Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia

J. Zinkstok*, N. Schmitz, T. Van Amelsvoort, M. Moeton, F. Baas, D. Linszen

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

40 Citations (Scopus)

Abstract

Haploinsufficiency of 22q11 genes including catechol-O-methyltransferase (COMT) and proline dehydrogenase (PRODH) may result in structural and functional brain abnormalities and increased vulnerability to schizophrenia as observed in patients with microdeletions of 22q11. Thus, COMT and PRODH could be modifier genes for schizophrenia. We examined association of polymorphisms in COMT and PRODH with brain anatomy in young patients with schizophrenia and schizoaffective disorder. We acquired structural magnetic resonance imaging data from 51 male patients and genotyped two single nucleotide polymorphisms (SNPs) in the COMT gene and three in the PRODH gene. Statistical Parametric Mapping software and optimized voxel-based morphometry were used to determine regional gray matter (GM) and white matter (WM) density differences, and total GM and WM volume differences between genotype groups. Two nonsynonymous SNPs in the PRODH gene were associated with bilateral frontal WM density reductions and an SNP in the P2 promoter region of COMT (rs2097603) was associated with GM increase in the right superior temporal gyrus. Furthermore, we found evidence for COMT and PRODH epistasis: in patients with a COMT Val allele (rs4680) and with one or two mutated PRODH alleles, we observed increased WM density in the left inferior frontal lobe. Our results suggest that genetic variation in COMT and PRODH has significant effects on brain regions known to be affected in schizophrenia. Further research is needed to investigate the role of 22q11 genes on brain structure and function and their role in vulnerability for schizophrenia.

Original languageEnglish
Pages (from-to)61-69
Number of pages9
JournalGenes, Brain and Behavior
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Feb 2008
Externally publishedYes

Keywords

  • 22q11
  • Brain anatomy
  • COMT
  • Gene
  • MRI
  • PRODH
  • Schizophrenia
  • Voxel-based morphometry

Fingerprint

Dive into the research topics of 'Genetic variation in COMT and PRODH is associated with brain anatomy in patients with schizophrenia'. Together they form a unique fingerprint.

Cite this