PHYSIOLOGIC STUDIES OF ANGER IN DEPRESSED PATIENTS

这是一份NIMH指导的以患者为导向的研究职业发展奖(K23)的申请书，标题为“抑郁症患者愤怒的生理学研究”。它允许具有临床精神药理学和正电子发射断层扫描(PET)激活研究经验的应聘者获得在严重抑郁障碍(MDD)情感调节失调研究中的心理生理学和体内神经受体成像技术方面的专业知识。大量的正电子发射计算机断层扫描研究表明，MDD患者的前缘旁结构存在异常代谢模式。在健康对照组中，许多跟踪负性情绪诱导范式的正电子发射计算机断层扫描研究表明，前缘旁结构参与了悲伤和厌恶等负面情绪的处理。很少有研究利用这些范式来研究患有MDD的受试者的情绪处理，MDD是一种以严重的情感调节障碍为特征的障碍。MDD患者有一种特征明确的MDD亚型，即MDD伴愤怒发作，患者出现突然的、不典型的愤怒发作，并伴有自主神经激活。MDD的这一亚型提供了在明确定义的临床人群中描述特定类型(ANGER)的情感失调的机会，最终有助于阐明MDD的病理生理学。我们建议研究三个人群：有愤怒发作的MDD，没有愤怒发作的MDD，以及健康对照受试者。我们将利用叙事脚本来诱导情绪状态(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活体神经受体成像技术评估研究人群的生理反应。根据这一建议，候选人寻求以下方面的培训：(1)MDD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学，以及(4)PET神经感受器成像。这一严格的培训计划，整合了强大的教学学和多学科的专业知识，将教会候选人如何在研究MDD的情绪失调时综合来自不同领域的信息。这一培训和研究的综合计划将增进我们对MDD病理生理学的了解，为研究情绪处理提供新的工具，并为应聘者提供在高度复杂的领域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.