Cognitive targets for medications development in early abstinent alcoholics

 描述（由申请人提供）：这是海伦·福克斯博士的K 02独立科学家奖申请，她目前是耶鲁大学医学院精神病学助理教授。2010年，Fox博士获得了NIH-NIDA资助的指导研究科学家发展奖，这使她在认知药物治疗和药物开发方面接受了无与伦比的培训。这也有助于帮助福克斯博士获得后续资金，并建立一个坚实的研究轨迹。福克斯博士已经收到了独立的资金，以检查免疫系统的变化，支持压力引起的酒精渴望和认知控制的早期戒酒者与抑郁症（R 01：AA 20095）。她还是一项在伴有和不伴有焦虑症的酗酒者中进行的12周哌唑嗪临床试验的共同PI（R 01：AA 20504）。其他项目包括评估有和没有抑郁症的依赖性个体（R 03：AA 022500）和危险的非依赖性饮酒者（Peter F MacManus慈善信托基金）的压力和免疫系统变化的潜在谨慎和收敛机制。在这项研究计划的基础上，她的职业发展目标是：1）描述有和没有焦虑和抑郁共病的酗酒者的压力和免疫系统适应性，以便为药物开发提供新的治疗靶点; 2）随后开发更好的定制药物，针对这些系统在共病人群中。通过K 02奖提供的集中研究时间实现这些目标对于福克斯博士保持目前的生产力水平并过渡到完全独立的科学家至关重要。5年职业生涯 还提出了发展计划，包括4个培训模块：1。教学内容：校内和校外课程和讲习班; 2.实践部分：监督研究项目和资金保障3.戒律4.专题讨论会和会议。拟议的K 02研究是在申请人资助的项目（R 01：AA 020504 /R 01：AA 020095）框架内进行的补充项目。目的是：a）评估3周哌唑嗪（16 mg，每日3次）与安慰剂相比，在伴有和不伴有焦虑的酗酒者中，在个性化意象应激源后，改善认知控制（Stroop，Go/No Go，停止信号表现）的有效性，以及B）检查认知控制测量作为同一人群结局标志物的效用。拟议的探索性目标将另外检查细胞因子的变化，认知控制过程后，个性化的压力，在酗酒者和抑郁症。父母研究和拟议的补充神经认知研究的目标与福克斯博士的职业目标和培训计划是一致的。检查抑制控制在预测结果中的效用以及哌唑嗪与安慰剂相比在加强这些机制中的功效与这两个目标是一致的。此外，阐明支撑这些机制的免疫系统变化也补充了开发治疗开发新靶点的需求。

 DESCRIPTION (provided by applicant): This is an application for a K02 Independent Scientist Award for Dr Helen Fox, who is currently an Assistant Professor in Psychiatry at Yale University School of Medicine. In 2010, Dr Fox received a NIH-NIDA funded Mentored Research Scientist Development Award which allowed her to received unparalleled training in cognitive pharmacotherapy and medications development. It was also instrumental in helping Dr Fox secure subsequent funding and establish a solid research trajectory. Dr Fox has received independent funding to examine immune system changes underpinning stress-induced alcohol craving and cognitive control in early abstinent alcoholics with and without depressive symptomatology (R01: AA 20095). She is also Co-PI of a 12 week clinical Prazosin trial in alcoholics with and without anxiety symptomatology (R01: AA 20504). Other projects include assessing discreet and converging mechanisms underlying stress and immune system changes in dependent individuals with and without depressive symptomatology (R03:AA022500) and hazardous non- dependent drinkers (Peter F MacManus Charitable Trust). On the basis of this research program, her career development goals are: 1) To characterize stress and immune system adaptations in alcoholics with and without anxiety and depressive comorbidity in order to provide novel treatment targets for medications development; 2) to subsequently develop better-tailored medications that target these systems in co-morbid populations. Attaining these goals via the focused research time afforded by the K02 award will be critical for Dr Fox to maintain her current level of productivity and transition to a fully independent scientist. A 5- year Career Development Plan is also proposed, comprising 4 training modules: 1. Didactic components: intramural and extramural courses and workshops; 2. Practical components: overseeing research projects and funding securement 3.Preceptorships 4. Symposia & Meetings. The proposed K02 research represents a supplementary project conducted within the framework of the applicants funded projects (R01: AA 020504 / R01: AA 020095). Objectives are to a) assess the efficacy of 3-weeks prazosin (16mgs t.i.d) versus placebo in improving cognitive control (Stroop, Go/No Go, Stop Signal performance), following a personalized imagery stressor in alcoholics with and without anxiety, and b) examine the utility of cognitive control measures as markers of outcome in the same population. The proposed exploratory aims will additionally examine cytokine changes underlying cognitive control processes following a personalized stressor in alcoholics with and without depressive symptomatology. The objectives of both parent studies and the proposed supplementary neurocognitive research are compatible with Dr Fox's career goals and training plan. Examining the utility of inhibitory control in predicting outcome and the efficacy of prazosin versus placebo in strengthening these mechanisms is compatible with both goals. In addition, elucidating immune system changes underpinning these mechanisms also complements the need to development novel targets for treatment development.