Genes involved in vulnerability to post-traumatic stress disorder - Printable Version
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Genes involved in vulnerability to post-traumatic stress disorder - mtwalsh01 - 01-10-2015
Variants of two genes named catechol-O-methyltransferase (COMT) and tryptophan hydroxylase 2 (TPH2), associated with dopamine and serotonin regulation respectively, have been linked to increased risk of post-traumatic stress disorder (PTSD) in a new study. The study is published in the February 2015 edition of the Journal of Affective Disorders.
Senior author Dr. Armen Goenjian, of the Semel Institute for Neuroscience and Human Behavior at UCLA, explains that not everyone experiences PTSD after a traumatic event and that there may be a genetic basis to this difference: "Many people suffer with post-traumatic stress disorder after surviving a life-threatening ordeal like war, rape or a natural disaster. But not everyone who experiences trauma suffers from PTSD. We investigated whether PTSD has genetic underpinnings that make some people more vulnerable to the syndrome than others."
The study involved 200 Caucasian Armenian adults who were exposed to the 1988 Spitak earthquake. Individuals were from 12 multigenerational (3–5 generations) families. Dr Goenjian travelled to Armenia at the time of the earthquake and helped establish two psychiatric clinics, with support from the Armenian Relief Society. The clinics treated earthquake survivors for 21 years. The participants in the study were recruited from these clinics and donated blood samples for genetic analysis by Dr Goenjian and his colleagues in UCLA. A previous study by the team published in 2012 showed that PTSD was more common among individuals carrying two depression-associated gene variants.
The current study focused on COMT and TPH-2. COMT is an enzyme involved degradation of the neurotransmitter dopamine, which controls the reward and pleasure centres of the brain and is involved in regulation of mood, thinking, attention and behaviour. Imbalance in dopamine levels is critical in various neurological and psychological disorders. TPH-2 is involved in control of serotonin production. Serotonin is a brain hormone involved in regulation of processes including mood, sleep and alertness, which are affected by PTSD. Selective serotonin reuptake inhibitors are antidepressants which are now being used in other disorders, including PTSD. In the study, the researchers assessed both PTSD and depression using the UCLA PTSD Reaction Index based on DSM-5 criteria, and the Beck Depression Inventory.
Results of the study indicated that the COMT allele rs4633C and the TPH-2 allele rs11178997T were associated with variance in PTSD severity. Dr Goenjian explains: "We found a significant association between variants of COMT and TPH-2 with PTSD symptoms, suggesting that these genes contribute to the onset and persistence of the disorder. Our results indicate that people who carry these genetic variants may be at higher risk of developing PTSD."
Key to the study was the use of up-to-date DSM-5 criteria for assessment of PTSD and assessment of genes' role in predisposition to the disorder. Dr Goenjian says: "Assessments of patients based upon the latest diagnostic criteria may boost the field's chances of finding new genetic markers for PTSD. We hope our findings will lead to molecular methods for screening people at risk for this disorder and identify new drug therapies for prevention and treatment."
However, Dr Goenjian cautions that in common with other psychiatric disorders, this complex disease is likely to be influenced by the effects of multiple genes and that studies should continue to identify further gene candidates. He concludes: "A diagnostic tool based upon PTSD-linked genes would greatly help us in identifying people who are at high risk for developing the disorder. Our findings may also help scientists uncover more refined treatments, such as gene therapy or new drugs that regulate the chemicals associated with PTSD symptoms."
Goenjian AK et al. Association of COMT and TPH-2 genes with DSM-5 based PTSD symptoms. Journal of Affective Disorders; http://dx.doi.org/10.1016/j.jad.2014.10.034
Goenjian AK et al. Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms. Journal of Affective Disorders 140(3): 244-52. doi: 10.1016/j.jad.2012.02.015
Press release: University of California - Los Angeles Health Sciences; available at http://www.eurekalert.org/pub_releases/2015-01/uoc--usi010615.php