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 β-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.
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We wish to thank Drs Takashi Morihara, Toyoko Hiroi, and Masasumi Kamohara for advice on real-time quantitative PCR. We also thank Dr Kenichiro Miura for advice of statistical analysis and Dr Vakkalanka Radhakrishna and Dr Bhaskar Kolachana for SNP genotyping and Dr Gerry Fischbach for review of the manuscript. This work was supported in part by the Essel Foundation through a NARSAD distinguished investigator award to DRW.
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Hashimoto, R., Straub, R., Weickert, C. et al. Expression analysis of neuregulin-1 in the dorsolateral prefrontal cortex in schizophrenia. Mol Psychiatry 9, 299–307 (2004). https://doi.org/10.1038/sj.mp.4001434
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