What impact does severe trauma have upon health? The answer, in part, has to do with the individual, research has shown. For biological and genetic reasons some people are more resilient than others to the stresses that trauma places upon the human system, affecting both brain and body.

A team of researchers led by Alicia K. Smith, Ph.D., and Kerry Ressler, M.D., Ph.D., set out to evaluate how trauma and PTSD affect the brain and the expected lifespan of sufferers, using brain scanning technology and a new assessment tool called GrimAge. Publishing their results in the journal Neuropsychopharmacology, their findings were consistent with prior research indicating that trauma and PTSD appears to significantly accelerate cellular aging. And they generated direct evidence that PTSD in some people is likely to shorten expected lifespan as well as increase the risk of neurodegeneration by thinning portions of the brain’s cortex.

A total of 854 people who are among those registered in the Grady Trauma Project based in Atlanta, Georgia, were selected for inclusion in the study by Drs. Smith, Ressler and colleagues. The Grady project, the authors note, seeks to gauge the influence of genetic and environmental factors on responses to stressful life events in a predominantly low-income, urban African-American population. Over 90% of participants in the PTSD study were African-American and 70% were female. The average age was about 43.

Exactly half (427) of the study subjects were “controls”; they had been exposed to trauma during their lives but had no history of PTSD. One-fourth (218) of the participants had current PTSD symptoms, and one-fourth (209) had a history of PTSD but had no current symptoms.

The “GrimAge” tool used to predict the impact of traumatic stress on expected lifespan is based on detection of changes in the human genome called epigenetic changes. GrimAge focuses on changes in molecular groupings called methyl groups which attach themselves to the DNA that forms the human genome, sometimes impacting the way genes are activated.

The presence or absence of methyl groups at particular locations in the genetic sequence can be altered by an individual’s exposure to stress—both chronic and acute. In this way, therefore, epigenetic changes can reflect the degree to which a given trauma or series of traumas have affected human cells at the deepest—genetic—level.

GrimAge has previously succeeded in correlating lifestyle habits such as smoking with epigenetic changes, and then using that data to predict likely impact upon expected lifespan. In the research by Drs. Smith, Ressler and colleagues, GrimAge related trauma and epigenetic alterations, and used these to predict expected lifespan.

The study found that a PTSD diagnosis at any age predicted shorter lifespan. Overall, people with current and “lifetime” trauma—but not people who experienced trauma without having post-traumatic stress reaction—had an “acceleration” in their GrimAge score, suggesting that the stress they have endured has shortened their predicted lifespan by some amount (which will vary according to the individual).

For those with trauma at some point in their lifespan but not currently, the GrimAge acceleration applied only in those with trauma in their adulthood, not those with childhood trauma only, provided they never suffered from PTSD.

Sixty-nine of the 854 study participants—all women, to avoid potential biological differences generated by gender—formed a subgroup whose MRI brain scan results were correlated with the study’s other findings. This portion of the study showed that those with GrimAge acceleration—i.e., expected quickening of cellular aging and shorter predicted lifespan as a result of trauma—had a thinning in the right lateral orbitofrontal cortex and right posterior cingulate cortex, brain areas associated with the regulation of emotions and threats. No thinning was seen in the control group who had experienced trauma but never suffered PTSD. These brain changes have been associated in other studies with depression and cognitive impairment often seen in aging.

Cell-type differences in study participants with GrimAge acceleration were found to most affect cells that play important roles in inflammation, suggesting at least one possible mechanism for the conversion of stress into biological damage to the brain and bodily systems.

The team urges future research using a study cohort that can be followed up over the long-term, and to explore whether the current findings hold up in populations of greater gender and ethnic/racial diversity.

The team also included Tanja Jovanovic, Ph.D., 2015 BBRF Independent Investigator and 2010 Young Investigator; Charles Gillespie, M.D., Ph.D., 2007 BBRF Young Investigator; Sanne van Rooij, Ph.D., 2018 BBRF Young Investigator; and Adriana Lori, Ph.D., 2013 BBRF Young Investigator.