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

⿢We assess NRG1⿿s relevance to schizophrenia in the GWAS era.⿢The past decade of clinical research on NRG1 and schizophrenia is summarized.⿢We review preclinical work on NRG1⿿s role in excitatory/inhibitory neurotransmission.⿢We propose a strategy forward for future NRG1 research in schizophrenia. 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.