This RFA supports studies designed to find genes that relate to functional """"""""behavioral phenotypes of relevance to patients, their families, and policymakers."""""""" In response to this RFA, this application will extend the existing body of information regarding the genetics of schizophrenia with a unique focus on understanding the genetic basis for functional deficits in schizophrenia patients. The PI has assembled a team of experts in the areas of schizophrenia research, functional assessment, neurophysiological and neurocognitive assessment, statistical genetics and structural equation modeling. The research team will have access to substantial existing infrastructure and patient resources via two mature and highly productive schizophrenia research programs. Cohorts of 400 schizophrenia patients and 100 nonpsychiatric comparison subjects (NCS) will be characterized by clinical, neurocognitive, neurophysiological, and multi- dimensional functional assessments. From these functional assessments, core and dissociable functional deficits in schizophrenia patients will then be identified via principal components analysis (PCA). PCA will capture the core features of the deficits that are responsible for the difficulties faced by schizophrenia patients as they """"""""navigate"""""""" through a maze of functional challenges in real-world day-to-day living. These features will be used as a means of understanding the complex genetic architecture underlying functional impairment in this disorder. The pathways from gene to function, including possible mediating and moderating neurobiological and neuropsychological processes, will then be identified via structural equation modeling. Thus, one key final product of this work will be the identification of core functional deficits in schizophrenia patients and the specification of genes that substantially contribute to those core deficits so that both gene-function and the possible biological pathways by which genes impact behavior and thereby regulate real world functioning will be explicated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH079777-04
Application #
7845512
Study Section
Special Emphasis Panel (ZMH1-ERB-A (04))
Program Officer
Morris, Sarah E
Project Start
2007-07-25
Project End
2013-05-31
Budget Start
2010-06-01
Budget End
2013-05-31
Support Year
4
Fiscal Year
2010
Total Cost
$347,625
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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Light, Gregory A; Swerdlow, Neal R; Rissling, Anthony J et al. (2012) Characterization of neurophysiologic and neurocognitive biomarkers for use in genomic and clinical outcome studies of schizophrenia. PLoS One 7:e39434
Thorp, Steven R; Sones, Heather M; Glorioso, Danielle et al. (2012) Older patients with schizophrenia: does military veteran status matter? Am J Geriatr Psychiatry 20:248-56

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