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有助于精神分裂症的动机的神经回路异常，并确定助攻性的定量行为和成像测量，以加速未来的转化和治疗性研究。动机的病理丧失是精神分裂症的“负面症状”之一，涉及情绪和社会能力的缺陷。加上其他负面症状，例如Anhedonia（减少愉悦），无情性（社交驱动力降低）和表达性降低，动机促进了精神分裂症引起的残疾。与通常对抗精神病药物反应的积极症状（幻觉，妄想）不同，包括动机在内的负面症状对当前治疗的反应较差，因此构成了精神病学的主要未满足治疗需求。尽管这一点很重要，但精神分裂症中的动机已经被研究了，导致这种赤字的大脑异常仍然在很大程度上未知。精神分裂症中实验室动机范式的验证和应用落后于享乐和情感处理缺陷的研究，而缩小这一差距是该建议的主要目的。四年来，拟议的研究将评估80名具有广泛负面症状的精神分裂症成年人的动机，以及40名健康对照受试者。具体目的是：1）使用翻译实验室任务来量化精神分裂症的动机缺陷，2）确定与精神分裂症动机缺陷相关的神经回路功能障碍，以及3）复杂的全脑表型预测了弹药的严重程度。为了实现这些目标，我们将与先进的多元模式分析技术一起应用新颖的行为和功能成像任务。这项研究将提供一种详细的脑行为模式，以预测无动力的严重性，这将有助于提高对精神分裂症的理解，治疗和预防。