Association between brain-derived neurotrophic factor Val66Met gene polymorphism and progressive brain volume changes in schizophrenia

Am J Psychiatry. 2007 Dec;164(12):1890-9. doi: 10.1176/appi.ajp.2007.05111903.


Objective: Factors underlying progressive brain volume changes in schizophrenia remain poorly understood. The authors investigated whether a gene polymorphism influencing neuroplasticity may contribute to longitudinal brain volume alterations.

Method: High-resolution magnetic resonance (MR) images of the whole brain were obtained for 119 patients with recent-onset schizophrenia spectrum disorders. Changes in brain volumes over an average of 3 years were compared between brain-derived neurotrophic factor (BDNF) val66met genotype groupings. Exploratory analyses were conducted to examine relationships between antipsychotic treatment and brain volume changes as well as the effects of BDNF genotype on changes in cognition and symptoms.

Results: Significant genotype effects were observed on within-subject changes in volumes of frontal lobe gray matter, lateral ventricles, and sulcal CSF. Met allele carriers had significantly greater reductions in frontal gray matter volume, with reciprocal volume increases in the lateral ventricles and sulcal (especially frontal and temporal) CSF than Val homozygous patients. Independent of BDNF genotype, more antipsychotic exposure between MRI scans correlated with greater volume reductions in frontal gray matter, particularly among patients who were initially treatment naive. There were no statistically significant genotype effects on within-subject changes in cognition or symptoms.

Conclusions: BDNF(Met) variant may be one of several factors affecting progressive brain volume changes in schizophrenia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use
  • Atrophy / pathology
  • Brain / pathology*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / psychology
  • Female
  • Frontal Lobe / pathology
  • Genetic Variation*
  • Genotype
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / statistics & numerical data
  • Male
  • Methionine / genetics
  • Neuronal Plasticity / genetics
  • Neuropsychological Tests
  • Polymorphism, Genetic / genetics*
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics*
  • Schizophrenia / pathology*
  • Schizophrenic Psychology
  • Severity of Illness Index
  • Valine / genetics


  • Antipsychotic Agents
  • Brain-Derived Neurotrophic Factor
  • Methionine
  • Valine