This is a pilot randomized controlled trial to assess the impact of a first-line treatment for posttraumatic stress disorder (PTSD) (Cognitive Processing Therapy; CPT) versus waitlist control on mechanisms of cardiovascular disease (CVD) risk. Further, this study will test the hypothesis that CPT reduces CVD risk through its effects on inflammation and autonomic function and that these changes are driven by changes in stress-related neural activity (SNA)

This study is a randomized controlled trial of CPT compared to waitlist control that is testing the effects of CPT on mechanisms of the PTSD-CVD link. Enrollment began in 2023 and is projected to continue through 2026. Participants include individuals with PTSD and CVD risk recruited from the Boston area (N = 30). Treatment assignment is randomized and stratified by sex. Participants are randomized to CPT (n = 15) or waitlist control (n = 15). Potentially eligible participants complete a screening visit to confirm inclusion/exclusion criteria. Upon confirmation of eligibility, participants are scheduled for a baseline session, where they complete surveys, brain and peripheral imaging, and resting measures of autonomic function. Following the baseline visit, participants are randomized into CPT or the waitlist control group. Those randomized to CPT complete sessions via telehealth. Following a 12-week treatment period, participants attend the post-treatment visit, consisting of the same assessments administered at baseline. Participants randomized to waitlist are offered CPT upon completion of the post-treatment visit.

Inclusion Criteria:

• age 18-65 years (upper limit chosen to optimize changes in brain activation that diminish with age);
• criterion A trauma exposure and PTSD symptoms (clinically significant symptoms in at least two symptom clusters);
• subclinical atherosclerotic CVD (e.g., coronary, cerebrovascular, or peripheral arterial plaque or calcifications on imaging), clinical atherosclerotic CVD (e.g., myocardial infarction or revascularization), or increased risk for atherosclerotic CVD (i.e., >2 of hypertension, diabetes mellitus, hyperlipidemia, and active smoking) ability to understand and sign informed consent
• fluent English speaker.

Exclusion Criteria:

• history of stroke, brain surgery, seizure
• use of certain CVD medications (e.g., beta-blockers, high-intensity statins [e.g., rosuvastatin 20/40 mg and atorvastatin 40/80 mg], PCSK-9 inhibitors);
• psychiatric or cardiovascular medication change within 4 weeks (i.e., stable regimen is allowed);
• currently in PTSD therapy;
• neurological or systemic inflammatory disease/current anti-inflammatory therapy;
• moderate/severe alcohol/substance use disorder;
• current mania/psychosis;
• weight >300 lbs., claustrophobia, pregnancy, metal implants that are incompatible with magnetic resonance imaging (MRI), or uncontrolled hyperglycemia (for imaging);
• significant radiation exposure (>2 nuclear tests, computed tomography images, or fluoroscopic procedures) for research purposes during the preceding 12-months.

Deidentified data from primary endpoints and analyses will be made available on a public website following study completion.

Within 6 months of study completion

To be determined based on website used

Individuals who interpret images and data will be blinded to assigned intervention