Researchers attempt to solve PTSD puzzle

A team of Penn State and University of Puerto Rico School of Medicine researchers is attempting to answer a question that has long puzzled experts: Why do some individuals suffer post-traumatic stress disorder (PTSD) after experiencing trauma, and others do not?

The research, led by Nanyin Zhang, professor of biomedical engineering and Lloyd & Dorothy Foehr Huck Chair in Brain Imaging at Penn State, explores whether individual vulnerability to PTSD is due to pre-existing conditions or to a response to trauma exposure.

The team used the predator scent model of PTSD in rats and longitudinal design, which involves repeated observations of the same subject over a period of time. Using this methodology, they measured pre-trauma, brain-wide, neural circuit functional connectivity; behavioral responses to trauma exposure; release of corticosterone, a steroidal hormone produced in the cortex of adrenal glands; and post-trauma anxiety.

The results, reported in a recent issue of Nature Communications, found that rats that freeze and become motionless in response to predator scent exposure, correlate with functional connectivity in a set of neural circuits in the brain of these rats. Functional connectivity is the connectivity between different regions of the brain that share functional properties, and is measured via magnetic resonance imaging.

The researchers found that pre-existing neural circuit function can predispose animals to different fearful responses to threats.

The data we gathered provides a framework of pre-existing circuit function in the brain that determines threat responses. This may directly relate to PTSD-like behaviors."

Nanyin Zhang, professor of biomedical engineering and Lloyd & Dorothy Foehr Huck Chair in Brain Imaging at Penn State

Such a framework has a variety of potential benefits for further research into PTSD prevention and treatment.

"This research can help us understand core components of the vulnerability to stress-induced neuropsychiatric disorders," Zhang said. "These components can potentially serve as indicators to not only predict risk for developing anxiety disorders like PTSD but also assist in evaluating different stages of PTSD and possible recovery."

Using rats as test subjects helped overcome a major obstacle of investigating risk factors of PTSD in humans -- the difficulty of monitoring PTSD development from pre- through post- trauma in humans via exposure to well-controlled traumatic events. Studies on humans focus on populations already exposed to a variety of uncontrolled traumatic events and can lead to inconsistent results. Such barriers were overcome in the present study by using rats and applying longitudinal design with controlled traumatic stressors.

"The outcomes of the research can potentially be translated to human studies," Zhang said. "For instance, a biomarker predicting a vulnerability to stress-induced disorders will help determine the risk of assigning an individual to a highly stressful environment, such as combat."

One interesting aside in the study was a counterintuitive finding. Rats with lower freezing behavior showed more avoidance of the predator scent, a prolonged corticosterone response, and higher anxiety long after exposure to the scent.

"It is very likely that they froze less as they adopted different reactions to threats, such as fleeing," Zhang said.

Zhang said the next steps for the research team include identifying neuroimaging biomarkers that can predict an individual's response to threats and developing a process for determining the probability an individual will develop PTSD-like behaviors when exposed to trauma. The team will also explore methods to protect animals with high-risk factors from developing PTSD-like behaviors, such as through optogenetics, which is the use of light to control the activities of individual neurons in freely moving animals.

Along with Zhang, other researchers working on the study include David Dopfel, doctoral candidate in bioengineering; Pablo Perez, postdoctoral fellow in bioengineering; Alexander Verbitsky, graduate research assistant in engineering science and mechanics; and Yuncong Ma, doctoral candidate in bioengineering, all at Penn State; Héctor Bravo-Rivera, graduate student, University of Puerto Rico School of Medicine; and Gregory Quirk, professor of psychiatry, University of Puerto Rico School of Medicine.



  1. Deborah Barr Deborah Barr United States says:

    Any current physiological or psychological stress adds to the stress of the trauma, as well as any lack of the endorphins or neurotransmitters that support positive moods, my personal experience being low GABA, having come off of depakote after over 20 years, but not being assessed for low GABA (now on Gabapentin) by a new and subcompetant psychiatrist.

    On top of that, with hypercupremia and hypervitaminosis B6 and low GABA, I started having flashbacks of traumatic events that had previously not caused flashbacks. Do not only do a wide range of causes for stress at the time of the trauma increase PTSD, and lack of supportive treatment and understanding directly after a trauma increase the chance and severity of PTSD, but increased stresses at various points after the trauma will increase temporarily the severity of the PTSD, and potentially add to it via retraumatization.

    While low cortisol acts as a shock absorber, high cortisol from emotional stresses before the trauma make the trauma worse. But physical issues, such as illness or poisoning (such as hypervitaminosis B6 or hypercupremia, which add stress through unusual and painful sensations, and by limiting the amount of toxins able to leave the body via the overworked kidneys) add also to psychological stress, which adds again to physiological stress by increasing cortisol and adrenaline, and preventing the body from doing standard housekeeping in favor of "fight, flight, freeze, or fawn."

    People with abuse backgrounds tend to higher cortisol, or might have hypervigilence syndrome, where even tiny stimulations have a much larger and more stressful effect. That constant or sudden higher stress response may give faster reactions in emergencies, but takes a physical toll, and since it usually goes with specific coping strategies as reactions, the reaction to a later event may be the wrong reaction, adding helplessness or frustration to the original trauma and the layers already added to it.

    I suspect that there is a critical level where the traumas add in a spiral which leads to panic attacks: when distracting oneself from the trauma by throwing up, curling up in a ball and/or screaming is safer than trying to deal with the problem. Push any harder and an ulcer (my experience), a heart attack or stroke may result. But not being able to deal with the cause of the stress or trauma can be equally deadly, in some cases.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
You might also like... ×
Individuals exposed to early life stress more likely to develop youth-onset depression