Neuregulin-1 and schizophrenia in the genome-wide association study era.
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.
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
Md Shaki
MS
Mostaid
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.
David
D
Lloyd
Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia.
Benny
B
Liberg
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.
Suresh
S
Sundram
Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
Avril
A
Pereira
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.
Christos
C
Pantelis
Schizophrenia Research Institute, Sydney, Australia; Western Sydney University, School of Medicine, Campbelltown, NSW, Australia.
Tim
T
Karl
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.
Cynthia Shannon
CS
Weickert
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.
Ian P
IP
Everall
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.
Chad A
CA
Bousman
D015870:Gene Expression; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020890:Neuregulin-1; D012559:Schizophrenia
D020890:Neuregulin-1
Excitatory neurotransmission; Genotype; Inhibitory neurotransmission; Neuregulin 1; Neuroimaging; Psychosis; Schizophrenia; Transcript