Exclusion of close linkage of bipolar disorder to the dopamine D3 receptor gene in nine Australian pedigrees

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Abstract

The recently cloned dopamine D3 receptor (DRD3) gene is of potential relevance to the aetiology of bipolar disorder because of an almost exclusive expression in limbic tissue, the region of the brain putatively responsible for control of emotion. We therefore aimed to determine whether bipolar disorder in nine pedigrees (with 171 members) was linked to this receptor gene, which has been mapped to chromosomal region 3q 13.3. Linkage of bipolar disorder and recurrent depression to the DRD3 gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness (ranging 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 ‘sporadic’ (non-genetic) presentations of illness were incorporated in the analysis.

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      Negative results have also been reported in unipolar depression (Manki et al 1996; Massat et al 2002). Most studies of the dopamine D3 receptor gene, DRD3, have not correlated DRD3 with unipolar or bipolar illness (Frisch et al 1999; Gomez-Casero et al 1996; Heiden et al 2000; Manki et al 1996; Massat et al 2002; Mitchell et al 1993; Serretti et al 2000; Souery et al 1996). However, there are reports of an increased frequency of specific DRD3 alleles in bipolar families (Parsian et al 1995) and unipolar patients (Dikeos et al 1999).

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