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Understanding the Neuropsychiatric Phenotype of Fragile X-Associated Tremor Ataxia Syndrome: a Systematic Review

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Abstract

Fragile X-associated tremor ataxia syndrome (FXTAS) is a recently identified X-linked neurodegenerative disorder affecting a proportion of premutation carriers of the Fragile X Mental Retardation 1 (FMR1) gene. Previous research suggests that cognitive and psychiatric features of FXTAS may include primary impairments in executive function and increased vulnerability to mood and anxiety disorders. A number of these reports, however, are based on overlapping cohorts or have produced inconsistent findings. A systematic review was therefore conducted to further elucidate the neuropsychiatric features characteristic of FXTAS. Fourteen papers met inclusion criteria for the review and were considered to represent nine independent FXTAS cohorts. Findings from the review suggest that the neuropsychiatric phenotype of FXTAS is characterised primarily by poorer performance on measures of executive function, working memory, information processing speed, and fine motor control when compared to matched comparison groups. Two studies were identified in which psychiatric symptoms in FXTAS were compared with controls, and these yielded mixed results. Overall the results of this review support previous reports that the neuropsychiatric profile of FXTAS is consistent with a dysexecutive fronto-subcortical syndrome. However, additional controlled studies are required to progress our understanding of FXTAS and how the neuropsychiatric profile relates to underlying pathological mechanisms.

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Acknowledgments

The authors acknowledge a number of sources of funding including: The New South Wales Institute of Psychiatry (Fellowship in Research Training awarded to RB); The Australian Research Council (Discovery Project Grant DP110103346 to KC and JT); and the Dementia Collaborative Research Centre – Assessment and Better Care, University of New South Wales as part of the Australian Government’s Dementia Initiative. The authors also thank Dr Kristan Kang (Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia) for assisting with the preparation of figures.

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Authors and Affiliations

  1. Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, Australia

    R. C. Birch & J. N. Trollor

  2. Monash School of Psychological Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia

    K. M. Cornish

  3. Olga Tennison Autism Research Centre, School of Psychological Sciences, La Trobe University, Melbourne, Australia

    D. R. Hocking

  4. Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia

    J. N. Trollor

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  1. R. C. Birch
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  2. K. M. Cornish
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  3. D. R. Hocking
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  4. J. N. Trollor
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Correspondence to J. N. Trollor.

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Birch, R.C., Cornish, K.M., Hocking, D.R. et al. Understanding the Neuropsychiatric Phenotype of Fragile X-Associated Tremor Ataxia Syndrome: a Systematic Review. Neuropsychol Rev 24, 491–513 (2014). https://doi.org/10.1007/s11065-014-9262-9

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  • DOI: https://doi.org/10.1007/s11065-014-9262-9

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