The Neuregulin 1 gene (NRG1) is one of the most promising loci in schizophrenia genetics. Neuregulins and their receptors, the ERBB protein tyrosine kinases, are essential for neuronal development. Interestingly, mutant mice with disruptions in NRG1 or its receptor, ErbB4, show a behavioral phenotype similar to psychosis suggesting that impaired NRG1-ErbB4 signaling may contribute to schizophrenia susceptibility.
In a study to be published in the American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, Gilad Silberberg and colleagues at the Sackler School of Medicine, Tel Aviv University, Israel have found evidence that polymorphisms in the ErbB4 gene increase risk for schizophrenia. The researchers investigated 19 SNPs in a sample of Ashkenazi schizophrenia patients and compared allele frequencies to matched controls. They found a highly significant difference between patient and control groups in three SNPs from one linkage disequilibrium block both in allele and genotype frequencies, as well as a risk haplotype.
To follow up these findings, expression analyses were performed on postmortem brain samples obtained from Caucasian patients and controls. The group found significant differences in the expression of various ErbB4 splice variants with the CYT-1 isoform being overexpressed in patients.
The authors conclude that their study provides a direct link between ErbB4 and schizophrenia. They propose that NRG1 and its receptor ErbB are components of a biological pathway, involved in the pathophysiology of this complex psychiatric disorder.
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