Adolescent Neurodevelopment and Impaired Intrinsic Motivation in Psychosis Risk

项目摘要 内在动机是对内在满足感的渴望，比如好奇心、挑战和掌握。它 取决于执行活动时自我产生奖励反应的能力，即使在缺席的情况下也是如此 没有任何外部奖励。这项拟议的研究旨在发现神经发育异常 导致有精神病风险的青少年的内在动机受损，以便加速 今后在早期发现、治疗和预防方面的努力。病理性动力丧失是一个关键的治疗方法- 精神分裂症患者残疾的抵抗力驱动因素。最近的研究表明，阴性症状包括 易患精神病的人在青春期常常会出现情绪失控。这些阴性症状 可能是疾病先兆的第一个指标，它们往往会持续存在，并导致较差的功能结果 即使是那些永远不会转变为坦率精神病的人。内在的动机缺陷似乎是 选择性地与临床损害有关，但它们在精神病风险中还没有被研究过，而且 大脑异常在很大程度上仍不为人所知。最近的研究表明，缺乏动力的人 精神分裂症与包括腹侧纹状体(VS)在内的大脑奖励回路功能低下有关。这 赤字不仅表现在对金钱奖励的反应上，也表现在对内在正确意识的反应上 认知表现，提供了内在动机受损的成像标记。然而，到目前为止，还没有 研究已经检验了精神病风险中内在动机的任何具体衡量标准，以及更大的 理解动机的内在和外在两个方面将是至关重要的。建议的五年 研究将在青年年龄的基线和两年的随访中对动机缺陷进行多水平的表型分析 16-23有精神病风险，利用和扩大来自费城神经发育中心的资源 一群人。这项工作将表征运动和发育的神经发育病理生理学。 预测性生物标记物，最终目标是改善精神病风险中的致残行为。这个 具体目标是：1)表征青少年对内在强化反应的神经回路；2) 确定大脑回路异常与精神病风险中的运动严重程度相关的横断面特征； 3)确定精神疾病风险中神经发育和运动障碍之间的纵向关系。

Project Summary Intrinsic motivation is the desire for internal satisfactions like curiosity, challenge, and mastery. It depends upon the ability to self-generate reward responses while performing an activity, even in the absence of any external rewards. The proposed study aims to discover the neurodevelopmental abnormalities contributing to impairment of intrinsic motivation in adolescents at risk for psychosis, in order to accelerate future efforts at early detection, treatment, and prevention. Pathological loss of motivation is a key treatment- resistant driver of disability in schizophrenia. Recent research shows that negative symptoms including amotivation often arise in adolescence in those who are vulnerable to psychosis. These negative symptoms can be the first indicators of the illness prodrome, and they tend to persist and cause poor functional outcomes even in those individuals who never convert to frank psychosis. Intrinsic motivation deficits appear to be selectively related to clinical impairment, but they have not been studied in psychosis risk, and the contributory brain abnormalities remain largely unknown. Recent research has shown that motivation deficits in schizophrenia are associated with hypofunction in brain reward circuitry including ventral striatum (VS). This deficit is not only evident in response to monetary reward, but also in response to internal awareness of correct cognitive performance, providing an imaging marker of impaired intrinsic motivation. However, so far no studies have examined any specific measures of intrinsic motivation in psychosis risk, and greater understanding of both intrinsic and extrinsic aspects of motivation will be essential. The proposed five-year study will conduct multilevel phenotyping of motivation deficits at baseline and at 2-year follow-up in youth age 16-23 at risk for psychosis, leveraging and extending resources from the Philadelphia Neurodevelopmental Cohort. This work will characterize the neurodevelopmental pathophysiology of amotivation and develop predictive biomarkers, with the ultimate goal of ameliorating disabling amotivation in psychosis risk. The specific aims are: 1) To characterize neural circuitry responsive to intrinsic reinforcement in adolescents; 2) To characterize brain circuit abnormalities associated cross-sectionally with amotivation severity in psychosis risk; and 3) To identify longitudinal relationships between neurodevelopment and amotivation in psychosis risk.