This Career Development Award application is entitled """"""""Functional Neuroiniaging of Reward and Motivation Deficits in Schizophrenia."""""""" The candidate will be an Assistant Professor of Psychiatry at the University of Pennsylvania. He will be mentored by Drs. Raquel Gur and Ruben Gur, renowned for their research on emotional and cognitive deficits of schizophrenia. The proposal is motivated by the candidate's prior experiences studying the neurochemistry of reward as an MD-PhD student, caring for patients with schizophrenia as a psychiatrist, and using functional MRI (fMRI) to study schizophrenia pathophysiology as a postdoctoral fellow. Negative symptoms (social, motivational, and emotional deficits) of schizophrenia have a strong impact on functional disability. They present an urgent need for better understanding and more effective treatments. The study will focus on the ventral striatum (VS), which plays a key role in converting rewarding experiences into future motivation. The candidate's preliminary data links VS hypofunction to global severity of negative symptoms. The proposed study will test the candidate's hypothesis that VS hypofunction will be specifically related to low motivation and reduced expectations of pleasure. VS activity will be measured using fMRI while subjects perform simple social and nonsocial reward tasks. A detailed negative symptom profile will be obtained, together with measures of nicotine dependence and depression, as these common comorbidities also impact VS function. First-degree family members, who often exhibit negative symptomatology, will be studied alongside the patients themselves. This will allow findings to be explored independently of medication and chronic illness effects. The study is specifically designed to develop the candidate's scientific expertise and independent research trajectory in line with his career goals. In addition, the candidate will pursue specialized training through coursework and mentored learning in the following areas: fMRI techniques, affective neuroscience, pharmacology, statistics, and the design of effective, ethical clinical trials. The proposed work will prepare the candidate for an independent research career focused on improving the understanding and treatment of schizophrenia.

Public Health Relevance

Schizophrenia is a common brain disorder that imposes enormous costs on patients, families, and society. Symptoms of low motivation and reduced pleasure contribute to chronic social and occupational impairment. This proposal aims to clarify the neurobiology of these deficits, and prepare the candidate for a career using powerful brain imaging technology to develop more effective treatments for patients with schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Wynne, Debra K
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University of Pennsylvania
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Sharma, Anup; Satterthwaite, Theodore D; Vandekar, Lillie et al. (2016) Divergent relationship of depression severity to social reward responses among patients with bipolar versus unipolar depression. Psychiatry Res 254:18-25
Hershenberg, Rachel; Satterthwaite, Theodore D; Daldal, Aylin et al. (2016) Diminished effort on a progressive ratio task in both unipolar and bipolar depression. J Affect Disord 196:97-100
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Wolf, Daniel H; Satterthwaite, Theodore D; Calkins, Monica E et al. (2015) Functional neuroimaging abnormalities in youth with psychosis spectrum symptoms. JAMA Psychiatry 72:456-65
Satterthwaite, Theodore D; Wolf, Daniel H; Roalf, David R et al. (2015) Linked Sex Differences in Cognition and Functional Connectivity in Youth. Cereb Cortex 25:2383-94
Satterthwaite, Theodore D; Shinohara, Russell T; Wolf, Daniel H et al. (2014) Impact of puberty on the evolution of cerebral perfusion during adolescence. Proc Natl Acad Sci U S A 111:8643-8
Satterthwaite, Theodore D; Vandekar, Simon; Wolf, Daniel H et al. (2014) Sex differences in the effect of puberty on hippocampal morphology. J Am Acad Child Adolesc Psychiatry 53:341-50.e1
Wolf, Daniel H; Satterthwaite, Theodore D; Kantrowitz, Jacob J et al. (2014) Amotivation in schizophrenia: integrated assessment with behavioral, clinical, and imaging measures. Schizophr Bull 40:1328-37
Satterthwaite, Theodore D; Elliott, Mark A; Gerraty, Raphael T et al. (2013) An improved framework for confound regression and filtering for control of motion artifact in the preprocessing of resting-state functional connectivity data. Neuroimage 64:240-56

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