Quantitative Behavioral and Imaging Phenotypes of Amotivation in Schizophrenia

精神分裂症动机缺失的定量行为和影像表型

基本信息

批准号：
8557254
负责人：
DANIEL H WOLF
金额：
$ 40万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-05 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8557254
关键词：
Adult Anhedonia Animal Experimentation Animal Model Animals Anterior Antipsychotic Agents Behavior Behavioral Biological Markers Biology Brain Brain Diseases Clinical Clinical assessments Complex Data Delusions Development Disease Emotional Emotions Family Functional Imaging Functional Magnetic Resonance Imaging Functional disorder Future Hallucinations Human Image Individual Interview Investigation Laboratories Measures Mental disorders Modeling Motivation Pattern Pharmaceutical Preparations Phenotype Prevention Process Psychiatry Quality of life Relative (related person)Research Rewards Risk Role Sampling Schizophrenia Severities Societies Staging Symptoms System Techniques Testing Therapeutic Therapeutic Human Experimentation Time Translational Research Translations Validation Variant Ventral Striatum Work behavior measurement brain behavior cost disability discount discounting drug development effective therapy functional disability hedonic motivated behavior neural circuit neurobehavioral neuroimaging novel pleasure prodromal psychosis public health relevance relating to nervous system response social

项目摘要

DESCRIPTION (provided by applicant): The proposed study aims to discover the neural circuit abnormalities contributing to amotivation in schizophrenia, and identify quantitative behavioral and imaging measures of amotivation that can accelerate future translational and therapeutic research. A pathological loss of motivation is one of the "negative symptoms" of schizophrenia, which involve deficits in emotional and social capacities. Together with other negative symptoms such as anhedonia (reduced pleasure), asociality (reduced social drive), and reduced expressivity, amotivation contributes strongly to the disability caused by schizophrenia. Unlike positive symptoms (hallucinations, delusions) which are generally responsive to antipsychotic medications, negative symptoms including amotivation respond poorly to current treatments, and therefore constitute a major unmet therapeutic need in psychiatry. Despite this importance, amotivation in schizophrenia has been understudied and the brain abnormalities causing this deficit remain largely unknown. Validation and application of laboratory motivation paradigms in schizophrenia has lagged behind research in hedonic and emotion- processing deficits, and narrowing this gap is a major aim of this proposal. Over four years, the proposed study will evaluate motivation in 80 adults with schizophrenia with a wide range of negative symptoms, as well as 40 healthy control subjects. The specific aims are: 1) To quantify motivational deficits in schizophrenia using translational laboratory tasks, 2) To identif neural circuit dysfunction associated with motivation deficits in schizophrenia, and 3) To define a complex whole-brain phenotype predicting amotivation severity. To achieve these aims we will apply novel behavioral and functional imaging tasks together with advanced multivariate pattern analysis techniques. This study will provide a detailed brain-behavior pattern predicting amotivation severity which will help advance the understanding, treatment, and prevention of schizophrenia.

描述（由申请人提供）：拟议的研究旨在发现导致精神分裂症动机缺失的神经回路异常，并确定动机缺失的定量行为和成像测量，以加速未来的转化和治疗研究。病理性动力丧失是精神分裂症的“阴性症状”之一，涉及情感和社交能力的缺陷。连同其他负面症状，如快感缺乏（快乐感减少）、不合群（社交动力减少）和表达能力下降，缺乏动机在很大程度上导致了精神分裂症引起的残疾。与通常对抗精神病药物有反应的阳性症状（幻觉、妄想）不同，包括动机丧失在内的阴性症状对当前的治疗反应不佳，因此构成了精神病学中未满足的主要治疗需求。尽管如此重要，但精神分裂症的动机缺失尚未得到充分研究，导致这种缺陷的大脑异常仍然很大程度上未知。实验室动机范式在精神分裂症中的验证和应用已经落后于享乐和情绪处理缺陷的研究，而缩小这一差距是该提案的主要目标。这项拟议的研究将在四年内评估 80 名患有各种阴性症状的精神分裂症成年人以及 40 名健康对照受试者的动机。具体目标是：1) 使用转化实验室任务量化精神分裂症的动机缺陷，2) 识别与精神分裂症动机缺陷相关的神经回路功能障碍，以及 3) 定义复杂的全脑表型预测动机缺失的严重程度。为了实现这些目标，我们将应用新颖的行为和功能成像任务以及先进的多元模式分析技术。这项研究将提供预测动机缺失严重程度的详细大脑行为模式，这将有助于促进对精神分裂症的理解、治疗和预防。