110 research outputs found
Inhibition Deficits Are Modulated by Age and CGG Repeat Length in Carriers of the \u3ci\u3eFMR1\u3c/i\u3e Premutation Allele Who Are Mothers of Children With Fragile X Syndrome
Individuals who carry a premutation (PM) allele on the FMR1 gene may experience executive limitations associated with their genetic status, including inhibition deficits. However, poor understanding of individualized risk factors has limited clinical management of this group, particularly in mothers who carry the PM allele who have children with fragile X syndrome (FXS). The present study examined CGG repeat length and age as factors that may account for variable expressivity of inhibition deficits. Participants were 134 carriers of the PM allele who were mothers of children with FXS. Inhibition skills were measured using both self-report and direct behavioral assessments. Increased vulnerability for inhibition deficits was observed at mid-range CGG lengths of approximately 80-100 repeats, with some evidence of a second zone of vulnerability occurring at approximately 130-140 CGG repeats. Risk associated with the genotype also became more pronounced with older age. This study identifies personalized risk factors that may be used to tailor the clinical management of executive deficits in carriers of the PM allele. Inhibition deficits may contribute to poor outcomes in carriers of the PM allele and their families, particularly in midlife and early old age, and clinical monitoring may be warranted
Age-Related Differences in Restricted Repetitive Behaviors in Autism Spectrum Disorders
Restricted repetitive behaviors (RRBs) were examined in a large group of children, adolescents and adults with ASD in order to describe age-related patterns of symptom change and association with specific contextual factors, and to examine if the patterns of change are different for the various types of RRBs. Over 700 individuals with ASD were rated on the Repetitive Behavior Scale â Revised. RRBs were less frequent and less severe among older than younger individuals, corroborating that autism symptoms abate with age. Our findings further suggest that repetitive behaviors are a heterogeneous group of behaviors, with the subtypes of RRBs having their own individual patterns across the lifespan, and in some cases, a differential association with age depending on intellectual functioning
Family History of FXTAS Is Associated With Age-Related Cognitive-Linguistic Decline Among Mothers With the fmr1 Premutation
BACKGROUND: Women who carry a premutation allele of the FMR1 gene are at increased vulnerability to an array of age-related symptoms and disorders, including age-related decline in select cognitive skills. However, the risk factors for age-related decline are poorly understood, including the potential role of family history and genetic factors. In other forms of pathological aging, early decline in syntactic complexity is observed and predicts the later onset of neurodegenerative disease. To shed light on the earliest signs of degeneration, the present study characterized longitudinal changes in the syntactic complexity of women with the FMR1 premutation across midlife, and associations with family history of fragile X-associated tremor/ataxia syndrome (FXTAS) and CGG repeat length. METHODS: Forty-five women with the FMR1 premutation aged 35-64 years at study entry participated in 1-5 longitudinal assessments spaced approximately a year apart (130 observations total). All participants were mothers of children with confirmed fragile X syndrome. Language samples were analyzed for syntactic complexity and participants provided information on family history of FXTAS. CGG repeat length was determined via molecular genetic testing. RESULTS: Hierarchical linear models indicated that women who reported a family history of FXTAS exhibited faster age-related decline in syntactic complexity than those without a family history, with that difference emerging as the women reached their mid-50 s. CGG repeat length was not a significant predictor of age-related change. CONCLUSIONS: Results suggest that women with the FMR1 premutation who have a family history of FXTAS may be at increased risk for neurodegenerative disease, as indicated by age-related loss of syntactic complexity. Thus, family history of FXTAS may represent a personalized risk factor for age-related disease. Follow-up study is needed to determine whether syntactic decline is an early indicator of FXTAS specifically, as opposed to being a more general age-related cognitive decline associated with the FMR1 premutation
The Symptoms of Autism Spectrum Disorders in Adolescence and Adulthood
This article describes the symptoms of autism spectrum disorders (ASD) manifested by 405 individuals between the ages of 10 and 53 years, all of whom had an ASD diagnosis. Data were collected using the Autism Diagnostic InterviewâRevised (ADI-R) to assess the pattern of autism symptoms in adolescence and adulthood. Findings include that although virtually all sample members met the criteria for Autistic Disorder earlier in their childhood, just over half (54.8%) would have met autism criteria if current scores were used to complete the diagnostic algorithm; that adolescents were more likely to improve in the Reciprocal Social Interaction domain than the adults, whereas the adults were more likely to improve in the Restricted, Repetitive Behaviors and Interests domain, and there were no differences in severity of symptoms between cohorts in the Communication domain; and that individual symptoms showed unique trajectories, with greatest symptom abatement between lifetime and current ADI-R ratings for speaking in at least three-word phrases and the least symptom improvement for having friendships. Findings were interpreted in the context of life course development, reformulations of diagnostic criteria, and changing service contexts for individuals with autism spectrum disorders.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44621/1/10803_2004_Article_474978.pd
Curvilinear Association Between Language Disfluency and FMR1 CGG Repeat Size Across the Normal, Intermediate, and Premutation Range
Historically, investigations of FMR1 have focused almost exclusively on the clinical effects of CGG expansion within the categories of the premutation (55â200 CGG repeats) and fragile X syndrome (\u3e200 CGG repeats). However, emerging evidence suggests that CGG-dependent phenotypes may occur across allele sizes traditionally considered within the ânormalâ range. This study adopted an individual-differences approach to determine the association between language production ability and CGG repeat length across the full range of normal, intermediate, and premutation alleles. Participants included 61 adult women with CGG repeats within the premutation (n = 37), intermediate (i.e., 41â54 repeats; n = 2), or normal (i.e., 6â40 repeats; n = 22) ranges. All participants were the biological mothers of a child with a developmental disorder, to control for the potential effects of parenting stress. Language samples were collected and the frequency of language disfluencies (i.e., interruptions in the flow of speech) served as an index of language production skills. Verbal inhibition skills, measured with the Hayling Sentence Completion Test, were also measured and examined as a correlate of language disfluency, consistent with theoretical work linking language disfluency with inhibitory deficits (i.e., the Inhibition Deficit Hypothesis). Blood samples were collected to determine FMR1 CGG repeat size. A general linear model tested CGG repeat size of the larger allele (allele-2) as the primary predictor of language disfluency, covarying for education level, IQ, age, and CGG repeats on the other allele. A robust curvilinear association between CGG length and language disfluency was detected, where low-normal (⌠\u3c25 \u3erepeats) and mid-premutation alleles (âŒ90â110 repeats) were linked with higher rates of disfluency. Disfluency was not associated with inhibition deficits, which challenges prior theoretical work and suggests that a primary language deficit could account for elevated language disfluency in FMR1-associated conditions. Findings suggest CGG-dependent variation in language production ability, which was evident across individuals with and without CGG expansions on FMR1
Objectum sexuality: a sexual orientation linked with autism and synaesthesia
Objectum-sexuality (OS) is a sexual orientation which has received little attention in the academic literature. Individuals who identify as OS experience emotional, romantic and/or sexual feelings towards inanimate objects (e.g. a bridge, a statue). We tested 34 OS individuals and 88 controls, and provide the first empirical evidence that OS is linked to two separate neurodevelopmental traits - autism and synaesthesia. We show that OS individuals possess significantly higher rates of diagnosed autism and significantly stronger autistic traits compared to controls, as well as a significantly higher prevalence of synaesthesia, and significant synaesthetic traits inherent in the nature of their attractions. Our results suggest that OS may encapsulate autism and synaesthesia within its phenomenology. Our data speak to debates concerning the biological underpinnings of sexuality, to models of autism and synaesthesia, and to psychological and philosophical models of romantic love
Associated features in females with an FMR1 premutation
Abstract Changes in the fragile X mental retardation 1 gene (FMR1) have been associated with specific phenotypes, most specifically those of fragile X syndrome (FXS), fragile X tremor/ataxia syndrome (FXTAS), and fragile X primary ovarian insufficiency (FXPOI). Evidence of increased risk for additional medical, psychiatric, and cognitive features and conditions is now known to exist for individuals with a premutation, although some features have been more thoroughly studied than others. This review highlights the literature on medical, reproductive, cognitive, and psychiatric features, primarily in females, that have been suggested to be associated with changes in the FMR1 gene. Based on this review, each feature is evaluated with regard to the strength of evidence of association with the premutation. Areas of need for additional focused research and possible intervention strategies are suggested
The Evolution of the Wisconsin Institutes for Discovery
In 2008, construction will begin on the Wisconsin Institutes for Discovery. These twin centers -- the private Morgridge Institute for Research (MIR) and the public Wisconsin Institute for Discovery (WID) -- will serve as a hub for interdisciplinary research on the UW-Madison campus.
For instance, WID will facilitate research and learning in the biological sciences by engaging a diversity of researchers from across the campus in an interdisciplinary, collaborative environment. Ultimately, the institute will produce scientific advances that can be translated into biomedical and related applications.
As WID Interim Director, Marsha Mailick Seltzer has been highly involved in the development of both WID and MIR. Join her for a discussion of the fundamental questions and issues that planners have encountered throughout this process. Topics will include public-private partnerships, public service and outreach, relationships with industrial and investment communities, undergraduate experiences, space and architecture, urban design, and others
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