A clinico-genetic study of psychiatric disorder in Huntington's chorea

The introduction in 1985 of a genetic linkage test programme to identify asymptomatic heterozygotes among subjects at 50% initial risk for Huntington's chorea required a review of all cases of Huntington's chorea and their families referred to the Department of Medical Genetics of the Oxford Regional Health Area (population 2.5 million). From a representative sample of these subjects, psychiatric data were collected to estimate the frequency and time of onset of functional psychiatric illness and behaviour disorder. The rationale and method of the linkage test is described. The frequency of functional psychiatric disorder found was compared with that reported for the general population and for Alzheimer's disease. The role in relation to the aetiology of functional psychiatric disorder (1) of the Huntington's chorea gene and (2) of the family disturbance produced, was investigated by comparison between the frequency of functional psychiatric disorder in populations containing different proportions of heterozygotes as shown by (a) the manifestation of Huntington's chorea, and (b) the result of the genetic linkage analysis. In order to investigate the influence of the onset of Huntington's chorea on the production of functional psychiatric disorder the time of onset of the various functional psychiatric disorders was compared between asymptomatic subjects at 50% risk for Huntington's chorea and their cohabiting spouses who were assumed to be at zero risk and who shared their environment. It is concluded that possessing the Huntington's chorea gene: (1) has no influence on the production of functional psychiatric disorder in asymptomatic subjects at risk for Huntington's chorea; and (2) increases the tendency to major depressive disorder in subjects already affected with physical signs of Huntington's chorea.