Smoking, Antidepressants and Response to Mental Stress

描述（由申请人提供）： 本提案是对最初于2003年2月提交并于2003年11月重新提交的申请的第二次修订。拟议的指导以患者为导向的研究职业发展奖的目标是建立在迈克尔Kotlyar，PharmD，在实验和临床药理学和精神病学终身助理教授以前的培训和经验。通过本申请中提出的指导，培训和研究，预计Kotlyar博士可以发展成为一名独立的，受资助的研究人员。为了进一步发展临床试验设计，生物统计学和伦理学方面的技能，Kotlyar博士将参加明尼苏达大学临床研究硕士课程的正式学习课程，获得硕士学位。烟草使用研究中心主任Dorothy Hatsukami博士将担任Kotlyar博士的导师。这项研究将评估帕罗西汀对生理反应（血压，心率和血浆儿茶酚胺浓度）和心理不适的影响，在实验室管理的精神压力任务中，吸烟后立即管理。该研究将在NIH资助的一般临床研究中心（GCRC）进行。我们假设，相对于安慰剂，帕罗西汀将减少生理反应，并减少心理应激任务期间感知的心理不适。这项研究的基本原理是，吸烟者经常报告吸烟是为了应对压力。吸烟和压力都在生理上导致交感神经活动的增加。当吸烟与压力相结合时，这些影响是累加的，如心率和血压的增加。虽然已知对压力的高反应性对心血管健康有害，但目前没有数据评估抗抑郁药对吸烟者或急性吸烟期间对压力的生理反应的影响。培训和指导的研究项目结合跨学科咨询小组提供的指导，应该为候选人作为一个独立的，成功的以患者为导向的研究人员的职业生涯做好准备。

DESCRIPTION (provided by applicant): This proposal is the second revision of an application originally submitted in February 2003 and resubmitted in November 2003. The goal of the proposed Mentored Patient-Oriented Research Career Development Award is to build upon the previous training and experience of Michael Kotlyar, PharmD, a tenure track assistant professor in Experimental and Clinical Pharmacology and Psychiatry. Via the mentorship, training and research proposed in this application, it is expected that Dr. Kotlyar can develop into an independent, funded investigator. To further develop skills in clinical trial design, biostatistics and ethics, Dr. Kotlyar will enroll in a formal program of study leading to a Master's degree in the Clinical Research Masters Program at the University of Minnesota. Dr. Dorothy Hatsukami, PhD, the director of the Tobacco Use Research Center will serve as Dr. Kotlyar's mentor. The research will assess the effect of paroxetine on the physiological response (blood pressure, heart rate and plasma catecholamine concentrations) and psychological discomfort during laboratory-administered mental stress tasks, administered immediately after smoking a cigarette. The research will be conducted in the NIH funded General Clinical Research Center (GCRC). We hypothesize that relative to placebo; paroxetine will decrease physiological response and reduce perceived psychological discomfort during mental stress tasks. The rationale for this research is that smokers often report smoking in response to stressful situations. Smoking and stress each result physiologically in an increase in sympathetic activity. When smoking is combined with stress, these effects are additive as assessed by measures such as increases in heart rate and blood pressure. Although high reactivity to stress is known to be detrimental to cardiovascular health, there is currently no data assessing the effect of antidepressants on the physiological response to stress in smokers or during the acute smoking period. The training and mentored research project combined with the guidance provided by an interdisciplinary advisory group should well prepare the candidate for a career as an independent, successful patient-oriented researcher.