Genetic overlap between schizophrenia and selective components of executive function

Abstract

Impairments in selective components of executive function are seen in unaffected family members of patients with schizophrenia and may represent the biological expression of increased genetic risk. However no study has quantified the extent to which liability to schizophrenia overlaps genetically with that of executive dysfunction. We studied a total of 418 monozygotic and dizygotic twins, including pairs concordant and discordant for schizophrenia. Participants completed the trail making test part A and verbal fluency tasks to assess initiation, TMT part B to test mental flexibility, and the WAIS-III to assess general intellectual function. Bivariate genetic modeling was used to investigate whether selective measures of executive processing are genetically linked to schizophrenia and to quantify the genetic (i.e. heritability) and environmental contributions to their variability. Genetic influences contributed substantially to test variance for initiation and mental flexibility. Genetic factors were the main source of the phenotypic correlations between schizophrenia and these processes. Verbal fluency tasks shared a large genetic correlation with IQ whilst TMT scales did not, suggesting that they measure discreet processes, and therefore indexing discreet endophenotypes. Both verbal fluency and mental flexibility meet some of the criteria for endophenotypes, but our data suggest that mental flexibility is a purer cognitive process sharing very little common variance with general intellectual functioning. The inclusion of this mental flexibility phenotype in linkage or association analysis should improve the power to detect susceptibility genes for schizophrenia.