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: 8505546
• 负责人: Theodore Satterthwaite
• 金额: $ 18.12万
• 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/8505546
• 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; 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）：快感缺乏是多种毁灭性精神疾病的核心。快感缺乏是精神分裂症的主要阴性症状之一，它会严重恶化受影响患者的长期结果。在双相情感障碍中，快感缺失也是周期性抑郁发作的核心特征，这种疾病的大部分发病率都是由周期性抑郁发作造成的。在精神分裂症和双相情感障碍中，快感缺失的症状通常始于青春期。无论潜在的临床诊断如何，快感缺乏都与治疗反应不佳有关。多项研究和我们的初步数据已将快感缺乏与大脑奖励系统功能障碍联系起来。然而，关于青春期奖赏功能障碍如何产生快感缺乏的情况，人们知之甚少。为了取得治疗进展，需要及早识别快感缺失的生物基质。在这里，我建议利用我们正在进行的大规模 RC2 Grand Opportunity（“GO”）神经发育研究。我计划对具有精神病或双相情感障碍症状的 GO 参与者的后续样本与典型发育中的青少年进行比较，全面评估快感缺失和奖励系统功能。将应用专门的临床测量、奖励系统反应的专用成像以及大脑结构和功能连接的后续纵向神经成像。多元模式分析技术将用于整合高维成像数据并产生基于大脑的快感缺乏维度测量。我们希望证明快感缺乏的存在与腹侧纹状体（奖励系统的关键节点）的反应性减弱和连接性破坏有关。在跨诊断类别的维度基础上将快感缺乏与奖励系统功能障碍联系起来，与最近发布的 NIMH 研究领域标准密切一致。拟议的工作将产生新颖的科学成果，并另外为即将完成神经精神病学博士后研究的精神病学家候选人提供批判性培训。该申请建立在候选人对奖励系统功能的既定兴趣和丰富的神经影像学经验（最近是 GO 研究）的基础上。候选人将受到经验丰富的导师委员会的指导，该委员会由主要导师 Raquel Gur 博士领导，他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。古尔博士和其他申请导师将确保拟议的培训计划所产生的经验将使候选人能够在青春期奖励系统功能障碍的神经科学领域建立独立的研究计划。