Response to Unpredictable Threat in Alcohol Dependence and Panic Disorder

描述(由申请者提供)：该奖学金的目标是进一步发展申请者在精神病理学、心理生理学和高级统计方法方面的知识和研究技能。根据这些目标，申请者培训的基石 将是与拟议的酒精依赖(AD)和惊恐障碍(PD)共病背后的心理生理过程研究相关的日常活动。该项目将作为申请者的论文工作，并允许她追求成为一名独立研究员的目标，并通过一个翻译项目研究与并存物质使用和内在化障碍相关的生物行为过程。由于学术临床心理学家的技能是多方面的，拟议的培训计划还包括课程工作、定期赞助商会议、临床实践和专业发展活动。除了申请者将获得的技能外，该项目还有可能极大地促进我们对共同患有AD和PD的过程的理解，这一目标与NIAAA和NIMH的战略计划的几个方面一致。这一研究领域也值得注意，因为AD-PD与代价高昂的社会和经济后果有关，因此具有极其重要的公共卫生意义。最近有人推测，酒精在不可预测的恐慌症发作之间抑制预期性焦虑的能力可能是AD-PD的核心机制。证据还表明，与单纯帕金森病患者相比，AD-PD患者对预期焦虑的反应可能表现出更高的厌恶反应。然而，这个问题尚未得到直接研究，而且很少有研究评估厌恶反应是如何随着时间的推移而变化的。研究进一步表明，长期饮酒会导致呼吸性窦性心律失常(RSA)的缺陷，这是与厌恶反应相关的一个重要因素，可能会导致对预期焦虑的反应性/反应性增强。因此，本研究的具体目的是检验是否：1)与仅有帕金森病的个体相比，AD-PD个体对不可预测的威胁(即预测性焦虑)表现出更高的反应性；2)与只有PD的个体相比，AD-PD个体在不可预测的威胁(例如，较少的习惯性)中表现出不同的厌恶反应；以及3)RSA介导了这些联系。45名AD-PD患者和45名单纯PD患者将被招募用于本研究，对不可预测的威胁的反应将使用公认的肌电惊吓范式进行评估。该项目的导师将由心理生理学和共病精神病理学领域的专家提供。赞助商是尚克曼博士和卡塞尔博士，顾问是柯廷博士和波吉斯博士。这一奖学金不仅将是申请人研究生涯中的重要一步，而且如果假设得到支持，将表明对预测性焦虑的反应性/反应可能是AD-PD的潜在风险因素或后果，因此，可能有助于为这一难以治疗的人群制定有针对性的干预措施。

DESCRIPTION (provided by applicant): The goals of this fellowship are to further develop the applicant's knowledge and research skills in comorbid psychopathology, psychophysiology, and advanced statistical methods. In line with these goals, the cornerstone of the applicant's training will be the daily activities associated with the proposed study of psychophysiological processes underlying comorbid alcohol dependence (AD) and panic disorder (PD). The project will serve as the applicant's dissertation work and allow her to pursue her goal of becoming an independent investigator with a translational program of research on biobehavioral processes associated with comorbid substance use and internalizing disorders. As the skills of an academic clinical psychologist are multidimensional, the proposed training plan also includes course work, regular sponsor meetings, clinical practica, and professional development activities. In addition to the skills to be gained by the applicant, the project also has the potenial to greatly advance our understanding of the processes underlying comorbid AD and PD, a goal consistent with several facets of both NIAAA's and NIMH's strategic plans. This area of research is also noteworthy given that AD-PD is associated with costly social and economic consequences and thus, is of the utmost public health significance. It has recently been postulated that alcohol's ability to dampen anticipatory anxiety between unpredictable panic attacks may be a core mechanism in AD-PD. Evidence also suggest that individuals with AD-PD may exhibit heightened aversive reactivity in response to anticipatory anxiety relative to PD-only individuals. However, this question has yet to be directly examined and few studies have assessed how aversive responses change over time. Research further suggests that prolonged alcohol use causes deficits in respiratory sinus arrhythmia (RSA), an important factor associated with aversive responding, which may subsequently lead to heightened reactivity/responding to anticipatory anxiety. As such, the specific aims of the study are to examine whether: 1) AD-PD individuals exhibit increased reactivity to unpredictable threat (i.e., anticipatory anxiety) compared with PD-only individuals, 2) AD-PD individuals exhibit a different time course of aversive responding during unpredictable threat (e.g., less habituation) compared with PD-only individuals, and 3) RSA mediates these associations. Forty-five individuals with AD-PD and 45 individuals with PD-only will be recruited for the present study and responses to unpredictable threat will be assessed using a well-established EMG startle paradigm. Mentorship for this project will be provided by experts in the areas of psychophysiology and comorbid psychopathology. The sponsors are Drs. Shankman and Kassel and the consultants are Drs. Curtin and Porges. This fellowship will not only be an important step in the applicant's research career, but if the hypotheses are supported, it would suggest that reactivity/responding to anticipatory anxiety may be a potential risk factor or consequence of AD- PD and thus, may aid in the development of targeted interventions for this difficult-to-treat population.