Genetic studies of manic-depressive illness

The Unipolar (UP) and Bipolar (BP) forms of affective illness appear not to be genetically and physiologically identical, although the degree of overlap in family and biologic pharmacologic studies is considerable. It appears likely that at least a subgroup of UP illness shares its genetic diathesis with BP illness. The hypothesis of monoamine alterations associated with the affective illnesses has led to studies of genetics of enzymes of monoamine metabolism as observed in peripheral blood, erythrocyte catechol-O-methyl-transferase (COMT), platelet monoamine oxidase (MAO), and plasma dopamine-beta-hydroxylase (DBH). These are under genetic control and show some differences between patients with affective illness and controls, but these differences have not been consistently propagated through families along with the disorder. Linkage of BP illness to markers on the X-chromosome has been reported, but the evidence has internal inconsistencies which must be resolved before the phenomenon can be accepted. Association of BP illness with specific HLA types has also been reported, but efforts at replication have been unsuccessful. Mathematical models of transmission applied to family study data do not consistently support the same mode of transmission when applied to data collected at different centers.