Neuroimaging of Dimensional Reward Dysfunction in Adolescence

青春期维度奖赏功能障碍的神经影像学

• 批准号: 8656442
• 负责人: Theodore Satterthwaite
• 金额: $ 18.05万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-07 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656442
• 关键词: Adolescence; Adolescent; Affect; Amygdaloid structure; Anhedonia; Attention; Base of the Brain; Basic Science; Behavioral; Biological; Bipolar Disorder; Brain; Brain imaging; Categories; Clinical; Clinical assessments; Corpus striatum structure; DSM-IV; Data; Development; Diagnosis; Diagnostic; Disease; Early identification; Early treatment; Economics; Evaluation; Fellowship; Functional Imaging; Functional Magnetic Resonance Imaging; Functional disorder; Genomics; Gur; Image; Individual; Interview; Investigation; Lead; Link; Literature; Magnetic Resonance Imaging; Measures; Mental disorders; Mentors; Mentorship; Methods; Metric; Morbidity - disease rate; National Institute of Mental Health; Neurobiology; Neurosciences; Outcome; Participant; Patients; Pattern; Phenotype; Population; Postdoctoral Fellow; Prefrontal Cortex; Psychiatrist; Psychopathology; Psychotic Disorders; Public Health; Recording of previous events; Recruitment Activity; Reporting; Research; Research Domain Criteria; Rest; Rewards; Sampling; Scanning; Schizophrenia; Seeds; Societies; Structure; Symptoms; System; Techniques; Training; Ventral Striatum; Weight; Youth; base; clinical Diagnosis; clinically significant; cost; depressive symptoms; discounting; effective therapy; experience; follow-up; innovation; insight; interest; multitask; neurobehavioral; neurodevelopment; neuroimaging; neuropsychiatry; novel; programs; response; treatment response

DESCRIPTION (provided by applicant): Anhedonia is at the center of multiple devastating psychiatric conditions. Anhedonia is one of the cardinal negative symptoms in schizophrenia, which substantially worsen long-term outcome in affected patients. In bipolar disorder, anhedonia is also a core feature of the cyclic depressive episodes that produce the majority of the morbidity of that illness. In both schizophrenia and bipolar disorder, symptoms of anhedonia often begin in adolescence. Regardless of the underlying clinical diagnosis, anhedonia is associated with poor treatment response. Several studies and our preliminary data have linked anhedonia to dysfunction of the brain's reward system. However, very little is yet known regarding how reward dysfunction develops in adolescence to produce anhedonia. Early identification of the biological substrates of anhedonia is needed for advances in treatment. Here, I propose to capitalize upon our ongoing large-scale RC2 Grand Opportunity ("GO") study of neurodevelopment. I plan to comprehensively assess anhedonia and reward system function in a follow-up sample of GO participants with symptoms of psychosis or bipolar disorder, compared to typically developing youths. Specialized clinical measures, dedicated imaging of reward system responses, and follow-up longitudinal neuroimaging of brain structure and functional connectivity will be applied. Multivariate pattern analysis techniques will be used to integrate high-dimensional imaging data and produce a brain-based, dimensional measure of anhedonia. We expect to demonstrate that the presence of anhedonia is related to diminished responsiveness and disrupted connectivity of the ventral striatum, a key node of the reward system. Relating anhedonia to reward system dysfunction on a dimensional basis across diagnostic categories coheres closely with the recently released NIMH Research Domain Criteria. The proposed effort will produce novel scientific results and additionally provide criticl training to the candidate, who is a psychiatrist finishing his post-doctoral neuropsychiatry fellowship. The application builds upon the candidate's established interest in reward system function and substantial neuroimaging experience, most recently with the GO study. The candidate will be mentored by an experienced mentorship committee, lead by primary mentor Dr. Raquel Gur, who is a renowned expert in schizophrenia and investigations of the biological basis of psychopathology. Dr. Gur and the other application mentors will assure that the experience resulting from the proposed training plan will enable the candidate to establish an independent research program in the neuroscience of reward system dysfunction in adolescence.

描述(由申请人提供)：快感缺失是多种破坏性精神疾病的中心。快感缺乏是精神分裂症的主要阴性症状之一，它大大恶化了受影响患者的长期结果。在双相情感障碍中，快感缺乏也是周期性抑郁发作的核心特征，而周期性抑郁发作是该疾病发病率的主要原因。在精神分裂症和双相情感障碍中，快感缺乏的症状通常在青春期就开始了。不管潜在的临床诊断是什么，快感缺乏与治疗反应差有关。一些研究和我们的初步数据已经将快感缺失与大脑奖励系统的功能障碍联系在一起。然而，关于奖赏功能障碍是如何在青春期发展成快感缺失的，目前还知之甚少。早期识别快感缺乏症的生物底物是治疗进展所必需的。在这里，我建议利用我们正在进行的关于神经发育的大规模RC2重大机遇(“GO”)研究。我计划对有精神病或双相情感障碍症状的围棋参与者的随访样本进行全面的快感缺乏和奖励系统功能评估，并与典型的发育中的年轻人进行比较。将应用专门的临床措施、奖励系统反应的专用成像以及对大脑结构和功能连接的后续纵向神经成像。多变量模式分析技术将被用于整合高维成像数据，并产生基于大脑的快感缺乏症的维度测量。我们期望证明快感缺乏的存在与反应减弱和腹侧纹状体的连接中断有关，腹侧纹状体是奖励系统的关键节点。将快感缺乏症与不同诊断类别的奖赏系统功能障碍联系起来，与最近发布的NIMH研究领域标准密切相关。拟议的努力将产生新的科学结果，并额外为候选人提供批判性培训，他是一名精神病学家，完成了他的博士后神经精神病学研究员职位。该应用程序建立在应聘者对奖励系统功能的既定兴趣和丰富的神经成像经验的基础上，最近的一次是围棋研究。候选人将由一个经验丰富的导师委员会指导，该委员会由主要导师拉克尔·古尔博士领导，古尔博士是精神分裂症和精神病理学生物学基础研究方面的著名专家。Gur博士和其他申请导师将保证，拟议的培训计划带来的经验将使候选人能够在青春期奖赏系统障碍的神经科学方面建立一个独立的研究计划。