Genes for schizophrenia? Recent findings and their pathophysiological implications

Lancet. 2003 Feb 1;361(9355):417-9. doi: 10.1016/S0140-6736(03)12379-3.


Context: Schizophrenia is highly heritable, but the genes have remained elusive. Identifying the genes is essential if the pathogenesis and pathophysiology of schizophrenia is finally to be understood, and to give the prospect of more effective treatment.

Starting point: H Stefansson and colleagues (Am J Hum Genet 2002; 71: 877-92) showed association of the neuregulin (NRG1) gene with schizophrenia. Other recent papers describe six additional susceptibility genes. Replications are already being reported for some of them. The genes are biologically plausible, and may have convergent effects on glutamatergic and other synapses. We review the evidence for each gene, the possible pathogenic mechanisms, and the implications of the findings. WHERE NEXT? Given earlier failures to replicate apparent breakthroughs, the results should be viewed with caution. Unequivocal replications remain the top priority. The respective contributions of each gene, epistatic effects, and functional interactions between the gene products, all need investigation. Confirmation that any of the genes is a true susceptibility gene for schizophrenia could trigger the same rapid therapeutic progress as has occurred recently in Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Catechol O-Methyltransferase / genetics
  • D-Amino-Acid Oxidase / genetics
  • Disease Models, Animal
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Genetic Linkage / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Mice
  • Neuregulin-1 / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Proline Oxidase / genetics
  • RGS Proteins / genetics
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology


  • Carrier Proteins
  • DTNBP1 protein, human
  • Dtnbp1 protein, mouse
  • Dysbindin
  • Dystrophin-Associated Proteins
  • Neuregulin-1
  • RGS Proteins
  • RGS4 protein
  • D-Amino-Acid Oxidase
  • Proline Oxidase
  • Catechol O-Methyltransferase