Polymorphisms in genes involved in neurodevelopment may be associated with altered brain morphology in schizophrenia: preliminary evidence

Psychiatry Res. 2009 Jan 30;165(1-2):1-9. doi: 10.1016/j.psychres.2007.08.011. Epub 2008 Dec 2.

Abstract

An abnormality in neurodevelopment is one of the most robust etiologic hypotheses in schizophrenia (SZ). There is also strong evidence that genetic factors may influence abnormal neurodevelopment in the disease. The present study evaluated in SZ patients, whose brain structural data had been obtained with magnetic resonance imaging (MRI), the possible association between structural brain measures, and 32 DNA polymorphisms, located in 30 genes related to neurogenesis and brain development. DNA was extracted from peripheral blood cells of 25 patients with schizophrenia, genotyping was performed using diverse procedures, and putative associations were evaluated by standard statistical methods (using the software Statistical Package for Social Sciences - SPSS) with a modified Bonferroni adjustment. For reelin (RELN), a protease that guides neurons in the developing brain and underlies neurotransmission and synaptic plasticity in adults, an association was found for a non-synonymous polymorphism (Val997Leu) with left and right ventricular enlargement. A putative association was also found between protocadherin 12 (PCDH12), a cell adhesion molecule involved in axonal guidance and synaptic specificity, and cortical folding (asymmetry coefficient of gyrification index). Although our results are preliminary, due to the small number of individuals analyzed, such an approach could reveal new candidate genes implicated in anomalous neurodevelopment in schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Brain / abnormalities*
  • Brain / pathology*
  • Cadherins / genetics*
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Cerebral Cortex / abnormalities
  • Cerebral Cortex / pathology
  • Cerebral Ventricles / pathology
  • Dominance, Cerebral / physiology
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genetic Markers / genetics*
  • Genotype
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Nerve Tissue Proteins / genetics*
  • Neuronal Plasticity / genetics
  • Polymorphism, Single Nucleotide / genetics*
  • Protocadherins
  • Reelin Protein
  • Schizophrenia / genetics*
  • Serine Endopeptidases / genetics*
  • Synaptic Transmission / genetics

Substances

  • Cadherins
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Genetic Markers
  • Nerve Tissue Proteins
  • PCDH12 protein, human
  • Protocadherins
  • Reelin Protein
  • RELN protein, human
  • Serine Endopeptidases