Exclusion of close linkage of bipolar disorder to dopamine D1 and D2 receptor gene markers

Philip Mitchell*, Lisa Selbie, Brent Waters, Jennifer Donald, Christina Vivero, Michele Tully, John Shine

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

Abstract

A potential role of dopamine in bipolar disorder has been suggested by several strands of evidence, namely the ability of dopaminergic agonists to induce mania and the effects of lithium, carbamazepine and the antipsychotics on central dopamine receptors and/or turnover. We therefore aimed to determine if bipolar disorder in two large bipolar pedigrees was linked to the recently cloned dopamine D1 (DRD1) and D2 (DRD2) receptors. (These have been mapped to chromosomal regions 5q35.1 and 11q22.3-q23, respectively). Linkage of bipolar disorder and recurrent depression to DRD1 and DRD2 was tested using a series of genetic models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective status (ranging from bipolar I alone to all affective illness). Close linkage to these markers was strongly excluded using each model and definition. The findings for DRD1 also persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis, but the DRD2 results did not remain statistically significant at high sporadic rates. The exclusion of linkage to DRD2 is consistent with other recent reports.

Original languageEnglish
Pages (from-to)1-11
Number of pages11
JournalJournal of Affective Disorders
Volume25
Issue number1
DOIs
Publication statusPublished - 1992

Keywords

  • Bipolar disorder
  • Chromosome 11
  • Chromosome 5
  • Dopamine receptors
  • Linkage

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