Adolescent Neurodevelopment and Impaired Intrinsic Motivation in Psychosis Risk

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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.