An exploratory model for G x E interaction on hippocampal volume in schizophrenia; obstetric complications and hypoxia-related genes

Research output: Contribution to journalReview article


Background Smaller hippocampal volume has repeatedly been reported in schizophrenia patients Obstetric complications (OCs) and single nucleotide polymorphism (SNP) variation in schizophrenia susceptibility genes have independently been related to hippocampal volume We investigated putative independent and interaction effects of severe hypoxia-related OCs and variation in four hypoxia-regulated schizophrenia susceptibility genes (BDNF, DTNBP1, GRM3 and NRG1) on hippocampal volume in schizophrenia patients and healthy controls. Methods Clinical assessment, structural MRI scans, and blood samples for genotyping of 32 SNPs were obtained from 54 schizophrenia patients and 53 control subjects Information on obstetric complications was collected from original birth records Results Severe OCs were related to hippocampal volume in both patients with schizophrenia and healthy control subjects Of the 32 SNPs studied, effects of severe OCs on hippocampal volume were associated with allele variation in GRM3 rs13242038, but the interaction effect was not specific for schizophrenia. SNP variation in any of the four investigated genes alone did not significantly affect hippocampal volume. Conclusions. The findings suggest a gene-environment (G x E) interaction between GRM3 gene variants and severe obstetric complications on hippocampus volume, independent of a diagnosis of schizophrenia Due to the modest sample size, the results must be considered preliminary and require replication in independent samples. (C) 2010 Elsevier Inc All rights reserved


  • Unn Kristin Haukvik
  • Peter Saetre
  • Thomas McNeil
  • Petr S. Bjerkan
  • Ole A. Andreassen
  • Thomas Werge
  • Erik G. Jonsson
  • Ingrid Agartz
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Environmental Health and Occupational Health


  • Obstetric complications, Hypoxia-regulated genes, GRM3, Hippocampus, Schizophrenia
Original languageEnglish
Pages (from-to)1259-1265
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Issue number7
Publication statusPublished - 2010
Publication categoryResearch