title: Delineation of the working memory profile in female FMR1 premutation carriers: the effect of cognitive load on ocular motor responses.
abstract: Fragile X mental retardation 1 (FMR1) premutation carriers (PM-carriers) are characterised as having mid-sized expansions of between 55 and 200 CGG repeats in the 5' untranslated region of the FMR1 gene. While there is evidence of executive dysfunction in PM-carriers, few studies have explicitly explored working memory capabilities in female PM-carriers. 14 female PM-carriers and 13 age- and IQ-matched healthy controls completed an ocular motor n-back working memory paradigm. This task examined working memory ability and the effect of measured increases in cognitive load. Female PM-carriers were found to have attenuated working memory capabilities. Increasing the cognitive load did not elicit the expected reciprocal increase in the task errors for female PM-carriers, as it did in controls. However female PM-carriers took longer to respond than controls, regardless of the cognitive load. Further, FMR1 mRNA levels were found to significantly predict PM-carrier response time. Although preliminary, these findings provide further evidence of executive dysfunction, specifically disruption to working memory processes, which were found to be associated with increases in FMR1 mRNA expression in female PM-carriers. With future validation, ocular motor paradigms such as the n-back paradigm will be critical to the development of behavioural biomarkers for identification of PM-carrier cognitive-affective phenotypes.
authors.affiliation: School of Psychological Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Shelton
authors.affiliation: School of Psychological Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Cornish
authors.affiliation: Cyto-molecular Diagnostic Research Laboratory, Victorian Clinical Genetics Services and Murdoch Childrens Research Institute, Royal Children's Hospital, Melbourne 3052, VIC, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: Godler
authors.affiliation: School of Psychological Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Meaghan
authors.initials: M
authors.lastname: Clough
authors.affiliation: School of Psychological Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia.
authors.forename: Claudine
authors.initials: C
authors.lastname: Kraan
authors.affiliation: Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne 3010, VIC, Australia.
authors.forename: Minh
authors.initials: M
authors.lastname: Bui
authors.affiliation: School of Psychological Science, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia. Electronic address: joanne.fielding@monash.edu.
authors.forename: Joanne
authors.initials: J
authors.lastname: Fielding
mesh_terms: D000293:Adolescent; D000328:Adult; D003071:Cognition; D005133:Eye Movements; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000235:genetics* / Q000523:psychology*; D006579:Heterozygote; D006801:Humans; D008570:Memory, Short-Term; D008875:Middle Aged; D009154:Mutation; D011597:Psychomotor Performance; D012333:RNA, Messenger; D011930:Reaction Time; D055815:Young Adult
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger
keywords: Cognition; Fragile X mental retardation 1 (FMR1) gene; Fragile X premutation; Ocular motor; Working memory