TCF4 gene polymorphism and cognitive performance in patients with first episode psychosis

Schizophr Res. 2014 Jan;152(1):124-9. doi: 10.1016/j.schres.2013.10.038. Epub 2013 Nov 22.

Abstract

Background: Single nucleotide polymorphisms in TCF4 gene have been consistently associated with schizophrenia in genome wide association studies, including the C allele of rs9960767. However, its exact role in modulating the schizophrenia phenotype is not known.

Aims: To comprehensively investigate the relationship between rs9960767 risk allele (C) of TCF4 and cognitive performance in patients with first episode psychosis (FEP).

Methods: 173 patients with FEP received a comprehensive neurocognitive evaluation and were genotyped for rs9960767. Carriers of the risk allele (CA/CC) were compared to non-carriers (AA) using Multivariate Analysis of Covariance MANCOVA. Ethnicity, negative symptoms and substance abuse were included as covariates.

Results: Carriers of the risk allele had a statistically significant lower performance in the cognitive domain of Reasoning/Problem-Solving compared to non-carriers (F1,172=4.4, p=.038). There were no significant genotype effects on the other cognitive domains or general cognition. This effect on the Reasoning/Problem-Solving domain remained significant even when controlling for IQ (F1,172=4.3, p=.039).

Conclusions: rs9960767 (C) of TCF4 appears to be associated with neurocognitive deficits in the Reasoning/Problem-Solving cognitive domain, in patients with FEP. A confirmation of this finding in a larger sample and including other TCF4 polymorphisms will be needed to gain further validity of this result.

Keywords: First episode psychosis; Genetics; Psychotic disorders; Schizophrenia; TCF4; rs9960767.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Cognition Disorders / genetics*
  • Female
  • Humans
  • Male
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide / genetics*
  • Problem Solving / physiology
  • Psychiatric Status Rating Scales
  • Psychotic Disorders / complications*
  • Psychotic Disorders / genetics*
  • Retrospective Studies
  • Transcription Factor 4
  • Transcription Factors / genetics*
  • Young Adult

Substances

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