title: Evidence linking FMR1 mRNA and attentional demands of stepping and postural control in women with the premutation.
abstract: Recent studies in young adult females with the fragile X mental retardation 1 (FMR1) gene premutation (PM) have shown subtle but significant impairments in executive control and postural stability. Less is known about the influence of age and FMR1 gene expression on executive control and postural stability in females with the PM. Here, we examined the attentional demands of reactive stepping using a well-validated measure of choice stepping reaction time under dual-task interference. We explored the interrelationships between step initiation times during a concurrent verbal fluency task and specific impairments in executive control previously reported in females with the PM. Our results showed increased dual-task interference on step initiation times and variability in female PM compared with control subjects. In addition, we observed greater choice stepping reaction time dual-task costs above the breakpoint of 81 CGG repeats relative to below this CGG range. Dual-task interference on both reaction time and movement time were significantly predicted by low working memory capacity in female PM carriers. Importantly, we revealed that FMR1 messenger RNA level is the most significant predictor accounting for dual-task stepping variability in both reaction time and movement time in PM females. These findings for the first time provide evidence linking elevated FMR1 messenger RNA levels that have been previously associated with FMR1 RNA toxicity and deficits in cerebellar motor and cognitive networks in a subgroup of at-risk PM women.
authors.affiliation: Olga Tennison Autism Research Centre, School of Psychological Science, La Trobe University, Bundoora, Victoria, Australia. Electronic address: d.hocking@latrobe.edu.au.
authors.forename: Darren R
authors.initials: DR
authors.lastname: Hocking
authors.affiliation: School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Claudine M
authors.initials: CM
authors.lastname: Kraan
authors.affiliation: Cyto-molecular Diagnostics Research, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: Godler
authors.affiliation: Centre for Epidemiology and Biostatistics, School of Population and Global Health, University of Melbourne, Carlton, Victoria, Australia.
authors.forename: Quang M
authors.initials: QM
authors.lastname: Bui
authors.affiliation: Cyto-molecular Diagnostics Research, Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Bradshaw
authors.affiliation: School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Sylvia A
authors.initials: SA
authors.lastname: Metcalfe
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, Australia; Victorian Clinical Genetics Services, Parkville, Victoria, Australia.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Archibald
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Erin
authors.initials: E
authors.lastname: Turbitt
authors.affiliation: School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Fielding
authors.affiliation: Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
authors.forename: Julian
authors.initials: J
authors.lastname: Trollor
authors.affiliation: Genetics Education and Health Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia; Centre for Developmental Disability Health Victoria, Monash University, Clayton, Victoria, Australia; Fragile X Alliance Inc (Clinic and Resource Centre), North Caulfield, Victoria, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.affiliation: School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia. Electronic address: kim.cornish@monash.edu.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cornish
mesh_terms: D003071:Cognition; D056344:Executive Function; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D006801:Humans; D009043:Motor Activity / Q000235:genetics*; D009154:Mutation; D004856:Postural Balance / Q000235:genetics*; D011187:Posture / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D012306:Risk; D012737:Sex Factors
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human
keywords: Cerebellar motor networks; Choice stepping reaction time; Cognitive-motor interference; FMR1 premutation carrier; Fragile X mental retardation gene 1 (FMR1); Motor symptoms; Postural control; Step initiation