Utilizing the World's Largest PTSD Brain Repository to Find New Treatments

Seven years ago, Congress designated the 27th of June as PTSD Awareness Day. While most Americans know that PTSD stands for posttraumatic stress disorder, few appreciate that this condition has haunted humanity since the beginning of recorded time. Despite its long history, scientists have only recently begun to understand the underlying biological causes of the disorder.

About 60 percent of men and 50 percent of women experience a traumatic event that can lead to PTSD. For women, this is experience is likely to be sexual assault or child sexual abuse. But for men, the trauma triggering PTSD is more likely to be physical violence such as assault, witnessing someone getting killed, or facing combat during a war. The susceptibility also varies between men and women. About 10 percent of women develop PTSD sometime in their lives, compared with 4 percent of men.

Civilian populations can experience PTSD from domestic violence, assault, natural disasters, and motor vehicle accidents. But it’s probably from reading stories of returning soldiers that most people even learn about PTSD, and for good cause. Around 8 percent of current and former service members are diagnosed with PTSD; the National Academies have designated the condition a “signature injury” of veterans serving in America’s foreign conflicts. A 2008 study estimated that dealing with veterans who have PTSD and depression could cost from $2.0 to $3.1 billion a year. Even more troubling are high-rates of suicide; more than 20 per day among servicemembers and veterans, continuing a trend that has plagued the U.S. military for at least seven years.

The epic Trojan War saw the first recorded mental disorders in soldiers, documenting Achilles’ rage as he dragged Hector’s corpse behind his chariot, circling the city walls of Troy and refusing to return the body so that Hector’s family could bury him with dignity. When the war ended and Ajax the Greater returned home, he terrorized his wife and child, and later slaughtered a herd of sheep he believed to be fellow Greeks. He later committed suicide by falling on his sword.

World War I triggered a series of government studies in England to understand a new condition called “shellshock” that was occurring at high rates in soldiers fighting trench warfare. By 1939, the British government granted awards for psychiatric disability to around 120,000 World War I veterans. Over 44,000 would later receive pensions for “soldier’s heart” or “effort-related syndrome.”

It wasn’t until 1980 that PTSD was officially classified as a mental disorder, a condition that we now know effects around 6.8% of people in the United States at some point in their lifetime.

So why does PTSD happen? When someone experiences a highly stressful traumatic event the brain processes the experience through a particular brain circuit called, for want of a better phrase, the fear pathway—the same circuitry that is important for learning from experience. Essentially, our brain is trying to understand a dangerous episode and learn to avoid or manage similar situations in the future.

In the last dozen or so years, we’ve come to recognize that this newly learned information gets stored in brain cells through a process called epigenetics. Epigenetics is a molecular process that regulates how genes in cells are turned on and off. It is not inherited in the usual sense of the term, but it does regulate based on experience the function of DNA in transcribing genes that make cells work. This means that the DNA sequences remain the same, but “epigenetic scars” will alter how often some DNA sequences gets expressed as genes in cells. Essentially, some genes will be silenced, while others might become more active.

Because traumatic events cause epigenetic changes in the brain, it is imperative that we study brain tissue from donors who suffered from PTSD. These brains are donated to the Lieber Institute by the next of kin, following an unexpected death, usually by suicide. Since opening in 2012, the Lieber Institute has acquired more than 100 brains from donors who meet the medical criteria for PTSD, making our brain repository the largest in the world for the study of PTSD.

In a recent study, scientists took blood samples from military veterans who had returned from combat and looked for epigenetic markers of PTSD. The researchers were able to identify three different locations in the genome where exposure to trauma marked possible susceptibility for developing PTSD.

While studies like this are important in the search for the cause of PTSD, we must continue to investigate the genetic and molecular mechanisms in the brain that are responsible for symptoms that manifest as PTSD. Insights into these mechanisms in the brain are critical to identifying novel treatments and prevention strategies.

So far for PTSD, we don’t have much to offer those affected. The only FDA approved medications for PTSD are drugs that were first developed to treat depression. They are minimally effective in reducing symptoms, and fail completely for many people. To come up with better approaches, we need more information about mechanisms that change the brain. Billions of dollars can be invested into modifications of current treatment options, but until we understand the true biology of this disorder the results will be inadequate. We must do more to get to the bottom of this crisis.

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