By Andrew Porterfield
Shell shock. Conversion reaction. Spanish military doctors called it “estar roto” (to be broken). What’s now known as post-traumatic stress disorder (PTSD) has been around as long as there have been wars. Descriptions of its symptoms—a variety of severe emotional turbulence, paralysis, tremors, self-inflicted wounds, and heart arrhythmias—have been recorded by military units dating back to the ancient Egyptians.
Despite its age, treatments for PTSD did not progress much until very recently. During the American Civil War, military physicians tried to muster out extreme cases, often putting them on trains in the general direction of home or letting the injured soldiers wander aimlessly. When the term PTSD was coined during the Vietnam War, psychiatrists treated soldiers with psychological therapy and somewhat effective drug therapies. They also noticed that the affliction could be found in anyone who experienced trauma, not just soldiers, sailors, or Marines.
In our century, soldiers deployed to Iraq, Afghanistan, and elsewhere have also suffered from PTSD. It’s estimated that 8% of Americans will at some time have the disorder. For soldiers who’ve experienced combat, that rate can climb up to 31%. Treatments include cognitive processing therapy (trying to change thoughts), or prolonged exposure to memories that sparked the trauma, which can take months to see results. Medical treatments include antidepressants (SSRIs and SNRIs) and other drugs that address specific symptoms (such as insomnia, nightmares, or brain injury). However, none of these treatments have been able to fully stem the recent tide of PTSD among soldiers returning home, and none do anything to alter the underlying memories that trigger PTSD.
Genome studies may help provide answers to how PTSD arises in some people and not in others, and may pave the way to treatments for the disorder. Twin studies have shown that genetics does account for between 30–36% of vulnerability to PTSD. Those with PTSD also have a greater risk of having other mental disorders, such as anxiety and panic, depression, and substance abuse. Therefore, knowing the genes behind PTSD could help identify vulnerable individuals and help refine treatments.
Genome-wide association studies (GWAS) and other genomic explorations have recently begun to determine associations between the disorder and any variation in the genome:
- Earlier this year, researchers from the University of California, San Diego, and Boston University, reported on a GWAS survey on 3,494 Marines and sailors who had been exposed to combat in the Middle East. This first multi-ethnic large GWAS trial of PTSD discovered a novel gene, PRTFDC1, short for the phosphoribibosyl transferase domain containing 1 gene, a 100 kb gene on chromosome 10. The researchers also found that many single nucleotide polymorphisms (SNPs) with smaller effects and an overlap with other psychiatric disorders may lead to a genetic profile unique to PTSD sufferers. Earlier studies have found other genes that may be linked to PTSD, as well.
- The epigenome may be a source of treatments, as well. An international team discovered that inhibitors of Histone deacetylase (HDAC-2) in mice could alter mouse memories and attenuate remote fears. HDAC2 is so far the only known epigenetic mechanism that’s been connected to memory.
It’s just the beginning, but things happen fast in genomic medicine.