Researchers studying nearly 147,000 veterans diagnosed with PTSD found that the disorder’s most characteristic symptom—re-experiencing—is associated with eight separate regions of the genome in whites. It is one of the largest genome-wide association studies (GWAS) of its kind to date.
“Post-traumatic stress disorder (PTSD) is a major problem among military veterans and civilians alike, yet its pathophysiology remains poorly understood,” wrote the authors of the paper.“These results provide new insights into the biology of PTSD in a well-powered GWAS,” the researchers wrote.
The study, which appearsin the 29 July 2019 issue of Nature Neuroscience, did not find any associations in a more than 19,000 African-American cohort. All of the individuals included in this study were part of the U.S. Veteran Program (MVP), a voluntary research program focused on studying the genetic bases of health. Key results were replicated using the UK Biobank sample, which has about 500,000 participants.
The government estimates that 11 to 15 percent of veterans who have seen active duty suffer with PTSD. Anyone who experiences a traumatic even that includes the threat of death or violence can experience PTSD. It is usually considered to have three main clusters of symptoms: re-experiencing, avoidance, and hyperarousal. Avoidance and hyperarousal are common to other anxiety conditions as well, but re-experiencing is largely unique to PTSD. Re-experiencing refers to intrusive thoughts, nightmares, and flashbacks of the traumatic event.
The approach in the current study was unique in that it used a symptom (re-experiencing) rather than the diagnosis (PTSD) to look for genetic associations. The researchers compared the genomes of 146,660 white veterans and 19,983 black veterans who had volunteered for MVP. Of the eight genomic regions associated with PTSD re-experiencing in whites, they found three were highly significant: gene CAMKV, a region near genes KANSL1 and CRHR1, and gene TCF4. The researchers suggested in the paper that the lack of associations in blacks was due to the much lower sample size.
The results in whites revealed genetic overlap between PTSD and other psychiatric, behavioral, and medical conditions. For example, the researchers found two genes previously associated with schizophrenia and bipolar disorder were also linked to re-experiencing in PTSD. This could mean that the hallucinations experienced in schizophrenia may share common biochemical pathways with the nightmares and flashbacks of people with PTSD, researchers said in a press release.
The team also found re-experiencing was genetically correlated with hypertension, previously observed in epidemiology studies. The new findings suggest a shared genetic basis with hypertension. The researchers suggest the drug prazosin may work well in those with both PTSD and hypertension. The drug is commonly used to treat hypertension and works in most cases. It is also used to treat nightmares in PTSD with some success, especially at high doses.
“Stratifying those patients with PTSD with increased polygenic risk for hypertension might identify a subgroup especially responsive to the anti-PTSD effects of prazosin — worth testing as the field moves toward a personalized approach to treatment, involving medication repurposing at the forefront of this movement.”
The study also adds evidence to the theory that the development of PTSD is related to the body’s steroid-hormone stress response. A variant located at the gene CRHR1 was linked to PTSD re-experiencing in this study. This gene is involved with the body’s stress response. In past studies, biological evidence has linked processes involving CRHR1 to PTSD.
All together, the researchers said the results “provide new insights into the biology of PTSD.”
