Developmental Trajectories of Negative Symptoms in Schizophrenia

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION (provided by applicant): 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 include: 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 resource for the community including individuals with schizophrenia, their families and care providers.