LINKAGE ANALYSIS OF THE D1-DOPAMINE RECEPTOR GENE AND MANIC-DEPRESSION IN 6 FAMILIES

Disturbances in dopaminergic activity may play an important role in the pathogenesis of manic depression. The effects of dopamine are mediated by at least five G protein coupled receptors, Dl, D2, D3, D4 and D5. Recently, three separate research groups have cloned and characterized the Dl dopamine receptor, which localizes to 5q35.1. We undertook a linkage analysis between the Dl receptor polymorphisms and manic depression in six families in which segregation of the disease was consistent with autosomal dominant inheritance. A highly polymorphic flanking DNA marker, CRI-L1200, was also analyzed as the Dl gene RFLPs were relatively uninformative in our families. Multipoint analyses of manic depression and these DNA markers resulted in lod scores of less than -3.0 at the D1 locus, indicating that the Dl dopamine receptor gene does not confer an inherited susceptibility to manic-depressive illness in the families studied.