Sleep disturbances are associated with greater healthcare utilization in children with autism spectrum disorder.

BACKGROUND: Sleep disturbances are frequently reported in children with autism spectrum disorder (ASD) and are associated with the severity of co-occurring symptoms. This study's aim was to examine the extent of healthcare utilization and clinical outcomes associated with sleep disturbances in children with ASD. STUDY DESIGN: A retrospective, cross-sectional study of 541 children with ASD from the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) whose parents completed the Children's Sleep Habits Questionnaire (CSHQ). Children with a total CSHQ score ≥ 48 were defined as having sleep disturbances. Sociodemographic characteristics, ASD diagnostic measures, chronic co-occurring conditions, medication usage, hospitalizations, visits to the emergency room (ER), and visits to specialists were compared in ASD children with and without sleep disturbances. Multivariate logistic regression models were then used to assess the independent association of sleep disturbances with clinical characteristics and healthcare utilization. RESULTS: Of the 541 children with ASD, 257 (47.5%) had sleep disturbances. Children with sleep disturbances exhibited higher rates of multiple (≥ 3) co-occurring conditions (19.1% vs. 12.7%; p = 0.0414) and prescribed medications (45.5% vs. 32.7%; p = 0.0031) than other children. Finally, ASD children with sleep disturbances were 1.72 and 2.71 times more likely to visit the ER and be hospitalized than their counterparts (aOR = 1.72; 99%CI = 1.01-2.95; and aOR = 2.71; 99%CI = 1.10-6.67, respectively). CONCLUSIONS: Our findings suggest that sleep disturbances are associated with greater healthcare utilization among children with ASD. Further studies could examine whether treating sleep disturbances in children with ASD yields additional clinical benefits beyond improvements in sleep.

Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo. Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.

The effects of a web-based 24-hour movement behavior lifestyle education program on mental health and psychological well-being in parents of children with autism spectrum disorder: A randomized controlled trial.

BACKGROUND AND PURPOSE: Compared with parents of neurotypical children or children diagnosed with other disabilities, parents of children with autism spectrum disorder (ASD) often experience poorer mental health, greater stress, and more depression and anxiety symptoms. This study aimed to assess the effects of a web-based 24-h movement behavior lifestyle education program on mental health and psychological well-being in parents of children with ASD. METHODS: This study employed a randomized controlled trial utilizing the Health Action Process Approach (HAPA) as a theoretical framework. A total of 318 parents of children with ASD were enrolled and randomly assigned to the experimental or control group. The experimental group received an 8-week web-based 24-h movement behavior lifestyle education program, while the control group followed their usual routine. Two instruments, the Depression Anxiety and Stress Scale (DASS-21) and the Satisfaction With Life Scale (SWLS), were used to measure mental health and psychological well-being, respectively. The data were collected at two time points-at the beginning and the end of the intervention. RESULTS: Compared with the baseline and control groups, the experimental group demonstrated significant improvements in all outcome measures (p < 0.01). There were significant differences in the DASS-21 and SWLS scores between the two groups before and after the intervention (p ≤ 0.01). CONCLUSION: This study represents the first randomized controlled trial involving a web-based 24-h movement behavior lifestyle education program specifically designed to address the mental health and psychological well-being of parents of children with ASD. The findings confirm the potential impact of 24-h movement behavior lifestyle education as a functional and effective strategy for parents of children with ASD.

New advances in the diagnosis and treatment of autism spectrum disorders.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders that affect individuals' social interactions, communication skills, and behavioral patterns, with significant individual differences and complex etiology. This article reviews the definition and characteristics of ASD, epidemiological profile, early research and diagnostic history, etiological studies, advances in diagnostic methods, therapeutic approaches and intervention strategies, social and educational integration, and future research directions. The highly heritable nature of ASD, the role of environmental factors, genetic-environmental interactions, and the need for individualized, integrated, and technology-driven treatment strategies are emphasized. Also discussed is the interaction of social policy with ASD research and the outlook for future research and treatment, including the promise of precision medicine and emerging biotechnology applications. The paper points out that despite the remarkable progress that has been made, there are still many challenges to the comprehensive understanding and effective treatment of ASD, and interdisciplinary and cross-cultural research and global collaboration are needed to further deepen the understanding of ASD and improve the quality of life of patients.

Public Dental Service Access Policies for People with Autism Spectrum Disorder (ASD) in Salvador, Bahia, Brazil: A Pre-Evaluation Study.

This study sought to carry out a systematic and preliminary evaluation of the policies on access to public dental services for people with ASD in a Brazilian city. The study, conducted between November/2019 and February/2020, was developed through document analysis, the design of the theoretical logical model of the policies, and seven semi-structured interviews with key informants. The sample was intentionally selected. We also considered the answers to 108 questionnaires from a pilot study on the access of people with ASD to dental services applied to caregivers, dentists, and non-dental professionals. No refusals were recorded. The availability study showed that the policies' objectives were not being achieved in terms of care network organization: there were no institutional flows, personal contacts were used between professionals to guarantee access to secondary attention, there was no specific training for the dentists about ASD, and the oral health care network was unknown to non-dentist professionals and caregivers. Most people with ASD have visited the dentist at least once in their lives, but a large percentage of those within this study did not do so in the last year. This study identified difficulties in implementing policies and suggested possible strategies for overcoming them as dimensions and subdimensions for evaluation.

The emerging role of extracellular vesicles in the diagnosis and treatment of autism spectrum disorders.

Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by restricted, repetitive behavioral patterns and deficits in social interactions. The prevalence of ASD has continued to rise in recent years. However, the etiology and pathophysiology of ASD remain largely unknown. Currently, the diagnosis of ASD relies on behavior measures, and there is a lack of reliable and objective biomarkers. In addition, there are still no effective pharmacologic therapies for the core symptoms of ASD. Extracellular vesicles (EVs) are lipid bilayer nanovesicles secreted by almost all types of cells. EVs play a vital role in cell-cell communications and are known to bear various biological functions. Emerging evidence demonstrated that EVs are involved in many physiological and pathological processes throughout the body and the content in EVs can reflect the status of the originating cells. EVs have demonstrated the potential of broad applications for the diagnosis and treatment of various brain diseases, suggesting that EVs may have also played a role in the pathological process of ASD. Besides, EVs can be utilized as therapeutic agents for their endogenous substances and biological functions. Additionally, EVs can serve as drug delivery tools as nano-sized vesicles with inherent targeting ability. Here, we discuss the potential of EVs to be considered as promising diagnostic biomarkers and their potential therapeutic applications for ASD.

Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients.

Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.

Comparative efficacy of family mediated intervention versus early intensive behavioural intervention on symptom domains in children with autism spectrum disorder: A randomized controlled trial.

BACKGROUND: Family Mediated Intervention (FMI) and Early Intensive Behavioural Intervention (EIBI) are found to be standard of care for children with Autism Spectrum Disorder (ASD). Comparison of their efficacy were assessed using ISAA as primary outcome measure. METHODS: This study was a parallel arm, open label, randomized active- controlled non-inferiority clinical trial. 50 Children diagnosed with ASD were randomized into FMI and EIBI groups. Clinical status was checked by using Indian scale for assessment of autism (ISAA), Oro- motor and sensory profile at baseline, after three and six months. RESULTS: Difference between change in mean ISAA score between FMI and EIBI group at the end of 6 months as per protocol (PP) analysis was -7.23 (CI=-18.41, 3.94), which was within pre-defined clinically relevant non-inferiority (NI) margin of - 24. FMI was found to be non-inferior to EIBI at the end of 6 months as the lower bound of 95% CI (-18.41) for ISAA score was higher than NI margin. ISAA scores were found to be statistically lower in both FMI and EIBI groups at the end point compared to baseline which indicated improvement in symptom severity. CONCLUSION: FMI was non-inferior to EIBI as therapy for children with ASD at the end of six months. Finding also indicated longer duration of treatment is required for FMI to be superior. FMI can be recommended for children with ASD in view of improved ISAA scores reported in our study. CLINICAL TRIAL REGISTRATION NUMBER: CTRI/2020/08/027099 (Registered with Clinical Trials Registry- India).

Time Limited Benefits of Physical and Proprioceptive Training on Physical Fitness Components in Children With Autism Spectrum Disorders.

In this study, we explored the immediate and three-month follow-up effects of physical training on physical fitness in children with autism spectrum disorder (ASD). We randomly assigned 20 children with ASD (age 8-11 years) into an experimental group (EG; n = 10) and a control group (CG; n = 10). The EG participated in an 8-week training program involving both strength and proprioceptive exercises (three 60-minute sessions/week), while the CG simply maintained their daily activities. We assessed physical fitness components for each participant at baseline, post-training, and at a 3-month follow-up. The physical training intervention significantly improved physical fitness of these children with ASD in terms of their flexibility (p < .001; 32.46%), lower limbs strength (p = .003; 36.98%), lower body power (p < .001; 41.78%) and functional mobility (p < .001; 25.56%). However, these addition training-induced gains were lost at follow-up for lower limbs strength (p < .001), flexibility (p < .001), and functional mobility (p = .034)). Physical training was effective for improving physical fitness in children with ASD, but the loss of these gains at three months follow-up underscored the need for continuous physical exercise.

Comparison of the efficacy of parent-mediated NDBIs on developmental skills in children with ASD and fidelity in parents: a systematic review and network meta-analysis.

BACKGROUND: Recently, studies on behavioral interventions for autism have gained popularity. Naturalistic Developmental Behavior Interventions (NDBIs) are among the most effective, evidence-based, and widely used behavior interventions for autism. However, no research has been conducted on which of the several NDBI methods is most effective for parents and children with autism spectrum disorders. Therefore, we conducted a network meta-analysis to compare the specific effects of each type of parental-mediated NDBI on children's developmental skills and parent fidelity. METHODS: PubMed, Embase, Cochrane Library, Medline, Web of Science, China National Knowledge Infrastructure (CNKI), CINAHL, and Wanfang databases were searched from inception to August 30, 2023. A total of 32 randomized controlled trial studies that examined the efficacy of different NDBIs were included. RESULTS: Parents of children with ASD who received Pivotal Response Treatment (PRT) reported significant improvements in their children's social skills (SUCRA, 74.1%), language skills (SUCRA, 88.3%), and parenting fidelity (SUCRA, 99.5%). Moreover, parents who received Early Start Denver Model (ESDM) reported significant improvements in their children's language (SMD = 0.41, 95% CI: 0.04, 0.79) and motor skills (SMD = 0.44, 95% CI: 0.09, 0.79). In terms of the efficacy of improving parent fidelity, the results showed that the Improving Parents as Communication Teachers (ImPACT) intervention significantly improved parent fidelity when compared with the treatment-as-usual group (TAU) (SMD = 0.90, 95% CI: 0.39, 1.42) and the parental education intervention (PEI) (SMD = 1.10, 95% CI:0.28, 1.91).There was a difference in parent fidelity among parents who received PRT(SMD = 3.53, 95% CI: 2.26, 4.79) or ESDM(SMD = 1.42, 95% CI: 0.76, 2.09) training compared with PEI. CONCLUSION: In conclusion, this study revealed that parents can achieve high fidelity with the ImPACT intervention, and it can serve as an early first step for children newly diagnosed with ASD. It also showed that parent-mediated ESDM is effective in improving language and motor skills for children with ASD and can be used as part of the second stage of parent training. Parent-mediated PRT can also be used as a third stage of parent training with sufficient training intensity to further improve language, social, and motor skills.

The potential of repetitive transcranial magnetic stimulation for addressing sleep difficulties in children with autism - A brief communication.

Sleep difficulties can co-occur with autistic traits and have been frequently reported in children diagnosed with autism. Thus, sleep difficulties may impact neural development, cognition, and behavioural functioning in children with autism. Interventions, such as repetitive transcranial magnetic stimulation (rTMS), that target aberrant neural structures underpinning autistic traits and sleep difficulties in children could have beneficial effects. The rTMS effects on the pathophysiological pathways hypothesised to underpin autism and sleep difficulties are well-established in the literature; however, clinical evidence of its potential to improve sleep difficulties in children with autism is limited. While the preliminary data is promising, further robust rTMS studies are warranted to encourage its use in clinical practices.

What Is Autism Spectrum Disorder?

This JAMA Patient Page describes autism spectrum disorder (ASD) and its signs and symptoms, diagnosis, and therapy options.

Metaverse in Mental Health: The Beginning of a Long History.

PURPOSE OF REVIEW: We review the first pilot studies applying metaverse-related technologies in psychiatric patients and discuss the rationale for using this complex federation of technologies to treat mental diseases. Concerning previous virtual-reality applications in medical care, metaverse technologies provide the unique opportunity to define, control, and shape virtual scenarios shared by multi-users to exploit the "synchronized brains" potential exacerbated by social interactions. RECENT FINDINGS: The application of an avatar-based sexual therapy program conducted on a metaverse platform has been demonstrated to be more effective concerning traditional sexual coaching for treating female orgasm disorders. Again, a metaverse-based social skills training program has been tested on children with autism spectrum disorders, demonstrating a significant impact on social interaction abilities. Metaverse-related technologies could enable us to develop new reliable approaches for treating diseases where behavioral symptoms can be addressed using socio-attentive tasks and social-interaction strategies.

ESDM intervention in severe preschool autism: an Italian Case report, psychological and social medicine reflections.

BACKGROUND: The goal of our contribution is to discuss a preschool intervention based on the Early Start Denver Model and the use of the main tools for the detection of adaptive behaviour in cases of autism: Vineland, ABAS. CASE PRESENTATION: the work is the presentation of a clinical case that has benefited from an intervention with the Early Start Denver Model methodology for the benefit of a child with socio-cultural and economic disadvantages. This early intervention, in a child of 36 months, which followed the diagnosis, was possible thanks to the intervention of many third-sector organizations which allowed this child, with a serious autism profile, to receive an evidence-based intervention for free. At the beginning of the intervention, the child presented a diagnosis of severe autism with absence of gaze, vocalizations and other communicative impairments. The level of motor clumsiness was also quite high, as were stereotypies. CONCLUSIONS: Research has shown the usefulness of intervening in this area with an early assessment and/or diagnosis and immediate intervention; however, public health services are not always able to maintain this pace. Our contribution therefore shows on the one hand the evidence of the improvements achieved by the child despite the low intensity of the treatment, and on the other hand, demonstrates the total versatility and adaptability of the Denver Model to the Italian context. In our conclusions, there are also some reflections on the tools used to measure adaptive behavior which seem to have a number of limitations and criticalities.

Attention-deficit Hyperactivity Disorder and Autism Spectrum Disorder: Towards Better Diagnosis and Management.

Background: Attention-deficit hyperactivity disorder (ADHA) is one of the most common comorbid disorders of autism spectrum disorder (ASD) that can accompany autism, triggered by it, or be a consequence of it. Objective: This review explored the prevalence of the comorbidity of both disorders, neurobiological background, symptoms, latest assessment methods, and therapeutic approaches. Results and Discussion: It concluded that effective assessment, diagnosis and management of ADHD in ASD children and adults is essential for this group of patients to thrive and live a good quality of life. Further research is recommended to explore the most effective intervention for such important members of our society. Conclusion: More studies are needed to understand the mechanisms underlying these comorbidities, and to prevent the misdiagnosis and mismanagement of these disorders. Also, to develop up to date personalized therapeutic plans for such children.

Identification and support of autistic individuals within the UK Criminal Justice System: a practical approach based upon professional consensus with input from lived experience.

BACKGROUND: Autism spectrum disorder (hereafter referred to as autism) is characterised by difficulties with (i) social communication, social interaction, and (ii) restricted and repetitive interests and behaviours. Estimates of autism prevalence within the criminal justice system (CJS) vary considerably, but there is evidence to suggest that the condition can be missed or misidentified within this population. Autism has implications for an individual's journey through the CJS, from police questioning and engagement in court proceedings through to risk assessment, formulation, therapeutic approaches, engagement with support services, and long-term social and legal outcomes. METHODS: This consensus based on professional opinion with input from lived experience aims to provide general principles for consideration by United Kingdom (UK) CJS personnel when working with autistic individuals, focusing on autistic offenders and those suspected of offences. Principles may be transferable to countries beyond the UK. Multidisciplinary professionals and two service users were approached for their input to address the effective identification and support strategies for autistic individuals within the CJS. RESULTS: The authors provide a consensus statement including recommendations on the general principles of effective identification, and support strategies for autistic individuals across different levels of the CJS. CONCLUSION: Greater attention needs to be given to this population as they navigate the CJS.

Neurofeedback training of executive function in autism spectrum disorder: distinct effects on brain activity levels and compensatory connectivity changes.

BACKGROUND: Deficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD. METHODS: Thirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity. RESULTS: The ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex. CONCLUSIONS: Neurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.

Beyond imagination: Sorting out and treating psychosis in the context of autism spectrum disorder.

In the last decades, growing caseness for Autism Spectrum Disorder (ASD) has been observed, owing to the diagnostic accretion of low-impairment forms, over and above other possible causes. Unrecognized ASD is likely to be mislabeled as a psychotic disorder (PD), as people in the spectrum may show 'pseudopsychotic' symptoms, resembling both negative and positive symptoms. On the other hand, PDs are likely to be overlooked when they arise in people with ASD, due to the 'diagnostic overshadowing' of new-onset conditions by lifelong core autistic symptoms. The three available metanalyses on the occurrence of psychosis in adults with ASD convergently reported a rate of PDs that is at least ten times higher than in the general population. Therefore, the lack of literature addressing risk factors, outcomes, and treatment options for psychosis in the context of ASD is utterly concerning. The present review aims to summarize up-to-date knowledge of PDs with comorbid ASD in terms of clinical features, course, and treatment.

Validation of key components in designing a social skills training content using virtual reality for high functioning autism youth-A Fuzzy Delphi method.

The use of virtual reality in social skills training for high functioning autism spectrum disorder (HFASD) youth has been found to be engaging and enjoyable. Despite the promising results, previous literature indicates that there has been no consensus on the social skills target in the training content. There is also limited research on how evidence-based strategies like cognitive and behaviour techniques are instantiated into the VR environment to teach social skills. The aim of this study is to determine the key components to design a social skills training content using virtual reality for youths with HFASD. The Fuzzy Delphi method (FDM) was used to obtain expert consensus on social skills difficulties and cognitive behavioral techniques included in the content in three phases. In phase 1, a questionnaire was developed from in-depth interviews and scientific literature review. The in-depth interviews were conducted with 13 HFASD youth, 7 parents and 6 experts. In phase 2, 3 experts rated the relevance of the items in the questionnaire using an item-level content validity index (I-CVI) assessment. In phase 3, the questionnaire was distributed to 10 experts to rate their level of agreement on each component using a 7-point Likert scale. Components that received a value above 75%, threshold value (d) ≤ 0.2, fuzzy score (A) ≥ α - cut value = 0.5 and higher rank based on defuzzification score were prioritized to be included in the content. Items that received higher expert consensus on social skills difficulties included assessing non-verbal responses, initiating, maintaining, and leaving conversations, emotional difficulties and difficulties in perspective taking. Cognitive and behavioral techniques that received higher expert consensus were psychoeducation, modelling, relaxation techniques, reinforcements, and perspective-taking questions. These key components can be used as a framework for the development of virtual learning content for social skills training in future studies.

Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles.

Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.