Bremner J Douglas, Wittbrodt Matthew T, Gurel Nil Z, Shandhi MdMobashir H, Gazi Asim H, Jiao Yunshen, Levantsevych Oleksiy M, Huang Minxuan, Beckwith Joy, Herring Isaias, Murrah Nancy, Driggers Emily G, Ko Yi-An, Alkhalaf MhmtJamil L, Soudan Majd, Shallenberger Lucy, Hankus Allison N, Nye Jonathon A, Park Jeanie, Woodbury Anna, Mehta Puja K, Rapaport Mark H, Vaccarino Viola, Shah Amit J, Pearce Bradley D, Inan Omer T
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia.
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia.
J Affect Disord Rep. 2021 Dec;6. doi: 10.1016/j.jadr.2021.100190. Epub 2021 Jul 10.
Posttraumatic stress disorder (PTSD) is a highly disabling condition associated with alterations in multiple neurobiological systems, including increases in inflammatory and sympathetic function, responsible for maintenance of symptoms. Treatment options including medications and psychotherapies have limitations. We previously showed that transcutaneous Vagus Nerve Stimulation (tcVNS) blocks inflammatory (interleukin (IL)-6) responses to stress in PTSD. The purpose of this study was to assess the effects of tcVNS on PTSD symptoms and inflammatory responses to stress.
Twenty patients with PTSD were randomized to double blind active tcVNS (N=9) or sham (N=11) stimulation in conjunction with exposure to personalized traumatic scripts immediately followed by active or sham tcVNS and measurement of IL-6 and other biomarkers of inflammation. Patients then self administered active or sham tcVNS twice daily for three months. PTSD symptoms were measured with the PTSD Checklist (PCL) and the Clinician Administered PTSD Scale (CAPS), clinical improvement with the Clinical Global Index (CGI) and anxiety with the Hamilton Anxiety Scale (Ham-A) at baseline and one-month intervals followed by a repeat of measurement of biomarkers with traumatic scripts. After three months patients self treated with twice daily open label active tcVNS for another three months followed by assessment with the CGI.
Traumatic scripts increased IL-6 in PTSD patients, an effect that was blocked by tcVNS (p<.05). Active tcVNS treatment for three months resulted in a 31% greater reduction in PTSD symptoms compared to sham treatment as measured by the PCL (p=0.013) as well as hyperarousal symptoms and somatic anxiety measured with the Ham-A p<0.05). IL-6 increased from baseline in sham but not tcVNS. Open label tcVNS resulted in improvements measured with the CGI compared to the sham treatment period p<0.05).
These preliminary results suggest that tcVNS reduces inflammatory responses to stress, which may in part underlie beneficial effects on PTSD symptoms.
创伤后应激障碍(PTSD)是一种严重致残的疾病,与多个神经生物学系统的改变有关,包括炎症和交感神经功能的增强,这些变化导致症状持续存在。包括药物治疗和心理治疗在内的现有治疗方法都存在局限性。我们之前的研究表明,经皮迷走神经刺激(tcVNS)可阻断PTSD患者对应激的炎症反应(白细胞介素(IL)-6)。本研究旨在评估tcVNS对PTSD症状及对应激的炎症反应的影响。
20例PTSD患者被随机分为两组,分别接受双盲主动tcVNS治疗(N = 9)或假刺激(N = 11),同时暴露于个性化创伤脚本,随后立即进行主动或假tcVNS刺激,并测量IL-6和其他炎症生物标志物。之后,患者每天自行进行两次主动或假tcVNS治疗,持续三个月。在基线和每隔一个月时,使用PTSD检查表(PCL)和临床医生管理的PTSD量表(CAPS)测量PTSD症状,使用临床总体印象量表(CGI)评估临床改善情况,使用汉密尔顿焦虑量表(Ham-A)评估焦虑程度,随后再次通过创伤脚本测量生物标志物。三个月后,患者每天自行进行两次开放标签的主动tcVNS治疗,持续三个月,之后使用CGI进行评估。
创伤脚本使PTSD患者的IL-6升高,而tcVNS可阻断这一效应(p < 0.05)。与假刺激相比,主动tcVNS治疗三个月后,根据PCL测量,PTSD症状减少了31%(p = 0.013),同时根据Ham-A测量的过度觉醒症状和躯体焦虑也有所减轻(p < 0.05)。在假刺激组中,IL-6从基线水平升高,而tcVNS组则未升高。与假刺激治疗期相比,开放标签的tcVNS治疗使CGI测量的结果有所改善(p < 0.05)。
这些初步结果表明,tcVNS可减轻对应激的炎症反应,这可能是其对PTSD症状产生有益影响的部分原因。