“I’m not mad, bad, and dangerous … simply wired differently”: Exploring factors contributing to good quality of life with autistic women

Background: There is increasing recognition of under-representation of autistic women in the academic literature and the impact of this on understanding, diagnosis, and support. Previous research has suggested that autistic women have poorer quality of life (QoL) than the general population. However, these findings have been established through use of QoL measures based on non-autistic norms and priorities. Methods: This qualitative study used bottom-up, reflexive thematic analysis methods to explore how ten autistic women defined good QoL, and the factors identified as key to achieving this, using individual semi-structured interviews. Results: Findings indicate four main themes that represent routes to good QoL: positive sense of self; feeling supported; autonomy; inclusion. Participants noted that being autistic itself was not a determinant of reduced QoL. Instead, participants’ QoL was underpinned by the extent to which participants understood themselves, others understood and accommodated their needs, and the person-environment fit. Conclusions: The findings of this study align with a positive approach to neurological difference and have implications for diagnosis, post-diagnostic support and applications of current QoL measures for autistic women.<br/

Topic maintenance in social conversation: What children need to learn and evidence this can be taught

Individual differences in children’s social communication have been shown to mediate the relationship between poor vocabulary or grammar and behavioural difficulties. Moreover, there is increasing evidence that social communication skills predict difficulties with peers over and above vocabulary and grammar scores. The essential social communicative skills needed to maintain positive peer relationships revolve around conversation. Children with weaker conversation skills are less likely to make and maintain friendships. While helping all children to participate actively in collaborative conversations is part of school curricula, evidence-based training on how to achieve this is rarely provided for teachers. In this review, we first provide an overview of the key components of conversation skills and the cognitive abilities required to maintain them. We then present a narrative review of randomised controlled trials and experimental studies that either trained child conversation skills or included conversation skills in both training and outcome measures. Most of the studies focussed on training conversational ability in autistic children. The general finding was that verbally fluent autistic children improve following conversation training on blind-assessed reciprocal conversational ability. Only two studies were found that trained conversation skills in typically developing children with adequate controls and outcome measures, which directly assessed conversational proficiency. Both studies focussed on typically developing children who, at baseline, were in the weaker third of the mainstream classroom. Importantly, training not only improved the conversational ability of these children, it also improved their rates of lunchtime interaction with peers and their peer popularity ratings. We argue that there is considerable potential for supporting conversation skills in the classroom as a universal or Tier 1 intervention. Future research should explore whether conversation skills training would benefit the whole classroom

A Subtle Profile With a Significant Impact: Language and Communication Difficulties for Autistic Females Without Intellectual Disability

From Frontiers via Jisc Publications RouterHistory: received 2020-10-26, collection 2021, accepted 2021-07-19, epub 2021-08-09Publication status: PublishedThe presentation of autism in females is poorly understood, which is thought to contribute to missed or later- age diagnosis, especially for those without intellectual disability. Dedicated research into social and behavioral differences has indicated a specific female phenotype of autism. However, less has been done to explore language and communication profiles, despite known sex/gender differences in typically developing populations. This article provides a synthesis of recent work from this small but emerging field. It focuses on a series of four preliminary and explorative studies conducted by the authors and embeds this within the wider literature. Findings suggest a specific profile of language and communication strengths and weaknesses for autistic females without intellectual disability (compared to autistic males and typically developing females). Furthermore, despite the relatively subtle presentation of difficulties (compared to autistic males), the impact on functionality, social inter-relations and emotional well-being, appears to be equitable and significant. The discussion highlights the need for further empirical research and proposes areas for investigation. Implications for clinical practice include the need for better recognition, testing and provision of interventions dedicated to the language and communication difficulties for autistic females. This has relevance for diagnostic, mental health and speech and language therapy services

Headache management : pharmacological approaches

Headache is one of the most common conditions presenting to the neurology clinic, yet a significant proportion of these patients are unsatisfied by their clinic experience. Headache can be extremely disabling; effective treatment is not only essential for patients but is rewarding for the physician. In this first of two parts review of headache, we provide an overview of headache management, emerging therapeutic strategies and an accessible interpretation of clinical guidelines to assist the busy neurologist

Chasing the conversation:Autistic experiences of speech perception

Background and aims: Humans communicate primarily through spoken language and speech perception is a core function of the human auditory system. Among the autistic community, atypical sensory reactivity and social communication difficulties are pervasive, yet the research literature lacks in-depth self-report data on speech perception in this population. The present study aimed to elicit detailed first-person accounts of autistic individuals’ abilities and difficulties perceiving the spoken word. Methods: Semi-structured interviews were conducted with nine autistic adults. The interview schedule addressed interviewees’ experiences of speech perception, factors influencing those experiences, and responses to those experiences. Resulting interview transcripts underwent thematic analysis. The six-person study team included two autistic researchers, to reduce risk of neurotypical ‘overshadowing’ of autistic voices. Results: Most interviewees reported pronounced difficulties perceiving speech in the presence of competing sounds. They emphasised that such listening difficulties are distinct from social difficulties, though the two can add and interact. Difficulties were of several varieties, ranging from powerful auditory distraction to drowning out of voices by continuous sounds. Contributing factors encompassed not only features of the soundscape but also non-acoustic factors such as multisensory processing and social cognition. Participants also identified compounding factors, such as lack of understanding of listening difficulties. Impacts were diverse and sometimes disabling, affecting socialising, emotions, fatigue, career, and self-image. A wide array of coping mechanisms was described. Conclusions: The first in-depth qualitative investigation of autistic speech-perception experiences has revealed diverse and widespread listening difficulties. These can combine with other internal, interpersonal, and societal factors to induce profound impacts. Lack of understanding of such listening difficulties – by the self, by communication partners, by institutions, and especially by clinicians – appears to be a crucial exacerbating factor. Many autistic adults have developed coping strategies to lessen speech-perception difficulties or mitigate their effects, and these are generally self-taught due to lack of clinical support. Implications: There is a need for carefully designed, adequately powered confirmatory research to verify, quantify, and disentangle the various forms of listening difficulty, preferably using large samples to explore heterogeneity. More immediate benefit might be obtained through development of self-help and clinical guidance materials, and by raising awareness of autistic listening experiences and needs, among the autistic community, communication partners, institutions, and clinicians

Clinical impairment in premanifest and early Huntington's disease is associated with regionally specific atrophy.

TRACK-HD is a multicentre longitudinal observational study investigating the use of clinical assessments and 3-Tesla magnetic resonance imaging as potential biomarkers for future therapeutic trials in Huntington's disease (HD). The cross-sectional data from this large well-characterized dataset provide the opportunity to improve our knowledge of how the underlying neuropathology of HD may contribute to the clinical manifestations of the disease across the spectrum of premanifest (PreHD) and early HD. Two hundred and thirty nine gene-positive subjects (120 PreHD and 119 early HD) from the TRACK-HD study were included. Using voxel-based morphometry (VBM), grey and white matter volumes were correlated with performance in four domains: quantitative motor (tongue force, metronome tapping, and gait); oculomotor [anti-saccade error rate (ASE)]; cognition (negative emotion recognition, spot the change and the University of Pennsylvania smell identification test) and neuropsychiatric measures (apathy, affect and irritability). After adjusting for estimated disease severity, regionally specific associations between structural loss and task performance were found (familywise error corrected, P < 0.05); impairment in tongue force, metronome tapping and ASE were all associated with striatal loss. Additionally, tongue force deficits and ASE were associated with volume reduction in the occipital lobe. Impaired recognition of negative emotions was associated with volumetric reductions in the precuneus and cuneus. Our study reveals specific associations between atrophy and decline in a range of clinical modalities, demonstrating the utility of VBM correlation analysis for investigating these relationships in HD

Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease

An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation