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

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 ​
Highlights • Non-invasive Vagal Nerve Stimulation (VNS) or sham stimulation was paired with personalized traumatic scripts. • Blood biomarkers for inflammation were compared between traumatized individuals with and without posttraumatic stress disorder (PTSD). • VNS blocked stress-induced increases in interleukin-6 (IL-6) and interferon-γ (IFNγ) in patients with PTSD.