Neuropsychological Endophenotypes in Schizophrenia and Bipolar I Disorder: Yields from the Finnish Family and Twin Studies

Abstract

This chapter summarizes findings related to the neuropsychology of schizophrenia and bipolar disorders and the use of neuropsychological functions as endophenotypes in genetic analyses in Finnish family and twin studies. The endophenotypes are the intermediate factors between the phenotype and genotype, and they are assumed to be contributed to by fewer genes than the clinical phenotypes of the complex psychiatric disorders. There is a long tradition of research both on schizophrenia and bipolar disorder in Finland, and large population based family and twin samples for clinical, neuropsychological, and genetic studies have been collected. In these samples, we have used the endophenotype strategy, first evaluating whether the neuropsychological test variables fulfill the criteria for valid endophenotypes and then using them in genomewide linkage and candidate gene association analyses. In the genomewide linkage analysis, several variables related to learning and memory were shown to enhance the linkage as compared with using the categorical clinical phenotype. Moreover, working memory, and several variables from the learning and memory process were found to be heritable and to show significant associations with DISC1, reelin, and AKT1 in schizophrenia, and with DISC1 in bipolar disorder, in which DAOA also associated with visuospatial ability. Although the associations are modest, our results support the validity of the endophenotype approach in investigating the genetic etiology of severe mental illnesses. Future studies should further evaluate endophenotypes derived from neuroscience to obtain optimal variables that help in tracking multiple genes of small effect predisposing to developing the complex psychiatric disorders.