Lithium long-term treatment in mood disorders: clinical and genetic predictors.

Lithium is the most widely used long-term treatment for recurrent mood disorders. Despite its proven efficacy, patients show a variable response, ranging from complete efficacy to no influence at all. This paper reviews possible predictors of response focusing on molecular genetic studies. The functional polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) has been associated with lithium long-term efficacy in two independent studies, marginal associations have been reported for tryptophan hydroxylase and inositol polyphosphate 1-phosphatase (INPP1). A number of other candidate genes and anonymous markers did not yield positive associations. Therefore, even though some positive results have been reported, no unequivocal susceptibility gene for lithium efficacy has been identified.