PMID- 34589887 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240403 IS - 2666-3546 (Electronic) IS - 2666-3546 (Linking) VI - 9 DP - 2020 Dec TI - Transcutaneous vagal nerve stimulation blocks stress-induced activation of Interleukin-6 and interferon-gamma in posttraumatic stress disorder: A double-blind, randomized, sham-controlled trial. PG - 100138 LID - 10.1016/j.bbih.2020.100138 [doi] LID - 100138 AB - 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-1beta, Tumor Necrosis Factor alpha (TNFalpha) and Interferon gamma (IFNgamma) 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 IFNgamma 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-1beta, or TNFalpha. These results demonstrate that tcVNS blocks behavioral and inflammatory responses to stress reminders in PTSD. CI - (c) 2020 The Author(s). FAU - Bremner, J Douglas AU - Bremner JD AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. AD - Departments of Radiology, and Medicine, Emory University School of Medicine, Atlanta, GA, USA. AD - Atlanta VA Medical Center, Decatur, GA, USA. FAU - Gurel, Nil Z AU - Gurel NZ AD - School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. FAU - Jiao, Yunshen AU - Jiao Y AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Wittbrodt, Matthew T AU - Wittbrodt MT AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. FAU - Levantsevych, Oleksiy M AU - Levantsevych OM AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Huang, Minxuan AU - Huang M AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Jung, Hewon AU - Jung H AD - School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. FAU - Shandhi, MdMobashir H AU - Shandhi MH AD - School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. FAU - Beckwith, Joy AU - Beckwith J AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. FAU - Herring, Isaias AU - Herring I AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. FAU - Rapaport, Mark H AU - Rapaport MH AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. FAU - Murrah, Nancy AU - Murrah N AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Driggers, Emily AU - Driggers E AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Ko, Yi-An AU - Ko YA AD - Departments of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA, USA. FAU - Alkhalaf, MhmtJamil L AU - Alkhalaf ML AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Soudan, Majd AU - Soudan M AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Song, Jiawei AU - Song J AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Ku, Benson S AU - Ku BS AD - Departments of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA. FAU - Shallenberger, Lucy AU - Shallenberger L AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Hankus, Allison N AU - Hankus AN AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Nye, Jonathon A AU - Nye JA AD - Departments of Radiology, and Medicine, Emory University School of Medicine, Atlanta, GA, USA. FAU - Park, Jeanie AU - Park J AD - Departments of Renal Medicine, Emory University School of Medicine, Atlanta, GA, USA. AD - Atlanta VA Medical Center, Decatur, GA, USA. FAU - Vaccarino, Viola AU - Vaccarino V AD - Departments of Cardiology, Emory University School of Medicine, Atlanta, GA, USA. AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Shah, Amit J AU - Shah AJ AD - Departments of Cardiology, Emory University School of Medicine, Atlanta, GA, USA. AD - Atlanta VA Medical Center, Decatur, GA, USA. AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. FAU - Inan, Omer T AU - Inan OT AD - School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA. AD - Coulter Department of Bioengineering, Georgia Institute of Technology, Atlanta, GA, USA. FAU - Pearce, Bradley D AU - Pearce BD AD - Departments of Epidemiology, Rollins School of Public Health, Atlanta, GA, USA. LA - eng GR - S10 RR016917/RR/NCRR NIH HHS/United States GR - R01 HL109413/HL/NHLBI NIH HHS/United States GR - K24 HL077506/HL/NHLBI NIH HHS/United States GR - R01 HL125246/HL/NHLBI NIH HHS/United States GR - R01 HL136205/HL/NHLBI NIH HHS/United States GR - R01 MH120262/MH/NIMH NIH HHS/United States GR - K23 HL127251/HL/NHLBI NIH HHS/United States GR - P01 HL101398/HL/NHLBI NIH HHS/United States GR - UG3 DA048502/DA/NIDA NIH HHS/United States GR - I01 RX003418/RX/RRD VA/United States GR - R61 AT010457/AT/NCCIH NIH HHS/United States GR - I01 CX001065/CX/CSRD VA/United States GR - R25 MH101079/MH/NIMH NIH HHS/United States GR - R01 MH056120/MH/NIMH NIH HHS/United States GR - K24 MH076955/MH/NIMH NIH HHS/United States GR - R01 HL088726/HL/NHLBI NIH HHS/United States PT - Journal Article DEP - 20200911 PL - United States TA - Brain Behav Immun Health JT - Brain, behavior, & immunity - health JID - 101759062 PMC - PMC8474180 OTO - NOTNLM OT - Inflammation OT - Interferon OT - Interleukin-6 OT - PTSD OT - Stress disorders, posttraumatic OT - Vagus nerve COIS- J.D.B has research funding support from ElectroCore LLC. Both active and sham stimulation devices used in this study were provided by ElectroCore free of charge. EDAT- 2021/10/01 06:00 MHDA- 2021/10/01 06:01 PMCR- 2020/09/11 CRDT- 2021/09/30 07:21 PHST- 2020/08/03 00:00 [received] PHST- 2020/08/24 00:00 [revised] PHST- 2020/08/26 00:00 [accepted] PHST- 2021/09/30 07:21 [entrez] PHST- 2021/10/01 06:00 [pubmed] PHST- 2021/10/01 06:01 [medline] PHST- 2020/09/11 00:00 [pmc-release] AID - S2666-3546(20)30103-4 [pii] AID - 100138 [pii] AID - 10.1016/j.bbih.2020.100138 [doi] PST - epublish SO - Brain Behav Immun Health. 2020 Sep 11;9:100138. doi: 10.1016/j.bbih.2020.100138. eCollection 2020 Dec.