Neuregulin1-induced cell migration is impaired in schizophrenia: association with neuregulin1 and catechol-o-methyltransferase gene polymorphisms

• Published in: Molecular psychiatry Vol. 12; no. 10; pp. 946 - 957
• Main Authors: Sei, Y, Ren-Patterson, R, Li, Z, Tunbridge, E M, Egan, M F, Kolachana, B S, Weinberger, D R
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-10-2007
• Subjects: Adult; AKT protein; Analysis of Variance; B-Lymphocytes - drug effects; Catechol; Catechol O-methyltransferase; Catechol O-Methyltransferase - genetics; Cell adhesion & migration; Cell migration; Cell Movement - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Cellular proteins; Cellular signal transduction; Central nervous system; Chemotaxis - drug effects; Cognition & reasoning; Enzyme Inhibitors - pharmacology; Epistasis; ErbB protein; Female; Gene Expression Regulation - drug effects; Gene polymorphism; Genes; Genetic aspects; Genetic diversity; Genomics; Health aspects; Humans; Kinases; Lymphoblasts; Lymphocytes; Male; Mental disorders; Mental health; Methyltransferase; Middle Aged; Nervous system; Neuregulin-1 - genetics; Neuregulin-1 - pharmacology; Phosphorylation; Polymorphism; Polymorphism, Genetic - drug effects; Psychiatry; Psychosis; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3 - metabolism; Risk factors; Schizophrenia; Schizophrenia - genetics; Schizophrenia - pathology; Signal Transduction - drug effects; Statistics, Nonparametric; United States; United States > US
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001994

Neuregulin1 (NRG1), a candidate susceptibility gene for schizophrenia, plays a critical role in neuronal migration and central nervous system development. However, its relation to schizophrenia pathogenesis is unknown. Here we show that B lymphoblasts migrate to NRG1 through the ErbB-signaling system as observed in neuronal cells. We assessed NRG1-induced cell migration in B lymphoblasts from patients with schizophrenia and found that NRG1-induced migration is significantly decreased compared with control individuals in two independent cohorts. This impaired migration is related at least in part to reduced AKT phosphorylation in the patients. Moreover, the magnitude of NRG1-induced migration is associated with polymorphisms of the NRG1 and catechol-o-methyltransferase genes and with an epistatic interaction of these genes. This study demonstrates that the migratory response of schizophrenia-derived cells to NRG1 is impaired and is associated with genetic variations in more than one schizophrenia susceptibility gene, providing a novel insight into potential neurodevelopmental mechanisms of schizophrenia.