The Renin-Angiotensin Pathway in Posttraumatic Stress Disorder

Abstract

Posttraumatic stress disorder (PTSD) is a debilitating stress-related illness associated with trauma exposure. The peripheral and central mechanisms mediating stress response in PTSD are incompletely understood. Recent data suggest that the renin-angiotensin pathway, essential to cardiovascular regulation, is also involved in mediating stress and anxiety. In this study, the authors examined the relationship between active treatment with blood pressure medication, including angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and PTSD symptom severity within a highly traumatized civilian medical population. Cross-sectional, observational data were analyzed from a larger study; patients were recruited from Grady Memorial Hospital's outpatient population from 2006 to November 2010. Multivariable linear regression models were fit to statistically evaluate the independent association of being prescribed an ACE inhibitor or ARB with PTSD symptoms, using a subset of patients for whom medical information was available (n = 505). Categorical PTSD diagnosis was assessed using the modified PTSD Symptom Scale (PSS) based on DSM-IV criteria, and PTSD symptom severity (the primary outcome of interest) was measured using the PSS and Clinician Administered PTSD Scale. A significant association was determined between presence of an ACE inhibitor/ARB medication and decreased PTSD symptoms (mean PSS score 11.4 vs 14.9 for individuals prescribed vs not prescribed ACE inhibitors/ARBs, respectively [P = .014]). After adjustment for covariates, ACE inhibitor/ARB treatment remained significantly associated with decreased PTSD symptoms (P = .044). Notably, other blood pressure medications, including β-blockers, calcium channel blockers, and diuretics, were not significantly associated with reduced PTSD symptoms. These data provide the first clinical evidence supporting a role for the renin-angiotensin system in the regulation of stress response in patients diagnosed with PTSD. Further studies should examine whether available medications targeting this pathway should be considered for future treatment and potential protection against PTSD symptoms.