Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism.
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 NRG1beta1 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.
Department of Molecular Neurobiology, Brain Research Institute, Niigata University, 1-757, Asahimachi-dori, Niigata, 951-8585, Japan.
M
M
Shibuya
E
E
Komi
R
R
Wang
T
T
Kato
Y
Y
Watanabe
M
M
Sakai
M
M
Ozaki
T
T
Someya
H
H
Nawa
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D020890:Neuregulin-1 / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D012737:Sex Factors
D014150:Antipsychotic Agents; C094131:NRG1 protein, human; D020890:Neuregulin-1; D006220:Haloperidol