Psychiatric Phenotype of the Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) in Males: Newly Described Fronto-Subcortical Dementia
Abstract
OBJECTIVE: The authors describe and quantify the neuropsychiatric symptoms present in a cohort of males with the fragile X mental retardation 1 (FMR1) premutation allele who have developed fragile X-associated tremor/ataxia syndrome (FXTAS). METHOD: Fourteen male carriers of the FMR1 premutation who had clinical manifestations of the FXTAS syndrome and 14 age- and education-matched controls were assessed with the Neuropsychiatric Inventory (NPI), formal cognitive testing, and genetic analysis. RESULTS: Males with FXTAS had significantly higher total NPI scores (p < .004) and significantly higher scores on the agitation/aggression (p < .004), depression (p < .004), apathy (p < .004), disinhibition (p < .004), and irritability (p < .004) scales, compared with controls. Cognitive performances on the Mini-Mental State Examination did not correlate with severity of symptoms on the NPI. CONCLUSIONS: The neuropsychiatric manifestations of FXTAS, based on this preliminary report, appear to cluster as a fronto-subcortical dementia. Clinicians encountering patients with clinical dementia with motor symptoms suggesting FXTAS should consider genetic testing to determine whether the patient's dementia syndrome is secondary to a fragile X premutation carrier status.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In premutation carriers, shyness, anxiety, social deficits, and ADHD are common, particularly in boys.
“In PM carriers, shyness, anxiety, social deficits, and ADHD are some of the most common features observed, particularly in boys (29)(30)(31).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [30]
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
The Neuropsychiatric Inventory: Comprehensive assessment of psychopathology in dementia
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A., & Gornbein, J. (1994) · Neurology · doi:10.1212/wnl.44.12.2308 · Cited by 7,568 · see citing works
Lyketsos, C. G., Lopez, O., Jones, B., Fitzpatrick, A. L., Breitner, J., & DeKosky, S. (2002) · JAMA · doi:10.1001/jama.288.12.1475 · Cited by 2,049 · see citing works
The Mini-Mental State Examination
Folstein, M. F. (1983) · Archives of General Psychiatry · doi:10.1001/archpsyc.1983.01790060110016 · Cited by 1,975 · see citing works
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease
Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., Friedhoff, L. T., & Donepezil Study Group* (1998) · Neurology · doi:10.1212/wnl.50.1.136 · Cited by 1,618 · see citing works
Lyketsos, C. G., Steinberg, M. I., Tschanz, J. T., Norton, M. C., Steffens, D. C., & Breitner, J. C. S. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.5.708 · Cited by 1,125 · see citing works
Tassone, F., Hagerman, R. J., Taylor, A. K., Gane, L. W., Godfrey, T. E., & Hagerman, P. J. (2000) · The American Journal of Human Genetics · doi:10.1086/302720 · Cited by 775 · see citing works
Self-citationNeuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers
Greco, C. (2002) · Brain · doi:10.1093/brain/awf184 · Cited by 560 · see citing works
Neuropsychiatric aspects of Huntington’s disease.
Paulsen, J. S. (2001) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.71.3.310 · Cited by 486 · see citing works
Fragile X Syndrome: Diagnosis, Treatment, And Research
Silverman, & Cronister, A. (1991) · Johns Hopkins University Press eBooks · Cited by 481 · see citing works
Report of the second dementia with Lewy body international workshop
McKeith, I. G., Perry, E. K., & Perry, R. H. (1999) · Neurology · doi:10.1212/wnl.53.5.902 · Cited by 464 · see citing works
Rousseau, F., Rouillard, P., Morel, M. L., Khandjian, E. W., & Morgan, K. (1995) · Europe PMC (PubMed Central) · Cited by 361 · see citing works
Fragile-X–Associated Tremor/Ataxia Syndrome (FXTAS) in Females with the FMR1 Premutation
Hagerman, R. J., Leavitt, B. R., Farzin, F., Jacquemont, S., Greco, C., Brunberg, J. A., Tassone, F., Hessl, D. R., Harris, S. W., Zhang, L., et al. (2004) · The American Journal of Human Genetics · doi:10.1086/420700 · Cited by 325 · see citing works
Self-citationComparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia
Noé, E., Marder, K. S., Bell, K. L., Jacobs, D. M., Manly, J. J., & Stern, Y. (2004) · Movement Disorders · doi:10.1002/mds.10633 · Cited by 267 · see citing works
REMOTE MEMORY FUNCTION IN ALZHEIMER'S DISEASE AND PARKINSON'S DISEASE
SAGAR, H. J., Cohen, N. J., Sullivan, E. V., Corkin, S., & Growdon, J. H. (1988) · Brain · doi:10.1093/brain/111.1.185 · Cited by 229 · see citing works
The concept of subcortical and cortical dementia: Another look
Whitehouse, P. J. (1986) · Annals of Neurology · doi:10.1002/ana.410190102 · Cited by 204 · see citing works
Differential cognitive impairment in alzheimer's disease and huntington's disease
Brandt, J., Folstein, S. E., & Folstein, M. F. (1988) · Annals of Neurology · doi:10.1002/ana.410230605 · Cited by 163 · see citing works
Parkinson?s disease: clinical aspects
Klockgether, T. (2004) · Cell and Tissue Research · doi:10.1007/s00441-004-0975-6 · Cited by 152 · see citing works
Frontotemporal Dementia: Behavioral Symptoms and Caregiver Distress
Mourik, J. C., Rosso, S. M., Niermeijer, M. F., Duivenvoorden, H. J., Swieten, J. C. V., & Tibben, A. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000080123 · Cited by 124 · see citing works
Neuropsychiatric Aspects of Parkinson’s Disease
Marsh, L. (2000) · Psychosomatics · doi:10.1016/s0033-3182(00)71169-8 · Cited by 118 · see citing works
Clinical features of frontal lobe dementia in comparison to Alzheimer’s disease
Gregory, C. A., & Hodges, J. R. (1996) · Journal of neural transmission. Supplementum · doi:10.1007/978-3-7091-6892-9_6 · Cited by 117 · see citing works
Neuropsychiatric Assessment of Patients With Hyperkinetic and Hypokinetic Movement Disorders
Litvan, I., Paulsen, J. S., Mega, M. S., & Cummings, J. L. (1998) · Archives of Neurology · doi:10.1001/archneur.55.10.1313 · Cited by 116 · see citing works
Litvan, I., Mohr, E., Williams, J. A., Gomez, C., & Chase, T. N. (1991) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.54.1.25 · Cited by 114 · see citing works
Bruni, A. C., Takahashi‐Fujigasaki, J., Maltecca, F., et al. (2004) · Archives of Neurology · doi:10.1001/archneur.61.8.1314 · Cited by 108 · see citing works
Psychological Dysfunction Accompanying Subcortical Dementias
Cummings, J. L., & Benson, D. F. (1988) · Annual Review of Medicine · doi:10.1146/annurev.me.39.020188.000413 · Cited by 91 · see citing works
Neumann, M., Adler, S., Schlüter, O. M., Kremmer, E., Benecke, R., & Kretzschmar, H. A. (2000) · Acta Neuropathologica · doi:10.1007/s004010000224 · Cited by 91 · see citing works
Distinctive Neurobehavioral Features Among Neurodegenerative Dementias
Hirono, N., Mori, E., Tanimukai, S., Kazui, H., Hashimoto, M., Hanihara, T., & Imamura, T. (1999) · Journal of Neuropsychiatry · doi:10.1176/jnp.11.4.498 · Cited by 81 · see citing works
The American Psychiatric Publishing Textbook of Clinical Psychiatry
(2003) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781585622689 · Cited by 79 · see citing works
Aphasia, Apraxia, and Agnosia in the Diagnosis of Dementia
Kramer, J. H., & Duffy, J. M. (1996) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000106848 · Cited by 64 · see citing works
Screening for FMR-1 premutations in 122 older Flemish males presenting with ataxia
Esch, H. V., Dom, R., Bex, D., et al. (2004) · European Journal of Human Genetics · doi:10.1038/sj.ejhg.5201312 · Cited by 64 · see citing works
Frontotemporal Dementia and Alzheimer’s Disease:Differential Diagnosis
Duara, R., Barker, W., & Luis, C. A. (1999) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000051210 · Cited by 53 · see citing works
Doddy, R. S., Massman, P. J., Mawad, M. E., & NANCE, M. A. (1998) · PubMed · Cited by 52 · see citing works
Choosing Appropriate Antidepressant Therapy in the Elderly
Flint, A. J. (1998) · Drugs & Aging · doi:10.2165/00002512-199813040-00003 · Cited by 50 · see citing works
Depression in the medically ill: choosing an antidepressant.
La, C. (1994) · PubMed · Cited by 34 · see citing works
Expanding Psychopharmacologic Treatment Options for the Depressed Medical Patient
Stoudemire, A. (1995) · Psychosomatics · doi:10.1016/s0033-3182(95)71700-5 · Cited by 33 · see citing works
Tremor/Ataxia syndrome in fragile X carrier males
Leehey, M. A., Hagerman, R. J., Landau, W. M., Grigsby, J., Tassone, F., & Hagerman, P. J. (2002) · Movement Disorders · doi:10.1002/mds.10208 · Cited by 32 · see citing works
Self-citationDementia in idiopathic Parkinson?s syndrome
Fuchs, G., Gemende, I., Herting, B., et al. (2004) · Journal of Neurology · doi:10.1007/s00415-004-1607-5 · Cited by 27 · see citing works
Measures to Assess the Noncognitive Symptoms of Dementia in the Primary Care Setting
Forester, B. P. (2003) · The Primary Care Companion For CNS Disorders · doi:10.4088/pcc.v05n0403 · Cited by 22 · see citing works
Delirium, Dementia, and Amnestic Disorders
First, M. B., & Tasman, A. (2006) · doi:10.1002/0470029528.ch11 · Cited by 12 · see citing works
Collins, B., Constant, J., Kaba, S. E., et al. (2004) · Clinical Neuropharmacology · doi:10.1097/01.wnf.0000148388.56605.d9 · Cited by 8 · see citing works
Blackson, T. C. (1995) · Journal of Clinical Psychology · doi:10.1002/1097-4679(199501)51:1 · Cited by 8 · see citing works
Abbeduto (2004) · doi:10.1352/0895-8017(2004)109
Flagged first, then by citations
Cited by
Sorted by citations
Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics
Bagni, C., Tassone, F., Neri, G., & Hagerman, R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci63141 · Cited by 321 · see citing works
Self-citationAdvances in understanding the molecular basis of FXTAS
Garcia-Arocena, D., & Hagerman, P. J. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq166 · Cited by 136 · see citing works
FMR1 premutation and full mutation molecular mechanisms related to autism
Hagerman, R., Au, J., & Hagerman, P. (2011) · Journal of Neurodevelopmental Disorders · doi:10.1007/s11689-011-9084-5 · Cited by 85 · see citing works
Self-citationDe Rubeis, S., Fernández, E., Buzzi, A., Di Marino, D., & Bagni, C. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-7091-0932-8_23 · Cited by 48 · see citing works
Fragile X-associated tremor/ataxia syndrome: Pathophysiology and management
Hagerman, R., & Hagerman, P. (2021) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000954 · Cited by 40 · see citing works
Self-citation
- Authors
- Bacalman, S., Farzin, F., Bourgeois, J. A., Cogswell, J., Goodlin-Jones, B. L., Gane, L. W., Grigsby, J., Leehey, M. A., Tassone, F., & Hagerman, R. J.
- Affiliations
- University of California Davis Medical Center (US)
- University of California, Davis (US)
- University of Colorado Health (US)
- Venue
- The Journal of Clinical Psychiatry
- Publisher
- Physicians Postgraduate Press, Inc
- Published
- 2006-01-15
- Volume
- 67
- Issue
- 01
- Pages
- 87-94
- ISSN
- 0160-6689 (ISSN-L)
- OpenAlex
- W2077967214
- Cited by
- 175
- References
- 42
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 7 · 2018: 1 · 2017: 3 · 2016: 17 · 2015: 5 · 2014: 10 · 2013: 11 · 2012: 9
- FWCI
- 9.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS 45352, NS 044299, R01NS044299)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 36071, HD 02274, P30HD002274, R01HD036071)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- fragile X-associated tremor/ataxia syndrome, fragile X premutation, neuropsychiatric symptoms, agitation and aggression, depression, apathy, disinhibition, irritability, male carriers, cognitive impairment, genetic testing
- MeSH terms
- Aged, Ataxia, Dementia, Fragile X Syndrome, Genetic Testing, Heterozygote, Genetic Carrier Screening, Humans, Male, Middle Aged, Personality Inventory, Phenotype, Psychiatric Status Rating Scales, Severity of Illness Index, Sex Factors, Syndrome, Tremor, Wechsler Scales, Genetic Predisposition to Disease, Fragile X Messenger Ribonucleoprotein 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review