Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia

Mol Psychiatry. 2004 Mar;9(3):299-307. doi: 10.1038/


Genetic linkage and association have implicated neuregulin-1 (NRG-1) as a schizophrenia susceptibility gene. We measured mRNA expression levels of the three major isoforms of NRG-1 (ie type I, type II, and type III) in the postmortem dorsolateral prefrontal cortex (DLPFC) from matched patients and controls using real-time quantitative RT-PCR. Expression levels of three internal controls-GAPDH, cyclophilin, and beta-actin-were unchanged in schizophrenia, and there were no changes in the absolute levels of the NRG-1 isoforms. However, type I expression normalized by GAPDH levels was significantly increased in schizophrenia DLPFC (by 23%) and positively correlated with antipsychotic medication dosage. Type II/type I and type II/type III ratios were significantly decreased (18 and 23% respectively). There was no effect on the NRG-1 mRNA levels of genotype at two SNPs previously associated with schizophrenia, suggesting that these alleles are not functionally responsible for abnormal NRG-1 expression patterns in patients. Subtle abnormalities in the expression patterns of NRG-1 mRNA isoforms in DLPFC may be associated with schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autopsy
  • Base Sequence
  • Carrier Proteins / genetics
  • DNA Primers
  • Gene Expression Regulation*
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Nerve Growth Factors / genetics
  • Neuregulin-1 / genetics*
  • Neuregulins
  • Polymerase Chain Reaction
  • Prefrontal Cortex / pathology
  • Prefrontal Cortex / physiopathology*
  • RNA, Messenger / genetics
  • Schizophrenia / genetics*
  • Transcription, Genetic


  • Carrier Proteins
  • DNA Primers
  • Intracellular Signaling Peptides and Proteins
  • NRG2 protein, human
  • NRG3 protein, human
  • Nerve Growth Factors
  • Neuregulin-1
  • Neuregulins
  • Nrg2 protein, mouse
  • RNA, Messenger