This project addresses two major bottlenecks to progress in detecting susceptibility genes for schizophrenia: 1) the probable genetic heterogeneity of the schizophrenia disorders and 2) uncertainty over the boundaries of the schizophrenia phenotype. This project was stimulated by the hypothesis that early (childhood) onset schizophrenia is associated with increased genetic loading for this disorder. The proposed project will replicate and extend important findings from the first phase of this project indicating that there is a significantly increased familial aggregation of schizophrenia, schizophrenia spectrum personality disorders, and certain neurocognitive impairments in families of probands with childhood-onset schizophrenia compared to families of community control and adult-onset schizophrenia probands. The long-term stability and predictive validity of schizophrenia spectrum diagnoses and neurocognitive impairments detected during adolescence in the siblings of probands with childhood-onset schizophrenia will be determined. Hypotheses about the role obstetric complications play in triggering an early onset of schizophrenia and about the relation between history of obstetric complications and impaired functioning of the hippocampal/temporal lobes will be tested. The hypothesis that relatives of probands with childhood-onset schizophrenia who have neurocognitive impairments will show subtle signs of formal thought disorder impaired discourse and impairments in working memory will also be tested. The proposed project will test a number of genetic models of the familial transmission of putative measures of the extended schizophrenia phenotype, including analyses to examine the evidence for a single vulnerability factor versus two familial vulnerability factors (one influencing mainly neurocognitive measures and the other mainly schizophrenia spectrum diagnosis. Whether chromosomal regions found in prior research to be associated with susceptibility to schizophrenia are associated with susceptibility to childhood-onset schizophrenia and potentially associated phenotypes (including neurocognitive impairments) will be determined.
These specific aims will be addressed by rediagnosing all previously studied (N = 50) probands and relatives with childhood-onset schizophrenia to confirm their original diagnoses, enrolling an additional 90 new families of probands with childhood-onset schizophrenia and 60 families of probands of community controls, and capitalizing on data from 120 families of adult-onset schizophrenia probands which has already been collected. We will conduct a genetic linkage analysis to determine whether putative susceptibility genes identified in prior research are associated with the presence of schizophrenia spectrum disorders and/or neurocognitive impairments in families of probands with childhood-onset schizophrenia. DNA will be retained for use in future linkage, linkage disequilibrium, association and other studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH045112-10
Application #
6391949
Study Section
Special Emphasis Panel (ZRG1-SNEM-2 (01))
Program Officer
Moldin, Steven Owen
Project Start
1989-08-15
Project End
2005-06-30
Budget Start
2001-07-01
Budget End
2002-06-30
Support Year
10
Fiscal Year
2001
Total Cost
$561,387
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Chen, Qiaolin; Sugar, Catherine A; Weiss, Robert E (2018) A Bayesian confirmatory factor model for multivariate observations in the form of two-way tables of data. Stat Med 37:1696-1710
Asarnow, Robert F; Forsyth, Jennifer K (2013) Genetics of childhood-onset schizophrenia. Child Adolesc Psychiatr Clin N Am 22:675-87
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
Fogelson, D L; Nuechterlein, K H; Asarnow, R A et al. (2007) Avoidant personality disorder is a separable schizophrenia-spectrum personality disorder even when controlling for the presence of paranoid and schizotypal personality disorders The UCLA family study. Schizophr Res 91:192-9
Subotnik, Kenneth L; Asarnow, Robert F; Nuechterlein, Keith H et al. (2005) MMPI vulnerability indicators for schizophrenia and attention deficit disorder: UCLA family study of biological parents of offspring with childhood-onset schizophrenia or ADHD. Behav Genet 35:159-75
Fogelson, David L; Nuechterlein, Keith H; Asarnow, Robert F et al. (2004) Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. Schizophr Res 68:309-17
Asarnow, Robert F; Nuechterlein, Keith H; Asamen, Joy et al. (2002) Neurocognitive functioning and schizophrenia spectrum disorders can be independent expressions of familial liability for schizophrenia in community control children: the UCLA family study. Schizophr Res 54:111-20
Nuechterlein, Keith H; Asarnow, Robert F; Subotnik, Kenneth L et al. (2002) The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study. Schizophr Res 54:121-30
Subotnik, Kenneth L; Goldstein, Michael J; Nuechterlein, Keith H et al. (2002) Are communication deviance and expressed emotion related to family history of psychiatric disorders in schizophrenia? Schizophr Bull 28:719-29
Asarnow, Robert F; Nuechterlein, Keith H; Subotnik, Kenneth L et al. (2002) Neurocognitive impairments in nonpsychotic parents of children with schizophrenia and attention-deficit/hyperactivity disorder: the University of California, Los Angeles Family Study. Arch Gen Psychiatry 59:1053-60

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