Etiologic Connections of Affective and Anxiety Disorders

情感障碍和焦虑障碍的病因学联系

• 批准号: 6644160
• 负责人: DEAN FREDERICK MACKINNON
• 金额: $ 15.77万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-07 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6644160
• 关键词: anxiety disorders; bipolar depression; carbon dioxide; clinical research; comorbidity; disease /disorder etiology; disease /disorder proneness /risk; family genetics; gene expression; genetic susceptibility; human subject; interview; mood disorders; panic disorder; phenotype

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.

描述（申请人提供）：情感障碍是一种常见、严重、反复发作、异质性精神疾病，其病理生理机制难以解释。其临床和病因学的复杂性可能会掩盖努力，以揭示机制和tc发现针对这些机制的治疗药物。一个共同的临床特征，加剧了复杂性是共病焦虑。焦虑和情感障碍综合征加剧了患者的功能性发病率和痛苦，但也可能提供了发现共同病因的机会。该职业发展奖的候选人是一家教学医院的学术精神科医生，对医学研究有着坚定的历史承诺。候选人已经建立了作为情感障碍临床专家的声誉，并具有情感障碍遗传学的研究背景;到奖励期结束时，他计划已经建立了一个旨在共病焦虑和情感障碍的临床和研究方向，并精通心理生理学方法。该奖项将通过提供时间和资源来促进这一过程，以进一步开展心理生理学，神经科学和遗传学方面的培训。本研究的出发点是：1）双相情感障碍和惊恐障碍通常同时发生的流行病学发现（共病风险）; 2）惊恐障碍的症状激发研究，揭示了惊恐障碍患者亲属中潜在的惊恐脆弱性（家族风险）; 3）家族研究结果，显示了惊恐障碍的家族和共病风险。本文提出的研究计划将通过使用二氧化碳吸入在双相情感障碍遗传连锁研究确定的研究受试者中引发恐慌症状来解决有关恐慌和双相情感障碍关系的进一步问题。将根据家族和共病风险（与阳性和阴性对照受试者的风险相比）来分析既往无惊恐障碍的受试者对二氧化碳的惊恐反应风险。如果有一个特定的遗传风险因素，为双相和恐慌症的一个子集的家庭，然后家庭和共病风险将相互作用，产生更高的风险挑起恐慌比将任何一个风险因素单独。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学研究，并将通知候选人的进一步研究情感和焦虑症的病因。