title: Genes and structural brain imaging in schizophrenia.
abstract: OBJECTIVE
  Schizophrenia is a complex genetic disorder, caused by multiple genetic and environmental factors. Recently, studies have focused on testing specific genetic markers in a known candidate gene for association with endophenotypes. These are measurable characteristics of a disorder that are assumed to be closer to the action of the gene, resulting in higher genetic signal-to-noise ratios. Structural brain parameters have been shown to be useful endophenotypes for studies in psychiatric illnesses.
  
  
  RESULTS
  After reviewing the available studies on the influence of genotype on brain volume in schizophrenia, it is evident that the BDNF and COMT genes are clearly favourites for genetic imaging studies. Results from these studies seem to be quite consistent, with the same associated alleles and direction of brain volume changes. The most frequently investigated polymorphisms suggest that sample sizes of approximately 50-100 patients are sufficient to report consistent findings. Considering the ongoing discussion about the sample size necessary to detect significant associations, however, larger sample sizes are needed.
  
  
  CONCLUSIONS
  There is sufficient evidence to defend the use of structural neuroimaging as an endophenotype to investigate a complex phenotype such as schizophrenia despite the notion that, so far, no single causal pathway emerges from these studies. Replication studies and larger numbers of patients are essential in this respect.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Centre Utrecht, The Netherlands.
authors.forename: Neeltje E
authors.initials: NE
authors.lastname: van Haren
authors.forename: Steven C
authors.initials: SC
authors.lastname: Bakker
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
mesh_terms: D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology* / Q000503:physiopathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D009419:Nerve Tissue Proteins / Q000235:genetics; D020890:Neuregulin-1; D020933:Neurotrophin 3 / Q000235:genetics; D011328:Prions / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053327:Apolipoprotein E4; D019208:Brain-Derived Neurotrophic Factor; C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; C094131:NRG1 protein, human; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; D020933:Neurotrophin 3; D011328:Prions; C498305:TSNAX protein, human; D002394:Catechol O-Methyltransferase; D019204:GTP-Binding Proteins