Neuregulin-1 and schizophrenia in the genome-wide association study era

Md Shaki Mostaid; David Lloyd; Benny Liberg; Suresh Sundram; Avril Pereira; Christos Pantelis; Tim Karl; Cynthia Shannon Weickert; Ian P Everall; Chad A Bousman

doi:10.1016/j.neubiorev.2016.06.001

Neuregulin-1 and schizophrenia in the genome-wide association study era

Neurosci Biobehav Rev. 2016 Sep:68:387-409. doi: 10.1016/j.neubiorev.2016.06.001. Epub 2016 Jun 6.

Authors

Affiliations

¹ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
² Schizophrenia Research Institute, Sydney, Australia; Schizophrenia Research Laboratory, Neuroscience Research Australia, Barker Street, Sydney, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.
³ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia; NorthWestern Mental Health, Melbourne, VIC, Australia; Monash University, Department of Psychiatry, Monash Medical Centre, Monash Health, Clayton, VIC, Australia.
⁴ Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
⁵ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
⁶ Schizophrenia Research Institute, Sydney, Australia; Western Sydney University, School of Medicine, Campbelltown, NSW, Australia.
⁷ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia; NorthWestern Mental Health, Melbourne, VIC, Australia.
⁸ Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia; Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia; The University of Melbourne, Department of General Practice, Parkville, VIC, Australia; Swinburne University of Technology, Centre for Human Psychopharmacology, Hawthorn, VIC, Australia. Electronic address: cbousman@unimelb.edu.au.

PMID: 27283360
DOI: 10.1016/j.neubiorev.2016.06.001

Abstract

Clinical and pre-clinical evidence has implicated neuregulin 1 (NRG1) as a critical component in the pathophysiology of schizophrenia. However, the arrival of the genome-wide association study (GWAS) era has yielded results that challenge the relevance of NRG1 in schizophrenia due to the absence of a genome-wide significant NRG1 variant associated with schizophrenia. To assess NRG1's relevance to schizophrenia in the GWAS era, we provide a targeted review of recent preclinical evidence on NRG1's role in regulating several aspects of excitatory/inhibitory neurotransmission and in turn schizophrenia risk. We also present a systematic review of the last decade of clinical research examining NRG1 in the context of schizophrenia. We include concise summaries of genotypic variation, gene-expression, protein expression, structural and functional neuroimaging as well as cognitive studies conducted during this time period. We conclude with recommendations for future clinical and preclinical work that we hope will help prioritize a strategy forward to further advance our understanding of the relationship between NRG1 and schizophrenia.

Keywords: Excitatory neurotransmission; Genotype; Inhibitory neurotransmission; Neuregulin 1; Neuroimaging; Psychosis; Schizophrenia; Transcript.

Publication types

Review
Systematic Review

MeSH terms

Gene Expression
Genome-Wide Association Study
Genotype
Humans
Neuregulin-1
Schizophrenia*

Substances

Neuregulin-1