Subjective Response to Alcohol and Associated Neural Systems in Bipolar Disorder

该指导研究科学家发展奖描述了一个研究和培训计划，该计划将 准备申请者，伊丽莎白·利帕德博士，过渡到一名具有研究的独立调查员 重点研究双相情感障碍的生物标记物(临床、行为和神经)及其相互作用 急性酒精中毒和大脑发育改变。成功改善临床预后至关重要 双相情感障碍的研究结果使更好的预测、诊断和治疗基于 个人的。申请人的提案解决了科学家需要研究的问题，即 导致病程的个体差异。申请者将研究预测风险的生物标志物。 用于双相情感障碍患者的酒精使用问题。我们假设发育异常的人 双相情感障碍扰乱了前额叶腹侧网络的功能，这可能是 疾病，也会改变人们对酒精的敏感度，从而增加饮酒/精神紊乱的风险。一个全面的 研究和培训计划由斯蒂芬·斯特拉科夫斯基、医学博士、金·弗罗姆、博士和 德克萨斯大学奥斯汀分校的卡梅隆·克拉多克博士对这一假说进行了验证。主要培训目标 1)接受双相情感障碍和酒精使用的诊断和临床评估方面的临床培训 紊乱；2)扩展申请人的方法学宝库以包括高级功能磁学 磁共振成像(FMRI)；以及3)训练安慰剂控制的酒精给药方法。这些目标 是申请者背景的自然延伸，采用结构神经成像和行为测试 在双相情感障碍中研究情绪和酒精相关的神经解剖和行为预测因素 在啮齿动物模型中酒精自我给药的问题和她的临床前工作。研究目标是(目标1) 确定酒精和(Aim)在刺激、镇静和缓解焦虑效果方面的个体差异 2)评估酒精对双相情感刺激和健康年轻人神经反应的影响。 在拟议的研究中，60名年轻人(50%患有双相情感障碍，50%为女性)将进行临床表型分析 以及完整的结构核磁共振扫描。然后，按照标准的饮料管理程序，参与者 将在酒精或酒精影响下完成对酒精和功能磁共振扫描的主观反应的测量 安慰剂(面对面的，平衡的)。我们预测双相情感障碍患者的报告会更低 与健康参与者相比，对酒精的主观反应与改变相关的反应较低 在腹侧前额叶网络中起作用。将调查与酒精使用模式的关系。这个K01 获奖对于继续接受高级培训以检验我们的假设以及对申请者过渡到 独立调查员，研究计划利用双相情感障碍领域的先进功能磁共振成像方法 精神障碍和酒精使用/精神障碍。调查结果将为新的、特定的目标提供早期发现风险和 预防。

This Mentored Research Scientist Development Award describes a research and training program that will prepare the applicant, Elizabeth Lippard, PhD, to transition to an independent investigator with a research program focused on biomarkers (clinical, behavioral, and neural) in bipolar disorder and interactions between acute alcohol intoxication and altered brain development. Essential to successfully improving clinical prognosis in bipolar disorder are research results that enable better prediction, diagnosis, and treatment based on the individual. The applicant’s proposal addresses the need for scientists working to understand mechanisms that contribute to individual differences in disease course. The applicant will investigate biomarkers predictive of risk for alcohol use problems in people with bipolar disorder. We hypothesize that developmental abnormalities in bipolar disorder that disrupt ventral prefrontal network function, and that likely underlie the development of the illness, also increase the risk for alcohol use/disorders by altering sensitivity to alcohol. A comprehensive research and training plan has been created with mentors, Stephen Strakowski, MD, Kim Fromme, PhD, and Cameron Craddock, PhD, at the University of Texas at Austin, to test this hypothesis. Primary training objectives are to: 1) obtain clinical training in the diagnosis and clinical assessment of bipolar disorder and alcohol use disorders; 2) extend the applicant’s methodological repertoire to include advanced functional magnetic resonance imaging (fMRI); and 3) train in placebo-controlled alcohol administration methods. These objectives are a natural extension of the applicant’s background employing structural neuroimaging and behavioral testing in bipolar disorder to investigate neuroanatomical and behavioral predictors of mood- and alcohol-related problems and her preclinical work on alcohol self-administration in rodent models. Research aims are to (Aim 1) identify individual differences in the experience of stimulating, sedating, and anxiolytic effects of alcohol and (Aim 2) assess alcohol-induced changes in neural responses to emotional stimuli in bipolar and healthy young adults. In the proposed research, 60 young adults (50% with bipolar disorder, 50% female) will be clinically phenotyped and complete structural MRI scans. Then, following standard beverage administration procedures, participants will complete measures of subjective response to alcohol and fMRI scans while under the influence of alcohol or a placebo (within-person, counter-balanced). We predict individuals with bipolar disorder will report lower subjective response to alcohol, compared with healthy participants, with lower response associated with altered function in ventral prefrontal networks. Relationships with alcohol use patterns will be investigated. This K01 award is critical to pursue the advanced training to test our hypothesis and for the applicant to transition to an independent investigator with a research program utilizing advanced fMRI approaches in the fields of bipolar disorder and alcohol use/disorders. Findings will inform new, specific targets for early detection of risk and prevention.