Conclusion And Perspectives For Future Research

Different approaches are available to identify genetic markers that could contribute to the response to mood stabilizers. The priority is a considerable need for improved methodology in case-control association studies. The different ways to improve it are discussed elsewhere (Lerer and Macciardi, 2002; Oswald et al., 2003). In the specific field of pharmacogenetics of BPAD, we will have to improve the specific design of mood stabilizers pharmacogenetic studies. In the "classical" studies, responsiveness is dichotomously defined (response or non-response). More recent studies use treatment response as a continuous measure allowing multivariate statistical analyses, including a large number of factors (Cusin et al., 2002).

Another way to consider future research is to focus on new candidate genes, believed to be the ultimate sites of action of mood stabilizers (see above). This must also be considered in parallel to a better understanding of the mode of action of "newer" mood stabilizers, i.e. atypical antipsychotics and lamotrigine. Some studies tend to show that lamotrigine may have neuroprotective effects, thus implicating gene regulation.

New lab techniques, such as expression and proteomic array technologies, will also help in defining new candidate genes.

Finally, it seems more and more obvious that, in addition to single-gene pharmacogenetic studies, it will be crucial to take into account gene-gene interactions, and certainly interactions with environment, which need to be incorporated in statistical models.

Many ethical issues need also to be resolved (Mancinelli et al., 2000). It has been shown that the cost of developing a new drug could be reduced to about 60% using pharmacogenetics, mainly by reducing the number of needed participants in clinical trials (Lipton, 2003). Pharmacogenetic studies will be therefore developed in the future with many stored genetic data for each participant. Obviously, information of this type must be carefully safeguarded to ensure privacy. In addition, there also questions about feedback to be given to the patient. For example, it may be possible to make some predictions on the propensity for a patient to respond to a medication and to classify him as a "bad responder", with all the psychological consequences. Another concern is that individuals may find it more difficult to find affordable health insurance as a consequence pharmacogenetic test. Many legal and economic issues will thus need to be resolved.

In the future, after refining the methodology and the investigated phenotypes of lithium pharmacogenetic studies, the prediction of drug efficacy and side effects, using a pharmacogenetic tool, could be considered as a helpful assistance in selection and monitoring of treatment in BPAD. In parallel to a better understanding of the neurobiology of BPAD, progress in pharmaco-genomics could improve the outcome of a still chronic disease, with a high rate of mortality.

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