Polymorphisms of the Fyn kinase gene and a performance on the Wisconsin Card Sorting Test in schizophrenia

The glutamatergic system has been implicated in the pathogenesis and prefrontal cortex dysfunctions in schizophrenia. The Src-family tyrosine kinase Fyn plays a key role in the interaction between brain-derived neurotrophic factor and glutamatergic receptor N-methyl-D-aspartate, in prefrontal cortex. We estimated an association between three polymorphisms of Fyn gene and performance on the Wisconsin Card Sorting Test, measuring prefrontal cortex functions, in 188 schizophrenic patients. Patients with T/T genotype of IVS10+T/C polymorphism and T/T genotype of Ex12+894T/G polymorphism made significantly less perseverative errors in the Wisconsin Card Sorting Test compared with patients with remaining genotypes, and obtained numerically better results in other Wisconsin Card Sorting Test domains. No significant differences in Wisconsin Card Sorting Test performance were found as to −93 A/G polymorphism. The main finding of the study is showing a relationship between polymorphisms of the Fyn gene, related to the function of glutamatergic system, and a performance on neuropsychological test of prefrontal cortex activity in schizophrenic patients.

[1]  E. Gershon,et al.  Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. , 1997, Genomics.

[2]  J. Hauser,et al.  An association study of dopamine receptors polymorphisms and the Wisconsin Card Sorting Test in schizophrenia , 2005, Journal of Neural Transmission.

[3]  M. Itokawa,et al.  [Susceptibility genes for schizophrenia]. , 2005, Nihon rinsho. Japanese journal of clinical medicine.

[4]  J. Hauser,et al.  Performance on the Wisconsin Card Sorting Test in schizophrenia and genes of dopaminergic inactivation (COMT, DAT, NET) , 2006, Psychiatry Research.

[5]  M. Leboyer,et al.  Lack of influence of COMT and NET genes variants on executive functions in schizophrenic and bipolar patients, their first‐degree relatives and controls , 2006, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[6]  J. Hauser,et al.  Polymorphism of the brain-derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients. , 2003, Bipolar disorders.

[7]  W. Bunney,et al.  Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia , 2000, Brain Research Reviews.

[8]  R. Gibbs,et al.  Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[9]  P. Goldman-Rakic,et al.  D1 receptors in prefrontal cells and circuits , 2000, Brain Research Reviews.

[10]  R. Heaton.  Wisconsin Card Sorting Test manual , 1993 .

[11]  J. Lieberman,et al.  Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophrenia , 2002, Biological Psychiatry.

[12]  Ajw Vanderdoes,et al.  WHAT DETERMINES WISCONSIN CARD SORTING PERFORMANCE IN SCHIZOPHRENIA , 1992 .

[13]  P. McKenna,et al.  Expression of Fyn, a non-receptor tyrosine kinase in prefrontal cortex from patients with schizophrenia and its correlation with clinical onset. , 2003, Brain research. Molecular brain research.

[14]  T. Arinami,et al.  Mutation and association analysis of the Fyn kinase gene with alcoholism and schizophrenia. , 2000, American journal of medical genetics.

[15]  D. Weinberger,et al.  Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. , 1986, Archives of general psychiatry.

[16]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[17]  K. Wada,et al.  Association of the Src Family Tyrosine Kinase Fyn with TrkB , 1998, Journal of neurochemistry.

[18]  J. Rybakowski,et al.  Eye movement and neuropsychological studies in first-degree relatives of schizophrenic patients , 2002, Schizophrenia Research.

[19]  S. Faraone,et al.  Neuropsychological functioning among the nonpsychotic relatives of schizophrenic patients: a diagnostic efficiency analysis. , 1995, Journal of abnormal psychology.

[20]  R. Straub,et al.  Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[21]  K. Lavoie,et al.  Performance of patients with schizophrenia on the Wisconsin Card Sorting Test (WCST). , 2001, Journal of psychiatry & neuroscience : JPN.