Etiologic Connections of Affective and Anxiety Disorders

描述（由申请人提供）：情感性障碍是一种常见的、严重的、复发的、异质性的精神疾病，其病理生理机制难以捉摸。其临床和病因的复杂性可能会使发现机制和发现针对这些机制的治疗药物的努力变得模糊。增加复杂性的一个常见临床特征是共病性焦虑。焦虑和情感障碍综合征的合并加剧了患者的功能失调和痛苦，但也可能提供了一个发现共同病因的机会。本职业发展奖的候选人是教学医院的学术精神病学家，在医学研究方面有很强的历史承诺。候选人已经在情感障碍方面建立了临床专家的声誉，并具有情感障碍遗传学的研究背景；在奖励期结束时，他计划建立一个针对共病焦虑和情感障碍的临床和研究方向，熟练运用心理生理学方法。该奖项将通过提供在心理生理学、神经科学和遗传学方面进行进一步培训的时间和资源来促进这一进程。本研究的出发点是：1)流行病学发现双相情感障碍和惊恐障碍通常同时发生（共病风险）；2)惊恐障碍症状激发研究揭示惊恐障碍患者亲属潜在的惊恐易感性（家族风险）；3)家庭研究结果显示惊恐障碍的家族性和共病风险。在此提出的研究计划将通过在双相情感障碍遗传连锁研究中确定的研究对象中使用二氧化碳吸入引起恐慌症状来解决有关恐慌与双相情感障碍关系的进一步问题。无惊恐障碍的受试者对二氧化碳的惊恐反应风险将作为家族性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）。如果在一部分家庭中存在双相情感障碍和惊恐障碍的特定遗传风险因素，那么家族和共病风险将相互作用，产生比单独任何一种风险因素更高的诱发性恐慌风险。这项工作的结果将应用于正在进行的双相情感障碍的遗传研究，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.