High-risk-for-schizophrenia research: sampling bias and its implications

The use of parental diagnosis in risk-for-schizophrenia identification has inadvertently resulted in two major sampling biases: an overrepresentation of females among index parents and a 100 percent concordance for schizophrenia between affected target offspring and their parents. The overrepresentation of females among index parents may increase the heterogeneity of the schizophrenic sample by virtue of either misdiagnosis or inclusion of atypical, schizoaffective schizophrenics. Thus, the target samples studied in current high-risk research are not only psychometrically unrepresentative of all schizophrenics, but also may contain a substantial number of offspring with atypical, largely affective schizophrenias. Complementary risk identification strategies are discussed, and the nature of the schizophrenias as a heterogeneous group of disorders is emphasized.