Functional neuroimaging of reward and motivation deficits in schizophrenia

描述（由申请人提供）：这个职业发展奖申请的题目是“精神分裂症的奖励和动机缺陷的功能神经成像”。候选人将成为宾夕法尼亚大学精神病学助理教授。他将由博士指导。Raquel Gur和Ruben Gur，他们以研究精神分裂症的情感和认知缺陷而闻名。该候选人在攻读医学博士学位期间研究奖励的神经化学，作为精神科医生照顾精神分裂症患者，并在博士后期间使用功能磁共振成像（fMRI）研究精神分裂症病理生理学。精神分裂症的阴性症状（社交、动机和情感缺陷）对功能性残疾有很强的影响。它们迫切需要更好的理解和更有效的治疗。这项研究将集中在腹侧纹状体（VS）上，它在将奖励经验转化为未来动机方面起着关键作用。候选人的初步数据将VS功能减退与阴性症状的总体严重程度联系起来。拟议的研究将验证候选人的假设，即VS功能障碍将与低动机和降低的快乐期望特别相关。当受试者执行简单的社会和非社会奖励任务时，将使用功能磁共振成像测量VS活动。将获得详细的阴性症状概况，以及尼古丁依赖和抑郁的测量，因为这些常见的合并症也会影响VS功能。通常表现为阴性症状的一级家庭成员将与患者本身一起进行研究。这将允许研究结果独立于药物和慢性疾病的影响。该研究是专门为培养候选人的科学专业知识和符合其职业目标的独立研究轨迹而设计的。此外，候选人将通过课程和指导学习在以下领域进行专业培训：功能磁共振成像技术，情感神经科学，药理学，统计学，以及有效的，合乎伦理的临床试验设计。建议的工作将为候选人的独立研究生涯做好准备，重点是提高对精神分裂症的理解和治疗。公共卫生相关性：精神分裂症是一种常见的脑部疾病，给患者、家庭和社会带来了巨大的成本。动机低下和快乐减少的症状会导致慢性社会和职业障碍。该提案旨在阐明这些缺陷的神经生物学，并为使用强大的脑成像技术开发更有效的精神分裂症患者治疗方法的候选人做好准备。

DESCRIPTION (provided by applicant): This Career Development Award application is entitled "Functional Neuroiniaging of Reward and Motivation Deficits in Schizophrenia." The candidate will be an Assistant Professor of Psychiatry at the University of Pennsylvania. He will be mentored by Drs. Raquel Gur and Ruben Gur, renowned for their research on emotional and cognitive deficits of schizophrenia. The proposal is motivated by the candidate's prior experiences studying the neurochemistry of reward as an MD-PhD student, caring for patients with schizophrenia as a psychiatrist, and using functional MRI (fMRI) to study schizophrenia pathophysiology as a postdoctoral fellow. Negative symptoms (social, motivational, and emotional deficits) of schizophrenia have a strong impact on functional disability. They present an urgent need for better understanding and more effective treatments. The study will focus on the ventral striatum (VS), which plays a key role in converting rewarding experiences into future motivation. The candidate's preliminary data links VS hypofunction to global severity of negative symptoms. The proposed study will test the candidate's hypothesis that VS hypofunction will be specifically related to low motivation and reduced expectations of pleasure. VS activity will be measured using fMRI while subjects perform simple social and nonsocial reward tasks. A detailed negative symptom profile will be obtained, together with measures of nicotine dependence and depression, as these common comorbidities also impact VS function. First-degree family members, who often exhibit negative symptomatology, will be studied alongside the patients themselves. This will allow findings to be explored independently of medication and chronic illness effects. The study is specifically designed to develop the candidate's scientific expertise and independent research trajectory in line with his career goals. In addition, the candidate will pursue specialized training through coursework and mentored learning in the following areas: fMRI techniques, affective neuroscience, pharmacology, statistics, and the design of effective, ethical clinical trials. The proposed work will prepare the candidate for an independent research career focused on improving the understanding and treatment of schizophrenia. PUBLIC HEALTH RELEVANCE: Schizophrenia is a common brain disorder that imposes enormous costs on patients, families, and society. Symptoms of low motivation and reduced pleasure contribute to chronic social and occupational impairment. This proposal aims to clarify the neurobiology of these deficits, and prepare the candidate for a career using powerful brain imaging technology to develop more effective treatments for patients with schizophrenia.