Psychophysiological and Neural Mechanisms of Emotion Dysregulation in Alcohol Disorders Comorbid with PTSD

 描述（由申请人提供）：许多患有酒精使用障碍（AUD）的个体也患有创伤后应激障碍（PTSD），这些个体的AUD严重程度高于仅患有AUD的个体。本研究基于Kevin Oschsner博士和Scott Coffey博士进行的交叉研究。科菲博士发现了一种AUD/PTSD症状交叉效应，即创伤相关的线索不仅会引发PTSD症状，还会引发对酒精的渴望。不良的情绪调节理论上是AUD和PTSD之间联系的基础，通过一种模式，情绪调节障碍使个体更有可能发展PTSD，并加强酒精的使用来调节负面情绪。与此同时，Ochsner博士在他的实验室中广泛研究了情绪调节，并开发了情绪认知控制模型（MCCE）。在这个模型中，有许多不同的策略，个人用来控制情绪。其中之一，“重新解释”，已被广泛研究，并发现比其他策略更有效地减少负面情绪。重新解释是基于这样一个前提，即对刺激的情绪反应取决于认知评价的性质（即，赋予的意义）刺激，这是一个中心原则 认知行为疗法的一部分研究已经确定了在压力下AUD和PTSD的异常神经过程。由于这些大脑区域和神经网络也与情绪控制有关，研究人员假设参与者试图调节对这些压力线索的情绪反应，但失败了。然而，我们不知道酒精共病研究，特别是测试有目的的情绪调节压力使用一个已知的和经过充分测试的策略（重新解释），或在情绪调节失败的客观生理措施收集，使异常的神经网络与故障可以客观地确定。在这项研究中，我们将首先确定与（1）仅AUD，（2）仅PTSD和（3）无AUD或PTSD的参与者相比，AUD/PTSD参与者调节对个性化创伤线索（症状激发）的情绪反应的能力。我们还将确定减少情绪反应是否会减少相关的酒精渴望（行为和主观痛苦）。其次，我们将确定与不良情绪调节（痛苦的客观测量）相关的生理指标（心率，皮肤电导，心率变异性）。最后，在这些生理指标的指导下，利用功能磁共振成像，我们将确定与情绪调节功能障碍相关的神经网络（压力回路和AUD回路相互作用）。这一主题是NIAAA的优先事项，他们指出必须找到AUD/PTSD的神经生物学机制，必须澄清压力回路和AUD回路的相互作用。一旦确定了这些神经生物学机制，并且明确了压力回路和AUD回路之间的关系，我们就可以将这些知识应用于改善治疗方法，不仅适用于AUD/PTSD患者，而且适用于那些患有AUD与其他以情绪调节问题为特征的疾病的患者。

 DESCRIPTION (provided by applicant): Many individuals with alcohol use disorders (AUD) also have posttraumatic stress disorder (PTSD) and these individuals have greater AUD severity than individuals with AUD-only. This study is based on the intersection of research conducted by Drs. Kevin Oschsner and Scott Coffey. Dr. Coffey identified an AUD/PTSD symptom cross-over effect where trauma-related cues elicit not only PTSD symptoms but also alcohol craving. Poor emotion regulation is theorized to underlie this link between AUD and PTSD via a pattern where emotion dysregulation makes individuals both more likely to develop PTSD and also reinforces alcohol use to regulate negative emotions. Dr. Ochsner, meanwhile, has studied emotion regulation extensively in his lab and developed a model of the cognitive control of emotion (MCCE). Within that model there are many different strategies that individuals employ to control emotion. One of these, "reinterpretation," has been the extensively studied and found to be more effective in reducing negative emotions than other strategies. Reinterpretation is based on the premise that emotional reactions to stimuli depend upon the nature of cognitive appraisals of (i.e., the meaning assigned to) stimuli, which is a central tenet of cognitive behavioral therapy. Research has identified aberrant neural processes in AUD and PTSD during stressors. Since these are brain regions and neural networks also associated with emotional control, researchers hypothesize that participants are attempting to regulate emotional responses to these stressful cues but failing. However, we do not know of alcohol comorbidity studies that specifically test the purposeful emotional regulation of stress using a known and well-tested strategy (reinterpretation), or where objective physiological measures of emotion regulation failure are collected, so that abnormal neural networks associated with failures can be objectively identified. In this study we will determine first the ability of particpants with AUD/PTSD, compared to participants with (1) AUD only, (2) PTSD only, and (3) no AUD or PTSD, to regulate emotional responses to personalized trauma cues (symptom provocation). We will also determine whether decreasing emotional responses reduces associated alcohol craving (behavior and subjective distress). Second, we will determine physiological indices (heart rate, skin conductance, heart rate variability) associated with poor emotion regulation (objective measure of distress). Finally, guided by those physiological indices and using fMRI, we will determine neural networks (stress circuit and AUD circuit interaction) associated with dysfunctional emotional regulation. This topic is a priority at NIAAA, who has stated that neurobiological mechanisms underlying AUD/PTSD must be found, and stress circuit and AUD circuit interaction must be clarified. Once these neurobiological mechanisms are identified and the relationship between stress circuits and AUD circuits is clear, we can apply this knowledge to improving treatment approaches, not only for AUD/PTSD patients, but also for those suffering from AUD comorbid with other disorders characterized by emotion regulation problems.