Electronic Resource
Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients.
| العنوان: | Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients. |
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| المؤلفون: | Bousman C., Sundram S., Mostaid M.S., Lee T.T., Chana G., Shannon Weickert C., Pantelis C., Everall I. |
| بيانات النشر: | Nature Publishing Group (Houndmills, Basingstoke, Hampshire RG21 6XS, United Kingdom) United Kingdom 2017-12-20 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | 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, EGFalpha, EGFbeta, pan-NRG1) in whole blood, and NRG1-beta1 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 EGFalpha (P = 0.0175), EGFbeta (P = 0.002) and type I(Ig2) (P = 0.023) containing transcripts, but lower NRG1-beta1 serum protein levels (P = 0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-beta1 serum levels (P = 0.050). Examination of clinical factors showed NRG1 EGFalpha (P = 0.02) and EGFbeta (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.Copyright © 2017 The Author(s). |
| مصطلحات الفهرس: | single nucleotide polymorphism, smoking, treatment outcome, chlorpromazine, clozapine/pd [Pharmacology], messenger RNA/ec [Endogenous Compound], neu differentiation factor/ec [Endogenous Compound], RNA isoform/ec [Endogenous Compound], protein blood level, adult, aged, article, controlled study, correlational study, disease duration, disease severity, female, genetic variation, human, major clinical study, male, mini international neuropsychiatric interview, onset age, peripheral blood mononuclear cell, Positive and Negative Syndrome Scale, protein expression, quantitative trait locus, schizophrenia/di [Diagnosis], schizophrenia/et [Etiology], Article |
| URL: | Translational Psychiatry Click here for full text options LibKey Link |
| الاتاحة: | Open access content. Open access content Copyright 2018 Elsevier B.V., All rights reserved. |
| Other Numbers: | AUSHL oai:repository.monashhealth.org:1/38455 Translational Psychiatry. 7 (12) (no pagination), 2017. Article Number: 1280. Date of Publication: 01 Dec 2017. 2158-3188 (electronic) https://repository.monashhealth.org/monashhealthjspui/handle/1/38455 29225331 [http://www.ncbi.nlm.nih.gov/pubmed/?term=29225331] 619596636 (Mostaid, Pantelis, Everall, Bousman) Melbourne Neuropsychiatry Center, Department of Psychiatry, University of Melbourne and Melbourne Health, Parkville, VIC, Australia (Mostaid, Pantelis, Everall, Bousman) Cooperative Research Center (CRC) for Mental Health, Carlton, VIC, Australia (Lee, Chana, Pantelis, Everall) Center for Neural Engineering, Department of Electrical and Electronic Engineering, University of Melbourne, Carlton, VIC, Australia (Chana, Sundram, Pantelis, Everall, Bousman) Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, Australia (Chana) Department of Medicine, Royal Melbourne Hospital, Parkville, VIC, Australia (Sundram, Pantelis, Everall) North Western Mental Health, Melbourne, VIC, Australia (Sundram) Department of Psychiatry, School of Clinical Sciences, Monash University and Monash Health, Clayton, VIC, Australia (Shannon Weickert, Everall) Schizophrenia Research Institute, Sydney, NSW, Australia (Shannon Weickert) Schizophrenia Research Laboratory, Neuroscience Research Australia, Baker Street, Sydney, NSW, Australia (Shannon Weickert) School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia (Bousman) Departments of Medical Genetics, Psychiatry, and Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada Bousman C.; Chad.bousman@ucalgary.ca 1305138434 |
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| رقم الانضمام: | edsoai.on1305138434 |
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