A Novel Model of Schizophrenia Age-of-Onset Data Challenges the Conventional Interpretations of the Discordance in Monozygote Twin Studies.

The relative importance of genetics and the environment in causing schizophrenia is still being debated. Although the high proportion of monozygote cotwins of schizophrenia patients who are discordant suggests that there may be a significant environmental contribution to the development of schizophrenia, this discordance is predicted by an accumulative multimutation model of schizophrenia onset constructed here implying a genetic origin of schizophrenia. In this model, schizophrenics are viewed as having been born with the genetic susceptibility to develop schizophrenia. As susceptible gene carriers age, they randomly accumulate the necessary mutations to cause schizophrenia, the last needed mutation coinciding with disease onset. The mutation model predicts that the concordance rate in monozygote twin studies will monotonically increase with age, theoretically approaching 100% given sufficient longevity. In dizygote cotwins of schizophrenia patients, the model predicts that at least 71% of cotwins are incapable of developing schizophrenia even though every cotwin and their schizophrenic twin shared a similar early environment. The multimutation model is shown to fit all of the monozygote and dizygote concordance rate data of the principle classical twin studies completed before 1970 considered in this paper. Thus, the genetic hypothesis of schizophrenia can be tested by bringing these studies up to date.