Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder.

To test for genetic linkage and association with GABAergic candidate genes in lithium-responsive bipolar disorder. Design: Polymorphisms located in genes that code for GABRA3, GABRA5 and GABRB3 subunits of the GABA, receptor were investigated using association and linkage strategies. Participants: A total of 138 patients with bipolar I disorder with a clear response to lithium prophylaxis, selected from specialized lithium clinics in Canada and Europe that are part of the International Group for the Study of Lithium-treated Patients, and 108 psychiatrically healthy controls. Families of 24 probands were suitable for linkage analysis. Outcome measures: The association between the candidate genes and patients with bipolar disorder versus that of controls and genetic linkage within families. Results: There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. Conclusions: This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.