Dysbindin and D-amino-acid-oxidase gene polymorphisms associated with positive and negative symptoms in schizophrenia

Abstract

Background: Schizophrenia is a genetically complex disorder with an unknown pathophysiology. Several genes implicated in glutamate metabolism have been associated with the disorder. Recent studies of polymorphisms in the dystrobrevin-binding protein 1 gene (DTNBP1; dysbindin) and D-amino-acid-oxidase (DAO) gene, both involved in glutamate receptor function, reported associations with negative symptoms and with anxiety and depression, respectively, when measured with the Positive and Negative Syndrome Scale (PANSS). Methods: In the present study, the suggested association between dysbindin and DAO single nucleotide polymorphisms (SNPs) and PANSS scores was analyzed in 155 Norwegian schizophrenia patients. Results: There was a significant association between the dysbindin SNP rs3213207 and severity of both negative symptoms and total symptom load, as well as between the DAO SNP rs2070587 and total symptom score and severity of anxiety and depression. Conclusion: The present association of dysbindin SNPs with negative symptoms and DAO SNPs with anxiety and depression is a replication of earlier findings and strengthens the hypothesis of a genetic association. It further indicates involvement of glutamate abnormalities in schizophrenia pathophysiology, as suggested by previous studies, and suggests that polymorphisms may be associated with subgroups of clinical characteristics in schizophrenia. © 2009 S. Karger AG, Basel.