Risk or resilience: the genetics of PTSD

Hysteria, nostalgia, homesickness, railroad spine, shell shock, battle fatigue—posttraumatic stress disorder has been with us for as long as recorded history. Today, PTSD is one of our most common psychiatric disorders—affecting an estimated 24 million adults in the U.S. alone. And yet, despite its prevalence, little is known about the biological roots of this debilitating condition.

But a new effort underway at the Broad’s Stanley Center for Psychiatric Research aims to change that. Earlier this year, in partnership with the Psychiatric Genomics Consortium, and with support from Cohen Veterans Bioscience, the Stanley Center launched the Global PTSD Genetics Initiative, the largest effort to date to understand the underlying biology of PTSD.

Here, Broad associate member and Initiative director Karestan Koenen gives us some insight into the challenges of studying PTSD, what her team hopes to achieve, and how a better understanding of genetics can change the lives of patients.

PTSD is brought on by trauma—how do our genes play a role in the disease?

Koenen: Studies comparing identical and fraternal twins have shown PTSD is heritable. The same studies also showed that there is some genetic overlap with other psychiatric disorders—so we know that genes play a role.

The fundamental question at the heart of my research is why, given the same trauma, do some people recover while others get PTSD? Even in the case of severe traumas—such as being a prisoner of war or a rape victim—a large proportion of those exposed don’t develop the disorder. I believe genes are one factor that contributes to this risk or resilience.

What are the challenges of studying PTSD, and how can genetics help?

Koenen: The primary challenge we face in studying PTSD is the same one we face in other common psychiatric disorders—namely, there is no objective biological test to say who has PTSD and who doesn’t. PTSD is only different in that the diagnosis requires exposure to a traumatic environmental event—therefore, it’s essential that we consider genes and environment.

A greater understanding of the genetics of the disease could provide an unbiased approach to identifying the biological pathways and genetic architecture behind the disease, and could also help us understand whether or not other biological findings related to PTSD—such as differences in gene expression—are causal or consequence.

How could a better understanding of the genetics of the disease shift treatment for patients?

Koenen: PTSD may be one of the most preventable of psychiatric disorders. The problem is we don’t know who, after a trauma, is most at risk. Genetics may help with this by providing a rational basis for identifying a biomarker or panel of markers of risk.

Most people exposed to trauma come into contact with some part of the health care system, like an emergency room, shortly after the event. There are some early interventions, such as trauma-informed cognitive behavioral therapy, that can prevent the development of PTSD if given after trauma. However, these treatments are resource intensive, and individually administered. It would just be impossible to give them to everyone after a mass traumatic event – such as Hurricane Katrina or a major terrorist attack. But if we could develop objective tests to determine who is at risk of PTSD – we could then direct our resources to those high-risk patients.

We also need a drug discovery revolution in PTSD. Today, the only FDA-approved drugs for treating PTSD are SSRIs (selective serotonin reuptake inhibitors), and they are only fully successful for less than a third of patients. Genetics can provide the basis for new therapeutics – and would help us better match treatments to patients.