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Executive Dysfunction in Female FMR1 Premutation Carriers

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Abstract

There is now growing evidence of cognitive weakness in female premutation carriers (between 55 and 199 CGG repeats) of the fragile X mental retardation gene, including impairments associated with executive function. While an age-related decline in assessments of executive function has been found for male premutation carriers, few studies have explored whether female carriers show a similar trajectory with age. A total of 20 female premutation carriers and 21 age- and IQ-matched healthy controls completed a battery of tasks assessing executive function tasks, including the behavioural dyscontrol scale (BDS), symbol digit modalities test (SDMT), paced auditory serial addition test (PASAT), Haylings sentence completion test and the digit span task (forward and backward). Performance was compared between premutation carriers and healthy controls, and the association between task performance and age was also ascertained. Compared to controls, female premutation carriers had significant impairment on the BDS, SDMT, PASAT, and Haylings sentence completion task, all of which rely on quick, or timed, responses. Further analyses revealed no significant association between age and task performance for either premutation carriers or controls. This study demonstrates that a cohort of female premutation carriers have deficits on a range of tasks of executive function that require the rapid temporal resolution of responses. We propose that the understanding of the phenotype of premutation carriers will be advanced through use of such measures.

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Acknowledgments

We express our thanks to the Fragile X Association of Australia and Fragile X Alliance for their support in recruitment. We also thank Jonathan Whitty from Healthscope Pathology and Erin Turbitt from the Murdoch Childrens Research Institute for their assistance on the molecular procedures. Finally, we are indebted to all the families who participated in this research.

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Authors and Affiliations

  1. School of Psychological Sciences and Monash Institute of Cognitive and Clinical Neurosciences (MICCN), Monash University, Melbourne, VIC, Australia

    Annie L. Shelton, Kim M. Cornish, Claudine M. Kraan & Joanne Fielding

  2. Seaver Autism Center for Research and Treatment, Departments of Genetics and Genomic Sciences, Psychiatry, and Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Reymundo Lozano

  3. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia

    Minh Bui

  4. Department of Medicine, University of Melbourne, Melbourne, VIC, Australia

    Joanne Fielding

Authors
  1. Annie L. Shelton
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  2. Kim M. Cornish
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  3. Claudine M. Kraan
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  4. Reymundo Lozano
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  5. Minh Bui
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  6. Joanne Fielding
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Corresponding author

Correspondence to Joanne Fielding.

Ethics declarations

Ethics approval for this study was granted by the Monash University and Southern Health Human Research Committees (Project Number 10147B); all participants gave their informed consent prior to inclusion in the study in accordance with the declaration of Helsinki.

Conflict of Interest

A. Shelton, K. Cornish, C. Kraan, Q. Bui, J. Fielding report no disclosures relevant to the manuscript. R. Lozano has consulted for Ambry genetics, Courtagen and ClearView Healthcare Partners.

Financial Disclosures

This work was funded by Australian Research Council (ARC) Discovery grant (DP110103346) to K. Cornish and J. Fielding; A. Shelton is an Australian Postgraduate Award Scholarship holder; C. Kraan holds a Monash Faculty of Medicine Nursing and Health Sciences Bridging Postdoctoral Fellowship; R. Lozano is an NIH (GM082773), Friedman Brain Institute and Seaver Faculty Scholar. All authors have no further financial disclosures to make.

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Shelton, A.L., Cornish, K.M., Kraan, C.M. et al. Executive Dysfunction in Female FMR1 Premutation Carriers. Cerebellum 15, 565–569 (2016). https://doi.org/10.1007/s12311-016-0782-0

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