This project is designed to test key hypotheses regarding the transmission of measurable nonsymptomatic characteristics of individuals that reflect their predisposition to schizophrenia. Identification of such vulnerability factors and of their interrelationships within and across biological relatives of patients with schizophrenia should allow us to accelerate our progress in detecting the nature of genetic contributions to schizophrenia. The next project phase will primarily focus on the interrelationships among neurocognitive dysfunctions mediated partially by the prefrontal cortex and the medial temporal region, subtle structural anomalies in these two regions, and liability to schizophrenia. Our search for vulnerability factors in neurocognitive functioning and regional brain structure is an attempt to identify intermediate phenotypes or """"""""endophenotypes"""""""" that are closer in causal chains to the effects of genes than is schizophrenia itself. Neurocognitive measures will involve the domains of attention, working memory, and consolidation of declarative memory. Morphometric indices from MRI will emphasize subtle volume and gray matter density alterations in the prefrontal cortex and medial temporal structures. Using family data, we will test whether the relationships between these brain structural anomalies, their hypothesized associated neurocognitive deficits, and schizophrenia spectrum disorder across first-degree relatives are consistent with one common underlying familial/genetic factor, or an alternative model in which there is more than one dimension of familial/genetic liability to schizophrenia. These goals will be addressed through data collection with schizophrenic probands and their first-degree relatives as well as with demographically matched community controls and their first-degree relatives.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH049716-08
Application #
6728205
Study Section
Special Emphasis Panel (ZRG1-SNEM-2 (01))
Program Officer
Lehner, Thomas
Project Start
1994-09-01
Project End
2007-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
8
Fiscal Year
2004
Total Cost
$586,205
Indirect Cost
Name
University of California Los Angeles
Department
Type
Other Domestic Higher Education
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Clark, Kristi A; Nuechterlein, Keith H; Asarnow, Robert F et al. (2011) Mean diffusivity and fractional anisotropy as indicators of disease and genetic liability to schizophrenia. J Psychiatr Res 45:980-8
Fogelson, D L; Asarnow, R A; Sugar, C A et al. (2010) Avoidant personality disorder symptoms in first-degree relatives of schizophrenia patients predict performance on neurocognitive measures: the UCLA family study. Schizophr Res 120:113-20

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