title: Age-Related Sexual Dimorphism in Temporal Discrimination and in Adult-Onset Dystonia Suggests GABAergic Mechanisms.
abstract: BACKGROUND
  Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants.
  
  
  OBJECTIVE
  We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients.
  
  
  METHODS
  We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of onset and (ii) an analysis of temporal discrimination thresholds in 220 unaffected first-degree relatives (125 women) of cervical dystonia patients.
  
  
  RESULTS
  In 53 studies of dystonia phenotypes, the proportion of men showed a highly significant negative association with mean age of onset (p < 0.0001, pseudo-R (2) = 59.6%), with increasing female predominance from 40 years of age. Age of onset and phenotype together explained 92.8% of the variance in proportion of men. Temporal discrimination in relatives under the age of 35 years is faster in women than men but the age-related rate of deterioration in women is twice that of men; after 45 years of age, men have faster temporal discrimination than women.
  
  
  CONCLUSIONS
  Temporal discrimination in unaffected relatives of cervical dystonia patients and sex ratios in adult-onset dystonia phenotypes show similar patterns of age-related sexual dimorphism. Such age-related sexual dimorphism in temporal discrimination and adult-onset focal dystonia may reflect common underlying mechanisms. Cerebral GABA levels have been reported to show similar age-related sexual dimorphism in healthy participants and may be the mechanism underlying the observed age-related sexual dimorphism in temporal discrimination and the sex ratios in AOIFD.
authors.affiliation: Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin , Dublin , Ireland.
authors.forename: John S
authors.initials: JS
authors.lastname: Butler
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland.
authors.forename: Ines M
authors.initials: IM
authors.lastname: Beiser
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: Williams
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland.
authors.forename: Eavan
authors.initials: E
authors.lastname: McGovern
authors.affiliation: Beaumont Hospital , Dublin , Ireland.
authors.forename: Fiona
authors.initials: F
authors.lastname: Molloy
authors.affiliation: Dublin Neurological Institute, Mater Misericordiae University Hospital , Dublin , Ireland.
authors.forename: Tim
authors.initials: T
authors.lastname: Lynch
authors.affiliation: Beaumont Hospital , Dublin , Ireland.
authors.forename: Dan G
authors.initials: DG
authors.lastname: Healy
authors.affiliation: Cork University Hospital , Cork , Ireland.
authors.forename: Helena
authors.initials: H
authors.lastname: Moore
authors.affiliation: Adelaide and Meath Hospital , Dublin , Ireland.
authors.forename: Richard
authors.initials: R
authors.lastname: Walsh
authors.affiliation: Trinity Centre for Bioengineering, School of Engineering, Trinity College Dublin , Dublin , Ireland ; School of Medicine, Trinity College Dublin , Dublin , Ireland.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Reilly
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland.
authors.forename: Seán
authors.initials: S
authors.lastname: O'Riordan
authors.affiliation: Department of Statistics, Trinity College Dublin , Dublin , Ireland ; Department of Mathematics and Statistics, University of Limerick , Limerick , Ireland.
authors.forename: Cathal
authors.initials: C
authors.lastname: Walsh
authors.affiliation: Department of Neurology, St. Vincent's University Hospital , Dublin , Ireland ; School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Hutchinson
keywords: adult-onset isolated focal dystonia; penetrance; sex ratio; sexual dimorphism; temporal discrimination