention, behaviour and physiological processes like sleep, digestion, or temperature.

    The serotonin explanation of aggression proposes that low levels of this neurotransmitter can impair self-control over impulses, resulting in an inability to regulate one's anger.

    Genetic Predisposition to Low Serotonin Levels

    It's possible that a genetic predisposition to lower serotonin levels could affect people's self-control over aggressive impulses in response to perceived provocation or threat. We therefore need to look into serotonin turnover rates.

    Two genes that influence serotonin levels have been linked to aggression– genes associated with the tryptophan hydroxylase enzyme and the MAOA gene; these genes affect serotonin production and metabolism.

    Passamonti et al. (2012) conducted a study investigating the effects of lower serotonin levels on aggression. The researchers manipulated the levels of serotonin in participants' brains by changing participants' diets.

    • To lower serotonin levels, participants in the experimental group consumed a drink that lacked tryptophan, an amino acid necessary for synthesising serotonin.
    • The participants were then asked to view stimuli consisting of different gendered angry, sad, and neutral faces while their brain activity was scanned with an fMRI.

    The findings demonstrated that the activity of the frontal lobe as well as the connection between the limbic system and the frontal lobe were reduced in participants with lower serotonin in response to angry faces only. These findings suggest that lower serotonin levels can impair one's control of aggressive impulses, as marked by lower frontal lobe activity.

    The study conducted by Passamonti et al. (2012) was a double-blind, placebo-controlled trial, meaning that the 30 participants recruited were assigned to either a diet low in tryptophan or a normal diet (placebo). Neither participants nor researchers knew what participant was in which condition to ensure objectivity in measurements.

    Genetical Research on Serotonin, doctor looking at MRI results, StudySmarterFig. 2 - To investigate how the prefrontal cortex activity is affected by depleted serotonin Passamonti et al. (2012) conducted fMRI scans on their participants.

    Another piece of evidence for the association between lower serotonin levels and aggression comes from the George et al. (2001) study.

    • This study compared the concentrations of serotonin and serotonin metabolite (5-HIAA) in the cerebral spinal fluid of alcoholic domestic violence perpetrators, non-alcoholic abusers, domestic violence perpetrators, and healthy controls.
    • The highest scores of physical aggression were found in non-alcoholic perpetrators, this group also had significantly lower serotonin levels compared to the other groups.

    Serotonin Gene Mutation

    Even though lower levels of serotonin have been associated with less control over impulsive aggression, a rare genetic mutation, which causes higher levels of serotonin, has also been associated with greater levels of aggression.

    Short-variant of the MAOA gene has been associated with impaired serotonin breakdown and, therefore, higher serotonin levels. Individuals with this variant of the MAOA gene have been found to display more aggressive and violent behaviour.

    The MAOA gene affects the Monoamine oxidase A enzyme (MAO-A), which breaks down several neurochemicals, including serotonin and dopamine.

    MAOA Gene Mutation

    Brunner et al. (1993) assessed male members of a Dutch family in which borderline mental retardation and complex behavioural problems were common and found a genetic mutation in the structure of the MAOA gene.

    • The researchers investigated the genotypes of five males within this family who were particularly aggressive and violent. They found that these individuals shared a short variation of the MAOA gene.
    • When researchers tested their urine, there were deficiencies in their enzymatic activity of MAO-A, which we know is involved in breaking down serotonin.

    The study concluded that the participants' behavioural issues were likely related to the abnormal variation of the MAOA gene.

    Genetic Research on Serotonin and Dopamine

    Brunner and colleagues' study was quasi-experimental; they couldn't manipulate the participants' genes, as it would be unethical. However, another study, which manipulated the MAOA genes in mice, has confirmed Brunner's findings.

    Cases et al. (1995) manipulated the gene that codes for MAOA in mice and caused the gene to be deleted that encodes for MAOA, which causes a deficiency of the MAO-A enzyme.

    • After the MAOA gene was deleted, serotonin concentrations in mice increased ninefold, this is because MAO-A could not break down the serotonin.
    • It was observed that baby mice started showing behavioural problems such as trembling and fearfulness. There was an increase in aggressive behaviours in adult mice as well.

    Both fearfulness and aggression are linked to the activity of the amygdala. Excessive fearfulness and aggression could be caused by the inability to regulate this activity due to an impaired connection between the orbitofrontal cortex and the limbic system.

    This study suggests that the inability to regulate serotonin levels causes behavioural issues in mice.

    Dopamine can also be implicated in the control of aggression. Lower levels of serotonin have also been found to elevate dopamine levels, which have also been associated with aggression in animals (Seo et al., 2008).

    • Serotonin is likely to be implicated in reactive aggression in response to threat or provocation.
    • Dopamine, which is implicated with the reward system, is likely to be associated with proactive aggression, which is goal-oriented.

    Genetical Research on Serotonin, scientist's hands with gloves on and a double helix in between them, StudySmarterFig. 2 - Individuals with this variant of the MAOA gene have been found to display more aggressive and violent behaviour.

    Serotonin Explanation of Aggression Evaluation

    Changes in serotonin levels have been linked to aggression by a variety of studies, including both correlational and experimental studies, which gives the serotonin explanation credibility. The evidence comes from both animal studies and studies conducted on humans.

    However, it is unclear why both elevated and lower levels of serotonin increase aggressive tendencies.

    This explanation of aggression can be considered reductionist, it ignores the potential social, cultural and environmental influences on aggression or how they interact with our biology. However, this reductionist model has allowed researchers to make testable hypotheses and collect experimental evidence.

    This theory also supports the notion of biological determinism. Abnormal levels of serotonin in the brain or genetic abnormalities are proposed to make people incapable of controlling their behaviour. This position is problematic, as it puts into question people's free will and the ethics of legal punishment of behaviours that people potentially can't control.


    Genetic Research on Serotonin - Key takeaways

    • Serotonin is a neurotransmitter linked with regulating mood, attention, behaviour and physiological processes like sleep, digestion, or temperature.
    • The serotonin explanation of aggression proposes that low levels of this neurotransmitter can impair self-control over impulses and an inability to regulate one's anger.
    • Passamonti et al. (2012) have found a link between serotonin depletion and the activity of the prefrontal cortex, which regulates anger and aggressive impulses.
    • Brunner et al. (1993) have found an association between a short MAOA gene variant and aggressive and violent behaviour.
    • The serotonin explanation of aggression has been supported by biological research. However, it can be considered to be reductionist and deterministic.

    References

    1. Brunner, H. G., Nelen, M., Breakefield, X. O., Ropers, H. H., & van Oost, B. A. (1993). Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science (New York, N.Y.), 262(5133), 578–580.
    2. Cases, O., Seif, I., Grimsby, J., Gaspar, P., Chen, K., Pournin, S., Müller, U., Aguet, M., Babinet, C., & Shih, J. C. (1995). Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science (New York, N.Y.), 268(5218), 1763–1766.
    3. Seo, D., Patrick, C. J., & Kennealy, P. J. (2008). Role of Serotonin and Dopamine System Interactions in the Neurobiology of Impulsive Aggression and its Comorbidity with other Clinical Disorders. Aggression and violent behavior, 13(5), 383–395. https://doi.org/10.1016/j.avb.2008.06.003
    4. Passamonti, L., Crockett, M. J., Apergis-Schoute, A. M., Clark, L., Rowe, J. B., Calder, A. J., & Robbins, T. W. (2012). Effects of acute tryptophan depletion on prefrontal-amygdala connectivity while viewing facial signals of aggression. Biological psychiatry, 71(1), 36–43. https://doi.org/10.1016/j.biopsych.2011.07.033
    5. George, D.T., Hibbeln, J.R., Ragan, P.W., Umhau, J.C.,Phillips, M.J., Doty, L., Hommer, D., Rawlings, R.R., 2000.Lactate-induced rage and panic in a select group of sub- jects who perpetrate acts of domestic violence. BiologicalPsychiatry 47, 804  812.
    Frequently Asked Questions about Genetic Research on Serotonin

    How does the serotonin transporter gene impact happiness?

    The transporter gene is responsible for transporting serotonin out of the synaptic cleft. This allows more serotonin to be released into the cleft and stops the action of serotonin when needed. If anything interferes with this process, it can cause problems with regulation of mood and emotions, including happiness. However, an excess of serotonin in the cleft eventually leads to desensitisation to serotonin and a lower level of happiness.

    What activities release serotonin?

    Several activities release serotonin: going out in the sun, experiencing or thinking about happy things, or conversely, being threatened or experiencing a fearful situation.

    How does genetics affect serotonin?

    Genes affect serotonin in multiple ways, through the synthesis of serotonin (lowering or increasing production), serotonin transportation, and the uptake of serotonin after it has been produced.

    Can genetics cause low serotonin?

    Yes. If the genetic components for serotonin production/synthesis are affected, it will cause issues that could result in low serotonin levels.

    What gene controls serotonin?

    There’s not a single gene that completely controls serotonin. However, genes such as the TPH gene and the MAOA gene affect the synthesis and degradation of serotonin.

    Test your knowledge with multiple choice flashcards

    What is serotonin?

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