No association between chromosome-18 markers and lithium-responsive affective disorders.

An allelic association study of excellent responders to lithium was conducted with a candidate gene (Golf, a G-protein receptor gene) and five other chromosome-18p markers. Golf is of special interest because it maps to a region of chromosome 18 where two independent groups (Berrettini et al., 1994; Stine et al., 1995) have found linkage to bipolar disorder. It has been proposed that G proteins are involved in the pathogenesis of bipolar disorder, and lithium, an effective prophylactic agent, is known to impair G-protein activation. To reduce heterogeneity--a common obstacle to genetic investigation--only patients who showed excellent response to lithium prophylaxis were studied. Fifty-five genetically unrelated excellent responders to lithium prophylaxis were compared with 94 normal subjects of similar ethnic background. The groups did not differ in either allele or genotype frequency for the tested markers. The data do not support the hypothesis that the tested loci confer a major susceptibility for affective disorders.