OVERVIEW

Response to long-term lithium treatment in bipolar disorder appears to be related to the family history of a patient. Conversely, some studies have indicated that treatment response could identify a subtype of bipolar disorder characterized by a stronger role of genetic factors and possibly by major-gene effects. Several research groups have now collected samples from patients treated with lithium and these are being studied by molecular genetic methods. These studies aim to identify genes associated with the treatment response or to map genes for bipolar disorder in homogeneous populations of treatment responders. Preliminary findings with a number of candidate genes have produced mostly negative findings, but several promising associations have been also identified, for instance, an association of lithium-responsive bipolar disorder with the gene for phospholipase Cγ1. Further research will be needed to examine differences between genetic factors involved in treatment response as opposed to genes associated with the illness. One possible research strategy appears to be a study of pairs of relatives concordant for the illness but discordant for their treatment response. Other important areas of research are phenotype definition, especially definition of long-term prophylactic response, and studies of biochemical phenotypes and alterations in gene expression.

Introduction

Lithium is the standard treatment for bipolar disorder. In recent years, several other treatments have appeared promising, mainly anticonvulsants, but also calcium channel blockers and other drugs.

Response to lithium appears to identify a more homogeneous subtype of bipolar disorder with higher heritability.