Suicidal Behaviours, Genes, and The Brain: It Is Always More Than It Seems

The number of people who died due to suicide has risen to almost 800.000 each year⁽¹⁾. Some of you may know someone who has died of suicide. Some of you may experience first-hand what it is like to have suicidal thoughts. Most of you might have seen depictions of suicide, for example in movies, TV series, and news reports. Those experiences can be thought-provoking: Why do people decide to end their own lives?

Recent news report about suicide often cited recently devastating or painful experience that someone has experienced before their suicide, for example a heartbreak. After reading the news, most of us may think that he killed himself because of the recent heartbreak.

This is normal. Our brains naturally, constantly, and adaptively think of the simplest, most familiar, and quickest way to understand the world (If you are interested to learn more, look up heuristics).

The fact is, understanding suicidal behaviour is not that simple. It is not a straight line. If heartbreak is the sole explanation of a suicide, why do most people who have recently gone through a break up did not exhibit suicidal behaviours?

Professor van Heeringen from Ghent University (Belgium) and Professor Mann from Columbia University (USA) reviewed past researches about suicidal behaviours and put forth the diathesis-stress model of suicide⁽²⁾. Their research reveals that life-stress (e.g. heartbreak) is not enough to explain suicidal behaviours. In fact, some people have higher vulnerabilities to suicidal behaviours that can be traced back to their genes, and the environment in which those genes are shaped. These predispositions can manifest as higher level of sensitivity to stress, impulsiveness, pessimism, or hopelessness.

Actually, these inherited properties can explain about 50% of the risk of suicide^{(3, 4, 5)}.

Since the amazing invention of brain imaging techniques, we are able to take a look at brain activities and make correlations to our thoughts, feelings, and behaviours. We figured out that they all can be traced back to our brain. Brain activity is the connection between those genetic predispositions and the actual behaviours⁽²⁾.

So according to Heeringen and Mann’s review, what do we know about the brain that increases the risk to suicidal behaviours.

Differences in the way brain cells talk to each other chemically

The brain is made up of cells (neurons) that communicate with each other to form who we are. One of the “languages” of their communication is through chemicals called neurotransmitters.

One of the neurotransmitters, called serotonin, is highly implicated in the literature of mental health well-being and depression^{(6, 7)}. Serotonin is involved in regulating numerous functions of the body, including for balancing mood of a person^{(7, 8)}.

The review concluded that there is an altered serotonin system in the brains of people who have exhibited suicidal behaviours⁽²⁾. This is shown by studies that looked at people who have died due to suicide and people who have attempted suicide but lived, compared with people who never had any suicidal intent.

The results have indicated that serotonin is found less in the brain of people who has a greater risk to suicidal behaviours⁽²⁾. However, just like everything about the brain, the full extent of how it works is still largely being studied. We can just agree that serotonin has an important role in suicidal behaviours^{(2, 8, 9)}.

Noradrenergic, or often called noradrenaline, is another chemical language of the brain, which is also important in understanding suicidal behaviours. This chemical is vital in keeping our physical body going, being the main neurotransmitter responsible for regulating our cardiovascular system⁽¹⁰⁾. Evidences have been found to point out the likelihood of abnormal noradrenaline transmission (deficit) in the brains of people who are more likely to exhibit suicidal behaviour⁽²⁾.

Differences in the way a particular brain circuit react to stress

The brain is like a super busy train station, there are a lot of activities coming and going from all different directions of different cells. When we look at a certain behaviour, we can’t really just look at a cell. Mostly we look at the important route that they are taking called a circuit. A particularly important circuit is the hypothalamic-pituitary-adrenal (HPA) axis in relation to suicidal behaviours^{(2, 11, 12)}.

HPA axis is known as our major stress response system. When we are stressed, this circuit will respond by activating brain areas and releasing hormones associated with it. This is actually good, because we want our body to react to stress so we can cope with it. However, research showed that if HPA axis is always on (meaning stress is never-ending), this circuit adapts to it and ends up being dull^{(2, 11, 12)}. As a result, it is not as ready to process and adapt stress optimally.

Back to our example, now we can add more complexities to the explanation. For example, Doe has genetic vulnerabilities to suicide, and those genes have been shaped in an environment that supported the expressions of those genes. As a result, Doe’s brain activities are reacting differently when exposed to stress. These brain activities make Doe more sensitive to stress, more impulsive, more pessimistic, and less able to see hope in situations.

This is not the whole explanation. The research is still going.

We can hope that by knowing these findings about suicidal behaviours in the field of genetics and neuroscience, we will be able to predict people who are more at risk. By doing that, we can better prevent and treat suicidal behaviours.

References

1. World Health Organisation (2018). Mental health: Suicide data. Retrieved from http://www.who.int/mental_health/prevention/suicide/suicideprevent/en/
2. Heeringen, K., & Mann, J. J. (2014). The neurobiology of suicide. The Lancet, 1, 63-72.
3. Statham, D. J., Heath, A. C., Madden, P. A., Bucholz, K. K., Bierut, L., Dinwiddie, S. H., Slutske, W. S., Dunne, M. P., & Martin, N. G. (1998). Suicidal behaviour: An epidemiological and genetic study. Psychological Medicine, 28(4), 839-855.
4. Althoff, R. R., Hudziak, J. J., Willemsen, G., Hudziak, V., Bartels, M., &Boomsma, D. I. (2012). Genetic and environmental contributions self-reported thoughts of self-harm and suicide. American Journal of Medical Genetic Part B: Neuropsychiatric Genetics, 159B(1), 120-127.
5. Risch, N., Herrell, R., & Lehner, T. (2009). Interaction between the Serotonin Transporter Gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. JAMA, 301(23), 2462-2471.
6. Munafo, M. R., Brown, S. M., & Hariri, A. R. (2008). Serotonin transpoter (5-HTTLPR) genotype and amygdala activation: A meta-analysis. Biological Psychiatry, 63(9), 852-857.
7. Gilihan, S. J., Rao, H., Wang, J., Detre, J. A., Breland, J., Sankoorikal, G. M. V., Brodkin, E. S., & Farah, M. J. (2010). Serotonin transporter genotype modulates amygdala activity during mood regulation. Social Cognition Affective Neuroscience, 5(1), 1-10.
8. Mann, J. J., Huang, Y., & Underwood, M. D. (2000). A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Archive of General Psychology, 57(8), 729-738.
9. Ryding, E., Lindstrom, M., & Traskman-Bendz, L. (2008). The role of dopamine and serotonin in suicidal behaviour and aggression. Progress in Brain Research, 172, 307-315.
10. Gordan, R., Gwathmey, J. K., & Xie, L. (2015). Autonomic and endocrine control of cardiovascular function. World Journal of Cardiology, 7(4), 204-214.
11. Melhem, N. M., Keilp, J. G., Porta, G., Oguendo, M. A., Stanley, B., Cooper, T. B., Mann, J. J., & Brent, D. A. (2016). Blunted HPA axis activity in suicide attempters compared to those at high risk for suicidal behaviour. Neuropsychopharmacology, 41(6), 1447-1456.
12. Roy, A. Hodgkinson, C. A., Deluca, V., Goldman, D., & Enoch, M. A. (2012). Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behaviour. Journal of Psychiatry Research, 46(1), 72-9.