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Genetic Predictors of Neuropsychological and Functional Outcomes in Schizophrenia

精神分裂症神经心理和功能结果的遗传预测因子

基本信息

批准号：
8301790
负责人：
MING T. TSUANG
金额：
$ 59.13万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-15 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8301790
关键词：
Activities of Daily Living Address Affect Antipsychotic Agents Basic Science Behavioral Biological Biological Models Candidate Disease Gene Case Management Cognition Cognitive Communities DNA Repository Data Delusions Development Dimensions Disease model Distant Family Funding Future Gene Combinations Generations Genes Genetic Genetic Polymorphism Genetic Research Genome Genotype Goals Hallucinations Haplotypes Health Heritability Heterogeneity Impaired cognition Individual Intervention Knowledge Lead Link Measures Mediating Methods Minisatellite Repeats Modeling Molecular Molecular Profiling Multivariate Analysis Neurobehavioral Manifestations Ontology Outcome Outcome Measure Pathology Pathway interactions Patients Performance Pharmaceutical Preparations Probability Process Proteins Quantitative Trait Loci RNA Research Residual state Role Sampling Scanning Schizophrenia Single Nucleotide Polymorphism Societies Source Specificity Symptoms Technology Testing Time Validation Variant Wages Work base cognitive function cost depressive symptoms endophenotype functional disability functional outcomes gene interaction genome wide association study genome-wide high risk improved infancy insertion/deletion mutation interest neuropsychological new therapeutic target non-genetic novel strategies pleiotropism prevent psychosocial skills sound stem theories trait

项目摘要

DESCRIPTION (provided by applicant): Second-generation antipsychotic medications have proven quite effective in reducing symptoms of schizophrenia, but little progress has been made in improving behavioral outcomes of relevance to affected individuals, their families, and policymakers. A major goal of research on functional outcomes in schizophrenia should be to understand for whom and under what circumstances interventions aimed at improving functional abilities are effective. Currently, research on the assessment or improvement of functional outcomes is usually conducted in a primarily psychosocial context, while genetic studies are typically viewed as conceptually quite distant from such studies. However, it is highly likely that there are significant direct and/or indirect genetic influences on functional outcomes such as interpersonal skills, participation in community activities, and work skills. In this proposal, we seek to bridge these two seemingly distant ends of the spectrum of schizophrenia research. Our previous non-genetic research showed that cognitive functions and negative symptoms influence functional capacity, which in turn influences functional outcomes in schizophrenia. On the other hand, depressive symptoms independently predicted functional outcomes. Separate work by our group and others has demonstrated the heritability of many cognitive abilities and symptoms, and some progress has been made in identifying specific genes that influence some of these traits. We now propose to test the hypothesis that several specific genes will contribute to functional outcomes either through direct pathways or through their influences on cognition and symptoms. To accomplish this goal, we are proposing the following specific aims: 1) To determine which specific neuropsychological functions and symptom dimensions predict functional capacity and functional outcomes in schizophrenia; 2) To detect direct and mediated effects of genetic polymorphisms on real-world functioning, specifically focusing on: a) empirically supported candidate polymorphisms; b) all haplotype-tagging single nucleotide polymorphisms in and around empirically supported candidate genes; and c) ontologically related candidate genes; and 3) To establish multivariate models of functional outcomes, by: a) evaluating possible additive and epistatic interactions between candidate genes; and b) evaluating pleiotropic effects of each candidate gene. Linking basic research with the study of functional performance is only a first step toward future development of novel therapeutics targeted at aberrant proteins, but it is an important one. The development of such treatments is likely to be a long-term process, but one that could ultimately enhance psychosocial interventions to improve real-world functioning.