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 Paul Everall, Chad A. Bousman

Research output: Contribution to journalReview ArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)387-409
Number of pages23
JournalNeuroscience and Biobehavioral Reviews
Volume68
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • Excitatory neurotransmission
  • Genotype
  • Inhibitory neurotransmission
  • Neuregulin 1
  • Neuroimaging
  • Psychosis
  • Schizophrenia
  • Transcript

Cite this

Mostaid, Md Shaki ; Lloyd, David ; Liberg, Benny ; Sundram, Suresh ; Pereira, Avril ; Pantelis, Christos ; Karl, Tim ; Weickert, Cynthia Shannon ; Everall, Ian Paul ; Bousman, Chad A. / Neuregulin-1 and schizophrenia in the genome-wide association study era. In: Neuroscience and Biobehavioral Reviews. 2016 ; Vol. 68. pp. 387-409.
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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.",
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Mostaid, MS, Lloyd, D, Liberg, B, Sundram, S, Pereira, A, Pantelis, C, Karl, T, Weickert, CS, Everall, IP & Bousman, CA 2016, 'Neuregulin-1 and schizophrenia in the genome-wide association study era' Neuroscience and Biobehavioral Reviews, vol. 68, pp. 387-409. https://doi.org/10.1016/j.neubiorev.2016.06.001

Neuregulin-1 and schizophrenia in the genome-wide association study era. / Mostaid, Md Shaki; Lloyd, David; Liberg, Benny; Sundram, Suresh; Pereira, Avril; Pantelis, Christos; Karl, Tim; Weickert, Cynthia Shannon; Everall, Ian Paul; Bousman, Chad A.

In: Neuroscience and Biobehavioral Reviews, Vol. 68, 01.09.2016, p. 387-409.

Research output: Contribution to journalReview ArticleResearchpeer-review

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T1 - Neuregulin-1 and schizophrenia in the genome-wide association study era

AU - Mostaid, Md Shaki

AU - Lloyd, David

AU - Liberg, Benny

AU - Sundram, Suresh

AU - Pereira, Avril

AU - Pantelis, Christos

AU - Karl, Tim

AU - Weickert, Cynthia Shannon

AU - Everall, Ian Paul

AU - Bousman, Chad A.

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AB - 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.

KW - Excitatory neurotransmission

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KW - Inhibitory neurotransmission

KW - Neuregulin 1

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