Leukemia inhibitory factor gene is associated with schizophrenia and working memory function

Yuko Okahisa, Hiroshi Ujike, Hiroshi Kunugi, Takeshi Ishihara, Masafumi Kodama, Manabu Takaki, Tatsuya Kotaka, Shigetoshi Kuroda

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


Leukemia inhibitory factor (LIF), a member of the interleukin-6 cytokine family, regulates the neuronal phenotype and coordinates astrocyte, oligodendrocyte, microglia, and inflammatory cell responses. The LIF gene is located on 22q12.1-q12.2, a hot spot for schizophrenia. Three polymorphisms of the LIF gene (rs929271, rs737812, and rs929273) were examined in a case-control association study of 390 patients with schizophrenia and 410 age- and sex-matched controls. Effects of a risk genotype of LIF on cognitive domains were evaluated by the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and Wisconsin Card Sorting Test (WCST) in 355 healthy volunteers. The LIF gene showed significant associations with schizophrenia at rs929271 and a haplotype consisting of rs929271-rs737812. After stratification by subtype of schizophrenia, the hebephrenic, but not paranoid, type was associated with the LIF gene at rs929271 (allele, P = 0.014) and the haplotype (permutation P = 0.013). Having the T-allele and T-carrier genotypes (TT and TG) of rs929271 were risks for hebephrenic schizophrenia, and the odds ratios were 1.38 (95% CI: 1.21-1.56) and 1.54 (95%CI: 1.19-1.98), respectively. Subjects with T-carrier genotypes made significantly more errors on the WCST compared with those without (P = 0.04). The present study indicated that the LIF gene variant may produce susceptibility to hebephrenic schizophrenia and deterioration of working memory function.

Original languageEnglish
Pages (from-to)172-176
Number of pages5
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number1
Publication statusPublished - Jan 20 2010


  • Case-control association
  • Cognitive function
  • Leukemia inhibitory factor
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry


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