Team Identifies 3 Possible Brain-Based Biotypes of Post-Trauma Psychiatric Vulnerability

Team Identifies 3 Possible Brain-Based Biotypes of Post-Trauma Psychiatric Vulnerability

Posted: December 14, 2022
Team Identifies 3 Possible Brain-Based Biotypes of Post-Trauma Psychiatric Vulnerability

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Researchers studying variations among people that may help indicate whether they are resilient or vulnerable to acute stresses and trauma have identified 3 possible biotypes of post-trauma psychiatric vulnerability.


Following a highly stressful or traumatic event, different people respond in different ways. Some people appear to be naturally resilient; they may weather such an event better than most. Others appear to be especially vulnerable, and liable to develop psychiatric symptoms of anxiety, post-traumatic stress disorder (PTSD) and/or depression.

Is there a way of assessing someone who has just experienced a trauma that would indicate how that person is most likely to respond in the weeks and months to come?

There is no established way to perform such a predictive assessment, but researchers are seeking reliable ways to do so, knowing that matching an individual to an appropriate treatment tends to support better outcomes over the long-term.

A large research team led by BBRF Scientific Council member Kerry J. Ressler, M.D., Ph.D., has been studying variations among people that may help indicate whether they are resilient or vulnerable to acute stresses and trauma. Their AURORA project (Advancing Understanding of Recovery After Trauma) seeks to discover post-trauma "biotypes" consisting of patterns that describe how the brain processes stress and trauma in both resilient and vulnerable individuals. Such biotypes might predict their mental health trajectory following a traumatic event.

Dr. Ressler, who is a 2017 BBRF Distinguished Investigator, 2009 winner of BBRF's Freedman Prize for Exceptional Basic Research, and a 2005 and 2002 BBRF Young Investigator, along with 50 co-authors (including 10 BBRF grantees) recently published preliminary results from the AURORA project in the American Journal of Psychiatry. Jennifer Stevens, Ph.D. was the paper's first author.

The team recruited 146 study participants from emergency departments at 22 hospitals in the Northeast, South, Mid-Atlantic, and Midwest regions. Each was recruited within 72 hours of a trauma and was followed over the next 6 months. The average participant was about 34 years old. Sixty-nine of the participants experienced a trauma related to a motor vehicle accident. Seventy-seven participants experienced motor vehicle and several other types of trauma. The second group made up a "replication cohort": attempts to discover "biotypes" in the first group would be tested for validity in this second group.

An fMRI brain scan conducted in each participant within 2 weeks of their trauma played a key role in the study. The scans enabled the team to identify among the first group of 69 motor-vehicle trauma participants four distinct clusters—potential biotypes—of post-trauma brain activity. These clusters were distinguished by their reactivity to threat and reward as well as their inhibitory response. Three of these clusters were also seen in the "replication" group of 77 trauma survivors, strengthening the argument that these clusters do describe commonly seen patterns of post-trauma brain responses. The results will have to be replicated in larger and more diverse groups in future studies.

The team noted that the clustering they observed in the traumatized subjects "likely reflects a combination of traits [in each participant] that predate the trauma, as well as acute stress responses in the wake of the traumatic event." The clusters were not related to demographic characteristics, nor to "background variables" such as gender or childhood trauma. Still, the team noted, the patterns of brain response seen in the clusters "could still plausibly reflect pre-trauma factors such as genetics, family history or individual temperament."

The important point for purposes of using the cluster-biotypes to help treat patients is that they were based on the data in the fMRI scans made within 2 weeks of the traumatic event. One biotype described by the team, for example, called the "reactive/disinhibited cluster," shows very specific post-trauma brain responses: hyper-reactivity to stress as evidenced by signals seen in the brain's insula and dorsal anterior cingulate cortex, accompanied by high reactivity to reward in an area called the nucleus accumbens, as well as higher subsequent PTSD and more general anxiety symptoms.

Another cluster, called "low reward/high threat," was characterized by moderate responsivity to stress along with notably low response to reward. These signals, observed in the fMRI scans, have been seen in people with major depressive disorder in past research. The same cluster also showed a heightened "startle" response to fearful stimuli. This was similar to patterns previously observed in people with co-morbid PTSD and major depression.

"Together, the findings suggest the possibility that PTSD-related symptom groups may be divided into a low reward/high threat group (driven more by operations of the cortex) and a reactive/disinhibited group (driven more by activity in the brainstem)," the team noted.

Contrary to their initial expectations, the study indicated that heightened reactivity to both threat and reward was associated with the highest levels of subsequent PTSD symptoms. Thus, the researchers say, "heightened reward reactivity in the early aftermath of a major stressor may be an unexplored risk mechanism for development of stress-related disorders." The AURORA project continues, as does the team's research to define biotypes in the response to stress and trauma.

The team also included: Sanne J.H. van Rooij, Ph.D., 2018 BBRF Young Investigator; Thomas Neylan, M.D., 1994 BBRF Young Investigator; Laura Germine, Ph.D., 2017 BBRF Young Investigator; Scott Rauch, M.D., 1996, 1993 BBRF Young Investigator; Jutta Joorman, Ph.D., 2006 BBRF Young Investigator; Deanna Barch, Ph.D., member, BBRF Scientific Council, 2013 BBRF Distinguished Investigator, 2006 Independent Investigator; 2000, 1995 Young Investigator; Diego Pizzagalli, Ph.D., 2017 BBRF Distinguished Investigator, 2008 Independent Investigator; Beatriz Luna, Ph.D., 1997 BBRF Young Investigator; Vishnu Murty, Ph.D., 2016 BBRF Young Investigator; and Tanja Jovanovic, Ph.D., 2015 BBRF Independent Investigator, 2010 Young Investigator.