Introduction

The overlapping spectra of clinical presentation in bipolar disorder and schizophrenia described elsewhere in this volume suggest overlapping etiology and a spectrum of pathophysiological mechanisms. Genetic studies provide a powerful route to dissecting such pathophysiological mechanisms and elucidating the etiological relationship between these syndromes. Many genetic traits display phenotypes with a similar spectrum presentation, better described as a quantitative genetic trait than a Mendelian one. Yet both bipolar disorder and schizophrenia have characteristics of both quantitative and dichotomous genetic traits, as does the relationship between the disorders. Various studies of families and twins have been conducted in order to understand the genetic relationships between these psychotic illnesses and the most appropriate genetic model. More recently, these questions have been informed by molecular genetic methods to identify the specific susceptibility genes. Together these data suggest that the complexity of the overlapping phenotype is a reflection of complex genetic underpinnings. In this chapter, these possible models and family studies will be reviewed, as well as the more recent molecular genetic studies. Possible models and genetic mechanisms responsible for these spectra will be discussed.

Genetic models

Single major locus models

The genetic models to be considered fall into two major categories. In the Mendelian or major locus model, one gene of large effect is primarily responsible for the genetic susceptibility to illness in each affected individual.