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Neuregulin 1 and susceptibility to schizophrenia.


ABSTRACT: The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous work, done in five populations, showing that schizophrenia maps to chromosome 8p. Extensive fine-mapping of the 8p locus and haplotype-association analysis, supplemented by a transmission/disequilibrium test, identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. NRG1 is expressed at central nervous system synapses and has a clear role in the expression and activation of neurotransmitter receptors, including glutamate receptors. Mutant mice heterozygous for either NRG1 or its receptor, ErbB4, show a behavioral phenotype that overlaps with mouse models for schizophrenia. Furthermore, NRG1 hypomorphs have fewer functional NMDA receptors than wild-type mice. We also demonstrate that the behavioral phenotypes of the NRG1 hypomorphs are partially reversible with clozapine, an atypical antipsychotic drug used to treat schizophrenia.

SUBMITTER: Stefansson H 

PROVIDER: S-EPMC378543 | biostudies-literature | 2002 Oct

REPOSITORIES: biostudies-literature

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Neuregulin 1 and susceptibility to schizophrenia.

Stefansson Hreinn H   Sigurdsson Engilbert E   Steinthorsdottir Valgerdur V   Bjornsdottir Soley S   Sigmundsson Thordur T   Ghosh Shyamali S   Brynjolfsson Jon J   Gunnarsdottir Steinunn S   Ivarsson Omar O   Chou Thomas T TT   Hjaltason Omar O   Birgisdottir Birgitta B   Jonsson Helgi H   Gudnadottir Vala G VG   Gudmundsdottir Elsa E   Bjornsson Asgeir A   Ingvarsson Brynjolfur B   Ingason Andres A   Sigfusson Sigmundur S   Hardardottir Hronn H   Harvey Richard P RP   Lai Donna D   Zhou Mingdong M   Brunner Daniela D   Mutel Vincent V   Gonzalo Acuna A   Lemke Greg G   Sainz Jesus J   Johannesson Gardar G   Andresson Thorkell T   Gudbjartsson Daniel D   Manolescu Andrei A   Frigge Michael L ML   Gurney Mark E ME   Kong Augustine A   Gulcher Jeffrey R JR   Petursson Hannes H   Stefansson Kari K  

American journal of human genetics 20020723 4


The cause of schizophrenia is unknown, but it has a significant genetic component. Pharmacologic studies, studies of gene expression in man, and studies of mouse mutants suggest involvement of glutamate and dopamine neurotransmitter systems. However, so far, strong association has not been found between schizophrenia and variants of the genes encoding components of these systems. Here, we report the results of a genomewide scan of schizophrenia families in Iceland; these results support previous  ...[more]

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