Researchers Combine Epigenetics and Brain Imaging to Help Combat PTSD

Epigenetic mechanism DNA methylation could help veterans with PTSD

Post-traumatic stress disorder (PTSD) is a mental health issue that some people develop after experiencing or witnessing a life-threatening or intensely stressful event. PTSD can exert an enormous toll on an individual’s life, affecting their daily activities and relationships. According to the National Center for PTSD, about 7 or 8 of every 100 people will experience this disorder at some point in their lives. Anyone can develop PTSD at any age, including children, war veterans, and people who have been through distressing events. Recent research published in PLoS ONE combined brain imaging and epigenetics to better predict the symptoms of PTSD, which may help physicians to diagnose and treat individuals with the disorder.

Numerous animal studies have shown that epigenetic modifications can affect gene expression following environmental stress. These changes in gene expression can influence stress-response functions, such as those mediated by the hypothalamic-pituitary-adrenal (HPA) axis. One epigenetic study found that a woman’s estrogen level could influence methylation of HDAC4 and determine if she may be susceptible to developing PTSD, potentially even epigenetically protecting her from the disorder. Although further research is needed, another preliminary research study suggests we may be able to increase a certain type of epigenetic enzyme to ease anxiety or alleviate PTSD by erasing troubling memories.

Many veterans exposed to physical and psychological trauma during combat continue to experience symptoms of PTSD after service. Prevalence rates of PTSD are especially high among the veteran population; between 11-20% of veterans who served in Afghanistan and Iraq after 9/11, 12% of Gulf War veterans and 15% of Vietnam veterans have PTSD in a given year.

A previous study observed reduced methylation of the glucocorticoid receptor (NR3C1-1F) region in the peripheral blood of veterans with PTSD compared to veterans without PTSD. The NR3C1-1F promoter region is believed to be vital for the HPA stress response pathway. Although cytosine methylations are generally stable, they may be dynamically altered in response to traumatic experience.

Researchers at Stanford University School of Medicine aimed to determine a better predictor of PTSD symptomology by combining brain imaging and epigenetics. Hippocampal volume and cytosine methylation of veterans were measured and used to generate a complex regression model of PTSD symptom severity.

The researchers focused on two canonical binding sites of the NR3C1-1F, believed to play an important role in regulating glucocorticoid receptor expression related to stress. The data revealed a significant interaction between NR3C1 methylation and hippocampal size that was reflected in a positive relationship between methylation and hippocampal volume for lower scores on the assessment for PTSD. By combining neuroimaging and epigenetics the researchers were able to obtain insight into the brain structure and biochemical pathways of modified gene expression associated with PTSD symptom severity.

These findings suggest that chronic induced stress can manifest as methylation changes and eventual hippocampal volume loss or that an innate hypomethylation state combined with a lower hippocampal volume can predispose individuals to PTSD. These results are compelling since there is such a strong relationship between the hippocampus and glucocorticoid stress response. It has been documented that the hippocampus is sensitive to stress on a biochemical and structural level and DNA methylation has been linked to changes in glucocorticoid receptor density in the hippocampus following exposure to environmental stress. Diminished volume of the hippocampus can reduce the inhibition of the HPA axis resulting in overexpression of stress signals, which in turn can potentially manifest as PTSD.

Overall, the findings of this study provide insight into the effective indicators of PTSD. However, more research has to be completed in order to understand the manifestation and treatment for PTSD. Multiple regression analyses indicate that hippocampal volume and methylation of the glucocorticoid receptor gene are a viable predictor of PTSD symptoms. Incorporation of these metrics may aid physicians in the identification and treatment of PTSD patients. Early treatment may help individuals seek proper treatment before this disorder takes a massive toll on their life.


Source: McNerney et al. Integration of neural and epigenetic contributions to posttraumatic stress symptoms: The role of hippocampal volume and glucocorticoid receptor gene methylation. PloS ONE. 2018, 13(2).

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About Estephany Ferrufino 12 Articles
Estephany Ferrufino received her M.S. in Biology from Hofstra University. Her thesis research was on Octopine Dehydrogenase response to environmental and physiological hypoxia and its possible regulation by Hypoxia-Inducible Factor. When she’s not in the lab you can find her either watching or playing soccer, or hiking with her beautiful Siberian husky.


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