The International Journal of Neuropsychopharmacology



Brief Report

A possible association between the −116C/G single nucleotide polymorphism of the XBP1 gene and lithium prophylaxis in bipolar disorder


Takuya Masui a1, Ryota Hashimoto a2c1, Ichiro Kusumi a1, Katsuji Suzuki a1, Teruaki Tanaka a1, Shin Nakagawa a1, Hiroshi Kunugi a2 and Tsukasa Koyama a1
a1 Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo, Japan
a2 Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan

Article author query
masui t   [PubMed][Google Scholar] 
hashimoto r   [PubMed][Google Scholar] 
kusumi i   [PubMed][Google Scholar] 
suzuki k   [PubMed][Google Scholar] 
tanaka t   [PubMed][Google Scholar] 
nakagawa s   [PubMed][Google Scholar] 
kunugi h   [PubMed][Google Scholar] 
koyama t   [PubMed][Google Scholar] 

Abstract

Bipolar disorder (BPD) is a severe, chronic, and life-threatening illness, and its pathogenesis remains unclear. Recently, a functional polymorphism (−116C/G) of the X-box binding protein 1 (XBP1) gene was reported to be a genetic risk factor for BPD. Moreover, the endoplasmic reticulum stress responses were impaired in cultured lymphocytes from BPD patients with the −116G allele and only valproate rescued such impairment among three major mood stabilizers. In this context, we hypothesized that BPD patients with different genotypes respond differently to mood stabilizers. We investigated the association between the −116C/G polymorphism of the XBP1 gene and lithium response in Japanese patients with BPD. We found that lithium treatment is more effective among BPD patients with the −116C allele carrier than in patients homozygous for the −116G allele. The association between the −116C/G polymorphism and clinical efficacy of mood stabilizers should be further investigated in a prospective study with a larger sample.

(Published Online June 1 2005)
(Received October 13 2004)
(Reviewed December 28 2004)
(Revised February 7 2005)
(Accepted February 20 2005)


Key Words: Bipolar disorder; lithium; SNP (single nucleotide polymorphism); XBP1.

Correspondence:
c1 Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashicho, Kodaira, Tokyo, 187-8502, Japan. Tel.: +81-42-341-2712 (ext. 5831) Fax: +81-42-346-1744 E-mail: rhashimo@ncnp.go.jp