Psychiatric Disorders

Complex disorders such as schizophrenia and bipolar disorder usually do not follow classic Mendelian inheritance patterns, but they can frequently mimic a pattern of autosomal dominance with reduced penetrance. Explanatory models for these complex disorders include multifactorial inheritance (multiple genes with nongenetic components) and epistasis (few genes acting jointly). But, since the mode of inheritance is unknown, a range of analytic methods must be used to study the genetic aspects of these disorders. Linkage and allelic association studies are frequently methods used to investigate possible causal genes for complex psychiatric disorders. However, in large populations, there are likely to be several causal or susceptibility genes and nongenetic causes, as well.

Historically, the first positive linkage study to have a major impact on psychiatry was the linkage of bipolar disorder to chromosome eleven in a large Amish family. However, a later assessment of the family failed to confirm the original linkage results. A similar situation occurred with the failure to replicate the findings of an early report of linkage of schizophrenia to a region on chromosome 5 in Icelandic and British families.

As a result of these early problems, it became clear that more rigorous methodology, such as more careful clinical phenotyping, the use of more genetic markers, and new analytic techniques would be necessary if molecular approaches were to be used in finding genes involved in psychiatric disorders.

Clinical genetic (family, twin, and adoptive) studies have been attempted in a large number of psychiatric disorders. However, these studies generally provide no information about what genes are involved in the disorder. Molecular studies are necessary to begin to elucidate this data. Schizophrenia and bipolar disorder are examples of psychiatric disorders that have been studied for nearly two decades.