Fragile X-associated disorders: Don't miss them.

BACKGROUND: Fragile X-associated disorders are a family of inherited disorders caused by expansions in the Fragile X Mental Retardation 1 (FMR1) gene. Premutation expansions of the FMR1 gene confer risk for fragile X-associated primary ovarian insufficiency and fragile X-associated tremor ataxia syndrome, as well as other medical and psychiatric comorbidities. Premutation expansions of the FMR1 gene are common in the general population. However, fragile X-associated disorders are frequently under-recognised and often misdiagnosed. OBJECTIVE: The aim of this article is to describe fragile X-associated disorders and identify specific considerations for general practitioners (GPs) during identification and management of these disorders. DISCUSSION: GPs have a critical role in the identification of fragile X-associated disorders, as well as coordination of complex care needs. Prompt recognition and appropriate management of these disorders and potential medical and psychiatric comorbidities will have important implications not only for the affected patient, but also other family members who may be at risk.

Cognitive Dysfunction in Chronic Fatigue Syndrome: a Review of Recent Evidence.

Cognitive difficulties represent a common and debilitating feature of the enigmatic chronic fatigue syndrome (CFS). These difficulties manifest as self-reported problems with attention, memory, and concentration and present objectively as slowed information processing speed particularly on complex tasks requiring sustained attention. The mechanisms underlying cognitive dysfunction remain to be established; however, alterations in autonomic nervous system activity and cerebral blood flow have been proposed as possibilities. Heterogeneity in the experience of cognitive impairment, as well as differences in the methods utilised to quantify dysfunction, may contribute to the difficulties in establishing plausible biological underpinnings. The development of a brief neurocognitive battery specifically tailored to CFS and adoption by the international research community would be beneficial in establishing a profile of cognitive dysfunction. This could also provide better insights into the underlying biological mechanisms of cognitive dysfunction in CFS and enhance the development of targeted treatments.

Problems managed and medications prescribed during encounters with people with autism spectrum disorder in Australian general practice.

Autism spectrum disorder is associated with high rates of co-occurring health conditions. While elevated prescription rates of psychotropic medications have been reported in the United Kingdom and the United States, there is a paucity of research investigating clinical and prescribing practices in Australia. This study describes the problems managed and medications prescribed by general practitioners in Australia during encounters where an autism spectrum disorder was recorded. Information was collected from 2000 to 2014 as part of the Bettering the Evaluation and Care of Health programme. Encounters where patients were aged less than 25 years and autism spectrum disorder was recorded as one of the reasons for encounter and/or problems managed ( n = 579) were compared to all other Bettering the Evaluation and Care of Health programme encounters with patients aged less than 25 years ( n = 281,473). At 'autism spectrum disorder' encounters, there was a significantly higher management rate of psychological problems, and significantly lower management rates of skin, respiratory and general/unspecified problems, than at 'non-autism spectrum disorder' encounters. The rate of psychological medication prescription was significantly higher at 'autism spectrum disorder' encounters than at 'non-autism spectrum disorder' encounters. The most common medications prescribed at 'autism spectrum disorder' encounters were antipsychotics and antidepressants. Primary healthcare providers need adequate support and training to identify and manage physical and mental health concerns among individuals with autism spectrum disorder.

Performance-Based Assessment of Instrumental Activities of Daily Living: Validation of the Sydney Test of Activities of Daily Living in Memory Disorders (STAM).

OBJECTIVES: The distinction between dementia and mild cognitive impairment (MCI) relies upon the evaluation of independence in instrumental activities of daily living (IADL). Self- and informant reports are prone to bias. Clinician-based performance tests are limited by long administration times, restricted access, or inadequate validation. To close this gap, we developed and validated a performance-based measure of IADL, the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). DESIGN: Prospective cohort study (Sydney Memory and Ageing Study). SETTING: Eastern Suburbs, Sydney, Australia. PARTICIPANTS: 554 community-dwelling individuals (54% female) aged 76 and older with normal cognition, MCI, or dementia. MEASUREMENTS: Activities of daily living were assessed with the STAM, administered by trained psychologists, and the informant-based Bayer-Activities of Daily Living Scale (B-ADL). Depressive symptoms were measured with the Geriatric Depression Scale (15-item version). Cognitive function was assessed with a comprehensive neuropsychological test battery. Consensus diagnoses of MCI and dementia were made independently of STAM scores. RESULTS: The STAM showed high interrater reliability (r = 0.854) and test-retest reliability (r = 0.832). It discriminated significantly between the diagnostic groups of normal cognition, MCI, and dementia with areas under the curves ranging from 0.723 to 0.948. A score of 26.5 discriminated between dementia and nondementia with a sensitivity of 0.831 and a specificity of 0.864. Correlations were low with education (r = 0.230) and depressive symptoms (r = -0.179), moderate with the B-ADL (r = -0.332), and high with cognition (ranging from r = 0.511 to r = 0.594). The mean time to complete the STAM was 16 minutes. CONCLUSIONS: The STAM has good psychometric properties. It can be used to differentiate between normal cognition, MCI, and dementia and can be a helpful tool for diagnostic classification both in clinical practice and research.

Cerebellar volume mediates the relationship between FMR1 mRNA levels and voluntary step initiation in males with the premutation.

Recent evidence indicates that adults with a premutation (PM: 55-199 CGG repeats) expansion in the fragile X mental retardation 1 (FMR1) gene show postural control deficits that may reflect disruption to cerebellar motor regions. Less is known about the influence of reduced cerebellar volume and structural changes, and increase in CGG repeat and FMR1 mRNA levels on the attentional demands of step initiation in PM males. We investigated the effects of a concurrent cognitive task on choice stepping reaction time (CSRT) and explored the associations between CSRT performance, cerebellar volume, CGG size, and FMR1 mRNA levels in blood in PM males. We examined 19 PM males (ages 28-75) and 23 matched controls (CGG <44; ages 26-77), who performed a verbal fluency task during CSRT performance and single-task stepping without a secondary cognitive task. Our results provide preliminary evidence that smaller cerebellar volume (ß = -2.73, p = 0.002) and increasing CGG repeat length (ß = 1.69, p = 0.003) were associated with greater dual-task step initiation times in PM males, but not in controls. There was evidence of a mediating effect of cerebellar volume on the relationship between FMR1 mRNA levels and single-task CSRT performance in PM males (estimate coefficient = 8.69, standard error = 4.42, p = 0.049). These findings suggest increasing CGG repeat and FMR1 mRNA levels have neurotoxic effects on cerebellar regions underlying anticipatory postural responses during stepping. Cerebellar postural changes may be predictive of the increased risk of falls in older PM males.

Erratum: Emerging topics in FXTAS.

[This corrects the article DOI: 10.1186/1866-1955-6-31.].

Emerging topics in FXTAS.

This paper summarizes key emerging issues in fragile X-associated tremor/ataxia syndrome (FXTAS) as presented at the First International Conference on the FMR1 Premutation: Basic Mechanisms & Clinical Involvement in 2013.