Dataset Information

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

ABSTRACT: Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in signal transduction, particularly in myelinated axons. We genotyped members of the large potassium channel gene family focusing on putatively functional single nucleotide polymorphisms (SNPs) in a population of 363 controls, 194 patients with schizophrenia spectrum disorder (SSD) and 28 patients with affective disorders with psychotic features who completed imaging and neuropsychological testing. We then performed three association analyses using three phenotypes - processing speed, whole-brain white matter fractional anisotropy (FA) and schizophrenia spectrum diagnosis. We extracted SNPs showing an association at a nominal P value of <0.05 with all three phenotypes in the expected direction: decreased processing speed, decreased FA and increased risk of SSD. A single SNP, rs8234, in the 3' untranslated region of voltage-gated potassium channel subfamily Q member 1 (KCNQ1) was identified. Rs8234 has been shown to affect KCNQ1 expression levels, and KCNQ1 levels have been shown to affect neuronal action potentials. This exploratory analysis provides preliminary data suggesting that KCNQ1 may contribute to the shared risk for diminished processing speed, diminished white mater integrity and increased risk of schizophrenia.

SUBMITTER: Bruce HA

PROVIDER: S-EPMC5457349 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Bruce H A HA Kochunov P P Paciga S A SA Hyde C L CL Chen X X Xie Z Z Zhang B B Xi H S HS O'Donnell P P Whelan C C Schubert C R CR Bellon A A Ament S A SA Shukla D K DK Du X X Rowland L M LM O'Neill H H Hong L E LE

Genes, brain, and behavior 20170313 5

Patients with schizophrenia show decreased processing speed on neuropsychological testing and decreased white matter integrity as measured by diffusion tensor imaging, two traits shown to be both heritable and genetically associated indicating that there may be genes that influence both traits as well as schizophrenia disease risk. The potassium channel gene family is a reasonable candidate to harbor such a gene given the prominent role potassium channels play in the central nervous system in si ...[more]

PMID: 28188958

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Project description:Background and purposeSecondary-progressive MS is characterized by reduced acute inflammation and contrast enhancement but with increased axonal degeneration and cognitive/clinical disability that worsens with advanced disease. Relative recirculation, extracted from DSC is a surrogate measure of BBB integrity. We hypothesized that normal-appearing white matter relative recirculation is reduced in cognitively impaired compared with nonimpaired secondary-progressive MS, reflecting more advanced disease.Materials and methodsCognitive performance was classified as impaired or nonimpaired by use of Minimal Assessment of Cognitive Function In MS test components. Demographic data, brain parenchymal fraction, WM lesion fraction, and weighted mean normal-appearing white matter relative recirculation were compared in cognitively dichotomized groups. Univariate and multivariate logistic regressions were used to study the association between cognitive test results and normal-appearing white matter relative recirculation.ResultsThe mean (SD) age of 36 patients with secondary-progressive MS studied was 55.9 ± 9.3 years; 13 of 36 (36%) patients were male. A highly significant difference between normal-appearing white matter relative recirculation and WM lesion relative recirculation was present for all patients (P < .001). Normal-appearing white matter relative recirculation in impaired patients was significantly lower than in nonimpaired subjects for the Symbol Digit Modalities Test (P = .007), Controlled Word Association Test (P = .008), and Paced Auditory Serial Addition Test (P = .024). The Expanded Disability Status Scale demonstrated an inverse correlation with normal-appearing white matter relative recirculation (r = -0.319, P = .075). After adjustment for confounders, significant normal-appearing white matter relative recirculation reduction persisted for the Symbol Digit Modalities Test (P = .023) and the Paced Auditory Serial Addition Test (P = .047) but not for the Controlled Word Association Test (P = .13) in impaired patients.ConclusionsSignificant normal-appearing white matter relative recirculation reduction exists in cognitively impaired patients with secondary-progressive MS, localizing to the domains of processing speed and working memory.

Dataset Information

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Publications

Potassium channel gene associations with joint processing speed and white matter impairments in schizophrenia.

Similar Datasets

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