Etiologic Connections of Affective and Anxiety Disorders

描述(由申请人提供)：情感障碍是一种常见的、严重的、反复发作的、具有难以捉摸的病理生理学的异质性精神疾病。它们的临床和病因的复杂性可能会掩盖揭示机制的努力，以及TC发现针对这些机制的治疗药物。增加复杂性的一个常见临床特征是共病焦虑。焦虑症和情感性障碍综合征的合并加重了患者的功能发病率和痛苦，但也可能提供了一个发现共同病因的机会。这一职业发展奖的候选人是一家教学医院的学术精神病学家，在医学研究方面有着坚定的历史承诺。候选人已经确立了情感障碍临床专家的声誉，并拥有情感障碍遗传学的研究背景；到颁奖期结束时，他计划坚定地确立旨在治疗焦虑症和情感障碍并存的临床和研究方向，并熟练掌握心理生理学方法。该奖项将通过提供时间和资源来继续进行心理生理学、神经科学和遗传学的进一步培训，从而促进这一进程。拟议研究的出发点是：1)流行病学发现，躁郁症和恐慌症通常同时发生(共病风险)，2)症状激发研究揭示了恐慌症患者亲属潜在的恐慌症易感性(家族性风险)，以及3)家庭研究结果显示惊恐障碍的家族性和共病风险。这里提出的研究计划将进一步解决有关恐慌和双相情感障碍的关系的问题，方法是在双相情感障碍的遗传连锁研究的研究对象中，通过吸入二氧化碳来引发恐慌症状。没有惊恐障碍的受试者对二氧化碳的惊恐反应的风险将作为家族和共病风险的函数进行分析(与阳性和阴性对照受试者的风险相比较)。如果在一组家庭中同时存在双相情感障碍和恐慌症的特定遗传风险因素，那么家族性和共病风险将相互作用，产生比单独使用任何一种风险因素更高的引发恐慌的风险。这项工作的结果将被应用于正在进行的双相情感障碍的遗传学研究，并将为候选人进一步研究情感和焦虑障碍的病因提供信息。

DESCRIPTION (provided by applicant): Affective disorder are common, severe, recurrent, heterogeneous psycniatric diseases with an elusive pathophysiology. Their clinical and etiological complexity may obscure efforts to uncover mechanisms and tc discover therapeutic agents against those mechanisms. One common clinical feature that heightens complexity is comorbid anxiety. Combined anxiety and affective disorder syndromes exacerbate functional morbidity and suffering of patients, but may also present an opportunity to discover shared etiologic factors The candidate for this career development award is an academic psychiatrist at a teaching hospital with a strong historical commitment to medical research. The candidate has already established a reputation as a clinical specialist in affective disorders and has a research background in the genetics of affective disorder; by the end of the award period he plans to have established firmly a clinical and research direction aimed a comorbid anxiety and affective disorders, with fluency in psychophysiological methods. The award will facilitate this process by providing the time and resources to pursue further training in psychophysiology, neuroscience, and genetics. The starting points for the proposed research are 1) epidemiological findings that bipolar and panic disorders commonly occur together (comorbid risk), 2) symptom provocation studies ir panic disorder that reveal latent panic vulnerability in relatives of panic disorder patients (familial risk), and 3 family study results that show both familial and comorbid risk for panic disorder. The research program proposed here will address further questions about the relationship of panic and bipolar disorders by the use of carbon dioxide inhalation to provoke panic symptoms in study subjects ascertained for genetic linkage study of bipolar disorder. Risk of panic response to carbon dioxide in subjects without prior panic disorder will be analyzed as a function of familial and comorbid risk (as compared to the risk in positive and negative control subjects). If there is a specific genetic risk factor for both bipolar and panic disorder in a subset of families, then familial and comorbid risk will interact to produce higher risk of provoked panic than will either risk factor alone. Results of this work will then be applied to ongoing genetic studies of bipolar disorder, and will inform the candidate's further research into affective and anxiety disorder etiology.