Article

Investigation of Phenotypes Associated with Mood and Anxiety Among Male and Female Fragile X Premutation Carriers

Behavior Genetics (Impact Factor: 2.61). 09/2008; 38(5):493-502. DOI: 10.1007/s10519-008-9214-3

ABSTRACT The fragile X disorder spectrum, due to a CGG expansion in FMR1, includes fragile X syndrome (>200 repeats) and the premutation-associated disorders of ovarian insufficiency and tremor/ataxia
syndrome (~55–199 repeats). Altered neurobehavioral profiles including variation of phenotypes associated with mood and anxiety
may be expected among younger premutation carriers given this spectrum of disorders. However, previous studies have produced
conflicting findings, providing the motivation to examine these phenotypes further. We investigated measures of mood and anxiety
in 119 males and 446 females age 18–50 ascertained from families with a history of fragile X syndrome and from the general
population. Scores were analyzed using a linear model with repeat length as the main predictor, adjusting for potential confounders.
Repeat length was not associated with anxiety, but was marginally associated with depression and negative affect in males
and negative affect only in females. These results suggest that premutation carriers may be at risk for emotional morbidity;
however, phenotypic differences were subtle and of small effect size.

0 Bookmarks
 · 
70 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: We utilised a sample of 299 adult females aged between 19 and 86 years, carrying FMR1 alleles with small CCG expansions ranging from 50 to 141 repeats to analyse the relationships between psychological symptoms as assessed by the Symptom Checklist-90-Revised (SCL-90-R) and the size of the CGG repeat in the FMR1 gene. There were highly significant (negative) correlations between the size of the CGG repeat and a great majority of SCL-90-R subscale scores and all the global indices, suggesting that carriers of premutations in the mid-size CGG repeat range may be at greatest risk for development of psychiatric disorder.
    Clinical Genetics 01/2014; · 4.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: FXTAS, a neurodegenerative disorder, affects Fragile X (FMR1) gene premutation carriers in late-life. Studies have shown cognitive impairments in FXTAS including executive dysfunction, working memory, and visuospatial deficits. However, less is known about cognition in females with FXTAS. Thus, we examined semantic processing and verbal memory in female FXTAS patients with event-related potentials (ERPs) and neuropsychological testing. 61 females (34 FXTAS Mage = 62.7, 27 controls Mage = 60.4) were studied with 32-channel ERPs during a category judgment task in which semantically congruous (50%) and incongruous items were repeated ~10-140s later. N400 and P600 amplitude data were submitted to ANCOVA. Neuropsychological testing demonstrated lower performance in verbal learning and executive function in females with FXTAS. ERP analyses revealed a significant reduction of the N400 congruity effect (incongruous - congruous) in the FXTAS group. The N400 congruity effect reduction in females with FXTAS was mainly due to increased N400 amplitude to congruous new words. No significant abnormalities of the N400 repetition effect or the P600 repetition effect were found, indicating preserved implicit memory and verbal memory, respectively, in females with FXTAS. The decreased N400 congruity effect suggests abnormal semantic expectancy and/or semantic network disorganization in female FXTAS patients. The enhanced N400 amplitude to congruous new words may reflect decreased cognitive flexibility among FXTAS women, making access to less typical category exemplar words more difficult.
    Genes Brain and Behavior 12/2013; · 3.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X mental retardation 1) premutation. Penetrance and expression appear to be significantly higher in males than females. Although the most obvious aspect of the phenotype is the movement disorder that gives FXTAS its name, the disorder is also accompanied by progressive cognitive impairment. In this review, we address the cognitive neuropsychological and neurophysiological phenotype for males and females with FXTAS, and for male and female unaffected carriers. Despite differences in penetrance and expression, the cognitive features of the disorder appear similar for both genders, with impairment of executive functioning, working memory, and information processing the most prominent. Deficits in these functional systems may be largely responsible for impairment on other measures, including tests of general intelligence and declarative learning. FXTAS is to a large extent a white matter disease, and the cognitive phenotypes observed are consistent with what some have described as white matter dementia, in contrast to the impaired cortical functioning more characteristic of Alzheimer's disease and related disorders. Although some degree of impaired executive functioning appears to be ubiquitous among persons with FXTAS, the data suggest that only a subset of unaffected carriers of the premutation - both female and male - demonstrate such deficits, which typically are mild. The best-studied phenotype is that of males with FXTAS. The manifestations of cognitive impairment among asymptomatic male carriers, and among women with and without FXTAS, are less well understood, but have come under increased scrutiny.
    Journal of Neurodevelopmental Disorders 01/2014; 6(1):28. · 3.45 Impact Factor