The mystery of the inheritance of schizophrenia has not yielded to the first generation of linkage studies. Our ability to discover predisposing genes for this disorder would be greatly enhanced if we had means with which to identify non-penetrant gene carriers and greater certainty concerning the boundaries of the clinical phenotype, how non-genetic influences (such as obstetric complications) contribute to liability, and the extent of genetic heterogeneity. Our preliminary work with siblings and offspring of schizophrenics has demonstrated associations between both familial and obstetric influences and disturbances in temporal and frontal lobe systems involved in attention, learning, memory, language, and executive functions. We now propose to extend this work by applying neuropsychological and neuroanatomical assessments to monozygotic (MZ) and dizygotic (DZ) twins concordant and discordant for schizophrenia We will conduct blind structured psychiatric interviews, blood tests for zygosity conformation, and comprehensive neuropsychological examinations on the total Finnish population of Mz and same-sex DZ twins born between 1940 and 1965 who are concordant and discordant for treated psychotic disorders (61 MZ and 107 DZ pairs), plus 60 Mz and 30 DZ control pairs. We will conduct magnetic resonance imaging scans for quantification of regional and whole brain volumes on 91 index pairs (61 Mz, 30 DZ) and 60 control pairs (30 MZ, 30 DZ). We will also collect and code the original prenatal clinic and obstetric hospital records for all of the pairs. This information will be used to examine: 1) the heritabilities of behavioral and anatomical indices of temporal and frontal lobe functioning and of putative schizophrenia-spectrum diagnostic categories, 2) the differential sensitivities of the temporal and frontal lobe measures as indicators of schizophrenia in twin pairs compared with measures of other neural systems, 3) expression of the cognitive and anatomical indicators among non-schizophrenic co- twins of schizophrenics compared with normal control twins, and 4) the contributions of obstetric complications to inter- and intra- pair differences in the cognitive and anatomical indicators and spectrum phenotypes.
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