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Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism

Journal of Neural Transmission volume 117, pages 887–895 (2010)Cite this article

Abstract

Neuregulin-1 (NRG1) gene is implicated in the etiology or neuropathology of schizophrenia, although its biological contribution to this illness is not fully understood. We have established an enzyme-linked immunosorbent assay (ELISA), which recognizes the NRG1β1 immunoglobulin-like (Ig) domain, and measured soluble Ig-NRG1 immunoreactivity in the sera of chronic schizophrenia patients (n = 40) and healthy volunteers (n = 59). ELISA detected remarkably high concentrations of Ig-NRG1 immunoreactivity in human serum (mean 5.97 ± 0.40 ng/mL, ~213 ± 14 pM). Gender and diagnosis exhibited significant effects on serum Ig-NRG1 immunoreactivity. Mean Ig-NRG1 immunoreactivity in the schizophrenia group was 63.2% of that measured in the control group. Ig-NRG1 immunoreactivity in women was 147.1% of that seen in men. We also attempted to correlate six SNPs of NRG1 genome with serum Ig-NRG1 immunoreactivity. Analysis of covariance with compensation for gender identified a significant interaction between diagnosis and SNP8NRG243177 allele. The T allele of this SNP significantly contributed to the disease-associated decrease in Ig-NRG1 immunoreactivity. Although we hypothesized a chronic influence of antipsychotic medications, there was no significant effect of chronic haloperidol treatment on serum Ig-NRG1 immunoreactivity in monkeys. These findings suggest that serum NRG1 levels are decreased in patients with chronic schizophrenia and influenced by their SNP8NRG243177 alleles.

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Abbreviations

NRG:

Neuregulin

SNP:

Single-nucleotide polymorphism

ELISA:

Enzyme-linked immunosorbent assay

LI:

Like immunoreactivity

ANOVA:

Analysis of variance

ANCOVA:

Analysis of covariance

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Acknowledgments

The authors thank the patients and healthy volunteers for their participation. This work was supported by Health and Labor Sciences Research Grants, a grant from the Promotion of Niigata University Research Projects, Core Research for Evolutional Science and Technology from the JST Corporation, and a grant-in-aid from the Ministry of Health, Labor and Welfare, Japan.

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Affiliations

  1. Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757, Asahimachi-dori, Niigata, 951-8585, Japan

    M. Shibuya, E. Komi, R. Wang, T. Kato, M. Sakai & H. Nawa

  2. Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 1-757, Asahimachi-dori, Niigata, 951-8510, Japan

    M. Shibuya, Y. Watanabe, M. Sakai & T. Someya

  3. Institute for Biomedical Engineering, Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513, Wasedatsurumaki-cho, Shinjuku-ku, Tokyo, 162-0041, Japan

    M. Ozaki

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  1. M. Shibuya
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  2. E. Komi
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  3. R. Wang
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  4. T. Kato
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  5. Y. Watanabe
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  6. M. Sakai
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  7. M. Ozaki
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  8. T. Someya
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  9. H. Nawa
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Correspondence to H. Nawa.

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Shibuya, M., Komi, E., Wang, R. et al. Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism. J Neural Transm 117, 887–895 (2010). https://doi.org/10.1007/s00702-010-0418-3

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  • DOI: https://doi.org/10.1007/s00702-010-0418-3

Keywords

  • Neuregulin
  • Schizophrenia
  • Serum
  • ELISA
  • SNP