EXCLUSION OF CLOSE LINKAGE OF BIPOLAR DISORDER TO THE DOPAMINE-D(3) RECEPTOR GENE IN 9 AUSTRALIAN PEDIGREES

The recently cloned dopamine D3 receptor (DRD3) gene is of potential r elevance to the aetiology of bipolar disorder because of an almost exc lusive expression in limbic tissue, the region of the brain putatively responsible for control of emotion. We therefore aimed to determine w hether bipolar disorder in nine pedigrees (with 171 members) was linke d to this receptor gene, which has been mapped to chromosomal region 3 q 13.3. Linkage of bipolar disorder and recurrent depression to the DR D3 gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was exami ned using a series of levels of definitions of affective illness (rang ing from bipolar I alone to all affective disorders). Close linkage to the DRD3 gene was strongly excluded using each model and definition, and these conclusions persisted when a wide range of rates of 'sporadi c' (non-genetic) presentations of illness were incorporated in the ana lysis.