Age-related Sexual Dimorphism in Temporal Discrimination and in Adult-onset Dystonia Suggests GABAergic Mechanisms

Title: Age-related Sexual Dimorphism in Temporal Discrimination and in Adult-onset Dystonia Suggests GABAergic Mechanisms
Authors: Butler, John S.
Beiser, Ines M.
Williams, Laura
McGovern, Eavan
O'Riordan, Sean
Hutchinson, Michael
et al.
Permanent link: http://hdl.handle.net/10197/7361
Date: Dec-2015
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. Objectives: 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-R2 = 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. Conclusion: 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.
Funding Details: Health Research Board
Type of material: Journal Article
Publisher: Frontiers
Copyright (published version): 2015 the Authors
Keywords: Adult-onset isolated focal dystonia;Sex ratio;Temporal discrimination;Sexual dimorphism;Penetrance
DOI: 10.3389/fneur.2015.00258
Language: en
Status of Item: Peer reviewed
Appears in Collections:Medicine Research Collection

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