Quantitative Behavioral and Imaging Phenotypes of Amotivation in Schizophrenia

描述（由申请人提供）：本研究旨在发现精神分裂症中与动机相关的神经回路异常，并确定动机的定量行为和影像学措施，以加速未来的转化和治疗研究。动机的病理性丧失是精神分裂症的“阴性症状”之一，它涉及情感和社交能力的缺陷。动机与其他负面症状一起，如快感缺乏（快感减少）、社交性（社会驱动力减少）和表达能力下降，是精神分裂症导致残疾的重要原因。与通常对抗精神病药物有反应的阳性症状（幻觉、妄想）不同，包括动机在内的阴性症状对目前的治疗反应不佳，因此构成精神病学未满足的主要治疗需求。尽管这一点很重要，但精神分裂症的动机尚未得到充分研究，导致这种缺陷的大脑异常在很大程度上仍然未知。实验室动机范式在精神分裂症中的验证和应用落后于享乐和情绪加工缺陷的研究，缩小这一差距是本研究的主要目的。在四年的时间里，这项拟议的研究将评估80名患有各种阴性症状的成年精神分裂症患者的动机，以及40名健康对照受试者。具体目标是：1)利用转化实验室任务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)定义精神分裂症的动机缺陷

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.