title: Clinically significant psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, and the mediating influence of executive functioning.
abstract: OBJECTIVE
  To clarify the neuropsychiatric phenotype of fragile X-associated tremor/ataxia syndrome (FXTAS), and assess the extent to which it is mediated by the dysexecutive syndrome that is a major feature of the disorder.
  
  
  METHODS
  We examined the prevalence of clinically meaningful psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, in comparison with men with a normal allele. Measures included the Neuropsychiatric Inventory (NPI), Symptom Checklist-90-R (SCL-90-R), and the Behavioral Dyscontrol Scale, a measure of executive functioning. Between-group differences were evaluated using logistic regression, followed by a mediation analysis with ordinary least squares regression to assess the contribution of dysexecutive syndrome to the observed psychiatric domains.
  
  
  RESULTS
  Men with FXTAS showed higher rates of clinically significant symptoms overall and in specific domains: somatization, obsessive compulsive, depression, anxiety, psychoticism, agitation/aggression, apathy/indifference, irritability, and nighttime behavior problems. Post hoc analyses suggested that findings of psychoticism among men with FXTAS may be associated with participants' accurate acknowledgment of cognitive and physical dysfunction, rather than reflecting psychosis. Asymptomatic carriers showed no evidence of clinically significant psychiatric symptoms, but when all carriers were compared with men having a normal FMR1 allele, executive function deficits were found to mediate scores in several domains on both NPI and SCL-90-R.
  
  
  CONCLUSIONS
  Building on prior research, the results provide evidence that the psychiatric phenotype for men includes clinically meaningful depression, hostility, and irritability, in association with behavioral and attentional disinhibition. It is likely that these problems reflect the effects of impaired executive functioning.
authors.affiliation: a Department of Psychology , University of Colorado Denver , Denver , CO , USA.|b Department of Medicine , University of Colorado Denver , Aurora , CO , USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Grigsby
authors.affiliation: c Department of Community and Behavioral Health , Colorado School of Public Health, University of Colorado Denver , Aurora , CO , USA.
authors.forename: Angela G
authors.initials: AG
authors.lastname: Brega
authors.affiliation: b Department of Medicine , University of Colorado Denver , Aurora , CO , USA.
authors.forename: Rachael E
authors.initials: RE
authors.lastname: Bennett
authors.affiliation: d Department of Psychiatry , University of California , San Francisco , CA , USA.|e Langley Porter Psychiatric Institute , University of California , San Francisco , CA , USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Bourgeois
authors.affiliation: d Department of Psychiatry , University of California , San Francisco , CA , USA.
authors.forename: Andreea L
authors.initials: AL
authors.lastname: Seritan
authors.affiliation: f Kaiser Permanente Institute for Health Research , Denver , CO , USA.
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Goodrich
authors.affiliation: g M.I.N.D. Institute , University of California, Davis , Sacramento , CA , USA.|h Department of Pediatrics , University of California, Davis, Medical Center , Sacramento , CA , USA.
authors.forename: Randi J
authors.initials: RJ
authors.lastname: Hagerman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001007:Anxiety / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D001259:Ataxia / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology*; D056344:Executive Function / Q000502:physiology*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics*; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics / Q000523:psychology; D014202:Tremor / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology*
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1
keywords: FXTAS; Fragile X; executive functioning; fragile X tremor/ataxia syndrome; premutation; psychiatric symptoms