Abstract
Introduction: Premutation expansions (55–200 CGG repeats) of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome are associated with a range of clinical features. Apart from the most severe - Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) - where the most typical white matter changes affect cerebellar peduncles, more subtle changes may include impairment of executive functioning, affective disorders and/or subtle motor changes. Here we aimed to examine whether performance in selected components of executive functioning is associated with subclinical psychiatric symptoms in non-FXTAS, adult females carrying the FMR1 premutation.Methods and Sample: A total of 47 female premutation carriers (sub-symptomatic for FXTAS) of wide age range (26–77 years; M = 50.3; SD = 10.9) were assessed using standard neuropsychological tests, three motor rating scales and self-reported measures of psychiatric symptoms using the Symptom Checklist-90-Revised (SCL-90-R).Results: After adjusting for age and educational level where appropriate, both non-verbal reasoning and response inhibition as assessed on the Stroop task (i.e., the ability to resolve cognitive interference) were associated with a range of primary psychiatric symptom dimensions, and response inhibition uniquely predicted some primary symptoms and global psychiatric features. Importantly, lower scores (worse performance) in response inhibition were also strongly correlated with higher (worse) scores on standard motor rating scales for tremor-ataxia and for parkinsonism.Conclusion: These results provide evidence for the importance of response inhibition in the manifestation of psychiatric symptoms and subtle tremor-ataxia motor features, suggestive of the presence of early cerebellar changes in female premutation carriers.
Highlights
Premutation expansions (55–200 CGG repeats) of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome are associated with a range of clinical features
We have shown that mild motor deficits were correlated with setshifting, working memory and psychomotor speed in female premutation expansion (PM) carriers without a diagnosis of Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) [23]
The present study explores the relationships between distinct subcomponents of cognitive-executive functioning and a range of psychiatric symptoms in a sample of non-FXTAS, clinically unaffected female PM carriers across a broad range of age and CGG expansion sizes
Summary
Premutation expansions (55–200 CGG repeats) of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome are associated with a range of clinical features. The premutation expansion (PM: 55–200 CGG repeats) of the Fragile X Mental Retardation 1 (FMR1) gene on the X chromosome is associated with a range of clinical features, including executive function impairments and affective disorders [1]. The clinical features include intention and/or postural tremor, gait ataxia, dementia, and in some cases parkinsonism This syndrome usually occurs after, and progresses from, the age of 55 years, and is more prevalent in male (45%) than in female (8–16%) PM carriers. In addition to FXTAS, women carrying the PM allele are at increased risk (∼20%) of developing premature ovarian failure [3] Apart from these two well-recognized disorders, subtle cognitiveexecutive and neuropsychiatric features are not uncommon [4], and the latter have more recently been recognized as a distinct group termed: Fragile X-Associated Neuropsychiatric Disorders (FXAND) [5]. These include cognitive-executive impairments, anxiety, social deficits, depression and obsessive compulsive features
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