Cognitive and Neuronal Markers in Posttraumatic Stress Disorder

Researchers have found increasing evidence that a dysfunction in the prefrontal cortex of some individuals’ brains plays a role in the development of posttraumatic stress disorder (PTSD). The dysfunction affects cognitive flexibility (CF), or the capacity to shift thought and action according to changing demands in the environment. That can include the ability to inhibit incorrect response.

Cognitive flexibility and higher order thinking are influenced by a protein, brain-derived neurotrophic factor (BDNF). A genetic variation, or single nucleotide polymorphism (SNP), on the BDNF gene has been shown to influence BDNF function and cognition. Previous research also has associated that genetic variation, known as BDNF Val66Met SNP, with risk for PTSD.

But little is known about the nature of the relationship between those factors and how they influence speed of response to therapy for PTSD.

In this STRONG STAR-affiliated study, Principal Investigator M. Danet Lapiz-Bluhm, PhD, RN, and her research team will measure CF and BDNF function in military members with PTSD prior to treatment with Cognitive Processing Therapy (CPT) and then following therapy. The study piggybacks on a Department of Defense-funded clinical trial led by Patricia Resick, PhD, providing CPT therapy to active-duty military members with PTSD after service in Iraq and Afghanistan. That study features an individualized approach to therapy by providing it at variable lengths until symptoms are resolved, rather than the standard regimen of 12 one-hour CPT sessions.

CPT was designed by STRONG STAR investigator Patricia Resick, PhD, of Duke University Medical Center. CPT is a cognitive-behavioral therapy that gives patients an understanding of how their thoughts about a traumatic event influence their feelings and reactions to it, then helps them develop a new way of thinking that alleviates their distress and allows them to regain control of their lives

Dr. Lapiz-Bluhm’s team will recruit participants from Dr. Resick’s parent CPT study, who will provide saliva and blood samples. Saliva and plasma will be analyzed for BDNF. Whole blood will undergo genetic analysis to identify which of the patients have the Val66Met SNP variation.

Study aims

With a goal of improving understanding of various factors influencing PTSD treatment outcome, this study will:

• Test active-duty military members with PTSD for cognitive flexibility performance and determine whether speed of response to CPT treatment is related to presence of the Val66Met SNP and the amount of BDNF detected in plasma and saliva. The researchers hypothesize that poor performance in tests for CF, presence of Val66Met SNP, and abnormal peripheral BDNF levels will be associated with delayed treatment response to CPT.
• Determine the relationship between change in performance in tests for CF and peripheral BDNF levels with the change in symptom severity following CPT. The researchers hypothesize that the amount of PTSD symptom reduction will be associated with changes in CF performance and BDNF levels.

Expected benefits

Understanding of cognitive and neurotrophic mechanisms in PTSD and following treatment with CPT will potentially contribute to the development of improved strategies to treat or prevent PTSD.