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 #
1R01MH079777-01
Application #
7233011
Study Section
Special Emphasis Panel (ZMH1-ERB-A (04))
Program Officer
Mayo, Donna J
Project Start
2007-07-25
Project End
2011-05-31
Budget Start
2007-07-25
Budget End
2008-05-31
Support Year
1
Fiscal Year
2007
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
Joshi, Yash B; Breitenstein, Barbara; Tarasenko, Melissa et al. (2018) Mismatch negativity impairment is associated with deficits in identifying real-world environmental sounds in schizophrenia. Schizophr Res 191:5-9
Bismark, Andrew W; Thomas, Michael L; Tarasenko, Melissa et al. (2018) Relationship between effortful motivation and neurocognition in schizophrenia. Schizophr Res 193:69-76
Thomas, Michael L; Green, Michael F; Hellemann, Gerhard et al. (2017) Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia. JAMA Psychiatry 74:37-46
Light, Gregory A; Swerdlow, Neal R; Thomas, Michael L et al. (2015) Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: characterization of demographic, clinical, cognitive, and functional correlates in COGS-2. Schizophr Res 163:63-72
Rissling, Anthony J; Miyakoshi, Makoto; Sugar, Catherine A et al. (2014) Cortical substrates and functional correlates of auditory deviance processing deficits in schizophrenia. Neuroimage Clin 6:424-37
Perez, Veronica B; Swerdlow, Neal R; Braff, David L et al. (2014) Using biomarkers to inform diagnosis, guide treatments and track response to interventions in psychotic illnesses. Biomark Med 8:9-14
Light, Gregory; Greenwood, Tiffany A; Swerdlow, Neal R et al. (2014) Comparison of the heritability of schizophrenia and endophenotypes in the COGS-1 family study. Schizophr Bull 40:1404-11
Young, J W; Geyer, M A; Rissling, A J et al. (2013) Reverse translation of the rodent 5C-CPT reveals that the impaired attention of people with schizophrenia is similar to scopolamine-induced deficits in mice. Transl Psychiatry 3:e324
Rissling, Anthony J; Park, Sung-Hyouk; Young, Jared W et al. (2013) Demand and modality of directed attention modulate ""pre-attentive"" sensory processes in schizophrenia patients and nonpsychiatric controls. Schizophr Res 146:326-35
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

Showing the most recent 10 out of 29 publications