Fonzo Gregory A, Goodkind Madeleine S, Oathes Desmond J, Zaiko Yevgeniya V, Harvey Meredith, Peng Kathy K, Weiss M Elizabeth, Thompson Allison L, Zack Sanno E, Lindley Steven E, Arnow Bruce A, Jo Booil, Gross James J, Rothbaum Barbara O, Etkin Amit
From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Veterans Affairs Palo Alto Healthcare System, Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia; and the Trauma and Anxiety Recovery Program, Department of Psychiatry, Emory University School of Medicine, Atlanta.
Am J Psychiatry. 2017 Dec 1;174(12):1163-1174. doi: 10.1176/appi.ajp.2017.16091072. Epub 2017 Jul 18.
Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but many patients do not respond. Brain functions governing treatment outcome are not well characterized. The authors examined brain systems relevant to emotional reactivity and regulation, constructs that are thought to be central to PTSD and exposure therapy effects, to identify the functional traits of individuals most likely to benefit from treatment.
Individuals with PTSD underwent functional MRI (fMRI) while completing three tasks assessing emotional reactivity and regulation. Participants were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30). A random subset of the prolonged exposure group (N=17) underwent single-pulse transcranial magnetic stimulation (TMS) concurrent with fMRI to examine whether predictive activation patterns reflect causal influence within circuits. Linear mixed-effects modeling in line with the intent-to-treat principle was used to examine how baseline brain function moderated the effect of treatment on PTSD symptoms.
At baseline, individuals with larger treatment-related symptom reductions (compared with the waiting list condition) demonstrated 1) greater dorsal prefrontal activation and 2) less left amygdala activation, both during emotion reactivity; 3) better inhibition of the left amygdala induced by single TMS pulses to the right dorsolateral prefrontal cortex; and 4) greater ventromedial prefrontal/ventral striatal activation during emotional conflict regulation. Reappraisal-related activation was not a significant moderator of the treatment effect.
Capacity to benefit from prolonged exposure in PTSD is gated by the degree to which prefrontal resources are spontaneously engaged when superficially processing threat and adaptively mitigating emotional interference, but not when deliberately reducing negative emotionality.
暴露疗法是治疗创伤后应激障碍（PTSD）的一种有效方法，但许多患者对此无反应。目前对决定治疗效果的脑功能尚未有充分的特征描述。作者研究了与情绪反应和调节相关的脑系统，这些结构被认为是PTSD和暴露疗法效果的核心，以确定最有可能从治疗中获益的个体的功能特征。
患有PTSD的个体在完成三项评估情绪反应和调节的任务时接受功能磁共振成像（fMRI）检查。然后将参与者随机分配到立即进行延长暴露治疗组（N = 36）或等待名单组（N = 30）。延长暴露组的一个随机子集（N = 17）在进行fMRI时同时接受单脉冲经颅磁刺激（TMS），以检查预测性激活模式是否反映了回路内的因果影响。采用符合意向性治疗原则的线性混合效应模型来研究基线脑功能如何调节治疗对PTSD症状的影响。
在基线时，与等待名单组相比，治疗相关症状减轻幅度较大的个体在情绪反应期间表现出：1）背侧前额叶激活增强；2）左侧杏仁核激活减弱；3）单次TMS脉冲刺激右侧背外侧前额叶皮质对左侧杏仁核的抑制作用更强；4）在情绪冲突调节期间腹内侧前额叶/腹侧纹状体激活增强。与重新评估相关的激活不是治疗效果的显著调节因素。
PTSD患者从延长暴露治疗中获益的能力取决于在表面处理威胁和适应性减轻情绪干扰时前额叶资源的自发参与程度，而不是在刻意减少负面情绪时的参与程度。
