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Genetic Predictors of Lithium Response in Bipolar Patients

Summary and Comment |
December 26, 2013

Genetic Predictors of Lithium Response in Bipolar Patients

  1. Peter Roy-Byrne, MD

A landmark study identifies three genetic variants that predict response to lithium maintenance therapy with high sensitivity and specificity.

  1. Peter Roy-Byrne, MD

Psychiatrists currently have no valid way to select among available mood stabilizers for treating patients with bipolar disorder. In this genetics study, researchers in Taiwan carefully measured lithium response with a reliable scale that confirmed adherence and documented severity, frequency, and duration of episodes, and they eliminated responders also receiving other mood stabilizers.

The researchers identified two single nucleotide polymorphisms (SNPs) in the GADL1 gene associated with response in a discovery cohort of 294 Han Chinese patients with bipolar I disease and a minimum of 2 years of lithium treatment (maximum, 28 years). Findings were confirmed in a replication cohort of 100 patients, with response in both cohorts predicted at 93% sensitivity and 87% specificity. In another cohort of 24 patients on lithium monotherapy, the SNPs perfectly identified 16 responders and 8 nonresponders. GADL1 resequencing identified a novel variant that was in linkage disequilibrium with one of the SNPs and seemed to control GADL1 splicing.

Comment

The careful delineation of true lithium response by ensuring adherence and controlling for concomitant mood stabilizer use, along with the homogeneity of this ethnic Han sample, allowed identification of a gene-predicting lithium response with high odds ratios. Although the physiological function of GADL1 is unknown and these alleles are rare in whites, one of the SNPs is present in 47% of Han Chinese, consistent with the lithium response rate experienced by most clinicians and with published data on lithium response. Examination of other GADL1 SNPs might be pursued in other populations. We look forward to the day when this test and similar ones useful in other populations might help routine care.

  • Disclosures for Peter Roy-Byrne, MD at time of publication Equity Valant Medical Solutions Grant / research support NIH-NIDA; NIH-NIMH Editorial boards Depression and Anxiety; UpToDate Leadership positions in professional societies Anxiety Disorders Association of America (Ex-Officio Board Member); Washington State Psychiatric Society (Treasurer)

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