title: Psychiatric and cognitive symptoms in Huntington's disease are modified by polymorphisms in catecholamine regulating enzyme genes.
abstract: Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative disorder characterized by motor, psychiatric, and cognitive manifestations. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene but the exact pathogenesis remains unknown. Dopamine imbalance has previously been shown in HD, and furthermore dopamine is thought to be implicated in cognition, behavioral and motor disturbances. A substantiated inverse correlation between motor onset and the elongated CAG repeat in the HTT has been established. This relation does not account for the full variability of the motor onset, and efforts have been put into finding genetic modifiers of motor onset, however, mostly with unsuccessful outcome. In this study, we took an alternative approach focusing on symptom complexes and searched for modifiers of cognitive impairment and psychiatric symptoms in a well-described cohort of Danish HD gene-expansion carriers. We show that cognitive impairment and psychiatric symptoms in HD are modified by polymorphisms in the monoamine oxidase A (MAOA) and catechol-O-methyltransferase (COMT) genes and by the 4p16.3 B haplotype. These results support the theory of dopamine imbalance in HD, and point toward more personalized treatment modalities of HD in the future.
authors.affiliation: Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Vinther-Jensen
authors.affiliation: Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T T
authors.initials: TT
authors.lastname: Nielsen
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: E
authors.initials: E
authors.lastname: Budtz-Jørgensen
authors.affiliation: Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Psychology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: I U
authors.initials: IU
authors.lastname: Larsen
authors.affiliation: Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M M
authors.initials: MM
authors.lastname: Hansen
authors.affiliation: Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Hasholt
authors.affiliation: Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: L E
authors.initials: LE
authors.lastname: Hjermind
authors.affiliation: Neurogenetics Clinic, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.|Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J E
authors.initials: JE
authors.lastname: Nielsen
authors.affiliation: Department of Cellular and Molecular Medicine, Section of Neurogenetics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Nørremølle
mesh_terms: D000328:Adult; D000368:Aged; D001519:Behavior; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003071:Cognition; D005260:Female; D006239:Haplotypes; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology / Q000235:genetics / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D002395:Catecholamines; D008995:Monoamine Oxidase; C579458:monoamine oxidase A, human; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Huntington's disease; catecholamines; cognitive impairment; genetic modifiers; psychiatric symptoms