Preliminary evidence on the association between XBP1-116C/G polymorphism and response to prophylactic treatment with valproate in bipolar disorders

Psychiatry Res. 2009 Aug 15;168(3):209-12. doi: 10.1016/j.psychres.2008.05.010. Epub 2009 Jun 28.


The 116C/G polymorphism in the promoter region of XBP1 is known to be associated with bipolar disorders. The G allele of the XBP1-116C/G polymorphism has reduced XBP1-dependent transcription activity compared with the C allele. Valproate treatment has been known to rescue the impaired response of cells with the G allele. We investigated the hypothesis that the G allele of XBP1-116C/G has better prophylactic treatment response to valproate compared to the C allele. This study involved 51 patients with bipolar disorder who were treated with valproate for prophylactic treatment. Prophylactic treatment response to valproate was retrospectively assessed using a scale described by Grof et al. [Grof, P., Duffy, A., Cavazzoni, P., Grof, E., Garnham, J., MacDougall, M., O'Donovan, C., Alda, M., 2002. Is response to prophylactic lithium a familial trait? Journal of Clinical Psychiatry 63, 942-947.]. We found that the patients with the G allele of XBP1-116C/G showed a better prophylactic treatment response to valproate compared to the C allele. This result is in agreement with in-vitro data showing that valproate ameliorates the endoplasmic reticulum (ER)-stress response compromised by the G allele.

MeSH terms

  • Adult
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / genetics
  • Bipolar Disorder / prevention & control
  • Chi-Square Distribution
  • DNA-Binding Proteins / genetics*
  • Drosophila Proteins / genetics*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Genetic / genetics*
  • Psychiatric Status Rating Scales
  • Retrospective Studies
  • Valproic Acid / therapeutic use*


  • Antimanic Agents
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Xbp1 protein, Drosophila
  • Valproic Acid