1. Neuregulin 1 and Susceptibility to Schizophrenia
- Author
-
Gardar Johannesson, Greg Lemke, Michael L. Frigge, Daniel F. Gudbjartsson, Donna Lai, Acuna Gonzalo, Vala G. Gudnadottir, Andres Ingason, Valgerdur Steinthorsdottir, Sigmundur Sigfusson, Hronn Hardardottir, Helgi Jonsson, Jesus Sainz, Engilbert Sigurdsson, Mark E. Gurney, Thordur Sigmundsson, Birgitta Birgisdottir, Brynjolfur Ingvarsson, Omar Ivarsson, Steinunn Gunnarsdottir, Jeffrey R. Gulcher, Hannes Petursson, Kari Stefansson, Shyamali Ghosh, Augustine Kong, Andrei Manolescu, Vincent Mutel, Hreinn Stefansson, Mingdong Zhou, J Brynjolfsson, Elsa Gudmundsdottir, Thomas T. Chou, Omar Hjaltason, Asgeir Björnsson, Soley Bjornsdottir, Thorkell Andresson, Daniela Brunner, and Richard P. Harvey
- Subjects
Male ,Candidate gene ,Psychosis ,Receptor, ErbB-4 ,Neuregulin-1 ,Molecular Sequence Data ,Epigenetics of schizophrenia ,Mice ,DISC1 ,Neuregulin 3 ,mental disorders ,medicine ,Genetics ,Animals ,Humans ,Genetic Predisposition to Disease ,Genetics(clinical) ,Neuregulin 1 ,Genetics (clinical) ,ERBB4 ,biology ,Chromosome Mapping ,Articles ,medicine.disease ,ErbB Receptors ,Mice, Inbred C57BL ,Disease Models, Animal ,Haplotypes ,Schizophrenia ,biology.protein ,Neuregulin ,Female ,Chromosomes, Human, Pair 8 - 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.
- Published
- 2002
- Full Text
- View/download PDF