title: Cognitive function, plasma MnSOD activity, and MnSOD Ala-9Val polymorphism in patients with schizophrenia and normal controls.
abstract: Excessive reactive oxygen species are thought to produce oxidative damage that underlies neurodegeneration and cognitive impairment in several disorders including schizophrenia. The functional Ala-9Val polymorphism of the mitochondrial enzyme manganese superoxide dismutase (MnSOD), which detoxifies superoxide radicals to hydrogen peroxide, has been associated with schizophrenia. However, no study has reported its role in cognitive deficits of schizophrenia as mediated through MnSOD activity. We recruited 923 schizophrenic inpatients and 566 healthy controls and compared them on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity, and the MnSOD Ala-9Val polymorphism. We assessed patient psychopathology using the Positive and Negative Syndrome Scale. We showed that the MnSOD Ala-9Val polymorphism may not contribute directly to the susceptibility to schizophrenia. The Ala variant was associated with worse attention performance among chronic schizophrenic patients but not among normal controls. Plasma MnSOD activity was significantly decreased in patients compared with that in normal controls. Moreover, MnSOD activity among the schizophrenic Ala allele carriers was correlated with the degree of cognitive impairments, especially attention and RBANS total score. We demonstrated an association between the MnSOD Ala-9Val variant and poor attention in schizophrenia. The association between higher MnSOD activity and cognitive impairment in schizophrenia is dependent on the MnSOD Ala-9Val polymorphism.
authors.affiliation: *To whom correspondence should be addressed; Research Building 109, Room 130, 2002 Holcombe Boulevard, Houston, TX 77030, US; tel: 713-791-1414, fax: 713-794-7938, e-mail: xyzhang@bcm.edu.
authors.forename: Xiang Y
authors.initials: XY
authors.lastname: Zhang
authors.forename: Da C
authors.initials: DC
authors.lastname: Chen
authors.forename: Mei H
authors.initials: MH
authors.lastname: Xiu
authors.forename: Fu D
authors.initials: FD
authors.lastname: Yang
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Tan
authors.forename: Xingguang
authors.initials: X
authors.lastname: Luo
authors.forename: Lingjun
authors.initials: L
authors.lastname: Zuo
authors.forename: Therese A
authors.initials: TA
authors.lastname: Kosten
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000201:enzymology / Q000235:genetics / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics; D012565:Schizophrenic Psychology; D013482:Superoxide Dismutase / Q000097:blood / Q000235:genetics*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2
keywords: association; cognition; genotype; manganese superoxide dismutase; polymorphism; schizophrenia