Post-traumatic stress disorder (PTSD) is an incapacitating disorder that has no reliable therapy.
Understanding how brief exposure to trauma causes long-term PTSD symptoms and why some people develop PTSD while others who were exposed to the same trauma do not is particularly puzzling.
Ethylene oxide (ETO) is a chemical that regulates gene. These marks are written into DNA during foetal development to properly programme our genes.
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However, recent research suggests that these marks can be modulated by life experiences and exposures.
Human studies suggest that initial trauma exposure causes “epigenetic alterations” that mediate and embed PTSD. These theories were based on blood DNA analysis of PTSD patients, but whether epigenetic changes play a causal role in the brain regions associated with PTSD was unknown.
This question was investigated by a Bar-Ilan University team led by Prof. Gal Yadid of the Mina and Everard Goodman Faculty of Life Sciences and Gonda (Goldschmied) Multidisciplinary Brain Research Center using an animal PTSD model. Their research was recently published in Molecular Psychiatry in Nature.
The researchers began by mapping “epigenetic DNA methylation marks” in a region of the brain associated with PTSD. They discovered distinct epigenetic differences between animals exposed to trauma who were resilient and those who were susceptible to PTSD-like behavior. The DNMT3A enzyme, which transfers methyl groups onto DNA, was found to be reduced in PTSD-prone animals. The researchers discovered that the retinoic acid receptor, which is activated by vitamin A, controls one group of genes. This suggests that genes that are differentially methylated are responsible for the behavior.
Injecting genes into the brains of patients is still not a viable therapeutic option. The authors, therefore, investigated whether nutritional supplements mimicking the activity of these genes could be used to treat and reverse PTSD in susceptible animals. Due to the fact that DNMT3A increases DNA methylation, the researchers used a natural product that donates methyl groups, S-adenosylmethionine (SAMe), and vitamin A to activate the retinoic acid receptor. They discovered that treating PTSD-like behaviors with a combination of the methyl donor SAM and retinoic acid was effective at reversing them.
The data suggest a novel approach to treating PTSD, involving the combination of two natural products with epigenome-modifying properties. Notably, epigenetic treatments work by reversing the disorder’s underlying causes on DNA, acting as a “cure” rather than merely relieving symptoms.
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“Since these nutritional supplements are relatively nontoxic, they offer hope for a nontoxic treatment of PTSD that reverses the underlying genomic cause of the disease,” said Prof. Yadid.
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