Impaired Autonomic Regulation in Posttraumatic Stress Disorder

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Post‐traumatic stress disorder (PTSD) is associated with a significantly increased risk of cardiovascular disease (CVD) and accumulating clinical evidence suggests that autonomic dysregulation due to sympathetic overactivity and/or parasympathetic insufficiency may contribute to progression of CVD in PTSD. Therefore, utilizing a translational approach, we sought to examine autonomic function in both a clinical PTSD population as well as in an animal model of PTSD. In experimental studies, mice were instrumented with radiotelemetry probes to evaluate autonomic indices following Pavlovian fear conditioning. Fear conditioning involves the pairing of a conditioned stimulus (e.g. tone) paired with an aversive uconditioned stimulus (e.g. foot shock) that evokes a conditioned response (e.g. freezing). Twenty‐four hours following fear conditioning, spectral analysis of heart rate was performed and the low‐to high‐frequency ratio (LF:HF) was used as an index of sympathovagal balance. Fear conditioned animals displayed a significant increase in the LF:HF ratio relative to baseline (1.21 ± 0.46; p<0.05) indicating a shift in sympathovagal balance. Two weeks following fear conditioning, we assessed the contribution of sympathetic activity to the maintenance of blood pressure using the ganglionic blocker chlorisondamine (12ug/g i.p.). In response to sympathetic nervous system blockade, fear conditioned animals had a greater fall in blood pressure compared to control (Δ Systolic −71.7± 1.9 vs −39.8 ± 5.8 mmHg; p<0.05). Collectively, these results suggest impairments in autonomic control in an animal model of PTSD prior to the onset of CVD. Finally, these findings will be compared to an ongoing clinical study using a population of combat‐related PTSD (n=13) versus age‐matched controls without PTSD (n=9). Continuous elecrocardiography, beat‐to‐beat arterial blood pressure (BP) measurements, and 24‐hour ambulatory BP measurements have been collected at rest, during, and following mental stress. In an effort to translate our pre‐clinical results, these data will be analyzed for spectral analysis of heart rate variability, BP variability, and 24‐hour ambulatory BP patterns.Support or Funding InformationNIH R00 HL107675‐03 American Heart Association ‐ 15CSA24340001