A genetic study of manic-depressive disorder among the old order Amish of Pennsylvania.

A genetic and epidemiological study of the genetic linkage of major affective disorders is being conducted for over 10 years among the Old Order Amish in Pennsylvania, a genetic isolate leading a uniform pattern of life. An autosomal dominant mode of inheritance was found to be most consistent with the transmission patterns in the Amish families. The advent of DNA technology suddenly revolutionised the field of genetic linkage studies. The finding that major affective disorders were linked to DNA markers on the short arm of chromosome 11 was reported in "Nature" as a first report of the location of a dominant gene conferring a strong predisposition to a common psychiatric condition. A strong linkage was shown to two DNA markers, insulin and the cellular oncogene Haras-1. Several other candidate genes should also be studied, for example, the structural gene encoding for tyrosine hydroxylase (TH gene). It is important to ask why certain people "at risk" remain well, whereas others develop major affective disorders. An effort is also underway to test whether other forms of affective disorder are part of the same genetic spectrum. The Amish study has to maintain a research strategy of interface between psychiatry and other scientific disciplines.