Novel schizophrenia risk gene TCF4 influences verbal learning and memory functioning in schizophrenia patients

Neuropsychobiology. 2011;63(3):131-6. doi: 10.1159/000317844. Epub 2011 Jan 13.


Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients.

Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT).

Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning.

Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Predisposition to Disease / psychology*
  • Genotype
  • Humans
  • Male
  • Memory*
  • Polymorphism, Single Nucleotide
  • Psychomotor Performance
  • Schizophrenia / genetics*
  • Schizophrenic Psychology*
  • Transcription Factor 4
  • Transcription Factors / genetics*
  • Verbal Learning*


  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • TCF4 protein, human
  • Transcription Factor 4
  • Transcription Factors