title: Transcriptomic evidence for immaturity of the prefrontal cortex in patients with schizophrenia.
abstract: BACKGROUND
  Schizophrenia, a severe psychiatric disorder, has a lifetime prevalence of 1%. The exact mechanisms underlying this disorder remain unknown, though theories abound. Recent studies suggest that particular cell types and biological processes in the schizophrenic cortex have a pseudo-immature status in which the molecular properties partially resemble those in the normal immature brain. However, genome-wide gene expression patterns in the brains of patients with schizophrenia and those of normal infants have not been directly compared. Here, we show that the gene expression patterns in the schizophrenic prefrontal cortex (PFC) resemble those in the juvenile PFC.
  
  
  RESULTS
  We conducted a gene expression meta-analysis in which, using microarray data derived from different studies, altered expression patterns in the dorsolateral PFC (DLFC) of patients with schizophrenia were compared with those in the DLFC of developing normal human brains, revealing a striking similarity. The results were replicated in a second DLFC data set and a medial PFC (MFC) data set. We also found that about half of the genes representing the transcriptomic immaturity of the schizophrenic PFC were developmentally regulated in fast-spiking interneurons, astrocytes, and oligodendrocytes. Furthermore, to test whether medications, which often confound the results of postmortem analyses, affect on the juvenile-like gene expressions in the schizophrenic PFC, we compared the gene expression patterns showing transcriptomic immaturity in the schizophrenic PFC with those in the PFC of rodents treated with antipsychotic drugs. The results showed no apparent similarities between the two conditions, suggesting that the juvenile-like gene expression patterns observed in the schizophrenic PFC could not be accounted for by medication effects. Moreover, the developing human PFC showed a gene expression pattern similar to that of the PFC of naive Schnurri-2 knockout mice, an animal model of schizophrenia with good face and construct validity. This result also supports the idea that the transcriptomic immaturity of the schizophrenic PFC is not due to medication effects.
  
  
  CONCLUSIONS
  Collectively, our results provide evidence that pseudo-immaturity of the PFC resembling juvenile PFC may be an endophenotype of schizophrenia.
authors.forename: Hideo
authors.initials: H
authors.lastname: Hagihara
authors.forename: Koji
authors.initials: K
authors.lastname: Ohira
authors.forename: Keizo
authors.initials: K
authors.lastname: Takao
authors.affiliation: Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. miyakawa@fujita-hu.ac.jp.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyakawa
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002675:Child, Preschool; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007223:Infant; D051379:Mice; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents