Functional neuroimaging of reward and motivation deficits in schizophrenia

描述(申请者提供)：这份职业发展奖申请书的标题是“精神分裂症患者奖赏和动机缺陷的功能神经再生”。候选人将是宾夕法尼亚大学的精神病学助理教授。他将得到拉克尔·古尔和鲁本·古尔博士的指导，他们以研究精神分裂症的情感和认知缺陷而闻名。这项提议的动机是，候选人作为医学博士研究生研究奖励的神经化学，作为精神病学家护理精神分裂症患者，并作为博士后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、动机和情绪缺陷)对功能残疾有很大影响。它们迫切需要更好的理解和更有效的治疗。这项研究将重点放在腹侧纹状体(VS)，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功能减退与全球阴性症状的严重程度联系起来。这项拟议的研究将检验候选人的假设，即VS功能减退将具体与动机低落和对快乐的期望降低有关。当受试者执行简单的社交和非社交奖励任务时，VS活动将使用fMRI进行测量。将获得详细的阴性症状描述，以及尼古丁依赖和抑郁的测量，因为这些常见的共病也影响VS功能。通常表现出阴性症状的一级家庭成员将与患者本身一起进行研究。这将允许独立于药物和慢性病的影响来探索研究结果。这项研究是专门为培养候选人的科学专长和独立研究轨迹而设计的，与他的职业目标保持一致。此外，应聘者将通过课程作业和指导学习在以下领域进行专门培训：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、合乎伦理的临床试验设计。这项拟议的工作将使候选人为专注于改善对精神分裂症的理解和治疗的独立研究生涯做好准备。公共卫生相关性：精神分裂症是一种常见的大脑疾病，给患者、家庭和社会带来了巨大的成本。动力不足和快感降低的症状会导致慢性社会和职业损害。这项提案旨在阐明这些缺陷的神经生物学，并为候选人利用强大的脑成像技术为精神分裂症患者开发更有效的治疗方法做好职业准备。

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.