Dopamine antagonists are effective in the treatment of episodes of acute mania. Conversely, drugs which increase dopamine activity can induce a switch to mania. Therefore, disturbances in dopamine transmission and dopamine receptors might be implicated in the pathophysiology of bipolar affective disorder. We have carried out linkage studies between the susceptibility gene for affective disorder and polymorphisms of dopamine DRD2, DRD3, and DRD4 receptor genes in four Japanese pedigrees. Linkages of both DRD2 and DRD3 have been excluded, at least for dominant and intermediate models. The result for DRD2 was consistent with previous studies. For DRD3 this is the first exclusion of affective disorder from this locus in the 3q13.3 where DRD3 has been localized. On the other hand, our data could not exclude linkage of DRD4.
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