Biomarker Establishment for Superior Treatment of PTSD Study (BEST)

Biomarker Establishment for Superior Treatment of PTSD Study (BEST)

Biomarker Establishment for Superior Treatment (BEST)

The Challenge

Despite years of pioneering work studying the brain’s behavior and how it functions in individuals with PTSD, the field of psychiatry lacks objective measures for understanding the many different biological effects of PTSD (e.g., sleepless nights, spontaneous moments of panic, faltering memory, poor cognition, or erratic moods). Additionally, there are currently no tools to predict treatment outcomes for patients suffering from PTSD.

Trauma-focused psychotherapies are the most evidence-based treatments for PTSD; however, only a minority of people with PTSD pursues this type of treatment, even though not seeking psychotherapy lowers the likelihood of recovery. Knowledge that patients would likely respond to psychotherapy could encourage them to pursue treatment. Further, developing a test to predict positive outcomes may expand the implementation of PTSD psychotherapy, motivating more patients to seek these treatments.

Our Goals
  • Exploring whether there are biological factors that can be measured before a patient begins therapy to predict their treatment response.
  • Bringing clarity to an individual’s response to psychotherapy through the use of biomarkers as potential companion diagnostics for developing and testing new interventions.
  • Establishing objective metrics to identify distinct, biological biomarkers of PTSD, which could serve as the basis for targeted treatment approaches and the development of novel therapeutics.
Our Solution

At CVB, we invested in the expertise of lead study investigator Amit Etkin, MD, PhD, Professor of Psychiatry and Behavioral Sciences, and his team at Stanford University to study clinical biomarkers and identify brain activity patterns – or neural signatures – in PTSD to help match patients to the most effective available treatment.

“Our goal is to create a brain signature specific to an individual and then tailor treatment accordingly,” says Dr. Etkin. “Ultimately, we hope to have a clinic-ready tool that will dramatically change how we care for patients with PTSD.”

What is a functional MRI (fMRI)?

Functional magnetic resonance imaging or functional MRI measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area of the brain is in use, blood flow to that region also increases. Clinical use of fMRI still lags behind research use. Patients with brain pathologies are more difficult to scan with fMRI than are young healthy volunteers and the availability and cost of the imaging prohibits regular use.

 

What is an EEG?

An electroencephalogram (EEG) is a noninvasive test that records electrical patterns in your brain. The test is used to help diagnose conditions such as seizures, epilepsy, head injuries, dizziness, headaches, brain tumors and sleeping problems. EEG is a much more accessible and clinic-friendly form of brain imaging, adapting the biomarker discovery to an EEG would greatly enhance the use of this treatment response biomarker in routine clinical care.

Biomarker Establishment for Superior Treatment (BEST)

In this study, we assessed whether PTSD ‘markers’ can help inform effective treatment decisions. By exploring both neural signatures of PTSD and differences in memory function using functional MRI (fMRI) and cognitive tests, we identified a novel method for disentangling the heterogeneity (variations) of PTSD through the characterization of patient sub-groups, or what is now known as biotyping. Through these findings, we discovered objective evidence for predicting a patient’s response to treatment, which enabled us to promote a transition from a subjective diagnosis of PTSD based on symptom reporting, to an objective diagnosis based on underlying biological causes. Findings from this study were published in the journal Science Translational Medicine in April 2019.

To expand on this study, we established the Biomarker Establishment for Superior Treatment (BEST)-PTSD study in a larger group of participants, which was also led by Dr. Etkin. The study involved Veterans with PTSD who received ongoing cognitive processing therapy (CPT) or prolonged exposure (PE) therapy. It also included a control group of Veterans without PTSD to establish “normative” responses for brain and behavioral assessments. The study was successful in that it replicated earlier findings, which demonstrated that PTSD patients can be “biotyped” into different sub-groups, and translated earlier findings that used functional MRI (fMRI) to a more widely accessible form of brain scanning, EEG.

To further validate these findings, we conducted a BEST replication study, which was led by Dr. Etkin and later published in the October 2020 issue of Nature Biomedical Engineering. The study revealed that EEG signals could be used to biotype people diagnosed with PTSD and ‘predict’ their response to psychotherapy and/or treatment. For people suffering from Major Depressive Disorder (MDD), the study also indicated EEG could predict patient response to selective serotonin reuptake inhibitors (SSRIs). These findings were significant as they enabled us to identify a first of its kind cross-diagnostic biomarker for both PTSD and MDD.

Once it’s further validated, this cross-diagnostic biomarker may help accelerate the discovery of effective treatments, leading researchers to develop personalized therapeutic approaches and matching patients with the best interventions more quickly. Importantly, the study also set the stage for future non-invasive brain stimulation approaches that may identify patients who are susceptible to developing PTSD, and may also be effective for treating patients with PTSD who are refractory to psychotherapy or first-line pharmacotherapy.

“Post-traumatic stress presents in patients in myriad of ways, which underscores the need for individualizing treatment,” says Magali Haas, MD, PhD, CEO & President of Cohen Veterans Bioscience. “Our collaboration with the talented team at Stanford allowed us to be one step closer to understanding the mechanisms underlying PTSD in specific individuals, which is critical if we are to develop diagnostic tests that can provide accurate diagnoses, new treatments, and tools to measure the effectiveness of a given treatment.”

Next Steps

The next steps for this program will be to develop these brain biomarkers as diagnostics tests through the FDA Center for Devices and Radiological Health (CDRH) devices program.

Impact to Veterans

The development of a Response Diagnostic Test for Veterans could become a Clinical Decisions Support Tool for doctors to use in guiding the best treatment options for patients from the start.