Functional neuroimaging of reward and motivation deficits in schizophrenia

精神分裂症奖励和动机缺陷的功能神经影像

• 批准号: 8401911
• 负责人: DANIEL H WOLF
• 金额: $ 17.87万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8401911
• 关键词: Affect; Anhedonia; Area; Award; Behavior; Biological Markers; Brain; Brain Diseases; Brain imaging; Chronic; Chronic Disease; Clinical Trials; Cognitive deficits; Comorbidity; Data; Doctor of Philosophy; Elements; Emotional; Emotions; Ethics; Exhibits; Face; Family; Family member; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Gur; Health; Imaging technology; Impairment; K-Series Research Career Programs; Knowledge; Learning; Link; Measures; Mental Depression; Mentors; Motivation; Neurobiology; Nicotine Dependence; Occupational; Patient Care; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Phenotype; Play; Postdoctoral Fellow; Principal Investigator; Psychiatrist; Psychiatry; Research; Research Personnel; Rewards; Risk; Ruthenium Ben; Schizophrenia; Severities; Signal Transduction; Smoking; Societies; Students; Symptoms; System; Techniques; Testing; Training; Universities; Ventral Striatum; Wolves; Work; affective neuroscience; career; cost; depressive symptoms; design; effective therapy; expectation; experience; functional disability; functional outcomes; improved; neurochemistry; neuroimaging; pleasure; professor; relating to nervous system; response; skills; social; statistics; tool

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.

描述（由申请人提供）：该职业发展奖的申请名为“精神分裂症的奖励和动机缺陷的功能性神经”。候选人将是宾夕法尼亚大学精神病学助理教授。他将受到博士的指导。拉奎尔·古尔（Raquel Gur）和鲁本·古尔（Ruben Gur）因其对精神分裂症的情感和认知缺陷而闻名。该提案是由候选人先前研究奖励作为MD-PHD学生的神经化学的经验的动机，照顾精神分裂症患者作为精神科医生，并使用功能性MRI（FMRI）来研究精神分裂症病理生理学作为商业后研究员。精神分裂症的负面症状（社会，动机和情绪缺陷）对功能障碍有很大的影响。他们迫切需要更好地理解和更有效的治疗方法。该研究将集中于腹纹状体（VS），该纹状体在将奖励体验转化为未来动机中起着关键作用。候选人的初步数据将功能障碍与负面症状的全球严重程度联系起来。拟议的研究将检验候选人的假设，即与功能障碍的障碍将特别与低动机和愉悦期望减少有关。 VS活动将使用fMRI进行测量，而受试者执行简单的社交和非社交奖励任务。将获得详细的负面症状特征，以及尼古丁依赖性和抑郁症的措施，因为这些常见合并症也影响了功能。经常表现出负面症状的一级家庭成员将与患者自己一起研究。这将使发现可以独立于药物和慢性病作用进行探索。该研究专门设计，旨在发展候选人的科学专业知识和独立的研究轨迹，该轨迹符合其职业目标。此外，候选人将在以下领域通过课程工作和指导学习进行专业培训：fMRI技术，情感神经科学，药理学，统计以及有效的，道德的临床试验的设计。拟议的工作将为候选人做好准备的独立研究职业，重点是改善精神分裂症的理解和治疗。

项目成果

Oral alprazolam acutely increases nucleus accumbens perfusion.

口服阿普唑仑可急剧增加伏隔核灌注。

• DOI: 10.1038/mp.2012.139
• 发表时间: 2013
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Wolf,DH;Pinkham,AE;Satterthwaite,TD;Ruparel,K;Elliott,MA;Valdez,J;Smith,MA;Detre,JA;Gur,RC;Gur,RE
• 通讯作者: Gur,RE

Diminished effort on a progressive ratio task in both unipolar and bipolar depression.

• DOI: 10.1016/j.jad.2016.02.003
• 发表时间: 2016-05-15
• 期刊: Journal of affective disorders
• 影响因子: 6.6
• 作者: Hershenberg R;Satterthwaite TD;Daldal A;Katchmar N;Moore TM;Kable JW;Wolf DH
• 通讯作者: Wolf DH

Steeper discounting of delayed rewards in schizophrenia but not first-degree relatives.

• DOI: 10.1016/j.psychres.2017.02.062
• 发表时间: 2017-06
• 期刊: Psychiatry research
• 影响因子: 11.3
• 作者: Yu LQ;Lee S;Katchmar N;Satterthwaite TD;Kable JW;Wolf DH
• 通讯作者: Wolf DH

Amotivation in schizophrenia: integrated assessment with behavioral, clinical, and imaging measures.

• DOI: 10.1093/schbul/sbu026
• 发表时间: 2014-11
• 期刊: Schizophrenia bulletin
• 影响因子: 6.6
• 作者: D. Wolf;T. Satterthwaite;J. Kantrowitz;Natalie Katchmar;Lillie Vandekar;M. Elliott;K. Ruparel