Hippocampal volume and the brain-derived neurotrophic factor Val66Met polymorphism in first episode psychosis

Schizophr Res. 2012 Feb;134(2-3):253-9. doi: 10.1016/j.schres.2011.11.022. Epub 2011 Dec 21.


Introduction: Small hippocampi and impaired memory are common in patients with psychosis and brain-derived neurotrophic factor (BDNF) plays a critical role in hippocampal neuroplasticity and memory. A common BDNF allele (Val66Met) has been the focus of numerous studies but results from the few BDNF-imaging studies are complex and contradictory. The objective of this study was to determine the association between Val66Met and hippocampal volume in patients with first episode psychosis. Secondary analyses explored age-related associations and the relationship between Val66Met and memory.

Method: Hippocampal volume and BDNF genotyping were obtained for 58 patients with first-episode psychosis and 39 healthy volunteers. Patients were recruited from an early psychosis program serving a catchment-area population.

Results: Hippocampal volume was significantly smaller in patients than controls (F(1,92)=4.03, p<0.05) and there was a significant group-by-allele interaction (F(1,92)=3.99, p<0.05). Hippocampal volume was significantly smaller in patients than controls who were Val-homozygotes but no group differences were found for Met carriers. Findings were not affected by diagnosis, antipsychotic medication, or age, and there was no change in hippocampal volume during a one-year follow-up. Val-homozygous patients had worse immediate and delayed memory than their Met counterparts.

Conclusions: Results suggest the effects of the BDNF Val66Met allele may be different in patients with psychosis than in healthy adults. Hippocampal volume in patient and control Met allele carriers was very similar suggesting that illness-related factors have minimal influence in this group. In contrast, Val homozygosity was related to smaller hippocampi and poorer memory functioning only in patients with psychosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Analysis of Variance
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cognition Disorders / etiology
  • Cognition Disorders / genetics
  • Cognition Disorders / pathology
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Hippocampus / pathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory
  • Methionine / genetics
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide / genetics*
  • Psychotic Disorders / complications
  • Psychotic Disorders / genetics*
  • Psychotic Disorders / pathology*
  • Valine / genetics
  • Young Adult


  • Brain-Derived Neurotrophic Factor
  • Methionine
  • Valine