LITHIUM-RESPONSIVE AFFECTIVE-DISORDERS - NO ASSOCIATION WITH THE TRYOSINE HYDROXYLASE GENE

Family, adoption, and twin studies have demonstrated the involvement o f genetic factors in the etiology of major affective disorders. In an attempt to identify the involved genes, several linkage and associatio n studies have focused on the gene coding for tyrosine hydroxylase, th e rate-limiting enzyme in catecholamine synthesis. The discrepant resu lts to date could be explained by etiological heterogeneity, which may be substantially reduced by selecting patients according to lithium r esponse. Therefore, we investigated 54 patients who had shown definite long-term response to lithium monotherapy in spite of a high risk of recurrence as indicated by the previous clinical course. All the subje cts suffered from major affective disorder by Research Diagnostic Crit eria (48 bipolar, 6 recurrent unipolar). They were compared to 94 popu lation controls of similar ethnic background to test for association w ith a penta-allelic microsatellite marker found within the tyrosine hy droxylase gene. No significant differences in allele and genotype freq uencies were observed between the two groups, providing further eviden ce against a major role for the tyrosine hydroxylase gene in the etiol ogy of major affective disorders.