Trauma and posttraumatic stress disorder (PTSD) are common in veteran and civilian populations. Meanwhile, observationally estimated half of people cared for at UW autonomic nervous system (ANS) disorder clinic have a history of trauma. Increasingly, research explains this observation through an evolving understanding of the complex interplay of peripheral and central catecholamine signaling that appear to underlie much of the persistent impact of trauma. An improved understanding of ANS changes in trauma and their relationship to the complex symptoms people experience is an important research frontiers to improve a) our understanding of PTSD, b) our ability to predict effective treatment for a given person, and c) the development of new treatments for PTSD. We propose implementing a novel analysis method for non-invasive autonomic testing in context of several clinical studies at VA Puget Sound. The proposed research aims to 1) make use of ANS testing results already available to provide quantitative data for adrenergic signaling, 2) test associations of extracted biomarkers with symptoms of PTSD, and 3) collect prospective data to test the relationship of peripheral autonomic signaling to quantitative measures of central nervous system (CNS) catecholamine signaling measured by event-related potential (ERP).
Patient Population: Veterans
From symptom relief to subtype identification: exploring patterns of cannabis use in PTSD
Post-traumatic stress disorder (PTSD) and substance use often go hand in hand, with many people using substances like cannabis to manage their symptoms. This concept, known as the self-medication hypothesis, suggests that people might use cannabis differently depending on the nature of their symptoms. Symptoms are classically split into domains – hyperarousal, emotional numbing, re-experiencing, and avoidance. However, it remains unclear whether different patterns of cannabis use might correspond to specific symptom domains, which could reveal distinct clinical phenotypes of PTSD.
By analyzing data from the PREDICT clinical trial, this study will apply advanced statistical methods to identify unobservable (“latent”) factors that characterize cannabis use in individuals with PTSD and examine their relationship with symptom presentation. In statistics and psychometrics, latent refers to a variable that cannot be directly observed—such as internal motivations, behavioral tendencies, or physiological dependence—but which can be inferred from patterns in observed data (e.g., questionnaire responses). These patterns could offer insights into subgroups of people with PTSD who experience different symptom profiles, also known as phenotypes, and may respond to treatments in unique ways. Ultimately, this research could contribute to more personalized, targeted interventions for individuals living with PTSD.
Evaluating the role of virtual whole health in PC-MHI
The COVID-19 pandemic facilitated simultaneous paradigm shifts in healthcare delivery: virtual care (telehealth and videoconferencing) and the need for “Whole Person” healthcare that targets mind, body, and spirit, per recent US Surgeon General1 and National Academy of Medicine2 calls-to-action. The pandemic also highlighted treatment delivery inequities involving rural Veterans. The current proposal will address these trends, assessing virtual VA Whole Health care use in Primary Care-Mental Health Integration (PC-MHI) for rural and non-rural Veterans with chronic pain and co-occurring posttraumatic stress disorder (PTSD).
Evaluation of the VHA Acute Pain Service Expansion Program implementation and impact
The objective of the project is to evaluate the implementation and impact of the Acute Pain Services Expansion Program (APSEP), an expansion of the independent and formal set of services that provide comprehensive inpatient pain management consultative services and is designed to meet perioperative care needs of veterans receiving inpatient pain management.
MOVED BY LOVE: MOVE! Disparities for Black Veterans Lowered through Veteran Engagement.
This multi-method, participatory study centers Black Veterans and seeks to understand barriers and facilitators to weight loss among Black Veterans. The overall goal of this project is to reduce disparities between Black Veterans and White Veterans in the effectiveness of weight loss treatments.
Telehealth-delivered peer support to improve quality of life among Veterans with multimorbidity
We developed VetASSiST (Veterans Activating Social Support for Self-management and Treatment engagement) to help patients with multimorbidity overcome barriers to self-management and improve HRQoL. This trial has several aims: 1) Test the effect of VetASSiST, compared to usual care, on the primary outcome of baseline to one-year change in physical HRQoL, and secondary outcomes of mental HRQoL and health care utilization; 2a) Describe differences between VetASSiST and usual care on baseline to one-year changes in intermediate outcomes reflecting the functions of peer support and intervention targets; 2b) Examine whether intermediate outcomes mediate intervention-associated differences in HRQoL; and 3) Evaluate feasibility of translating VetASSiST into practice.
Opportunities for trainees may exist but a VA WOC appointment is required.
Harnessing the power of social support for weight management: a randomized controlled trial of HealthyTogether
We developed a behavioral intervention that seeks to support healthy lifestyles among Veterans by harnessing their social support networks called HealthyTogether. This trial has several aims: 1) Test whether HealthyTogether results in greater weight loss than usual care at six months among Veterans (primary); 2) Examine differences between HealthyTogether and usual care groups in secondary Veteran and partner outcomes, including health behaviors and relationship quality; 3) Examine Veteran and partner contributions to changes in their own and each other’s outcomes using dyadic analyses; and 4) Assess determinants of implementation.
Opportunities for trainees may exist but a VA WOC appointment is required.
Sequenced Treatment Effectiveness for Posttraumatic Stress (STEPS)
The proposed research will determine whether primary care clinics should offer medications or talk therapy first to treat posttraumatic stress. In addition, for patients who do not respond to the first treatment, the STEPS trial will determine what treatment should be offered next. More information on our info sheet.
Biomarkers in the retina for prognosticating mental health treatments (BRIGHT)
This clinical trial is designed to pilot an electroretinogram (ERG) biomarker for predicting treatment response to SSRIs in PTSD. Serotonergic brain centers project to the retina, and ERG allows assessment of brain serotonergic signals via retinal signals. In this study we are characterizing the ERG waveform in veterans with PTSD before and after SSRI administration. Patients then enter an open label phase of the study, with those who have initiated an SSRI through routine medication management invited back for a follow up study visit. This pilot data will: 1)be valuable as a feasibility study for assessing the practical application of ERG in the setting of a mental health clinic and 2)serve as a foundation for a long-term goal of developing physiologic biomarkers to match veterans to corresponding pharmacological treatments in PTSD and other mental health disorders.
The PREDICT study: a personalized medicine approach to prazosin for PTSD
Prazosin, like many of our most effective treatments for PTSD, seems to be significantly more effective for some individuals than others. We have hypothesized that this is because prazosin works to compensate for increased noradrenergic signaling, which is a primary driver of symptoms in some, but not all, individuals with PTSD. If we could identify individuals where increased or inappropriate noradrenergic signaling is driving PTSD symptoms, it would not only help us match individuals with treatments that will work well for them, but would also help us identify new treatment options.
The PREDICT study is a 5-year clinical trial designed to (1) test whether clinically-relevant biomarkers can predict in advance who is most likely to benefit from prazosin for PTSD; and (2) test a working model of how pre-synaptic and post-synaptic changes in the regulation of noradrenaline may combine together to produce the symptoms of PTSD.
