Quantitative Behavioral and Imaging Phenotypes of Amotivation in 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失动的神经回路异常，并确定可加速未来转化和治疗研究的失动的定量行为和成像测量。精神分裂症的一种“阴性症状”是病理性的动机丧失，它涉及情感和社会能力的缺陷。与其他负面症状，如快感缺乏（减少的快乐），社会性（减少的社会驱动力），和减少的表达，动机强烈有助于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，阴性症状（包括失动）对当前治疗的反应较差，因此构成精神病学中主要未满足的治疗需求。尽管这一重要性，精神分裂症的动机已经研究不足，大脑异常导致这种赤字仍然在很大程度上未知。精神分裂症的实验室动机范式的验证和应用已经落后于享乐和情绪处理缺陷的研究，缩小这一差距是本提案的主要目的。在四年的时间里，这项拟议中的研究将评估80名患有精神分裂症的成年人的动机，以及40名健康对照受试者。具体目标是：1）使用翻译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，3）定义一个 复杂的全脑表型预测失动的严重程度。为了实现这些目标，我们将应用新的行为和功能成像任务与先进的多元模式分析技术。这项研究将提供一个详细的脑行为模式预测动机严重程度，这将有助于促进理解，治疗和预防精神分裂症。

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.