Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial

J Douglas Bremner; Nil Z Gurel; Yunshen Jiao; Matthew T Wittbrodt; Oleksiy M Levantsevych; Minxuan Huang; Hewon Jung; MdMobashir H Shandhi; Joy Beckwith; Isaias Herring; Mark H Rapaport; Nancy Murrah; Emily Driggers; Yi-An Ko; MhmtJamil L Alkhalaf; Majd Soudan; Jiawei Song; Benson S Ku; Lucy Shallenberger; Allison N Hankus; Jonathon A Nye; Jeanie Park; Viola Vaccarino; Amit J Shah; Omer T Inan; Bradley D Pearce

doi:10.1016/j.bbih.2020.100138

Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-γ in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial

Brain Behav Immun Health. 2020 Sep 11:9:100138. doi: 10.1016/j.bbih.2020.100138. eCollection 2020 Dec.

Authors

J Douglas Bremner^{1

2

3}, Nil Z Gurel⁴, Yunshen Jiao⁵, Matthew T Wittbrodt¹, Oleksiy M Levantsevych⁵, Minxuan Huang⁵, Hewon Jung⁴, MdMobashir H Shandhi⁴, Joy Beckwith¹, Isaias Herring¹, Mark H Rapaport¹, Nancy Murrah⁵, Emily Driggers^{1

5}, Yi-An Ko⁶, MhmtJamil L Alkhalaf⁵, Majd Soudan⁵, Jiawei Song⁵, Benson S Ku¹, Lucy Shallenberger⁵, Allison N Hankus⁵, Jonathon A Nye², Jeanie Park^{7

3}, Viola Vaccarino^{8

5}, Amit J Shah^{8

3

5}, Omer T Inan^{4

9}, Bradley D Pearce⁵

Affiliations

¹ Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
² Departments of Radiology, and Medicine, Emory University School of Medicine, Atlanta, GA, USA.
³ Atlanta VA Medical Center, Decatur, GA, USA.
⁴ School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
⁵ Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA.
⁶ Departments of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA, USA.
⁷ Departments of Renal Medicine, Emory University School of Medicine, Atlanta, GA, USA.
⁸ Departments of Cardiology, Emory University School of Medicine, Atlanta, GA, USA.
⁹ Coulter Department of Bioengineering, Georgia Institute of Technology, Atlanta, GA, USA.

Abstract

Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory function. Vagus nerve stimulation (VNS) decreases inflammation, however few studies have examined the effects of non-invasive VNS on physiology in human subjects, and no studies in patients with PTSD. The purpose of this study was to assess the effects of transcutaneous cervical VNS (tcVNS) on inflammatory responses to stress. Thirty subjects with a history of exposure to traumatic stress with (N = 10) and without (N = 20) PTSD underwent exposure to stressful tasks immediately followed by active or sham tcVNS and measurement of multiple biomarkers of inflammation (interleukin-(IL)-6, IL-2, IL-1β, Tumor Necrosis Factor alpha (TNFα) and Interferon gamma (IFNγ) over multiple time points. Stressful tasks included exposure to personalized scripts of traumatic events on day 1, and public speech and mental arithmetic (Mental Stress) tasks on days 2 and 3. Traumatic scripts were associated with a pattern of subjective anger measured with Visual Analogue Scales and increased IL-6 and IFNγ in PTSD patients that was blocked by tcVNS (p < .05). Traumatic stress had minimal effects on these biomarkers in non-PTSD subjects and there was no difference between tcVNS or sham. No significant differences were seen between groups in IL-2, IL-1β, or TNFα. These results demonstrate that tcVNS blocks behavioral and inflammatory responses to stress reminders in PTSD.

Keywords: Inflammation; Interferon; Interleukin-6; PTSD; Stress disorders, posttraumatic; Vagus nerve.

Abstract

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