Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-beta -50T/C single nucleotide polymorphism

Biol Psychiatry. 2007 Dec 1;62(11):1295-302. doi: 10.1016/j.biopsych.2007.03.023. Epub 2007 Jul 12.


Background: Glycogen synthase kinase 3-beta (GSK3B) is a serine/threonine kinase which is directly inhibited by lithium. A -50T/C single nucleotide polymorphism (SNP) localized within the promoter region of the GSK3B gene has previously been shown to be associated with response to lithium prophylaxis in bipolar disorder. This study investigates the association of the GSK3B -50T/C SNP and response to lithium augmentation in acutely depressed antidepressant nonresponders.

Methods: Eighty-one patients who had not responded to at least one adequate trial of antidepressant monotherapy underwent a standardized trial of lithium augmentation for up to 8 weeks. We genotyped for the GSK3B -50T/C SNP using polymerase chain reaction and restriction fragment length polymorphism methods and investigated the association with remission.

Results: The allele frequencies in our sample were CC 14.8%, CT 48.2% and TT 37% (no deviation from the Hardy-Weinberg equilibrium). Carriers of the C-allele of the -50T/C SNP showed a significantly better response to lithium augmentation (hazard ratio: 2.70, p = .007), with a mean remission rate of 56.25% after 4 weeks compared to 31% in patients with the TT-genotype (chi(2) = 4.1; p = .04).

Conclusions: Our results support the finding of recent studies demonstrating a superior response of C-allele carriers with bipolar disorder to lithium prophylaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use*
  • Antimanic Agents / therapeutic use*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / genetics*
  • Drug Resistance
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Glycogen Synthase Kinase 3 / genetics*
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Lithium Chloride / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Regression Analysis
  • Survival Analysis


  • Antidepressive Agents
  • Antimanic Agents
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Lithium Chloride