期刊
TRANSLATIONAL PSYCHIATRY
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41398-017-0041-2
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资金
- CRC for Mental Health
- National Health and Medical Research Council of Australia [386500]
- Pratt Foundation
- Ramsay Health Care
- Viertel Charitable Foundation
- Schizophrenia Research Institute
- Cooperative Research Center
- One-in-Five Association Incorporated
- Schizophrenia Research Institute (NSW Ministry of Health)
- Schizophrenia Research Institute (Macquarie Group Foundation)
- University of New South Wales
- Neuroscience Research Australia
- National Health and Medical Research Council (Australia) Principal Research Fellowship (PRF) [1117079]
- NHMRC Senior Principal Research Fellowship [628386, 1105825]
- Brain and Behavior Research Foundation (NARSAD)
- NHMRC [1127700]
- Brain and Behavior Research Foundation (NARSAD) [20526]
- National Health and Medical Research Council of Australia [1127700] Funding Source: NHMRC
Differential expression of neuregulin-1 (NRG1) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. In this study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I((Ig2)), type II, type III, type IV, EGF alpha, EGF beta, pan-NRG1) in whole blood, and NRG1-beta 1 protein in serum of clozapine-treated schizophrenia patients (N = 71) and healthy controls (N = 57). In addition, using cultured peripheral blood mononuclear cells (PBMC) from 15 healthy individuals, we examined the effect of clozapine on NRG1 mRNA isoform and protein expression. We found elevated levels of NRG1 mRNA, specifically the EGF alpha (P = 0.0175), EGF beta (P = 0.002) and type I((Ig2)) (P = 0.023) containing transcripts, but lower NRG1-beta 1 serum protein levels (P = 0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-beta 1 serum levels (P = 0.050). Examination of clinical factors showed NRG1 EGF alpha (P = 0.02) and EGF beta (P = 0.02) isoform expression was negatively correlated with age of onset. However, we found limited evidence that NRG1 mRNA isoform or protein expression was associated with current chlorpromazine equivalent dose or clozapine plasma levels, the latter corroborated by our PBMC clozapine exposure experiment. Our SNP analysis found no robust expression quantitative trait loci. Our results represent the first comprehensive investigation of NRG1 isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest levels of some NRG1 transcripts are upregulated in those with schizophrenia.
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