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Bipolar disorder is a major psychiatric illness that has evidence for a significant genetic contribution toward its development. In recent years, the BalI RFLP (restriction fragment length polymorphism) in the dopamine D3 receptor gene has been examined as a possible susceptibility factor for both schizophrenia and bipolar disorder. While analysis in schizophrenia has produced examples of increased homozygosity in patients, less encouraging results have been found for bipolar disorder. Recently, however, a family-based association study has found a significant excess of allele 1 and allele 1–containing genotypes in transmitted alleles to bipolar probands over nontransmitted controls. In a large bipolar case control sample (n = 454), we have been unable to replicate the family-based association study (chi-square = 0.137, P = 0.71, 1 df) or detect an effect similar to the positive homozygosity findings in schizophrenia (chi-square = 0.463, P = 0.50, 1 df). A meta-analysis of previous association studies also revealed no difference in allele distributions between bipolar patients and controls for this polymorphism in ethnically homogeneous samples (odds ratio, OR, = 1.04; P = 0.60; 95% confidence interval, CI, = 0.89–1.20). In view of this evidence, we conclude that variation at the BalI RFLP is not an important factor influencing the susceptibility to bipolar disorder. It remains possible, however, that other sequence variations within the DRD3 gene could play a role. © 2001 Wiley-Liss, Inc.

A number of lines of evidence point to the possible involvement of estrogen pathways in the pathophysiology of bipolar disorder in general and puerperal psychosis in particular. There is strong evidence from clinical, follow-up, and genetic studies to support the hypothesis that most cases of puerperal psychosis are manifestations of an affective disorder diathesis with a puerperal trigger and that genes influence susceptibility to both diathesis and trigger. The nature of the trigger is unknown but in view of the abrupt onset at a time of major physiological change it is widely believed that biological, probably hormonal, mechanisms are of paramount importance, with estrogen receiving the most attention to date. We have undertaken a case control association study of bipolar disorder and puerperal psychosis at two known polymorphisms within the estrogen receptor α gene (ESR 1) in a sample of 219 unrelated bipolar probands and 219 controls. We could exclude these polymorphisms from an important contribution to susceptibility to bipolar disorder with a high level of confidence. We found no support for the hypothesis that they contribute specific susceptibility to the puerperal trigger, but due to the small numbers of puerperal probands (n = 26) no firm conclusions can be drawn regarding their involvement in puerperal psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:850–853, 2000. © 2000 Wiley-Liss, Inc.