Molecular Genetic Study on Schizophrenia

Schizophrenia is a disease of the brain that manifests with multiple signs and symptoms involving thought, perception, emotion, movement, and behavior. A number of studies have evidenced that schizophrenia is a familial disorder and that the familial aggregation is due largely to genetic factors. In order to find specific genes that confer susceptibility to schizophrenia, we employed two fundamentally distinct strategies: tests of association and linkage. The former was carried out using unrelated schizophrenic probands as subjects while the later is a family-based study. During the past two years, we have collected 130 muclear families each with no less than two individuals afflicted with schizophrenia, and 50 sporadic schizophrenic patients. Candidate genes with neuropsychopharmacological significance, such as genes of dopamine receptors and androgen receptors, were chosen as markers. Polymorphism of these genes were analyzed and their association with schizophrenia were tested. Genes with high polymorphic informative index such as DRD4 were used as marker loci in the sib-pair analysis. Advanced analysis using anonymous polymorphic markers and combining our samples with other races have been done. Collaborating with international schizophrenic gene hunters, the Taipei Group of Schizophrenic Genetic Study will probe further refining of schizophrenia phenotype and specific responsible genes. The present results reveal encouraging findings of linkage with anonymous markers at Chromosome 6p, 8p, 11, 19 and 22q. The candidate gene approach has not found sustaining evidence of association yet. We believe our approach, complemented by basic neuropsychopharmacological studies and refined phenotype definition, will offer substantial promise for finding at least some specific genes that underline the susceptibility to schizophrenia.

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