Stressed By His Short Allele




BioPsychoSocial Health CategoryThe serotonin (neurochemical) system in the brain has long been a target for interventions aimed at reducing depression and stress. Selective Serotonin Reuptake Inhibitors (SSRIs) are often used to balance mood and counteract high levels of anxiety. It is not surprising then that scientists are now finding that individual differences in the genetic makeup of this serotonin system may have a significant impact on one’s vulnerability to mental illness.

Individual differences in the genetic makeup of the serotonin system have been shown to increase one’s vulnerability to depression, anxiety and other psychiatric conditions, particularly if individuals are exposed to stressful events in their lives. Studies are showing that certain people (those that have the short allele of the serotonin transporter gene) have a greater biological reactivity to stressful events, including a larger hormonal response to stress and a greater brain reactivity to threat. In other words, both the hormonal and brain systems (amygdala) involved in fear and anxiety are more active in response to stress in those individuals who have a certain genetic makeup (short allele). This genetic difference may also account for individual differences in personality; those people who have a short allele for the serotonin transporter have been suggested to exhibit more “anxious” personality traits. This means our differences in gene function may bias our brains and our personalities to create a tendency to be more “negative,” “anxious” or reactive to stress.

StressThis begs the question: should modern medicine and psychotherapeutic approaches be extended to better account for these individual genetic variations in the stress response (and the serotonin system)? The idea that we may be able to refine our approach to medicine to account for these types of individual differences (in genetics, personality, the stress response and beyond) is pertinent to the continuing evolution of medicine and science, and one that is indeed increasingly being adopted by clinicians interested in a “personalized medicine” approach to traditional medical treatment and other forms of therapy. Furthermore, looking at a person’s biological make-up has applications for being able to better predict which individuals may be more at risk for mental health difficulties.

While the idea that our genetics may be used to tailor our individual medical treatments and to screen us for vulnerabilities could appear to some like a vision from the movie Gattaca (1997 science fiction film), such refinement in our medical approach may prove to be a significant step forward.

References

I GOTLIB, J JOORMANN, K MINOR, J HALLMAYER (2008). HPA Axis Reactivity: A Mechanism Underlying the Associations Among 5-HTTLPR, Stress, and Depression Biological Psychiatry, 63 (9), 847-851 DOI: 10.1016/j.biopsych.2007.10.008

M MUNAFO, S BROWN, A HARIRI (2008). Serotonin Transporter (5-HTTLPR) Genotype and Amygdala Activation: A Meta-Analysis Biological Psychiatry, 63 (9), 852-857 DOI: 10.1016/j.biopsych.2007.08.016

B S Shastry (2005). Pharmacogenetics and the concept of individualized medicine The Pharmacogenomics Journal, 6 (1), 16-21 DOI: 10.1038/sj.tpj.6500338

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  • http://neuroskeptic.blogspot.com Neuroskeptic

    The 5HTTLPR variant – the most researched genetic variant in the serotonin transporter gene – is very interesting. Most studies find it to be associated the “short” allele to be linked with depression or anxiety. But what’s most interesting about that is that the “short” allele leads to less of the serotonin transporter protein being produced.

    Less of the transporter would be expected to lead to more serotonin and hence less depression and anxiety – assuming a very simple relationship between serotonin and mood. So either this simple relationship is wrong, or something more complicated is going on.

    Currently theory is that the short version of 5HTTLPR might lead to raised serotonin during early development which might alter brain function later. In animal studies giving SSRIs in early life can cause later anxious & depressive behaviour so it’s plausible…

  • imanbahrani

    very interesting read…not a well known fact that the Serotonin levels are genetic rather than influenced mainly by the environment.

  • http://hdreviewspot.net/ Harley Davidson

    This is the exact reason why we should abandon the prohibition of the use of MDMA in treatment for those who have serotonin related issues.

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Erin Falconer, MS, PhD (c)

Erin Falconer, MS, PhD candidate, has published several refereed journal articles that have a neuroscience/psychology focus. He is currently in marketing and communications for a 'brain biotech' company that offers brain medicine and health solutions to clinicians, researchers, pharmaceutical companies and US managed care. He holds MS degree (Neuroscience) where he investigated the role of stress and hormones on the growth of new neurons in the adult brain (neurogenesis). He has since wrote and designed studies investigating the Placebo Effect in Parkinson's Disease and PTSD. He recently completed his PhD dissertation, for which he delineated a brain model of PTSD using behavioral assessments, functional and structural neuroimaging and electrophysiological brain measurements.
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