Biomarkers: The Future of PTSD Diagnosis and Treatment Monitoring?

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By Maria A. Morgan, Ph.D.
July 10, 2017

When I tell people my background is in physiological psychology they respond with enthusiastic curiosity. Rats, brain lesions, fear conditioning – “so interesting.” But their eyes glaze over as soon as I start in on neural circuitry and the inhibitory influence of the ventromedial prefrontal cortex on the amygdala. I get it. It sounds like a foreign language or you find it extremely boring. Or maybe it sounds irrelevant to psychological health. After all, what does understanding physiology have to do with helping people who suffer with mental health disorders? I’m glad you asked.

What are biomarkers?

First, what are biomarkers? Biological markers, or biomarkers, are objectively measurable, physical traits of a biological system that can indicate a normal state, a disorder, or a therapeutic response to treatment. Translation: they are pretty much anything inside the body that can be measured and objectively assessed for signs of a disease, as well as for signs of response to treatment. For example, biomarkers for pre-diabetes would include indicators of abnormal metabolism in a blood sample.

The use of biomarkers to assess and diagnose medical conditions has been in use for well over a century, and today it’s routine clinical practice to measure blood pressure and temperature and have blood and urine samples sent out for analysis. Once upon a time, medical doctors didn’t have lab tests to inform them, so they based their diagnoses and treatments wholly on the information they obtained from observing their patients, getting a health history, and discussing with them any symptoms they may be experiencing. Sound familiar?

Relevance to mental health

Some might argue that current diagnostic procedures within clinical psychology follow a similar process to the medical practices of yore. But, you might object, mental health disorders aren’t amenable to objective biological measures the way medical diseases are. They have a far more complex, multifactorial causal process and expression than medical diseases. And I would agree, to a certain extent.

The beautiful complexity of the human psyche may be part of why psychological disorders are so compelling – and so difficult to treat. Nonetheless, there’s a lot of scientific research indicating that mental health disorders are biologically based, often as the interplay between a biological predisposition and the impact of social and environmental stressors. Discovering a genetic variant underlying susceptibility to, e.g., posttraumatic stress disorder (PTSD) – the disorder which garners the most attention currently in military mental health – does not mean there is a single cause of PTSD. 

Potential of biomarkers

Let me present a scenario where biomarkers would be very useful – diagnostic uncertainty. PTSD is a complex disorder that fluctuates over time and is frequently comorbid with other mental health disorders. Whether a service member receives a diagnosis depends on a number of factors, which may include: the service member’s willingness or ability to describe symptoms he or she is experiencing or relate them to past trauma; clinician expertise in diagnosing PTSD; attitudes towards seeking mental health care, etc. A large number of service members receive diagnoses of unspecified anxiety disorder, which may be, in part, attributable to difficulties in diagnosing.

If, at some future time, we had a blood test or other method of measuring PTSD-specific biomarkers, these could be incorporated into routine and urgent care. Further, even with the use of evidence-based treatments (EBTs), treatment effectiveness, including non-responders and non-completers, often doesn’t top 50 percent. Access to biomarkers could greatly improve treatment matching. Current genetics-based research is looking at genes predictive of treatment responsiveness. The use of biomarkers to determine which therapy would be most effective for an individual has the potential to greatly reduce the rate of non-responders and non-completers.

Research has identified multiple abnormal processes associated with mental health disorders, so let’s consider some of the neurobiological findings that should ultimately yield biomarkers. Using PTSD as an example of underlying abnormal processes (and their unit of analysis), research has shown that people with PTSD may have:  

  • shorter telomeres, a region at the end of chromosomes (genetics) 
  • reduced hippocampal cortex thickness, a brain region involved in memory (brain regions)
  • increased activity in the amygdala and reduced activity in the prefrontal cortex, brain regions involved in fear expression and extinction, respectively (neural circuitry)
  • dysregulated hypothalamic-pituitary-adrenal (HPA) axis stress response (physiology)

This is great stuff and just a miniscule sample of what’s known. But here’s the big BUT: just because science has found, say, that some people with PTSD have a variant of a stress response gene, this does not automatically make it a clinically useful biomarker. Why not?

And then there’s reality

I’ll cut to the chase and tell you that, at present, no biomarkers have yet been discovered that indicate with diagnostic certainty the presence of PTSD, or any other specific mental health disorder. Looking at a patient with a variant of a stress response gene, it may turn out that lots of people have the genetic variant but don’t develop PTSD. Or childhood trauma in combination with the genetic variant may be a necessary precondition for an increased susceptibility to PTSD following trauma as an adult. That would help explain why some people develop PTSD and some don’t, which is hugely important, but, at a clinical level, are you really going to get a DNA sample or brain scan of every patient at the start of treatment? Well, not currently. Add to that that some of these same biomarkers found in PTSD may also be present in anxiety, depression, even schizophrenia, and it’s clear that we have a long way to go before biomarkers can be used as clinical indicators of specific-disease risk, pathology onset, or diagnosis. 

I think it will be a long time before biomarkers are used routinely for mental health diagnosis and treatment the way they are currently used in medical health. Yet, there have been great advances in our understanding of the neurobiology of the brain and nervous systems, and these have helped inform our understanding of mental health disorders. The trend towards methodological rigor in clinical psychology can be seen in the push for use of EBTs. Familiarity with the biological basis of mental health is important both for case conceptualization and patient education, and should be part of the demand for greater methodological rigor. In the not too distant future, I hope biomarkers will be used in conjunction with the more traditional practices of patient self-report and clinician assessment and treatment.

Dr. Maria Morgan is a contracted senior research psychologist at the Deployment Health Clinical Center. She has a master’s degree in clinical psychological science and a doctorate in experimental psychology/behavioral neuroscience.


The views expressed in Clinician's Corner blogs are solely those of the author and do not necessarily reflect the opinion of the Psychological Health Center of Excellence or Department of Defense.


Comments

  • Dr. Morgan,

    I enjoyed your blog. Your enthusiasm and optimism appear unbridled. For what it is worth, I would like to argue that the neurobio personalized medicine including psychological intervention is a pipe dream. An example of what I refer to as "neuromania". Now, this does not mean that neuroscientists should not continue to conduct their elegant work. The more we come to know about brain mechanisms and behavior, the closer we come to apply such knowledge. So which is it? Proponent of neuromania or neuroscience?
    There is not space here to submit philosophical, methodological, and public health propositions for us to debate. Maybe in another venue? My bottom line is that psychology and its clinical specialties primary scientific foci are behavior. Let neuroscientists study neuroscience; hence, my opinion that psychologists are not neuroscientists, that's why we call ourselves psychologists. Fundamentally there are critical "levels of analysis" conceptual and methods disjunctions between the two approaches. They are incommensurable, I submit (as do many others). The second fundamental issue is the clinical and most broadly the public health implications of the two approaches. NIH is tripping with manic excitement over neural networks and RDoCs, literally, and this is a huge psychology ethics correlate of the approaches, at the literal expense (as in funding) of psychological (social-cognitive, emotional-motivational, and behavioral-interpersonal).
    I have been one those, early in my training, captivated with the technology and the "objectiveness" and "medicalization" of it all. As a clinical psychologist, over several decades now, I have seen how the allure of the bio-medical/neuromania approach has consumed, over the last decade for example, the overwhelming majority of funding to support both clinical research work and careers, and the opportunity cost of "un-funding" behavioral psychology research that has made the clearest and vastly more substantial knowledge and application gains in the advancement of public mental health.
    I admire your clear knowledge and sincerity in your work and research program and career. Keep it up and like the scientists we aspire to be, fight hard to keep your mind open to alternative positions. Working to keep our cognitive biases in check as we review the empirical evidence will keep us honest to our professional identities, the quality of our research, and the prevention /reduction in the burden of illness we march on to ameliorate.
    All the best.

  • Research and applicable findings in this field is so long overdue. Great to hear of more consideration and effort along such themes. If one considers that variant change at a molecular level must occur to produce changes at a more macro level then pushing forward with such considerations is important. The brain receives diagnosis based on narratives and observation of behavior. A great day when we as clinicians are able to look at the brain as other organ systems are observed and analyzed for diagnosis and treatment. Nice article.

  • I suggest clinicians with both the Dx and the experiential learning that goes along with combat exposure get involved in studying this in a parallel track called " Diseases of Consciousness". Sorry if I may be asking for too much- but if we want to get at this we need better access at the conscious level and that means a clinician pop. with the disease interacting with an objective scientific platform. Not just hypothesis testing, theory and the search for an easy biomarker.

  • As a veteran being treated aggressively for PTSD I cannot say enough about how critical the understanding of the physiology of PTSD is for effective treatment. I applaud the advancements in treatment and research implemented by the Veterans' Administration since 2010 to reduce the incidence of suicide and promote recovery for suffering veterans. I am appreciative of the coordination between the VA and local integrative behavioral medicine programs to increase the variety of effective treatments for veteran PTSD sufferers. It took about 24 months to find the right mix of medication for me to stop my suicidal/homicidal ideation, but the side effects and adverse reactions I endured made it difficult to continue taking the medications, and I had to seriously consider stopping the medication and risk the return of my lethal thinking so that I had some reliable ability to function.

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The views expressed in Clinician's Corner blogs are solely those of the author and do not necessarily reflect the opinion of the Psychological Health Center of Excellence or Department of Defense.