Translating knowledge of genetics and pharmacology into improving everyday practice

Authors


  • Development of this manuscript was supported by an educational grant from AstraZeneca.

Dr Lakshmi N Yatham, Department of Psychiatry, UBC Hospital, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada.
Fax: +1 604 822 7922;
e-mail: yatham@interchange.ubc.ca

Abstract

Bipolar disorder is associated with significant morbidity and mortality; however, many aspects of this disorder remain poorly understood. It is likely that rapid advances in molecular genetics and neuroimaging will play a major role in advancing our understanding of bipolar disorder in future.

Molecular genetics studies have already identified some candidate genes; for example, the BDNF, G72 and XBP1 genes, and chromosomal ‘hot spots’, which may confer a predisposition to development of bipolar disorder. Such advances may facilitate earlier, easier and more accurate diagnosis and provide novel targets for the treatment of this condition.

Brain imaging studies using positron emission tomography and single photon emission computed tomography have shown that reduction in brain 5-hydroxytryptamine type 2 (5-HT2) receptors may be associated with prevention of or relief from depressive symptoms. Similarly, other imaging studies suggest that increased dopamine levels in the synapse mediate the symptoms of bipolar mania and that reduction in dopamine transmission through reduction in dopamine synthesis or blockade of dopamine D2 receptors may be associated with antimanic effects. The ability of atypical antipsychotics to block both 5-HT2 and D2 receptors and downregulate 5-HT2 receptors may explain how these drugs treat both the depressive and manic symptoms of bipolar disorder.

Although molecular genetics and imaging techniques are not yet used as clinical tools for bipolar disorder, they provide valuable data to improve the understanding of the pathophysiology of bipolar disorder and should lead to new treatments and potentially episode prevention.

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