Posttraumatic Stress Disorder (PTSD) is a major public health challenge and a growing problem for the Veteran's Affairs (VA) Health System and the Department of Defense (DoD)[1]. While effective treatments for PTSD such as Prolonged Exposure (PE) have been developed [4], a significant number of patients remain symptomatic or are unable to utilize these treatments to their full potential [4, 5]. Thus, optimization of these treatments is essential. Optimizing PE is ot simple, and isolating specific components and then empirically testing them requires multiple studies, large numbers of subjects and thus, is prohibitively expensive. Alternatively, integrating affective neuroscience methods, such as identifying specific potential biomarkers of treatment change can make each study more informative, effective, and less expensive. Neurobiological studies of PTSD have linked specific candidate biomarkers [endogenous glucocorticoids and neurosteroids, i.e. cortisol, allopregnanolone (ALLO) and metabolites, and dehydroepiandrosterone (DHEA/DHEAS)] to PTSD severity and potentially to treatment response. Identifying the mechanisms involved in treatment response can assist in improving therapeutic techniques by targeting specific neurobiological processes involved. Identifying the mechanisms involved in treatment response can assist in improving therapeutic techniques by targeting specific neurobiological processes involved. For instance, identified biomarkers may be used to guide augmentation prior to PE or may lead to directing certain patients to alternate PTSD treatment To this end, we propose an add-on study for an ongoing STRONG STAR affiliated PTSD treatment trial comparing Prolonged Exposure-Web (PE-Web) and Present Centered Therapy (PCT). In our add-on study, we will examine the role of specific candidate biomarkers (endogenous glucocorticoids and neurosteroids, i.e. cortisol awakening response, cortisol response to specific challenge, ALLO and metabolites, and DHEA/DHEAS) collected at Baseline, week 4, Week 8 (post), and one month follow-up as: a) predictors of treatment response, and b) indices of therapeutic change during PTSD treatment.
We aim to: 1) identify specific changes in neuroendocrine and neurosteroid patterns that track PTSD symptom changes following effective treatment, 2) examine the specificity of PE-induced neuroendocrine and neurosteroid changes by directly comparing patterns across PE-Web and PCT, and 3) examine whether treatment response related changes in these peripheral biomarkers are directly associated with treatment changes. We expect that increased cortisol responsivity and increases in neurosteroid levels between Baseline and week 8 will be associated with PTSD symptom reduction. Establishing the link between treatment responses and specific biomarkers will allow: mechanism-informed selection of effective treatment (optimizing PE effectiveness), more feasible and effective treatment response studies (increasing efficiency), as well as better individualized treatment tailoring (personalized medicine).
The proposed project aims to provide critical information on potential neuroendocrine and neurosteroid biomarkers relevant to effective treatment of PTSD among combat Veterans and service members. Specifically, direct and comprehensive analysis of candidate peripheral biomarkers that are involved in emotion processing and effective PTSD treatment promises to enhance our understanding of the neurobiology of PTSD and guide the improvement of treatment efficiency and effectiveness. Given the large numbers of returning Veterans from the current conflicts and the Veterans of other eras suffering from PTSD, improving effectiveness and efficiency of treatment is a top priority for DOD and VHA. Utilizing cutting-edge mechanistic research to probe the abnormal processes involved in the PTSD development and the mechanisms involved in effective treatment will allow 'fine tuning' of state of the art treatments, increasing efficiency and allowing more Veterans and service members to access effective care.
