PHYSIOLOGIC STUDIES OF ANGER IN DEPRESSED PATIENTS

这是一份申请NIMH指导患者导向研究职业发展奖（K23）的申请，标题为“抑郁症患者愤怒的生理学研究”。具有临床精神药理学和正电子发射断层扫描（PET）激活研究经验的候选人可以获得心理生理学和体内神经受体成像技术方面的专业知识，用于研究重度抑郁症（MDD）的情感失调。大量的PET研究表明MDD患者的前边缘旁结构代谢模式异常。大量的正电子发射断层扫描（PET）研究在健康对照中采用了消极情绪诱导范式，结果表明，前旁缘结构参与了诸如悲伤和厌恶等消极情绪的处理。很少有研究利用这些范式来研究重度抑郁症患者的情绪处理，重度抑郁症是一种以情感调节严重紊乱为特征的疾病。有典型的重度抑郁症亚型的患者，伴有愤怒发作的重度抑郁症，表现为突然的非特征性愤怒，并伴有自主神经激活。这种亚型的重度抑郁症提供了一个机会来表征特定类型的情感失调（愤怒）在一个明确定义的临床人群中，最终有助于阐明重度抑郁症的病理生理学。我们建议研究三种人群：有愤怒发作的MDD、无愤怒发作的MDD和健康对照。我们将利用叙事脚本诱导情绪状态（愤怒、悲伤和中性状态），并利用心理生理学测量、PET激活研究和PET体内神经受体成像技术评估研究人群的生理反应。通过这项提议，候选人寻求以下方面的培训：(1)重度抑郁症的临床研究，(2)情感神经科学，(3)与功能神经成像相关的统计，以及(4)PET神经受体成像。这个严格的训练计划，整合了强大的教学和多学科专业知识，将教会候选人如何综合来自不同领域的信息来研究MDD的影响失调。这个综合的培训和研究项目将提高我们对重度抑郁症病理生理学的认识，为研究情绪处理提供新的工具，并为候选人提供在高度复杂的领域中实现独立所需的技能。

This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K23) titled "Physiologic Studies of Anger in Depressed Patients". It allows the candidate, who has experience with clinical psychopharmacology and positron emission tomography (PET) activation studies, to gain expertise in psychophysiology and in vivo neuroreceptor imaging techniques in the study of affective dysregulation in major depressive disorder (MDD). Numerous PET studies have demonstrated abnormal metabolic patterns in anterior paralimbic structures in patients with MDD. Numerous PET studies following negative emotion induction paradigms in healthy controls have demonstrated that anterior paralimbic structures are involved in the processing of negative emotions such as sadness and disgust. Few studies have utilized these paradigms to study emotional processing in subjects with MDD, a disorder characterized by profound disturbances of affect regulation. Patients with a well-characterized subtype of MDD, MDD with anger attacks, present with sudden uncharacteristic spells of anger accompanied by autonomic activation. This subtype of MDD provides an opportunity to characterize affect dysregulation of a specific type (anger) in a well-defined clinical population, ultimately helping to elucidate the pathophysiology of MDD. We propose to study three populations: MDD with anger attacks, MDD without anger attacks, and healthy control subjects. We will utilize narrative scripts to induce emotional states (angry, sad, and neutral states) and assess physiologic responses in the study populations utilizing psychophysiologic measures, PET activation studies, and PET in vivo neuroreceptor imaging techniques. By this proposal, the candidate seeks training in (1) clinical studies of MDD, (2) affective neuroscience, (3) statistics relevant to functional neuroimaging, and (4) neuroreceptor imaging with PET. This rigorous training plan, integrating strong didactics and multidisciplinary expertise, will teach the candidate how to synthesize information from diverse fields in studying affect dysregulation in MDD. This integrated program of training and research will advance our knowledge of the pathophysiology of MDD, yield new tools for studying emotional processing, and give the candidate the skills needed to achieve independence in a highly complex field.