The goal of the Conte Center is to probe brain circuitry that underlies the core negative symptoms of schizophrenia, diminished emotional expressivity and social drive, in humans and mice. The Center will enhance and expand the Penn Schizophrenia Research Center, a nucleus of joint discovery and infrastructure directed at understanding neural substrates of schizophrenia. It capitalizes on new collaborations and advances in the field, pursuing translational aims with multi-level complementary approaches focused on dissecting major phenotypic features of schizophrenia that are of clinical importance yet poorly understood.
Major aims i nclude: 1. Relate negative symptoms and social dysfunction in adolescence to neurobehavioral and neurophysiological measures of amygdala circuit dysfunction during aversive learning. 2. Determine the role of amygdala circuit NMDAR1 signaling in social-emotional behavior during development. 3. Determine the role of NMDAR1 signaling in amygdala physiology and social behavior in vivo. 4. Delineate NMDA receptor dysfunction in the postmortem amygdala of patients in relation to modulation of synaptic connectivity. 5. Investigate genomic underpinnings for NMDAR hypofunction and its association with phenotypes of impaired affective and social functioning during development. The Center will have five Projects: I. Neurophysiology of aversive learning and social dysfunction in youths;II. Early development of social and emotional behaviors and amygdala function in mice;III. Electrophysiological markers of social function;IV. NMDA receptor hypofunction in the amygdala;V. Integrative genomic analyses of NMDA receptor pathway in schizophrenia. Two Cores will support the Projects: Core A Administration and Core B Data and Biostatistics. The Center capitalizes on the collaborative expertise of investigators and resources at Penn for conducting this challenging interdisciplinary translational research. In addition to advancing its scientific agenda, the Center will be an educational resource for faculty, fellows, residents, graduate and undergraduate students. It will also be a clinical and educational.

Public Health Relevance

Negative symptoms are core features of schizophrenia and a critical unmet treatment need that limits functional recovery. The Center fosters an interdisciplinary approach, applying multiple levels of analysis, spanning behavior, circuits and genes in humans and model systems toward advancing the understanding of a significant scientific gap. This effort may contribute to early identification, development of biomarkers and novel therapeutics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
3P50MH096891-03S1
Application #
8849542
Study Section
Special Emphasis Panel (ZMH1-ERB-S (02))
Program Officer
Garvey, Marjorie A
Project Start
2012-09-01
Project End
2017-05-31
Budget Start
2014-07-08
Budget End
2015-05-31
Support Year
3
Fiscal Year
2014
Total Cost
$158,400
Indirect Cost
$59,400
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Fromer, Menachem; Roussos, Panos; Sieberts, Solveig K et al. (2016) Gene expression elucidates functional impact of polygenic risk for schizophrenia. Nat Neurosci 19:1442-1453
White, R S; Siegel, S J (2016) Cellular and circuit models of increased resting-state network gamma activity in schizophrenia. Neuroscience 321:66-76
Moore, Tyler M; Reise, Steven P; Roalf, David R et al. (2016) Development of an itemwise efficiency scoring method: Concurrent, convergent, discriminant, and neuroimaging-based predictive validity assessed in a large community sample. Psychol Assess 28:1529-1542
Roalf, David R; Quarmley, Megan; Elliott, Mark A et al. (2016) The impact of quality assurance assessment on diffusion tensor imaging outcomes in a large-scale population-based cohort. Neuroimage 125:903-19
Ferri, Sarah L; Kreibich, Arati S; Torre, Matthew et al. (2016) Activation of basolateral amygdala in juvenile C57BL/6J mice during social approach behavior. Neuroscience 335:184-94
Egbujo, Chijioke N; Sinclair, Duncan; Hahn, Chang-Gyu (2016) Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia. Curr Psychiatry Rep 18:77
Carlson, G C; Lin, R E; Chen, Y et al. (2016) Dexras1 a unique ras-GTPase interacts with NMDA receptor activity and provides a novel dissociation between anxiety, working memory and sensory gating. Neuroscience 322:408-15
Moore, T M; Martin, I K; Gur, O M et al. (2016) Characterizing social environment's association with neurocognition using census and crime data linked to the Philadelphia Neurodevelopmental Cohort. Psychol Med 46:599-610
Gur, Ruben C; Gur, Raquel E (2016) Social cognition as an RDoC domain. Am J Med Genet B Neuropsychiatr Genet 171B:132-41
Barz, Claudia S; Bessaih, Thomas; Abel, Ted et al. (2016) Sensory encoding in Neuregulin 1 mutants. Brain Struct Funct 221:1067-81

Showing the most recent 10 out of 50 publications