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Autism spectrum disorder (ASD) is a collection of neurodevelopmental disorders whose pathobiology remains elusive. This study aimed to investigate the possible neural mechanisms underlying ASD using a dynamic brain network model and a relatively large-sample, multi-site dataset. Resting-state functional magnetic resonance imaging data were acquired from 208 ASD patients and 227 typical development (TD) controls, who were drawn from the multi-site Autism Brain Imaging Data Exchange (ABIDE) database. Brain network flexibilities were estimated and compared between the ASD and TD groups at both global and local levels, after adjusting for sex, age, head motion, and site effects. The results revealed significantly increased brain network flexibilities (indicating a decreased stability) at the global level, as well as at the local level within the default mode and sensorimotor areas in ASD patients than TD participants. Additionally, significant ASD-related decreases in flexibilities were also observed in several occipital regions at the nodal level. Most of these changes were significantly correlated with the Autism Diagnostic Observation Schedule (ADOS) total score in the entire sample. These results suggested that ASD is characterized by significant changes in temporal stabilities of the functional brain network, which can further strengthen our understanding of the pathobiology of ASD. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1β), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1β, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved. [ABSTRACT FROM AUTHOR]

Autistic spectrum disorder (ASD) is a neurodevelopmental disability characterised by the impairment of social interaction and communication ability. The alarming increase in its prevalence in children urged researchers to obtain a better understanding of the causes of this disease. Genetic factors are considered to be crucial, as ASD has a tendency to run in families. In recent years, with technological advances, the importance of structural variations (SVs) in ASD began to emerge. Most of these studies, however, focus on the Caucasian population. As a populated ethnicity, ASD shall be a significant health issue in China. This systematic review aims to summarise current case-control studies of SVs associated with ASD in the Chinese population. A list of genes identified in the nine included studies is provided. It also reveals that similar research focusing on other genetic backgrounds is demanded to manifest the disease etiology in different ethnic groups, and assist the development of accurate ethnic-oriented genetic diagnosis. [ABSTRACT FROM AUTHOR]

Excessive inflammatory reactions and oxidative stress are well-recognized molecular findings in autism and these processes can affect or be affected by the epigenetic landscape. Nonetheless, adequate therapeutics are unavailable, as patient-specific brain molecular markers for individualized therapies remain challenging. Methods: We used iPSC-derived neurons and astrocytes of patients with autism vs. controls (5/group) to examine whether they replicate the postmortem brain expression/epigenetic alterations of autism. Additionally, DNA methylation of 10 postmortem brain samples (5/group) was analyzed for genes affected in PSC-derived cells. Results: We found hyperexpression of TGFB1, TGFB2, IL6 and IFI16 and decreased expression of HAP1, SIRT1, NURR1, RELN, GPX1, EN2, SLC1A2 and SLC1A3 in the astrocytes of patients with autism, along with DNA hypomethylation of TGFB2, IL6, TNFA and EN2 gene promoters and a decrease in HAP1 promoter 5-hydroxymethylation in the astrocytes of patients with autism. In neurons, HAP1 and IL6 expression trended alike. While HAP1 promoter was hypermethylated in neurons, IFI16 and SLC1A3 promoters were hypomethylated and TGFB2 exhibited increased promoter 5-hydroxymethlation. We also found a reduction in neuronal arborization, spine size, growth rate, and migration, but increased astrocyte size and a reduced growth rate in autism. In postmortem brain samples, we found DNA hypomethylation of TGFB2 and IFI16 promoter regions, but DNA hypermethylation of HAP1 and SLC1A2 promoters in autism. Conclusion: Autism-associated expression/epigenetic alterations in iPSC-derived cells replicated those reported in the literature, making them appropriate surrogates to study disease pathogenesis or patient-specific therapeutics. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest. [ABSTRACT FROM AUTHOR]

The prevalence of autism spectrum disorder (ASD) is still increasing, which means that this neurodevelopmental lifelong pathology requires special scientific attention and efforts focused on developing novel therapeutic approaches. It has become increasingly evident that neuroinflammation and dysregulation of neuro-immune cross-talk are specific hallmarks of ASD, offering the possibility to treat these disorders by factors modulating neuro-immunological interactions. Mesenchymal stem cell-based therapy has already been postulated as one of the therapeutic approaches for ASD; however, less is known about the molecular mechanisms of stem cell influence. One of the possibilities, although still underestimated, is the paracrine purinergic activity of MSCs, by which stem cells ameliorate inflammatory reactions. Modulation of adenosine signaling may help restore neurotransmitter balance, reduce neuroinflammation, and improve overall brain function in individuals with ASD. In our review article, we present a novel insight into purinergic signaling, including but not limited to the adenosinergic pathway and its role in neuroinflammation and neuro-immune cross-talk modulation. We anticipate that by achieving a greater understanding of the purinergic signaling contribution to ASD and related disorders, novel therapeutic strategies may be devised for patients with autism in the near future. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders (NDDs) with a high unmet medical need. The diagnosis of ASD is currently based on behavior criteria, which overlooks the diversity of genetic, neurophysiological, and clinical manifestations. Failure to acknowledge such heterogeneity has hindered the development of efficient drug treatments for ASD and other NDDs. DEPI® (Databased Endophenotyping Patient Identification) is a systems biology, multi-omics, and machine learning-driven platform enabling the identification of subgroups of patients with NDDs and the development of patient-tailored treatments. In this study, we provide evidence for the validation of a first clinically and biologically defined subgroup of patients with ASD identified by DEPI, ASD Phenotype 1 (ASD-Phen1). Among 313 screened patients with idiopathic ASD, the prevalence of ASD-Phen1 was observed to be ~24% in 84 patients who qualified to be enrolled in the study. Metabolic and transcriptomic alterations differentiating patients with ASD-Phen1 were consistent with an over-activation of NF-κB and NRF2 transcription factors, as predicted by DEPI. Finally, the suitability of STP1 combination treatment to revert such observed molecular alterations in patients with ASD-Phen1 was determined. Overall, our results support the development of precision medicine-based treatments for patients diagnosed with ASD. [ABSTRACT FROM AUTHOR]

The rising prevalence of autism internationally has been accompanied by an increased appreciation of the poorer mental health experienced by people with this condition and also of their family care-givers. In particular, higher incidences of anxiety and depression are reported in high-income nations and these conditions are likely to be under-recognised and under-reported in lower-resourced regions or countries. Mainstream mental health services seem to be ill-equipped to respond adequately to the needs of autistic persons and their care-givers. This literature review of 29 recently published reviews covering nearly 1000 journal articles summarises the insights and strategies that have been shown to promote the mental health and emotional wellbeing of autistic persons. In particular, a focus on family-centred, community-based supports is recommended that aim to enhance social communication, extend social connections and promote an individual's self-esteem, self-determination and social motivation. These low-cost interventions are especially pertinent in low-resourced settings, but they can be used internationally to prevent mental illness and assist in the treatment of anxiety and depression in autistic persons and their family carers. The priority is to focus on primary-care responses with cross-sectoral working rather than investing in high-cost psychiatric provision. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories. [ABSTRACT FROM AUTHOR]

Background and Objectives: It is known that inflammatory processes play a role in the pathogenesis of autism spectrum disorder (ASD). It is also reported that immune activation induces the kynurenine pathway (KP), as known as the tryptophan destruction pathway. In our study, we aimed to investigate whether the serum levels of KP products and interleukin (IL)-6 activating indolamine 2–3 dioxygenase (IDO) enzyme are different in healthy developing children and children with ASD. Materials and Methods: Forty-three ASD children aged 2–9 were included in this study. Forty-two healthy developing children, similar to the patient group in terms of age and gender, were selected as the control group. Serum levels of kynurenic acid, kynurenine, quinolinic acid and IL-6 were analyzed using the ELISA method. ASD severity was evaluated with the Autism Behavior Checklist (ABC). Results: The mean age of children with ASD was 42.4 ± 20.5 months, and that of healthy controls was 48.1 ± 15.8 months. While the serum levels of kynurenic acid, kynurenine and interleukin-6 were higher in the group with ASD (p < 0.05), there was no significant difference (p > 0.05) in terms of the quinolinic acid level. There was no significant difference between the ABC total and subscale scores of children with ASD and biochemical parameters (p > 0.05). Conclusions: We conclude that these biomarkers must be measured in all ASD cases. They may be important for the diagnosis of ASD. [ABSTRACT FROM AUTHOR]

The language used by teachers, school staff, and parents to talk about autistic students can send either positive or negative messages to other school staff, parents, and all students—with or without autism—about autistic students. Ultimately, these messages also extend to autistic people. Using qualitative focus group methods, we talked to parents, teachers, administrators, and other school staff to better understand how people speak about the inclusion of autistic students in general education classrooms in public schools. Overall, we found that many of our participants thought (1) autistic students need to earn their way into general education classrooms, unlike their peers without disabilities, (2) segregating students with disabilities away from their peers without disabilities is acceptable, and sometimes preferable, in school settings, and (3) there is power in inclusive education opportunities for students with and without disabilities in school settings. The findings from this study suggest that inclusive opportunities for autistic students were largely driven by stakeholder mindsets. These results should encourage school staff to think about and reflect on how they talk about autistic students in inclusive settings with the ultimate goal of creating more welcoming inclusive environments for autistic students. [ABSTRACT FROM AUTHOR]

Spasm of near reflex (SNR) involves intermittent spasm of one or more of the three near reflex components. Psychiatric disorders are one cause of SNR. We describe a patient with SNR diagnosed with autism spectrum disorder (ASD). A 36-year-old male with esotropia since childhood was referred due to headache and dizziness. The alternate prism cover test showed 30 prism diopters at both near and distant fixation. Four months after his first visit, he was diagnosed with ASD. Twenty-nine months after his first visit, he underwent strabismus surgery to treat concomitant esotropia. Postoperatively, the angle of strabismus improved but remained variable. Because the angle of strabismus varied, we suspected SNR; the diagnosis was performed after evaluating the patient's microfluctuations in accommodation with Speedy-K. However, it was difficult to distinguish convergence spasm from concomitant esotropia in this patient because he has had a history of esotropia since childhood. In a patient with concomitant esotropia, if the symptoms are not exclusively due to strabismus, SNR should be suspected. Although the relationship between SNR and the pathology of ASD is unknown, it is possible that patients with ASD are more likely to develop SNR. [ABSTRACT FROM AUTHOR]

The chromosome 17q21.31 microduplication syndrome is a rare genetic syndrome presenting with craniofacial dysmorphisms, psychomotor delay, microcephaly, behavioral disorders, and poor social interaction. Only ten patients have been reported in the literature until today. All patients share some specific features, including psychomotor delay, behavioral disorders, and autism spectrum disorder (ASD). Here, a new case of this syndrome is reported in an 11-year-old Caucasian child who presented the classical clinical features of the 17q21.31 microduplication syndrome in association with new clinical characteristics previously unreported. The Array-Comparative Genomic Hybridization (aCGH) revealed a partial duplication of the long arm of chromosome 17. A literature review of previously studied patients with 17q21.31 microduplication syndrome is reported. [ABSTRACT FROM AUTHOR]

Children with autism spectrum disorder (ASD) face several challenges in the healthcare setting. This study defines the challenges experienced by children with autism in hospitals in Saudi Arabia. A cross-sectional study was conducted using a questionnaire for guardians of autistic children in outpatient clinics, autism support groups, and rehabilitation centers. A total of 199 participants were included. The medical procedures causing the most anxiety to children were injections and getting their blood drawn (68.3%), vital sign measurement (41.6%), and height and weight measurement (37.8%). Long waiting hours (44.1%), increased sensory stimuli (33.2%), and overcrowding of hospital staff (27.9%) were stress-inducing in the healthcare environment. The guardians recommended that loud noises (44.7%), crowdedness (41.2%), and long waiting hours (42.1%) be avoided. The nonverbal children experienced significantly higher levels (p < 0.001) of agitation, irritability, and outbursts during doctor visits than their verbal counterparts. The children with intellectual disabilities were more tense and unresponsive during doctor visits (33.3%) than their intellectually able counterparts, who more frequently were calm and responsive (44.9%) during visits. Most patients with ASD face hardships during hospital visits. Nonverbal patients and those with intellectual disabilities have a higher tendency for hospital setting anxiety-induced outbursts, which may be eased by avoiding loud noise and overcrowding. [ABSTRACT FROM AUTHOR]

Background: Most children with ASD require orthodontic treatment to correct a malocclusion, to restore masticatory function, and for cosmetic reasons. The use of orthodontic devices, however, could lead to a distortion of the child's routine, causing mood alterations, on the one hand, and a worsening of their oral hygiene status, on the other. The aim of this study is to evaluate the impact of orthodontic therapy on the daily management and level of collaboration of children with ASD determined using the Frankl scale. Materials and methods: An anonymous questionnaire was administered to 20 pairs of parents of children in which they were asked to evaluate any behavioral changes and/or difficulties encountered at the beginning of orthodontic treatment as well as their degree of satisfaction with the level of information received from medical personnel. Results: In about half of the sample, there were behavioral changes and difficulties in managing the treatment. Most of the responses received indicated parental satisfaction both with regard to the emotional impact on the children with respect to the introduction of the treatment and with regard to the attention received from the medical staff. Furthermore, there was a statistically significant increase (p = 0.001) in the Frankl scale score after treatment. Conclusions: Home management, which has always been the most difficult obstacle to overcome, with the support of a competent team can not only improve the quality of life of patients affected by ASD but also improve their collaboration and state of oral health without altering their emotionality. [ABSTRACT FROM AUTHOR]

Limb-girdle muscular dystrophies are a group of genetic disorders classically manifesting with progressive proximal muscle weakness. Affected individuals present with atrophy and weakness of the muscles of the shoulders and hips, and in some cases, intellectual disability or developmental delay has also been reported. Limb-girdle muscular dystrophy-3 is a recessive disorder caused by biallelic variants in the SGCA gene. Similarly, symptoms include proximal muscle weakness, elevated CPK, calf muscle pseudohypertrophy, and mobility issues. Cardiac symptoms and respiratory insufficiency are also common symptoms. This case report details a 3-year-old male with muscular weakness, elevated CK, and a neurodevelopmental disorder in whom a homozygous missense variant in c.229C>T (p.Arg77Cys) associated with limb-girdle muscular dystrophy-3 was found. This report shows the association between SGCA c.229C>T and neurodevelopmental disorders as observed in other muscular dystrophies. [ABSTRACT FROM AUTHOR]

The number of autistic people entering higher education (HE) is increasing steadily across the globe, yet research on understanding their experiences and support needs still focuses almost exclusively on the perspectives of autistic students attending HE in the U.S., U.K. and Australia. The present study sought to explore and understand (i) the experiences, opportunities, and challenges of autistic students in HE in Singapore; and (ii) non-autistic HE students' experiences of studying alongside and socially engaging with their autistic peers. Twenty autistic and twenty-two non-autistic HE students in Singapore completed an online survey with open-ended questions. Framework analysis identified themes similar to those in the extant literature (e.g., autistic students enjoyed greater autonomy in HE compared to school, but often found difficulty juggling their numerous academic responsibilities) and novel themes pertaining to Singapore's unique sociocultural context (e.g., Singaporean autistic people face high pressure to "blend in" due to societal values of conforming to social norms). Participants also noted considerable social isolation of autistic students, likely linked to a double empathy problem between autistic and non-autistic students. Improving inclusiveness both within HE and in the wider society is a necessarily joint effort among many stakeholders. Recommendations include HE stakeholders working together to develop and improve supports (e.g., implementing formal transition programmes) for autistic students and incorporating neurodiversity education into school curricula for all students. [ABSTRACT FROM AUTHOR]

Previous studies have shown that autistic people often display atypical responses when processing sensory information, with particular prevalence within the auditory domain. Often provoked by common everyday sounds, auditory hypersensitivity can result in self-regulatory fear responses. This can be potentially harmful to autistic individuals and the people around them and is associated with greater occurrence of anxiety, depression, and poorer overall quality of life in the autistic population. Rather than a physiological causation, the literature suggests that hypersensitivity to sound is likely to be caused by how auditory stimuli are processed in the brain. This paper reports a home-based digital intervention aimed to address auditory hypersensitivity in autistic children. Developed as an interactive virtual reality game, the system integrates exposure-based therapy techniques into game mechanics and delivers target auditory stimuli to the player rendered via binaural-based spatial audio. The performance of the platform was evaluated in a 10-week feasibility study, during which children (n = 7) engaged weekly with the game during a 30 min session. Following this period, a comparison of pre- and post-study measurements showed a decrease in sensitivity for five participants, with qualitative feedback highlighting an increase in tolerance towards real-world stimuli and challenging environments. These results provide initial support for SoundFields as a home-based intervention targeting auditory hypersensitivity experienced by autistic children. [ABSTRACT FROM AUTHOR]

In a typical school day, young people need to do many tasks which rely on the ability to predict. Since prediction underpins cognitive and social skills, difficulties with prediction lead to multiple challenges to learning. In this review, we consider the evidence that autistic people often have difficulty making predictions about other people's behaviour, or understanding what they are required to do, contributing to high rates of anxiety and intolerance of uncertainty. The focus of the review is to consider what we already know about effective strategies used by schools to support learning and social inclusion and to consider how we might build on these approaches. We propose a number of so far unexplored ideas with the potential to build predictive skills and which require evaluation. [ABSTRACT FROM AUTHOR]

An integrated plan within a defined care pathway for the diagnosis, continuative interventions, and periodic redefinition of care of autistic people is essential for better outcomes. Challenges include delivering services across all domains or life stages and effective coordination between health/social care providers and services. Further, in the 'real world', service provision varies greatly, and in many settings is significantly weighted towards diagnosis and children's services rather than treatment and support or adult care. This study aims to identify existing care pathways for Autism Spectrum Disorder (ASD) from referral to care management after diagnosis. The study reviewed the international literature in PubMed and PsycInfo databases and collected information on care for autistic individuals from the Autism Spectrum Disorders in Europe (ASDEU) project partners. The study found that published data mainly focused on specific components of care pathways rather than an integrated and coordinated plan of care and legislative indications. They should be aimed at facilitating access to the services for support and the inclusiveness of autistic individuals. Given the need for care addressing the complex and heterogeneous nature of ASD, effective coordination between different health/social care providers and services is essential. It is also suggested that research priority should be given to the identification of an integrated care pathway 'model' centered around case management, individualization, facilitation, support, continuous training and updating, and quality management. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) comprise a group of neurodevelopmental disorders (NDD) characterized by deficits in communication and social interaction, as well as repetitive and restrictive behaviors, etc. The genetic implications of ASD have been widely documented, and numerous genes have been associated with it. The use of chromosomal microarray analysis (CMA) has proven to be a rapid and effective method for detecting both small and large deletions and duplications associated with ASD. In this article, we present the implementation of CMA as a first-tier test in our clinical laboratory for patients with primary ASD over a prospective period of four years. The cohort was composed of 212 individuals over 3 years of age, who met DSM-5 diagnostic criteria for ASD. The use of a customized array-CGH (comparative genomic hybridization) design (KaryoArray®) found 99 individuals (45.20%) with copy number variants (CNVs); 34 of them carried deletions (34.34%) and 65 duplications (65.65%). A total of 28 of 212 patients had pathogenic or likely pathogenic CNVs, representing approximately 13% of the cohort. In turn, 28 out of 212 (approximately 12%) had variants of uncertain clinical significance (VUS). Our findings involve clinically significant CNVs, known to cause ASD (syndromic and non-syndromic), and other CNVs previously related to other comorbidities such as epilepsy or intellectual disability (ID). Lastly, we observed new rearrangements that will enhance the information available and the collection of genes associated with this disorder. Our data also highlight that CMA could be very useful in diagnosing patients with essential/primary autism, and demonstrate the existence of substantial genetic and clinical heterogeneity in non-syndromic ASD individuals, underscoring the continued challenge for genetic laboratories in terms of its molecular diagnosis. [ABSTRACT FROM AUTHOR]

This article proposes a model to diagnose autism patients using graphical neural networks. A graphical neural network relates the subjects (nodes) using the features (edges). In our model, radiomic features obtained from sMRI are used as edges, and spatial-temporal data obtained through rs-fMRI are used as nodes. The similarity between first-order and texture features from the sMRI data of subjects are derived using radiomics to construct the edges of a graph. The features from brain summaries are assembled and learned using 3DCNN to represent the features of each node of the graph. Using the structural similarities of the brain rather than phenotypic data or graph kernel functions provides better accuracy. The proposed model was applied to a standard dataset, ABIDE, and it was shown that the classification results improved with the use of both spatial (sMRI) and statistical measures (brain summaries of rs-fMRI) instead of using only medical images. [ABSTRACT FROM AUTHOR]

Developments in the study of sexuality in the lives of disabled people have been relatively slow, as the spectre of a medicalised model continues to dominate most debates and invalidate any form of sexual identity. The social model of disability has enabled the amplification of voices that have been previously silenced; however, progress has stalled. Within autism studies, however, the rise of neurodiversity studies coupled with intersectionality, has presented an opportunity to explore sexualities in terms of difference rather than deficiency, therefore bypassing deficit models which have dominated any study of non-heterosexual lives. Such deficit models have focussed upon discovering what it is about autism that leads autistic people to think they are non-heterosexual, often resulting in a lack of support for young LGBT+ people as sexuality is dismissed as a result of autism. Reflecting upon findings from my own ongoing work alongside emerging social research, this article explores important developments and potential future directions. This will highlight the progress made and the barriers remaining. Using a sociological approach and a framework inspired by Plummer, which focusses upon the importance of sexual stories, the article will show that much needs to be done. The diversity of goals and multiplicity of stories means that disabled and autistic sexuality stories have not been accepted into the public consciousness. [ABSTRACT FROM AUTHOR]

Electrodermal Activity (EDA) has become of great interest in the last several decades, due to the advent of new devices that allow for recording a lot of psychophysiological data for remotely monitoring patients' health. In this work, a novel method of analyzing EDA signals is proposed with the ultimate goal of helping caregivers assess the emotional states of autistic people, such as stress and frustration, which could cause aggression onset. Since many autistic people are non-verbal or suffer from alexithymia, the development of a method able to detect and measure these arousal states could be useful to aid with predicting imminent aggression. Therefore, the main objective of this paper is to classify their emotional states to prevent these crises with proper actions. Several studies were conducted to classify EDA signals, usually employing learning methods, where data augmentation was often performed to countervail the lack of extensive datasets. Differently, in this work, we use a model to generate synthetic data that are employed to train a deep neural network for EDA signal classification. This method is automatic and does not require a separate step for features extraction, as in EDA classification solutions based on machine learning. The network is first trained with synthetic data and then tested on another set of synthetic data, as well as on experimental sequences. In the first case, an accuracy of 96% is reached, which becomes 84% in the second case, thus demonstrating the feasibility of the proposed approach and its high performance. [ABSTRACT FROM AUTHOR]

Leptin, which plays a key role in energy homeostasis, is known as a neurotrophic factor possibly linking nutrition and neurodevelopment. Available data on the association between leptin and autism spectrum disorder (ASD) are confusing. The aim of this study was to explore whether plasma levels of leptin in pre- and post-pubertal children with ASD and/or overweightness/obesity differ from those of BMI- and age-matched healthy controls. Leptin levels were determined in 287 pre-pubertal children (mean age 8.09 years), classified as follows: ASD with overweightness/obesity (ASD+/Ob+); ASD without overweightness/obesity (ASD+/Ob−); non-ASD with overweightness/obesity (ASD−/Ob+); non-ASD without overweightness/obesity (ASD−/Ob−). The assessment was repeated in 258 of the children post-pubertally (mean age 14.26 years). There were no significant differences in leptin levels either before or after puberty between ASD+/Ob+ and ASD−/Ob+ or between ASD+/Ob− and ASD−/Ob−, although there was a strong trend toward significance for higher pre-pubertal leptin levels in ASD+/Ob− than in ASD−/Ob−. Post-pubertal leptin levels were significantly lower than pre-pubertal levels in ASD+/Ob+, ASD−/Ob+, and ASD+/Ob− and higher in ASD−/Ob−. Leptin levels, elevated pre-pubertally in the children with overweightness/obesity as well as in children with ASD and normal BMI, decrease with age, in contrast to the increasing leptin levels in healthy controls. [ABSTRACT FROM AUTHOR]

Featured Application: Two case studies are presented in which gamification is implemented with tangible user interfaces, extended reality and universal design for the learning of blind and autistic people. The present study investigates the use of gamification to foster commitment and engagement among users with disabilities. Two case studies demonstrating the application of gamification are provided. The first is the development of an application to teach a blind person Mexican currency, and the second one is the creation of an application to aid individuals with autism spectrum disorder (ASD) in navigating their environment. The study reveals that universal design for learning principles can be used indirectly to adjust apps for users to utilize the software consistently. This study provides preliminary evaluations for both case studies, which were undertaken with relatively small samples. The first case study revealed that three blind individuals who took part in the review scored an average of 91.7 on the system usability scale. At the same time, the second case study involving the observation of a single individual with ASD also revealed that utilizing the designed app improved performance. Despite the limited sample size, the findings suggest that gamification may effectively encourage and generate commitment among the users with disabilities. [ABSTRACT FROM AUTHOR]

Recently the Lancet published a Commission on the future of care and clinical research of autism, which included a side panel arguing for the adoption of "profound autism", a term in- tended to describe autistic people who require constant supervision or care, thought to usually have significant intellectual disability, limited or no language, and an inability to advocate for themselves. This state-of-the-art review deconstructs problems with autism sublabels such as "profound autism" and low- and high-functioning labels. It then examines the communicative and cognitive capacities of minimally speaking autistic people, finding that such individuals can communicate (especially with responsive partners) and need nonverbal testing that allows them to demonstrate their potential strengths. It concludes with the ability of minimally speaking autistic people to self-advocate, and the influences of other people to both support and frustrate their communication. [ABSTRACT FROM AUTHOR]

Background: The objective of this retrospective study was to assess the oral health status and treatment needs of children with ASD and to explore the differences in risk factors and oral health care status and the risk factors for treatment under GA. Methods: Dental charts of children between 6 and 14 years of age who were examined at a dental facility associated with the College of Dentistry, University of Saskatchewan between 2016 to 2019 were assessed. Children who were identified as having ASD, as well as an age- and gender-matched control group consisting of otherwise healthy children were included in the study. Results: The sample included 346 dental records, with 173 children having a diagnosis of ASD. Children diagnosed with ASD had significantly higher experience with caries (91.3% vs. 65.9%, p = 0.003) and severity (mean DMFT/dmft = 8.18 ± 1.62 vs. 4.93 ± 0.58 p = 0.007). Children with ASD were also older when visiting the dentist for the first time (age of 5.97 ± 1.18 vs. 2.79 ± 1.09, p = 0.02)). Children with ASD were less likely to brush once a day (66.5% vs. 88.4%, p = 0.02), were more likely to have bruxism (35.8% vs. 10.4%, p = 0.003) and were less likely to have class I occlusion (64.7% vs. 80.9%, p = 0.03). Findings from the logistic regression analysis revealed that children with ASD were also 2.13 times more likely to receive a referral for general anesthesia when all other variables were held constant (p = 0.03). Conclusions: This research demonstrates that children diagnosed with ASD may face more barriers with access to oral health care, leading to poorer outcomes and greater treatment dental needs. [ABSTRACT FROM AUTHOR]

Individuals with autism spectrum disorder (ASD) are characterized by impairments in flexibly acquiring and maintaining new information, as well as in applying learned information for problem solving. However, the neural mechanism underpinning such impairments remains unclear. This study investigated the flexibility in the acquisition and application of visual information in ASD (aged 14–21) when they performed the Wisconsin Card Sorting Test (WCST). Behavioral data including response accuracy and latency, and prefrontal hemodynamic data measured by functional near-infrared spectroscopy (fNIRS), were collected when individuals performed WCST. Canonical general linear model and functional connectivity analyses were performed to examine the prefrontal activation and synchronization patterns, respectively. Results showed that although ASD individuals (n = 29) achieved comparable accuracy rates when compared with age- and intelligence quotient (IQ)-matched typically developing (TD; n = 26) individuals (F1,53 = 3.15, p = 0.082), ASD individuals needed significantly more time to acquire and apply WCST card sorting rules (F1,53 = 17.92, p < 0.001). Moreover, ASD individuals showed significantly lower prefrontal functional connectivity than TD individuals during WCST (F1,42 = 9.99, p = 0.003). The hypoconnectivity in ASD individuals was highly significant in the right lateral PFC in the acquisition condition (p = 0.005) and in the bilateral lateral PFC in the application condition (ps = 0.006). Furthermore, slower WCST reaction time was correlated with lower bilateral lateral PFC functional connectivity only in the application condition (ps = 0.003) but not the acquisition condition. Impairment in information acquisition and application is evident in ASD individuals and is mediated by processing speed, which is associated with lower functional connectivity in the bilateral lateral PFC when these individuals apply learned rules to solve novel problems. [ABSTRACT FROM AUTHOR]

Research has shown that genetics play a key role in the development of autism spectrum disorder (ASD). ASD has been linked to many genes and is a prominent feature in numerous genetic disorders. A genetic evaluation should be offered to any patient who receives a diagnosis of ASD, including deep phenotyping and genetic testing when clinically indicated. When insurance does not cover genetic testing for ASD patients, the lack of medical utility is often cited as a reason for prior authorization request denial. However, ample evidence exists that genetic testing has the power to change clinical management in many of these patients. Genetic testing that results in a diagnosis guides clinicians to screen for associated medical conditions and can direct targeted medical interventions. Given the potential for clinically actionable results, it is important that genetic testing be available and accessible to all patients with ASD. [ABSTRACT FROM AUTHOR]

The architecture of spaces for people on the autistic spectrum is evolving toward inclusive design, which should fit the requirements for independent, autonomous living, and proper support for relatives and caregivers. The use of smart sensor systems represents a valuable support to internal design in order to achieve independent living for impaired people. Accordingly, these devices can monitor or prevent hazardous situations, ensuring security and privacy. Acoustic sensor systems, for instance, could be used in order to realize a passive monitoring system. The correct functioning of such devices needs optimal indoor acoustic criteria. Nevertheless, these criteria should also comply with dedicated acoustic requests that autistic individuals with hearing impairment or hypersensitivity to sound could need. Thus, this research represents the first attempt to balance, integrate, and develop these issues, presenting (i) a wide literature overview related to both topics, (ii) a focused analysis on real facility, and (iii) a final optimization, which takes into account, merges, and elucidates all the presented unsolved issues. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) can be understood as a social interaction disorder. This makes the emerging "second-person approach" to social cognition a more promising framework for studying ASD than classical approaches focusing on mindreading capacities in detached, observer-based arrangements. According to the second-person approach, embodied, perceptual, and embedded or interactive capabilities are also required for understanding others, and these are hypothesized to be compromised in ASD. We therefore recorded the dynamics of real-time sensorimotor interaction in pairs of control participants and participants with High-Functioning Autism (HFA), using the minimalistic human-computer interface paradigm known as "perceptual crossing" (PC). We investigated whether HFA is associated with impaired detection of social contingency, i.e., a reduced sensitivity to the other's responsiveness to one's own behavior. Surprisingly, our analysis reveals that, at least under the conditions of this highly simplified, computer-mediated, embodied form of social interaction, people with HFA perform equally well as controls. This finding supports the increasing use of virtual reality interfaces for helping people with ASD to better compensate for their social disabilities. Further dynamical analyses are necessary for a better understanding of the mechanisms that are leading to the somewhat surprising results here obtained. [ABSTRACT FROM AUTHOR]

Oxytocin (OT) is a nonapeptide that plays an important role in social behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects. As is consistent with the nature of a peptide, OT has some unfavorable characteristics: it has a short half-life in plasma and shows poor permeability across the blood-brain barrier. Analogs with long-lasting effects may overcome these drawbacks. To this end, we have synthesized three analogs: lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues, lipo-oxytocin-2 (LOT-2) and lipo-oxytocin-3 (LOT-3), which include one palmitoyl group conjugated at the cysteine or tyrosine residue, respectively. The following behavioral deficits were observed in CD38 knockout (CD38-/-) mice: a lack of paternal nurturing in CD38-/- sires, decreased ability for social recognition, and decreased sucrose consumption. OT demonstrated the ability to recover these disturbances to the level of wild-type mice for 30 min after injection. LOT-2 and LOT-3 partially recovered the behaviors for a short period. Conversely, LOT-1 restored the behavioral parameters, not for 30 min, but for 24 h. These data suggest that the lipidation of OT has some therapeutic benefits, and LOT-1 would be most useful because of its long-last activity. [ABSTRACT FROM AUTHOR]

Baron-Cohen's Empathizing-Systemizing theory plays a central role in this study due to its success in interpreting the core impairments and strengths in autism. The theory states that low empathizing skills are responsible for the social difficulties in autism, and that high levels of systemizing are accountable for the restricted, repetitive patterns of behavior in autism. We therefore hypothesized that there is a significant discrepancy between a child's empathizing and systemizing abilities when autism is present. We developed Dutch versions of the questionnaires that are associated with the theory: the Autism Quotient questionnaire, the Empathizing Quotient questionnaire and the Systemizing Quotient questionnaire. As hypothesized, the scores of children with autism on the Empathizing Quotient questionnaire and on the Systemizing Quotient questionnaire (EQ-SQ Child_NL) show a significant difference. Furthermore, the EQ-SQ Child_NL predicts the score of children in general on the Dutch version of the Autism Quotient questionnaire (AQ Child_NL). [ABSTRACT FROM AUTHOR]

The emergence of cognitive impairment and dementia in people with Lewy body spectrum disorders (LBS) significantly impacts the quality of life of the individual and their care partner. Coping well with the condition may depend, in part, on the degree of psychological resilience or capacity to 'bounce back' from adversity. We explored resilience in people with Parkinson's disease mild cognitive disorder or dementia, or dementia with Lewy bodies, and their care partners, and its relation to outcomes related to their mental well-being and quality of life. This exploratory, cross-sectional study recruited 76 participant-dyads. Resilience, quality of life, depression, anxiety, and relationship satisfaction were evaluated in both members of the dyad. In care partners, care burden and stress were also assessed. Over 70% of both care partners and recipients reported high levels of resilience. Lower resilience in both members of the dyad was associated with higher anxiety and lower quality of life. Additionally, lower resilience in care partners was associated with lower well-being, relationship satisfaction, and higher burden and stress. Resilience in persons with LBS and their care partners is important to consider when assessing mental health, relationship, and care burden outcomes, acting as a focus of intervention to support positive outcomes. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak has disrupted the daily routine of the population worldwide, including autistic people and their caregivers, with severe consequences on mental health. On one hand, the reduced social contacts and the interruption of outpatient and daycare services during the lockdown have represented a real challenge for autistic people and their caregivers. On the other hand, confinement has allowed individuals to spend more time pursuing their interests and stay home with their family members without feeling the pressure of social expectations. The present study aimed to compare the levels of personal wellbeing, family distress, insomnia, and resilience between caregivers of autistic people and caregivers of people with other neurodevelopmental, psychiatric, or relational disabilities. A web survey was completed by 383 participants, of which 141 were primary caregivers of autistic people. We did not find any significant difference between caregivers of autistic and non-autistic people in any of the considered psychological variables. Lower age of the autistic family member and lower resilience levels were significantly associated with higher individual distress in the group of caregivers of autistic people. Our findings do not corroborate the hypothesis that caregivers of autistic individuals have had more severe consequences than other caregivers during the lockdown. However, they confirm the importance of promoting resilient coping strategies in autistic people and their caregivers. [ABSTRACT FROM AUTHOR]

The sulphate-reducing bacteria (SRB) of genus Desulfovibrio are a group of prokaryotes associated with autism spectrum disorders (ASD). The connection between the elevated numbers of Desulfovibrio in the gut of children with ASD compared with healthy children remains unresolved. A conceivable consequence of SRB overgrowth in the gut is the conversion of bioavailable iron into low-soluble crystalline iron sulphides, causing iron deficiency in the organism. In this study, we report the draft genome sequence and physiological features of the first cultivable isolate from a patient with ASD, Desulfovibrio desulfuricans strain AY5.The capability of the strain to produce crystalline iron sulphides was studied under different pH conditions. The most notable greigite(Fe3S4) and pyrite (FeS2) formation was revealed at pH 6.0, which suggests that the iron loss due to insoluble sulphide formation may occur in the proximal part of the gastrointestinal tract. Strain AY5 was adapted to grow under nitrogen-limiting conditions by N2 fixation. The urease found in the strain's genome may play a role in resistance to acidic pH. [ABSTRACT FROM AUTHOR]

Intellectual disability (ID) and autism spectrum disorder (ASD) belong to neurodevelopmental disorders and occur in ~1% of the general population. Due to disease heterogeneity, identifying the etiology of ID and ASD remains challenging. Exome sequencing (ES) offers the opportunity to rapidly identify variants associated with these two entities that often co-exist. Here, we performed ES in a cohort of 200 patients: 84 with isolated ID and 116 with ID and ASD. We identified 41 pathogenic variants with a detection rate of 22% (43/200): 39% in ID patients (33/84) and 9% in ID/ASD patients (10/116). Most of the causative genes are genes responsible for well-established genetic syndromes that have not been recognized for atypical phenotypic presentations. Two genes emerged as new candidates: CACNA2D1 and GPR14. In conclusion, this study reinforces the importance of ES in the diagnosis of ID/ASD and underlines that "reverse phenotyping" is fundamental to enlarge the phenotypic spectra associated with specific genes. [ABSTRACT FROM AUTHOR]

Patients with autism spectrum disorder (ASD) may have an increase in blood acyl-carnitine (AC) concentrations indicating a mitochondrial fatty acid β-oxidation (mtFAO) impairment. However, there are no data on systematic mtFAO analyses in ASD. We analyzed tritiated palmitate oxidation rates in fibroblasts from patients with ASD before and after resveratrol (RSV) treatment, according to methods used for the diagnosis of congenital defects in mtFAO. ASD participants (N = 10, 60%; male; mean age (SD) 7.4 (3.2) years) were divided in two age-equivalent groups based on the presence (N = 5) or absence (N = 5) of elevated blood AC levels. In addition, electron transport chain (ETC) activity in fibroblasts and muscle biopsies and clinical characteristics were compared between the ASD groups. Baseline fibroblast mtFAO was not significantly different in patients in comparison with control values. However, ASD patients with elevated AC exhibited significantly decreased mtFAO rates, muscle ETC complex II activity, and fibroblast ETC Complex II/III activity (p < 0.05), compared with patients without an AC signature. RSV significantly increased the mtFAO activity in all study groups (p = 0.001). The highest mtFAO changes in response to RSV were observed in fibroblasts from patients with more severe symptoms on the Social Responsiveness Scale total (p = 0.001) and Awareness, Cognition, Communication and Motivation subscales (all p < 0.01). These findings suggested recognition of an ASD patient subset characterized by an impaired mtFAO flux associated with abnormal blood AC. The study elucidated that RSV significantly increased fibroblast mtFAO irrespective of plasma AC status, and the highest changes to RSV effects on mtFAO were observed in the more severely affected patients. [ABSTRACT FROM AUTHOR]

Autistic people face many challenges in various aspects of daily life such as social skills, repetitive behaviors, speech, and verbal communication. They feel hesitant to talk with others. The signs of autism vary from one individual to another, with a range from mild to severe. Autistic children use fewer communicative gestures compared with typically developing children (TD). With time, the parents may learn their gestures and understand what is occurring in their child's mind. However, it is difficult for other people to understand their gestures. In this paper, we propose a wearable-sensors-based platform to recognize autistic gestures using various classification techniques. The proposed system defines, monitors, and classifies the gestures of the individuals. We propose using wearable sensors that transmit their data using a Bluetooth interface to a data acquisition and classification server. A dataset of 24 gestures is created by 10 autistic children performing each gesture about 10 times. Time- and frequency-domain features are extracted from the sensors' data, which are classified using k-nearest neighbor (KNN), decision tree, neural network, and random forest models. The main objective of this work is to develop a wearable-sensor-based IoT platform for gesture recognition in children with autism spectrum disorder (ASD). We achieve an accuracy of about 91% with most of the classifiers using dataset cross-validation and leave-one-person-out cross-validation. [ABSTRACT FROM AUTHOR]

Machine learning methods are widely used in autism spectrum disorder (ASD) diagnosis. Due to the lack of labelled ASD data, multisite data are often pooled together to expand the sample size. However, the heterogeneity that exists among different sites leads to the degeneration of machine learning models. Herein, the three-way decision theory was introduced into unsupervised domain adaptation in the first time, and applied to optimize the pseudolabel of the target domain/site from functional magnetic resonance imaging (fMRI) features related to ASD patients. The experimental results using multisite fMRI data show that our method not only narrows the gap of the sample distribution among domains but is also superior to the state-of-the-art domain adaptation methods in ASD recognition. Specifically, the ASD recognition accuracy of the proposed method is improved on all the six tasks, by 70.80%, 75.41%, 69.91%, 72.13%, 71.01% and 68.85%, respectively, compared with the existing methods. [ABSTRACT FROM AUTHOR]

Autism is a neurodevelopmental condition associated with increased levels of anxiety. However, whether autism is related to heightened test anxiety as one situation-specific type of anxiety has not yet been examined. This question may be relevant for the achievement and well-being of autistic people in educational settings (e.g., at universities). In this study, we took a first step to investigate whether autistic university students have increased test anxiety. A sample of 16 German-speaking university students completed an established diagnostic instrument to measure test anxiety and its components of worry, emotionality, cognitive interference, and lack of confidence. The scores of the autistic students were compared with the test anxiety means and percentile ranks of the standardization sample for the applied test anxiety measure (n = 1350). For an additional comparison, the test anxiety means and percentile ranks of non-autistic university students (n = 101) were assessed during the last third of the semester; that is, close to the examinations. Overall, the results suggest that autistic university students have remarkably increased test anxiety. Although the present findings must be considered preliminary, they suggest that text anxiety in educational settings may be a neglected significant problem for autistic people that requires further attention in research and practice. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder originating in infancy and childhood that may cause language barriers and social difficulties. However, in the diagnosis of ASD, the current machine learning methods still face many challenges in determining the location of biomarkers. Here, we proposed a novel feature selection method based on the minimum spanning tree (MST) to seek neuromarkers for ASD. First, we constructed an undirected graph with nodes of candidate features. At the same time, a weight calculation method considering both feature redundancy and discriminant ability was introduced. Second, we utilized the Prim algorithm to construct the MST from the initial graph structure. Third, the sum of the edge weights of all connected nodes was sorted for each node in the MST. Then, N features corresponding to the nodes with the first N smallest sum were selected as classification features. Finally, the support vector machine (SVM) algorithm was used to evaluate the discriminant performance of the aforementioned feature selection method. Comparative experiments results show that our proposed method has improved the ASD classification performance, i.e., the accuracy, sensitivity, and specificity were 86.7%, 87.5%, and 85.7%, respectively. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) are a group of neurodevelopmental syndromes with both genetic and environmental origins. Several recent studies have shown that inflammation and oxidative stress may play a key role in supporting the pathogenesis and the severity of ASD. Thus, the administration of anti-inflammatory and antioxidant molecules may represent a promising strategy to counteract pathological behaviors in ASD patients. In the current review, results from recent literature showing how natural antioxidants may be beneficial in the context of ASD will be discussed. Interestingly, many antioxidant molecules available in nature show anti-inflammatory activity. Thus, after introducing ASD and the role of the vitamin E/vitamin C/glutathione network in scavenging intracellular reactive oxygen species (ROS) and the impairments observed with ASD, we discuss the concept of functional food and nutraceutical compounds. Furthermore, the effects of well-known nutraceutical compounds on ASD individuals and animal models of ASD are summarized. Finally, the importance of nutraceutical compounds as support therapy useful in reducing the symptoms in autistic people is discussed. [ABSTRACT FROM AUTHOR]

Although intracranial pressure is considered to be normal in children with autism spectrum disorder (ASD), we aimed to assess whether such children may have increased intracranial pressure using noninvasive computed tomography (CT). Head CT scans of children with ASD (109 cases, male 91 and female 18, average age 4.3 years) and of children with typical development (60 cases, male 35 and female 25, average age 4.5 years) were acquired. The images were processed to map the shape of the inner skull surface. We predicted that a complex skull shape, based on a marked digital impression, would be indicative of chronically increased intracranial pressure. The data of the scans were extracted and processed to automatically establish inner and outer cranial circumferences. The circularity (reflecting inner skull shape and area) and C-ratio (ratio of inner/outer circumference) were determined and statistically analyzed. The circularity and C-ratio were significantly lower in children with ASD than in children with typical development. A lower circularity was associated with a more complex shape of the inner skull surface, which indicated the presence of intracranial hypertension. Our study suggests that children with ASD may be at a risk for chronic intracranial hypertension. Our technique incorporating the circularity and C-ratio is a useful noninvasive method for screening such patients and could impact future investigations of ASD. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASDs) are hard to characterize due to their clinical heterogeneity. Whether epilepsy and other highly prevalent comorbidities may be related to specific subphenotypes such as regressive ASD (i.e., the onset of symptoms after a period of apparently typical development) is controversial and yet to be determined. Such discrepancies may be related to the fact that age, level of cognitive functioning, and environmental variables are often not taken into account. We considered a sample of 20 subjects (i) between 20 and 55 years of age, (ii) with severe/profound intellectual disability, (iii) living in the same rural context of a farm community. As a primary aim, we tested for the association between epilepsy and regressive ASD. Secondly, we explored differences in behavioral and pharmacological profiles related to the presence of each of these conditions, as worse behavioral profiles have been separately associated with both epilepsy and regressive ASD in previous studies. An initial trend was observed for associations between the presence of epilepsy and regressive ASD (odds ratio: 5.33; 95% CI: 0.62–45.41, p-value: 0.086). Secondly, subjects with either regressive ASD or epilepsy showed worse behavioral profiles (despite the higher pharmacotherapy they received). These preliminary results, which need to be further confirmed, suggest the presence of specific associations of different clinical conditions in subjects with rarely investigated phenotypes. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by difficulties with social interaction, repetitive behavior, and additional features, such as special interests. Its precise etiology is unclear. Recently, immunological mechanisms, such as maternal autoantibodies/infections, have increasingly been the subject of discussion. Cerebrospinal fluid (CSF) investigations play a decisive role in the detection of immunological processes in the brain. This study therefore retrospectively analyzed the CSF findings of adult patients with ASD. CSF basic measures (white blood cell count, total protein, albumin quotient, immunoglobulin G (IgG) index, and oligoclonal bands) and various antineuronal antibody findings of 36 adult patients with ASD, who had received lumbar puncture, were compared with an earlier described mentally healthy control group of 39 patients with idiopathic intracranial hypertension. CSF protein concentrations and albumin quotients of patients with ASD were significantly higher as compared to controls (age corrected: p = 0.003 and p = 0.004, respectively); 17% of the patients with ASD showed increased albumin quotients. After correction for age and gender, the group effect for total protein remained significant (p = 0.041) and showed a tendency for albumin quotient (p = 0.079). In the CSF of two ASD patients, an intrathecal synthesis of anti-glutamate decarboxylase 65 (GAD65) antibodies was found. In total, more of the ASD patients (44%) presented abnormal findings in CSF basic diagnostics compared to controls (18%; p = 0.013). A subgroup of the patients with adult ASD showed indication of a blood–brain barrier dysfunction, and two patients displayed an intrathecal synthesis of anti-GAD65 antibodies; thus, the role of these antibodies in patients with ASD should be further investigated. The results of the study are limited by its retrospective and open design. The group differences in blood–brain barrier markers could be influenced by a different gender distribution between ASD patients and controls. [ABSTRACT FROM AUTHOR]

Disability progression is a prominent feature of multiple sclerosis (MS). However, little is known about the extent to which physical condition parameters and perceived fatigue evolve during the disease. We analyzed how strength, balance, core stability and perceived fatigue differ among different cohorts of people with MS (PwMS) with different disability degrees and how these contribute to patients' gait speed and functional mobility. Sixty-three PwMS divided into three groups according to the "Expanded Disability Status Scale" (MS1: EDSS ≤ 1.5; MS2: 2 ≤ EDSS ≤ 3.5; MS3: 4 ≤ EDSS ≤ 6) and 22 healthy controls (HC) participated in this study. MS1 showed lower balance and hip strength compared to HC. MS2 showed lower balance, core stability, gait speed, and functional mobility than MS1. MS3 showed lower gait speed, functional mobility, balance, and knee flexion strength than MS2. No between-group differences were observed in perceived fatigue. Relative weight analysis showed that strength, balance and core stability explained 60%–70% of the variance in gait speed and functional mobility. The decline of each parameter did not evolve at the same rate across the different stages of the disease, being knee flexion strength and balance the most influential factors in the disability progression. Overall, these results provide useful information to guide exercise prescription at different stages of MS. [ABSTRACT FROM AUTHOR]

The role of infections in the pathogenesis of autism spectrum disorder (ASD) is still controversial. In this study, we aimed to evaluate markers of infections and immune activation in ASD by performing a meta-analysis of publicly available whole-genome transcriptomic datasets of brain samples from autistic patients and otherwise normal people. Among the differentially expressed genes, no significant enrichment was observed for infectious diseases previously associated with ASD, including herpes simplex virus-1 (HSV-1), cytomegalovirus and Epstein–Barr virus in brain samples, nor was it found in peripheral blood from ASD patients. Interestingly, a significant number of genes belonging to the "prion diseases" pathway were found to be modulated in our ASD brain meta-analysis. Overall, our data do not support an association between infection and ASD. However, the data do provide support for the involvement of pathways related to other neurodegenerative diseases and give input to uncover novel pathogenetic mechanisms underlying ASD. [ABSTRACT FROM AUTHOR]

Background: Research suggests that people with anorexia nervosa (AN) experience subjective hypersensitivity to external sensations that may require consideration in treatment. These difficulties may be particularly pronounced in people with AN and high autistic traits. The purpose of this pilot study was to explore the use of a brief screening tool to assess sensory sensitivity in individuals receiving treatment for AN, and to assess if self-rated sensitivity in AN is related to autistic traits. Methods: 47 individuals receiving treatment for AN completed a brief sensory screening tool and self-rated their autistic traits. Individuals were also asked to give qualitative feedback on the screening tool. Results: People with AN and high autistic traits rated themselves as more hypersensitive compared to people with AN and low autistic traits. Feedback surrounding the use of the screener was positive. Conclusions: The results of this study suggest that the use of this screener may be beneficial in eating disorder settings to help adjust and calibrate treatment to personal needs, although further research and psychometric evaluation around the clinical use of the screener is required. The finding that people with AN and high autistic traits may experience elevated hypersensitivity also warrants further exploration in future research. [ABSTRACT FROM AUTHOR]