Methodological issues in molecular genetic studies of mental disorders.

The development of methodologies for assaying genetic variation at high resolution throughout the genome has revolutionized the search for susceptibility genes for common diseases. This search, however, has been less successful in psychiatry than in other areas of medicine. It is hypothesized that the imprecision and uncertain validity of psychiatric diagnoses are major factors in this disappointing progress. Here we discuss the methodologies employed for genetic investigation of mental disorders, including phenotyping strategies, approaches to genetic mapping, and use of animal models of psychopathology.