A holistic approach to fragile X syndrome integrated guidance for person-centred care.

BACKGROUND: The Fragile X community has expressed a desire for centralised, national guidelines in the form of integrated guidance for Fragile X Syndrome (FXS). METHODS: This article draws on existing literature reviews, primary research and clinical trials on FXS, a Fragile X Society conference workshop and first-hand experience of clinicians who have worked with those living with FXS over many years. RESULTS: The article scopes proposed integrated guidance over the life course, including appendices of symptoms, comorbidities and referral options for FXS and Fragile X Premutation Associated Conditions. CONCLUSION: Integrated guidance would provide an authoritative source for doctors, health professionals, therapists, care workers, social workers, educators, employers, families and those living with FXS, so that a holistic, person-centred approach can be taken across the United Kingdom to garner the best outcomes for those with FXS.

Predictors of psychotic symptoms among young people with special educational needs.

BACKGROUND: Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.AimsTo examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability. METHOD: Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS). RESULTS: The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54-1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3-9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6-50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97. CONCLUSIONS: Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.Declaration of interestNone.

Negative symptoms and longitudinal grey matter tissue loss in adolescents at risk of psychosis: preliminary findings from a 6-year follow-up study.

BACKGROUND: Negative symptoms are perhaps the most disabling feature of schizophrenia. Their pathogenesis remains poorly understood and it has been difficult to assess their development over time with imaging techniques. AIMS: To examine, using tensor-based structural imaging techniques, whether there are regions of progressive grey matter volume change associated with the development of negative symptoms. METHOD: A total of 43 adolescents at risk of psychosis were examined using magnetic resonance imaging and whole brain tensor-based morphometry at two time points, 6 years apart. RESULTS: When comparing the individuals with significant negative symptoms with the remaining participants, we identified five regions of significant grey matter tissue loss over the 6-year period. These regions included the left temporal lobe, the left cerebellum, the left posterior cingulate and the left inferior parietal sulcus. CONCLUSIONS: Negative symptoms are associated with longitudinal grey matter tissue loss. The regions identified include areas associated with psychotic symptoms more generally but also include regions uniquely associated with negative symptoms.

Visual social attention in SYNGAP1-related intellectual disability.

SYNGAP1-ID is a neurodevelopmental disorder caused by a mutation of the SYNGAP1 gene. Characterized by moderate to severe developmental delay, it is associated with several physical and behavioral issues as well as additional diagnoses, including autism. However, it is not known whether social cognitive differences seen in SYNGAP1-ID are similar to those previously identified in idiopathic or other forms of autism. This study therefore investigated visual social attention in SYNGAP1-ID. Eye movements were recorded across three passive viewing tasks (face scanning, pop-out, and social preference) of differing social complexity in 24 individuals with SYNGAP1-ID and 12 typically developing controls. We found that SYNGAP1-ID participants looked at faces less than the controls, and when they did look at faces, they had less time looking at and fewer fixations to the eyes. For the pop-out task, where social and nonsocial objects (Phone, car, face, bird, and face-noise) were presented in an array, those with SYNGAP1-ID spent significantly less time looking at the phone stimulus as well as fewer fixations to the face compared with the typically developing controls. When looking at two naturalistic scenes side by side, one social in nature (e.g., with children present) and the other not, there were no differences between the SYNGAP1-ID group and typically developing controls on any of the examined eye tracking measures. This study provides novel findings on the social attention of those with SYNGAP1-ID and helps to provide further evidence for using eye tracking as an objective measure of the social phenotype in this population in future clinical trials.

The Behavioral Profile of SYNGAP1-Related Intellectual Disability.

This study aimed to describe the behavioral profile of individuals with SYNGAP1-ID. Parents/carers of 30 individuals aged 3-18 years old with a diagnosis of SYNGAP1-ID and 21 typically developing individuals completed the Vineland-3 Adaptive Behavior Scale and the Child Behavior Checklist. We found that those with SYNGAP1-ID showed fewer adaptive behaviors and higher levels of internalizing and externalizing behaviors across almost all domains compared to typically developing controls. There was some evidence that these differences were greatest in older children, and more apparent in those with co-occuring epilepsy. This characterization of the phenotype of SYNGAP1-ID significantly aids our understanding of the behavioral profile of this population and is a step towards the development of tailored interventions.

Profiling Autism and Attention Deficit Hyperactivity Disorder Traits in Children with SYNGAP1-Related Intellectual Disability.

SYNGAP1-related ID is a genetic condition characterised by global developmental delay and epilepsy. Individuals with SYNGAP1-related ID also commonly show differences in attention and social communication/interaction and frequently receive additional diagnoses of Autism Spectrum Disorder (ASD) or Attention Deficit Hyperactivity Disorder (ADHD). We thus set out to quantify ASD and ADHD symptoms in children with this syndrome. To assess ASD and ADHD, parents and caregivers of a child with SYNGAP1-related ID (N = 34) or a typically developing control (N = 21) completed the Social Responsiveness Scale-2, the Social Communication Questionnaire with a subset of these also completing the Conners-3. We found that those with SYNGAP1-related ID demonstrated higher levels of autistic traits on both the SRS and SCQ than typically developing controls. On the SRS, those with SYNGAP1-related ID scored highest for restricted repetitive behaviours, and were least impaired in social awareness. On the Conners-3, those with SYNGAP1-related ID also showed a high prevalence of ADHD traits, with scores demonstrating difficulties with peer relations but relatively low occurrence of symptoms for DSM-5 conduct disorder and DSM-5 oppositional defiant disorder. Hierarchical clustering analysis highlighted distinct SYNGAP1-related ID subgroups for both ASD and ADHD traits. These findings provide further characterisation of the SYNGAP1-related ID behavioural phenotype, guiding diagnosis, assessment and potential interventions.

Human RAD52 double-ring remodels replication forks restricting fork reversal.

Human RAD52 1,2 is a multifunctional DNA repair protein involved in several cellular events that support genome stability including protection of stalled DNA replication forks from excessive degradation 3-7 . In its gatekeeper role, RAD52 binds to and stabilizes stalled replication forks during replication stress protecting them from reversal by SMARCAL1 5 . The structural and molecular mechanism of the RAD52-mediated fork protection remains elusive. Here, using P1 nuclease sensitivity, biochemical and single-molecule analyses we show that RAD52 dynamically remodels replication forks through its strand exchange activity. The presence of the ssDNA binding protein RPA at the fork modulates the kinetics of the strand exchange without impeding the reaction outcome. Mass photometry and single-particle cryo-electron microscopy show that the replication fork promotes a unique nucleoprotein structure containing head-to-head arrangement of two undecameric RAD52 rings with an extended positively charged surface that accommodates all three arms of the replication fork. We propose that the formation and continuity of this surface is important for the strand exchange reaction and for competition with SMARCAL1.

Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies.

OBJECTIVE: Several neuroimaging studies have reported structural brain differences in bipolar disorder using automated methods. While these studies have several advantages over those using region of interest techniques, no study has yet estimated a summary effect size or tested for between-study heterogeneity. We sought to address this issue using meta-analytic techniques applied for the first time in bipolar disorder at the level of the individual voxel. METHODS: A systematic review identified 16 voxel-based morphometry (VBM) studies comparing individuals with bipolar disorder with unaffected controls, of which eight were included in the meta-analysis. In order to take account of heterogeneity, summary effect sizes were computed using a random-effects model with appropriate correction for multiple testing. RESULTS: Compared with controls, subjects with bipolar disorder had reduced grey matter in a single cluster encompassing the right ventral prefrontal cortex, insula, temporal cortex, and claustrum. Study heterogeneity was widespread throughout the brain; though the significant cluster of grey matter reduction remained once these extraneous voxels had been removed. We found no evidence of publication bias (Eggers p = 0.63). CONCLUSIONS: Bipolar disorder is consistently associated with reductions in right prefrontal and temporal lobe grey matter. Reductions elsewhere may be obscured by clinical and methodological heterogeneity.

A systematic review of the utility of 1.5 versus 3 Tesla magnetic resonance brain imaging in clinical practice and research.

OBJECTIVE: MRI at 3 T is said to be more accurate than 1.5 T MR, but costs and other practical differences mean that it is unclear which to use. METHODS: We systematically reviewed studies comparing diagnostic accuracy at 3 T with 1.5 T. We searched MEDLINE, EMBASE and other sources from 1 January 2000 to 22 October 2010 for studies comparing diagnostic accuracy at 1.5 and 3 T in human neuroimaging. We extracted data on methodology, quality criteria, technical factors, subjects, signal-to-noise, diagnostic accuracy and errors according to QUADAS and STARD criteria. RESULTS: Amongst 150 studies (4,500 subjects), most were tiny, compared old 1.5 T with new 3 T technology, and only 22 (15 %) described diagnostic accuracy. The 3 T images were often described as "crisper", but we found little evidence of improved diagnosis. Improvements were limited to research applications [functional MRI (fMRI), spectroscopy, automated lesion detection]. Theoretical doubling of the signal-to-noise ratio was not confirmed, mostly being 25 %. Artefacts were worse and acquisitions took slightly longer at 3 T. CONCLUSION: Objective evidence to guide MRI purchasing decisions and routine diagnostic use is lacking. Rigorous evaluation accuracy and practicalities of diagnostic imaging technologies should be the routine, as for pharmacological interventions, to improve effectiveness of healthcare. KEY POINTS : • Higher field strength MRI may improve image quality and diagnostic accuracy. • There are few direct comparisons of 1.5 and 3 T MRI. • Theoretical doubling of the signal-to-noise ratio in practice was only 25 %. • Objective evidence of improved routine clinical diagnosis is lacking. • Other aspects of technology improved images more than field strength.

EEG as a translational biomarker and outcome measure in fragile X syndrome.

Targeted treatments for fragile X syndrome (FXS) have frequently failed to show efficacy in clinical testing, despite success at the preclinical stages. This has highlighted the need for more effective translational outcome measures. EEG differences observed in FXS, including exaggerated N1 ERP amplitudes, increased resting gamma power and reduced gamma phase-locking in the sensory cortices, have been suggested as potential biomarkers of the syndrome. These abnormalities are thought to reflect cortical hyper excitability resulting from an excitatory (glutamate) and inhibitory (GABAergic) imbalance in FXS, which has been the target of several pharmaceutical remediation studies. EEG differences observed in humans also show similarities to those seen in laboratory models of FXS, which may allow for greater translational equivalence and better predict clinical success of putative therapeutics. There is some evidence from clinical trials showing that treatment related changes in EEG may be associated with clinical improvements, but these require replication and extension to other medications. Although the use of EEG characteristics as biomarkers is still in the early phases, and further research is needed to establish its utility in clinical trials, the current research is promising and signals the emergence of an effective translational biomarker.

"The Languages That You Know Draw the Boundary of Your World": A Thematic Analysis of the Experiences of Autistic Bilingual Adults Living in the United Kingdom.

Background: Although being bilingual (knowing two or more languages) is becoming a more common experience globally, little is known about the combined experience of bilingualism and autism. Research currently available focuses on quantifying language and cognitive development, and the only two qualitative accounts of first-hand experiences are from either bilingual children or highly multilingual adults (with four languages or more), which may not represent the wider autistic bilingual population. All other accounts focus on parents or practitioners. This qualitative study reports the experiences of autistic bi- and multilingual adults, focusing on barriers and enablers to language learning and the reported benefits of bilingualism. Methods: Thirty-nine U.K.-based autistic bilingual adults (41% female, mean age = 33.2 years, range = 16-61) with knowledge of two to seven languages (mean = 3.6, standard deviation = 1.4) completed an online Demographic and Language Questionnaire, including three open-ended questions about the interplay between autism and bilingualism. A thematic analysis was conducted on the responses to these open-ended questions. Results: Participants perceived many opportunities and benefits brought by bilingualism, in terms of relationships, hobbies, mobility, employment, education, and cultural insight. Respondents reported social communication as being a major benefit of being bilingual, and discussed how bilingualism had broadened their mindset, while identifying factors that had enabled or challenged their language learning journey. Conclusions: This study builds upon the few reports available to highlight the experiences that are shared by autistic bilingual people regardless of the number of languages they know. It is the first study to report the perspectives of U.K.-based autistic bilingual adults who, in most cases, grew up in a bilingual environment. Accounts of the factors that can facilitate or hinder language learning will inform the development of strategies to better support autistic people. These findings have implications for bilingual families and practitioners supporting autistic bilingual people.

Why is this an important issue?: At least half the world's population is bilingual or lives in a bilingual environment. However, the experiences of autistic bilingual people are rarely represented or acknowledged. So far, research in this field has concentrated primarily on parent perspectives and on the effects of bilingualism for autistic children's skills. Only one study to date has focused on understanding the experiences of autistic bilingual adults themselves, but this research focused on multilinguals with four or more languages. It is essential to represent the whole autistic bi- or multilingual community, including those with two or three languages. What was the purpose of this study?: The study explored the experiences of autistic bilingual people, focusing on the perceived benefits of bilingualism; the shared experiences of autism, bilingualism, especially regarding identity; and the elements that make language learning easier or more difficult. What did the researchers do?: Thirty-nine autistic bilingual adults completed an online questionnaire. The questionnaire included quantitative questions about the participants' language profile, and open-ended questions about their experiences of being autistic and bilingual. The answers were analyzed and summarized using a method called thematic analysis. What were the results of the study?: Participants reported that being bilingual had shaped their ability to communicate socially; it had helped them to understand the perspectives of others, and better express themselves. Participants also identified many additional opportunities and benefits of bilingualism in terms of relationships, hobbies, mobility, employment, education, and cultural insight. They discussed how bilingualism had influenced their self-understanding in terms of increased awareness of their own skills, and it had contributed to a broadened mindset. Participants also listed several difficulties in becoming bilingual that they considered linked to being autistic. Participants highlighted several elements that had made their language learning easier or harder, including the learning environment, opportunities for practice, or specific language competencies. What do these findings add to what was already known?: Previous studies describing the experiences of autistic bilingual people only represented people with four or more languages, and most of these studies only involved one or two people. This study is more representative of the wider autistic bilingual population. It shows that autistic people benefit from bilingualism in their daily life, even when they know "only" two languages. It highlights that being bilingual is a part of autistic bilingual people's identity. It reports that different autistic people need different learning strategies to best learn additional languages. What are potential weaknesses in the study?: Participants answered our pre-set questions online, and our questions had very few prompts. As a result, it is possible that many topics were not mentioned. Future research should build upon the topics presented here to describe them more specifically. How will these findings help autistic adults now or in the future?: There are still many barriers to equal access to additional language learning for autistic people. This study shows how valuable autistic people find bilingualism, and it supports autistic people's advocacy movement for equal rights and opportunities.

A functional MRI facial emotion-processing study of autism in individuals with special educational needs.

This study aimed to investigate the functional imaging associations of autism in individuals with special educational needs and demonstrate the feasibility of such research. The study included 18 individuals (3 female,15 male; mean age 24.3; mean IQ 69.7) with special educational needs (SEN), of whom 9 met criteria for autism. The task examined the Blood-oxygen-level dependant response to fearful and neutral faces. Individuals in the autism group had 2 clusters of significantly reduced activity centred on the left superior frontal gyrus and left angular gyrus compared to those with SEN alone in response to the fearful faces. In the response to neutral faces, individuals in the autism group also had a cluster of significantly greater activity centred on the right precentral gyrus compared to those with SEN alone. We suggest that autistic characteristics in individuals with SEN are associated with changes in fearful facial emotion processing analogous to those previously reported in autistic individuals without SEN, and who are of average or above average cognitive ability. The finding of enhanced response to neutral facial stimuli needs further investigation, although we speculate this may relate to reports of the experience of 'hyper-mentalisation' in social situations as reported by some autistic individuals.

"A Group of Fellow Travellers Who Understand": Interviews With Autistic People About Post-diagnostic Peer Support in Adulthood.

Receiving a diagnosis of autism in adulthood can be a life changing event, impacting identity, relationships, and mental health. A lack of post-diagnostic support has been highlighted by autistic adults, their allies, clinicians, and service providers. It can be a source of distress for autistic adults, reinforcing feelings of social isolation and rejection. Peer support could be a cost-effective, flexible, and sustainable model to provide community-based support for autistic adults. However, there is little research on the value of peer support, despite calls from the autistic community. This qualitative study explored autistic experiences and needs post-diagnosis, identifying specific ways that peer support may benefit them, and exploring the limitations of peer support. Twelve autistic adults who had all received an autism diagnosis in adulthood completed a semi-structured interview focussing on the diagnostic experience, post-diagnostic support needed and provided, engagement with the autistic community, and post-diagnostic peer support. Thematic analysis of interview transcripts resulted in four themes: (1) Mismatch in support needed and provided; (2) Community connection; (3) Flexible and personalised support; and (4) Sustainability. Participants indicated that peer support may be a useful mechanism to support autistic adults' post-diagnosis and offers unique opportunities not available through other support channels. Though informal peer support exists, it could be more sustainable and effective if well-supported and funded.

Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description.

BACKGROUND: SYNGAP1-related intellectual disability (ID) is a recently described neurodevelopmental disorder that is caused by pathogenic variation in the SYNGAP1 gene. To date, the behavioural characteristics of this disorder have mainly been highlighted via the prevalence of existing diagnoses in case series. We set out to detail the behavioural features of this disorder by undertaking interviews with those who have a child with SYNGAP1-related ID to allow them to describe their child's behaviour. METHODS: We conducted 27 semi-structured interviews with parents and caregivers which covered basic information (e.g., age, gender), family history, perinatal history, past medical history, developmental history, epilepsy, behavioural history, and a general description of their child's behaviour. RESULTS: Using a mixed quantitative and qualitative approach, the responses from the parents indicated that those with SYNGAP1-related ID showed high rates of autism spectrum disorder (52%), difficulties with fine and gross motor skills, delays in language development, and a high prevalence of epilepsy (70%). A qualitative analysis highlighted their general behaviour affected the themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences. Sensory features described involved auditory, visual, tactile, gustatory, and proprioceptive themes. CONCLUSIONS: Our findings and behavioural descriptions provide important insights as well as implications for the diagnosis and care of those with SYNGAP1-related ID.

Impact of cannabis use on thalamic volume in people at familial high risk of schizophrenia.

BACKGROUND: No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia. AIMS: To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential thalamic and amygdala-hippocampal complex volume change in high-risk individuals exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period was investigated using repeated-measures analysis of variance. RESULTS: Cannabis exposure was associated with bilateral thalamic volume loss. This effect was significant on the left (F = 4.47, P = 0.04) and highly significant on the right (F= 7.66, P= 0.008). These results remained significant when individuals using other illicit drugs were removed from the analysis. CONCLUSIONS: These are the first longitudinal data to demonstrate an association between thalamic volume loss and exposure to cannabis in currently unaffected people at familial high risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.

Genetic variation in CNTNAP2 alters brain function during linguistic processing in healthy individuals.

Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66). Against a background of normal performance and lack of behavioral abnormalities, healthy individuals with the putative risk allele versus those without demonstrated significant increases in activation in the right inferior frontal gyrus (Broca's area homologue) and right lateral temporal cortex. These findings demonstrate that risk associated variation in the CNTNAP2 gene impacts on brain activation in healthy non-autistic individuals during a language processing task providing evidence of the effect of genetic variation in CNTNAP2 on a core feature of ASDs.

Perspectives and Experiences of Autistic Multilingual Adults: A Qualitative Analysis.

Background: The combined experience of autism and bilingualism is poorly understood, leading to poor support for autistic people in multilingual environments or those interested in languages. While most available studies focus on the language and cognitive profiles of autistic bilinguals, or on the experiences of parents, little is known about the lived experiences of autistic multilinguals. Methods: To address this question, this study examined the impact of autism and multilingualism on the lives of 54 autistic multilingual adults who completed an online survey assessing the profiles of autistic bi- and multilinguals. We conducted a thematic analysis of responses to the survey's open-ended questions to explore motivations for learning languages and the perceived benefits of being both autistic and multilingual. Results: There was a wide range of language profiles in the sample, with various levels of proficiency, ages of acquisition, and learning environments. Respondents felt that being autistic can both positively and negatively influence language learning. They reported various motivating factors for the acquisition of multiple languages, including social aspects and a predisposition for language learning. Respondents reported many benefits of multilingualism, such as educational, employment, or leisure opportunities; social skills and understanding of other people; self-confidence in their own abilities; and relationships with family, friends, and the worldwide autistic community. Conclusions: Unlike previous work with autistic multilinguals involving case studies, the larger sample involved here offers valuable insight into the profiles and experiences of this overlooked population. Importantly, autistic people can experience numerous benefits from multilingualism. These findings will have implications for language education practices as well as for multilingual families and the practitioners who support them. Lay summary: Why was this study done?: We wanted to understand what it feels like to be both autistic and multilingual, in a world where it is often assumed that both cannot go together. The combined experience of autism and bilingualism is poorly understood. This leads to poor support for autistic people in bilingual environments or for those interested in languages. Most studies available focus on the language and mental abilities of autistic bilinguals, or on the experiences of parents. However, very few studies focus on the lived experiences of autistic multilinguals themselves.What was the purpose of this study?: The purpose of this study was to understand the experiences of autistic multilingual adults. We focused on their learning motivations and the perceived benefits of being autistic and multilingual.What did the researchers do?: Fifty-four autistic multilingual adults completed an online questionnaire designed for autistic bi- and multilinguals. The questionnaire included questions about the respondents' language history and language profiles. There were also open-ended questions about the respondents' motivations for learning languages, and their general experience of being both autistic and multilingual. We analyzed and summarized the responses to these open-ended questions to understand the experience of autistic multilingual adults.What were the results of the study?: Our sample had a diverse range of language profiles and experiences. Respondents thought that autism could be both an advantage and a disadvantage for language learning. They reported a range of motivations for language learning, including a predisposition for language learning. They considered relationships as both a motivation to learn languages and a benefit of multilingualism. Respondents thought that being multilingual had brought them many opportunities for leisure, travels, education, and employment. They considered that being multilingual had improved their self-confidence. They also thought that being multilingual had increased their awareness and understanding of autism, allowing them to connect with the wider autistic population.What do these findings add to what was already known?: Previous research with autistic multilinguals involved only one or two participants. The larger group of autistic multilinguals involved in this study offers valuable insight into the lived experiences of this overlooked population.What are potential weaknesses in the study?: The online questionnaire was not originally designed to collect in-depth data on lived experiences. This means that the questions included very few prompts: respondents were able to discuss the aspects of their experience that were the most important to them. The absence of specific topics in the results does not mean that they are not experienced, but simply that the participants did not spontaneously mention them. Future research should build upon our findings and focus on specific topics, such as learning environments or opportunities.How will these findings help autistic adults now or in the future?: These findings will help autistic adults by highlighting the diversity and richness of their language profiles, abilities, and experiences. This will prompt families, educators, and practitioners to better support and include autistic people in multilingual environments or those interested in languages.

Glutamate and functional connectivity - support for the excitatory-inhibitory imbalance hypothesis in autism spectrum disorders.

It has been proposed that the Glutamate (Glu) system is implicated in autism spectrum disorders (ASD) via an imbalance between excitatory and inhibitory brain circuits, which impacts on brain function. Here, we investigated the excitatory-inhibitory imbalance theory by measuring Glu-concentrations and the relationship with resting-state function. Nineteen adult males with ASD and 19 age and sex-matched healthy controls (HC) (23 - 58 years) underwent Proton Magnetic Resonance Spectroscopy of the dorsal anterior cingulate cortex (dACC) and resting-state functional Magnetic Resonance Imaging (fMRI). Glu and Glx concentrations were compared between groups. Seed-based functional connectivity was analyzed with a priori seeds of the right and left dACC. Finally, metabolite concentrations were related to functional connectivity coefficients and compared between both groups. Individuals with ASD showed significantly negative associations between increased Glx concentrations and reduced functional connectivity between the dACC and insular, limbic and parietal regions. In contrast, HC displayed a positive relationship between the same metabolite and connectivity measures. We provided new evidence to support the excitatory-inhibitory imbalance theory, where excitatory Glx concentrations were related to functional dysconnectivity in ASD. Future research is needed to investigate large-scale functional networks in association with both excitatory and inhibitory metabolites in subpopulations of ASD.

Sleep Abnormalities in the Synaptopathies-SYNGAP1-Related Intellectual Disability and Phelan-McDermid Syndrome.

Neurodevelopmental disorders are frequently associated with sleep disturbances. One class of neurodevelopmental disorders, the genetic synaptopathies, is caused by mutations in genes encoding proteins found at the synapse. Mutations in these genes cause derangement of synapse development and function. We utilized a validated sleep instrument, Children's Sleep Habits Questionnaire (CSHQ) to examine the nature of sleep abnormalities occurring in individuals with two synaptopathies-Phelan-McDermid syndrome (PMD) (N = 47, male = 23, female = 24, age 1-46 years) and SYNGAP1-related intellectual disability (SYNGAP1-ID) (N = 64, male = 31, female = 33, age 1-64 years), when compared with unaffected siblings (N = 61, male = 25, female = 36, age 1-17 years). We found that both PMD and SYNGAP1-ID have significant sleep abnormalities with SYNGAP1-ID having greater severity of sleep disturbance than PMD. In addition, sleep disturbances were more severe for PMD in individuals 11 years and older compared with those less than 11 years old. Individuals with either disorder were more likely to use sleep aids than unaffected siblings. In conclusion, sleep disturbances are a significant phenotype in the synaptopathies PMD and SYNGAP1-ID. Improved sleep is a viable endpoint for future clinical trials for these neurodevelopmental disorders.

Bilingualism in autism: Language learning profiles and social experiences.

LAY ABSTRACT: Bilingualism changes the way people relate to others. This is particularly interesting in the case of autism, where social interaction presents many challenges. A better understanding of the overlap between the social variations of bilingualism and autism could unveil new ways to support the social experiences of autistic people. This research aims to understand the language learning and social experiences of autistic people who speak one, two or more languages. A total of 297 autistic adults (aged between 16 and 80 years) completed an online questionnaire that included general demographic questions, social life quality self-rating questions, language history questions, and open questions about the respondents' bilingualism experience. Respondents had a wide range of language experiences: there were 89 monolingual English speakers, 98 bilinguals, 110 respondents knew three languages or more, all with a wide range of abilities in their languages. In the full group, younger respondents were more satisfied with their social life, and respondents with many languages were more satisfied with their social life than respondents with few languages. In the multilingual group, younger respondents were more satisfied with their social life, and the more skilled in their third language the more satisfied with their social life. This is the first study describing the language history and social experiences of a large group of bilingual and multilingual autistic adults. It highlights how autistic people can encounter a new language, learn it and use it in their daily life, and how their bilingualism experiences shape their social life.