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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH085096-02
Application #
7772244
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Wynne, Debra K
Project Start
2009-04-01
Project End
2013-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
2
Fiscal Year
2010
Total Cost
$179,582
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Walton, E; Hibar, D P; van Erp, T G M et al. (2017) Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium. Acta Psychiatr Scand 135:439-447
Yu, Linda Q; Lee, Sangil; Katchmar, Natalie et al. (2017) Steeper discounting of delayed rewards in schizophrenia but not first-degree relatives. Psychiatry Res 252:303-309
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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
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; Kable, Joseph W; Vandekar, Lillie et al. (2015) Common and Dissociable Dysfunction of the Reward System in Bipolar and Unipolar Depression. Neuropsychopharmacology 40:2258-68
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

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