Gurel Nil Z, Jiao Yunshen, Wittbrodt Matthew T, Ko Yi-An, Hankus Allison, Driggers Emily G, Ladd Stacy L, Shallenberger Lucy, Murrah Nancy, Huang Minxuan, Haffar Ammer, Alkhalaf Mhmtjamil, Levantsevych Oleksiy, Nye Jonathon A, Vaccarino Viola, Shah Amit J, Inan Omer T, Bremner J Douglas, Pearce Bradley D
School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
Compr Psychoneuroendocrinol. 2020 Oct 27;4:100012. doi: 10.1016/j.cpnec.2020.100012. eCollection 2020 Nov.
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide that plays a key role in the neurobiology of the stress response, and prior studies suggest that its function is dysregulated in post-traumatic stress disorder (PTSD). Transcutaneous cervical vagus nerve stimulation (tcVNS) acts through PACAP and other neurobiological systems to modulate stress responses and/or symptoms of PTSD. In this pilot study, we examined the effects of tcVNS on PACAP in a three day chronic stress laboratory paradigm involving serial traumatic and mental stress exposures in healthy individuals with a history of exposure to psychological trauma (n = 18) and patients with PTSD (n = 12).
A total of 30 subjects with a history of exposure to psychological trauma experience were recruited (12 with PTSD diagnosis) for a three-day randomized double-blinded study of tcVNS or sham stimulation. Subjects underwent a protocol that included both personalized trauma recall and non-personalized mental stressors (public speaking, mental arithmetic) paired to tcVNS or sham stimulation over three days. Blood was collected at baseline and multiple time points after exposure to stressors. Linear mixed-effects models were used to assess changes in PACAP over time (in response to stressors) and its relation to active tcVNS or sham stimulation.
PACAP blood levels increased over the course of three days for both active tcVNS and sham groups. This increase was statistically-significant in the sham group at the end of the second (Cohen's d = 0.35, p = 0.04), and third days (d = 0.41, p = 0.04), but not in the active tcVNS group (d = 0.21, d = 0.18, and p > 0.20).
These pilot findings suggest tcVNS may attenuate this neurobiological stress-response. Larger studies are needed to investigate gender and interaction effects.
垂体腺苷酸环化酶激活肽(PACAP)是一种神经肽,在应激反应的神经生物学中起关键作用,先前的研究表明其功能在创伤后应激障碍(PTSD)中失调。经皮颈迷走神经刺激(tcVNS)通过PACAP和其他神经生物学系统发挥作用,以调节PTSD的应激反应和/或症状。在这项初步研究中,我们在一个为期三天的慢性应激实验室范式中,研究了tcVNS对PACAP的影响,该范式涉及对有心理创伤暴露史的健康个体(n = 18)和PTSD患者(n = 12)进行系列创伤性和精神应激暴露。
总共招募了30名有心理创伤暴露史的受试者(12名患有PTSD诊断),进行为期三天的tcVNS或假刺激随机双盲研究。受试者接受了一个方案,其中包括个性化创伤回忆和非个性化精神应激源(公开演讲、心算),在三天内与tcVNS或假刺激配对。在基线和暴露于应激源后的多个时间点采集血液。使用线性混合效应模型来评估PACAP随时间的变化(对应激源的反应)及其与活性tcVNS或假刺激的关系。
活性tcVNS组和假刺激组的PACAP血液水平在三天过程中均升高。在假刺激组中,这种升高在第二天结束时(科恩d = 0.35,p = 0.04)和第三天(d = 0.41,p = 0.04)具有统计学意义,但在活性tcVNS组中没有(d = 0.21,d = 0.18,且p > 0.20)。
这些初步研究结果表明tcVNS可能会减弱这种神经生物学应激反应。需要更大规模的研究来调查性别和交互作用效应。