UNASSIGNED: Evidence on the efficacy of social skills training for adolescents with Level 1 Autism Spectrum Disorder (ASD) is unclear.
UNASSIGNED: We searched Pubmed, Scopus, and Web of Science until July 27th, 2023, for randomized controlled trials (RCTs) of social skills training for pre-adolescents and adolescents (aged 9-18) with Level 1 ASD. We then pooled data on efficacy from individual RCTs by conducting multivariate mixed-effects meta-analyses in R. We estimated possible bias in the retained RCTs using the RoB2 tool.
UNASSIGNED: We retained 36 RCTs (encompassing 2796 participants), including 18 RCTs comparing an experimental treatment to a waiting list, and 18 RCTs comparing it to standard care/control treatment. Meta-analyses showed that experimental treatments were significantly more efficacious than waiting list or standard care/ control treatments in improving social skills (SMD = 0.3745; 95%CI = [0.2396; 0.5093]), as well as reducing behavioral symptoms (0.3154;0.1783, 0.4525) and anxious/depressive symptoms (0.2780; 0.0432, 0.5128). However, for some outcomes there was significant heterogeneity across studies and evidence of publication bias. Subgroup analyses and meta-regressions did not identify any specific clinical or demographic factors as significant predictors of outcome. The most common risk of bias across studies was related to deviations from intended interventions and measurement of the outcomes.
UNASSIGNED: At the group level, social skills training for adolescents with Level 1 ASD is efficacious, with small-to-moderate effect size. Future research should focus on personalized medicine approaches, aimed at tailoring interventions to specific characteristics of adolescents with Level 1 ASD.

Autism spectrum disorders (ASD) comprise a range of neurodevelopmental pathologies characterized by deficits in social interaction and repetitive behaviors, collectively affecting almost 1% of the worldwide population. Deciphering the etiology of ASD has proven challenging due to the intricate interplay of genetic and environmental factors and the variety of molecular pathways affected. Epigenomic alterations have emerged as key players in ASD etiology. Their research has led to the identification of biomarkers for diagnosis and pinpointed specific gene targets for therapeutic interventions. This review examines the role of epigenetic alterations, resulting from both genetic and environmental influences, as a central causative factor in ASD, delving into its contribution to pathogenesis and treatment strategies.

Autism spectrum disorders (ASD) are neurodevelopmental disorders of varying intensity and disability. The reference health strategy in France for the care of young children with autism is day care hospital (DCH). As the number of places in DCH is insufficient, medically coordinated care programs by the mental health consultation centers (MHCC) are being developed in response.
OBJECTIVE: Our objective is to evaluate the effectiveness of a medically coordinated care program in a MHCC versus the care in DCH of child psychiatry.
METHODS: Non-inferiority retrospective study comparing the evolution after one year of care of 20 ASD children divided into two groups DCH and MHCC. In the DCH ASD group, the child is taken care of two half-days a week in a day hospital with individual educational care. In the MHCC ASD group, the child benefits from a medically coordinated care program. The medical care is reinforced by more frequent and longer consultations with guidance offered to parents. In both groups, the child receives speech therapy and psychomotor therapy in private practice at the same rate. Comparison is made using a composite criterion associating CARS-2 and VABS-II. Non-inferiority of the medically coordinated care program in autism in reference to DCH was tested on the difference between the changes (DCH group variation - MHCC group variation) with a non-inferiority threshold of 10% of the initial value of each score.
RESULTS: We observed a reduction in autism severity at the CARS-2 and a moderate improvement in socio-adaptive behavior at the VABS-II in both groups. This trend was even more pronounced in the MHCC group than in the DCH group, but only the greater reduction in CARS-2 severity in the MHCC was statistically significant.
CONCLUSIONS: As it is necessary to integrate the two scales into the composite criterion, it is not possible to retain the non-inferiority of the MHCC with care program. However, both those children followed in DCH and those in the MHCC care program progress. This shows the relevance of the care offered at the MHCC for children suffering from ASD, in the context of a growing lack of space in DCH. The continuation of this research work through multicenter studies with larger numbers could demonstrate the non-inferiority of coordinated care programs in the MHCC versus DCH. It would also allow subgroups to be set up, taking into account the initial characteristics of the children in order to have more precise indications concerning the relevance of each treatment.

OBJECTIVE: Pain in children and adolescents with autism spectrum disorders remains underdiagnosed due to their inherent communication difficulties. The goal of this review is to identify the most suitable methods for assessing pain in this population and for evaluating the specific perceptions of, or behavioural reactions to, pain whilst considering disorder severity and specifiers (with or without accompanying intellectual impairment, with or without accompanying language impairment).
METHODS: A systematic review and analysis of the international literature was conducted.
RESULTS: Fourteen studies were selected. No difference was found in pain-related behaviours based on the age or gender of children or adolescents with autism. Three studies showed pain-related behaviours in autism spectrum disorders to be similar to control groups. Other studies showed specific behavioural responses in autism spectrum disorders with a longer physiological and behavioural recovery time associated with an episode of acute pain in this population. Similarly, the three studies that focused on sensory perceptions of pain all showed differences in the autism spectrum disorders population compared to control groups. In hospital or daily life contexts, studies essentially showed idiosyncratic expressions, hypervigilance, motor agitation, negative emotional reactions, or vocalizations. Regarding the association of autism severity with hyposensitivity to pain, the results remain unclear even when language disorders or intellectual disabilities are also present (in conjunction with autism). The Non-Communicative Children Pain Checklist and its translation into French and Italian showed good internal validity and was used by almost half of the studies in hetero-assessment, mostly by parents. Studies recommend the inclusion of parents in the assessment in order to optimise the evaluation process. Similarly, analysis of parent/child/caregiver interviews from the studies highlights the importance of personalizing pain assessment of children and adolescents, taking into account subject-specific characteristics, pathology, and context.
CONCLUSIONS: An integrative and personalized approach to pain assessment appears to be the most appropriate for enhancing the understanding and detection of pain in individuals with autism spectrum disorders. This approach aligns well with a care setting where a nominated professional with a good expertise in autism is responsible for pain assessment. Given the complexity of identifying pain in individuals with autism, further qualitative studies, in conjunction with new pain exploration technologies, are considered necessary as well as a more extensive categorization of the population studies.

Children with autism spectrum disorder (ASD) often face challenges in early social communication skills, prompting the need for a detailed exploration of specific behaviors and their impact on cognitive and adaptive functioning. This study aims to address this gap by examining the developmental trajectories of early social communication skills in preschoolers with ASD aged 18-60 months, comparing them to age-matched typically developing (TD) children. Utilizing the early social communication scales (ESCS), the research employs a longitudinal design to capture changes over time. We apply a principal component analysis (PCA) to ESCS variables to identify underlying components, and cluster analysis to identify subgroups based on preverbal communication profiles. The results reveal consistent differences in early social communication skills between ASD and TD children, with ASD children exhibiting reduced skills. PCA identifies two components, distinguishing objects-directed behaviors and social interaction-directed behaviors. Cluster analysis identifies three subgroups of autistic children, each displaying specific communication profiles associated with distinct cognitive and adaptive functioning trajectories. In conclusion, this study provides a nuanced understanding of early social communication development in ASD, emphasizing the importance of low-level behaviors. The identification of subgroups and their unique trajectories contributes to a more comprehensive understanding of ASD heterogeneity. These findings underscore the significance of early diagnosis, focusing on specific behaviors predicting cognitive and adaptive functioning outcomes. The study encourages further research to explore the sequential development of these skills, offering valuable insights for interventions and support strategies.

OBJECTIVE: Naturalistic developmental behavioral interventions for children with autism spectrum disorder show evidence for effectiveness for specific social communication targets such as joint attention or engagement. However, combining evidence from different studies and comparing intervention effects across those studies have not been feasible due to lack of a standardized outcome measure of broader social communication skills that can be applied uniformly across trials. This investigation examined the usefulness of the Brief Observation of Social Communication Change (BOSCC) as a common outcome measure of general social communication skills based on secondary analyses of data obtained from previously conducted randomized controlled trials of 3 intervention models, Early Social Intervention (ESI), Early Start Denver Model (ESDM) and Joint Attention Symbolic Play Engagement and Regulation (JASPER).
METHODS: The subset of datasets from the 3 randomized controlled trials was created to examine differences in the BOSCC scores between intervention and control groups over the course of the interventions.
RESULTS: Based on 582 videos from 207 caregiver-child dyads, the BOSCC noted significant differences between intervention vs control groups in broad social communication skills within 2 of the 3 intervention models, which were longer in duration and focused on a broad range of developmental skills.
CONCLUSIONS: The BOSCC offers the potential to take a uniform measurement approach across different intervention models to capture the effect of intervention on general social communication skills but may not pick up the effects of some brief interventions targeting proximal outcomes.
BACKGROUND: Comparing Parent-Implemented Interventions for Toddlers With Autism Spectrum Disorders; https://www.
RESULTS: gov/; NCT00760812. Intensive Intervention for Toddlers With Autism (EARLY STEPS); https://www.
RESULTS: gov/; NCT00698997. Social and Communication Outcomes for Young Children With Autism; https://www.
RESULTS: gov/; NCT00953095.

BACKGROUND: The constellation of pre and perinatal predictors are introduced as predictor for autism spectrum disorders (ASD), however, the information about the direction and strength of these predictors are lacking in Western, Iran. The current study aimed to determine the pre and perinatal predictors of ASD among children in this region.
METHODS: This case-control study was conducted in Hamadan, Western Iran during January to March 2022. The study included 100 children with ASD who referred to the autism center as case group. Hundred children without ASD from registration system of health service centers were selected as control group and were matched (1:1) to cases by age and place of residency. A structured questionnaire about pre and perinatal predictors of ASD was developed by an expert panel. The questionnaire was administered by interviewing the mothers of children.
RESULTS: Boy gender (OR: 3.51, 95% CI: 1.74-7.10, p-value < 0.001), small for gestational age (SGA) (3.92, 1.64-9.39, 0.002), maternal diabetes (3.51, 1.03-24.95, 0.04) and family history of mental disorders (3.64, 1.18-11.27, 0.04) were identified as significant predictors in a multivariable analysis.
CONCLUSIONS: Our study emphasizes on the importance of screening and monitoring for ASD in the boys, those with history of SGA, from mothers with history of diabetes and with family history of mental disorders. Proposing the replication of findings emphasizes the necessity of conducting studies with larger sample sizes.

BACKGROUND: Exaggerated responses to sensory stimuli, a hallmark of Fragile X syndrome (FXS), contribute to anxiety and learning challenges. Sensory hypersensitivity is recapitulated in the Fmr1 knockout (KO) mouse model of FXS. Recent studies in Fmr1 KO mice have demonstrated differences in activity of cortical interneurons and a delayed switch in the polarity of GABA signaling during development. Previously, we reported that blocking the chloride transporter NKCC1 with the diuretic bumetanide, could rescue synaptic circuit phenotypes in primary somatosensory cortex (S1) of Fmr1 KO mice. However, it remains unknown whether bumetanide can rescue earlier circuit phenotypes or sensory hypersensitivity in Fmr1 KO mice.
METHODS: We used acute and chronic systemic administration of bumetanide in Fmr1 KO mice and performed in vivo 2-photon calcium imaging to record neuronal activity, while tracking mouse behavior with high-resolution videos.
RESULTS: We demonstrate that layer (L) 2/3 pyramidal neurons in S1 of Fmr1 KO mice show a higher frequency of synchronous events at postnatal day (P) 6 compared to wild-type controls. This was reversed by acute administration of bumetanide. Furthermore, chronic bumetanide treatment (P5-P14) restored S1 circuit differences in Fmr1 KO mice, including reduced neuronal adaptation to repetitive whisker stimulation, and ameliorated tactile defensiveness. Bumetanide treatment also rectified the reduced feedforward inhibition of L2/3 neurons in S1 and boosted the circuit participation of parvalbumin interneurons.
CONCLUSIONS: This further supports the notion that synaptic, circuit, and sensory behavioral phenotypes in Fmr1 KO can be mitigated by inhibitors of NKCC1, such as the FDA-approved diuretic bumetanide.

Despite their importance, little is known about how social drivers of health shape communicative outcomes in autism. Even less is known when considering the intersection of race and language impairment. An understanding of factors in communicative outcomes is key for characterizing developmental trajectories and informing supports. This cross-sectional observational study examined the role of social drivers of health in communicative outcomes of racially and ethnically minoritized autistic adolescents and adults. Participants ages 13 to 30 (N = 73) completed a behavioral assessment protocol, including language and nonverbal cognitive skills, as well as social drivers of health (sense of community, unmet services, barriers to services). Correlational analyses revealed associations between social drivers of health on social communication impairment and real-world communication. Generalized linear mixed-effects modeling revealed that language predicted real-world communication, but sense of community predicted social communication impairment. Findings point to the importance of assessing both individual differences and social drivers of health in outcomes in autism research. Future work should focus on social drivers of health in larger-scale analyses of outcomes in minoritized autistic individuals during the transition to adulthood, considering supports that align with service eligibility and person-centered outcomes.

BACKGROUND: Virtual Reality (VR) based diagnostic and therapeutic interventions have opened up new possibilities for addressing the challenges in identifying and treating individuals with Autism Spectrum Disorders (ASD).
OBJECTIVE: To conduct a systematic review and meta-analysis of Randomized Controlled Trials to investigate the impact of Immersive VR techniques on the cognitive, social, and emotional skills of under-18 children and adolescents with ASD.
METHODS: Four databases were systematically searched as per \"Preferred Reporting Items for Systematic Reviews and Meta-analyses\" guidelines and assessed six RCTs for further analysis. The Cochrane Risk of Bias tool was used to assess the methodological quality of the studies.
RESULTS: Pooled results favoured VR and reported significant differences between experimental and control groups concerning social skills (SMD:1.43; 95 % CI: 0.01-2.84; P: 0.05), emotional skills (SMD: 2.45; 95 % CI: 0.21-4.18; P: 0.03) and cognitive skills.
CONCLUSIONS: VR offers an array of benefits that make it a promising tool for children and adolescents with ASD to improve their cognitive, social and emotional skills in a safe and supportive setting. However, accessibility, affordability, customization, and cost are also significant aspects to consider when developing and implementing VR-based interventions for ASD.