1. Attallah A, Ardourel M, Gallazzini F, Lesne F, De Oliveira A, Togbé D, Briault S, Perche O. Lack of FMRP in the retina: Evidence of a retinal specific transcriptomic profile. Exp Eye Res;2024 (Sep);246:110015.

Fragile X Syndrome (FXS), the most common inherited form of human intellectual disability, is a monogenic neurodevelopmental disorder caused by a loss-of-function mutation of the FMR1 gene. FMR1 is encoding the Fragile X Messenger Ribonucleo Protein (FMRP) an RNA-binding protein that regulates the translation of synaptic proteins. The absence of FMRP expression has many important consequences on synaptic plasticity and function, leading to the FXS clinical phenotype. Over the last decade, a visual neurosensorial phenotype had been described in the FXS patients as well as in the murine model (Fmr1(-/y)mice), characterized by retinal deficits associated to retinal perception alterations. However, although the transcriptomic profile in the absence of FMRP has been studied in the cerebral part of the central nervous system (CNS), there are no actual data for the retina which is an extension of the CNS. Herein, we investigate the transcriptomic profile of mRNA from whole retinas of Fmr1(-/y)mice. Interestingly, we found a specific signature of Fmrp absence on retinal mRNA expression with few common genes compared to other brain studies. Gene Ontology on these retinal specific genes demonstrated an enrichment in retinal development genes as well as in synaptic genes. These alterations could be linked to the reported retinal phenotype of the FXS condition. In conclusion, we describe for the first time, retinal-specific transcriptomic changes in the absence of FMRP.

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2. Balabanovska M, Leadbitter K, Jurek L, Mengarelli F, Falissard B, Ngan N, Aldred C, Green J, Geoffray MM. Parent and professional perspectives on implementing the Pediatric Autism Communication Therapy: A mixed-methods analysis. Autism;2024 (Jul 30):13623613241262943.

Factors influencing the implementation of parent-mediated intervention are insufficiently studied. This study examines for the first-time factors of implementation into clinical practice across the world of Pediatric Autism Communication Therapy, an internationally disseminated, evidence-based, parent-mediated therapy. From both the parents’ and the professionals’ perspectives, parents attitudes (e.g. self-reflection abilities and videotaping management) and life-circumstances (e.g. stressed families condition and time) were central factors. In this type of therapy, the target is a child’s development; still, this improvement is dependent on the parent’s behavior when interacting with their child. What’s more, Pediatric Autism Communication Therapy method (video reflection, empowerment of parent, play-based) was enabler according to most of the parents. And more, most professionals report factors linked to the Implementation Process that is planning, execution, reflection and assessment in implementation of a new therapy. Indeed, the professionals underlined barriers related to the population seen in practice, flexibility of schedule, support from colleagues and manager. All these factors could be improved and addressed with a formal implementation plan including factors related to the parents of each country.

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3. Beaurenaut M, Kovarski K, Destais C, Mennella R, Grèzes J. Spontaneous instrumental approach-avoidance learning in social contexts in autism. Mol Autism;2024 (Jul 31);15(1):33.

BACKGROUND: Individuals with Autism Spectrum Condition (ASC) are characterized by atypicalities in social interactions, compared to Typically Developing individuals (TD). The social motivation theory posits that these difficulties stem from diminished anticipation, reception, and/or learning from social rewards. Although learning from socioemotional outcomes is core to the theory, studies to date have been sparse and inconsistent. This possibly arises from a combination of theoretical, methodological and sample-related issues. Here, we assessed participants’ ability to develop a spontaneous preference for actions that lead to desirable socioemotional outcomes (approaching/avoiding of happy/angry individuals, respectively), in an ecologically valid social scenario. We expected that learning abilities would be impaired in ASC individuals, particularly in response to affiliative social feedback. METHOD: We ran an online social reinforcement learning task, on two large online cohorts with (n = 274) and without (n = 290) ASC, matched for gender, age and education. Participants had to indicate where they would sit in a waiting room. Each seat was associated with different probabilities of approaching/avoiding emotional individuals. Importantly, the task was implicit, as participants were not instructed to learn, and emotional expressions were never mentioned. We applied both categorical analyses contrasting the ASC and TD groups and dimensional factor analysis on affective questionnaires. RESULTS: Contrary to our hypothesis, participants showed spontaneous learning from socioemotional outcomes, regardless of their diagnostic group. Yet, when accounting for dimensional variations in autistic traits, as well as depression and anxiety, two main findings emerged among females who failed to develop explicit learning strategies: (1) autism severity in ASC correlated with reduced learning to approach happy individuals; (2) anxiety-depression severity across both ASC and TD participants correlated with reduced learning to approach/avoid happy/angry individuals, respectively. CONCLUSIONS: Implicit spontaneous learning from socioemotional outcomes is not generally impaired in autism but may be specifically associated with autism severity in females with ASC, when they do not have an explicit strategy for adapting to their social environment. Clinical diagnosis and intervention ought to take into account individual differences in their full complexity, including the presence of co-morbid anxiety and depression, when dealing with social atypicalities in autism.

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4. Bent CA, Aulich A, Constantine C, Fidock E, Dwyer P, Green C, Smith J, Gurba AN, Harrington LT, Gore KE, Rabba AS, Ayton LN, Fordyce K, Green J, Jellett R, Kennedy LJ, MacDuffie KE, Meera SS, Watson LR, Whitehouse AJ, Hudry K. Autistic and autism community perspectives on infant and family support in the first two years of life: Findings from a community consultation survey. Autism;2024 (Jul 30):13623613241262077.

Most support programmes for Autistic children are available only after they are diagnosed. Research suggests that parenting supports may be helpful for parents and their infants, when provided in the first 2 years of life – before a formal diagnosis is given, but when information suggests an infant is more likely to be Autistic. However, we do not know how acceptable these types of supports might be to the Autistic and autism communities. We asked 238 Autistic and non-autistic people – some of whom were parents, and some of whom were professionals working in research, health and education – about their perspectives on very-early supports. People generally agreed that it could be acceptable to work with parents to help them understand and support their child’s specific needs and unique ways of communicating. People suggested a variety of support strategies could be acceptable, including parent education, changing the environment to meet an infant’s needs, and creating opportunities for infants’ to make choices and exercise control. People preferred respectful and accurate language – including the term ‘support’ (rather than ‘intervention’) and ‘early-in-life’ (rather than ‘at-risk’ of autism, or ‘pre-emptive’ when describing developmental stage). Continuing to work with community members will help to make sure autism support programmes are relevant and helpful.

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5. Cannon J, Cardinaux A, Bungert L, Li C, Sinha P. Reduced precision of motor and perceptual rhythmic timing in autistic adults. Heliyon;2024 (Jul 30);10(14):e34261.

Recent results suggest that autistic individuals exhibit reduced accuracy compared to non-autistic peers in temporally coordinating their actions with predictable external cues, e.g., synchronizing finger taps to an auditory metronome. However, it is not yet clear whether these difficulties are driven primarily by motor differences or extend into perceptual rhythmic timing tasks. We recruited autistic and non-autistic participants for an online study testing both finger tapping synchronization and continuation as well as rhythmic time perception (anisochrony detection). We fractionated each participant’s synchronization results into parameters representing error correction, motor noise, and internal time-keeper noise, and also investigated error-correcting responses to small metronome timing perturbations. Contrary to previous work, we did not find strong evidence for reduced synchronization error correction. However, we found compelling evidence for noisier internal rhythmic timekeeping in the synchronization, continuation, and perceptual components of the experiment. These results suggest that noisier internal rhythmic timing processes underlie some sensorimotor coordination challenges in autism.

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6. Climent-Pérez P, Martínez-González AE, Andreo-Martínez P. Contributions of Artificial Intelligence to Analysis of Gut Microbiota in Autism Spectrum Disorder: A Systematic Review. Children (Basel);2024 (Jul 31);11(8)

BACKGROUND: Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder whose etiology is not known today, but everything indicates that it is multifactorial. For example, genetic and epigenetic factors seem to be involved in the etiology of ASD. In recent years, there has been an increase in studies on the implications of gut microbiota (GM) on the behavior of children with ASD given that dysbiosis in GM may trigger the onset, development and progression of ASD through the microbiota-gut-brain axis. At the same time, significant progress has occurred in the development of artificial intelligence (AI). METHODS: The aim of the present study was to perform a systematic review of articles using AI to analyze GM in individuals with ASD. In line with the PRISMA model, 12 articles using AI to analyze GM in ASD were selected. RESULTS: Outcomes reveal that the majority of relevant studies on this topic have been conducted in China (33.3%) and Italy (25%), followed by the Netherlands (16.6%), Mexico (16.6%) and South Korea (8.3%). CONCLUSIONS: The bacteria Bifidobacterium is the most relevant biomarker with regard to ASD. Although AI provides a very promising approach to data analysis, caution is needed to avoid the over-interpretation of preliminary findings. A first step must be taken to analyze GM in a representative general population and ASD samples in order to obtain a GM standard according to age, sex and country. Thus, more work is required to bridge the gap between AI in mental health research and clinical care in ASD.

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7. Dias C, Mo A, Cai C, Sun L, Cabral K, Brownstein CA, Rockowitz S, Walsh CA. Cell-type-specific effects of autism-associated 15q duplication syndrome in the human brain. Am J Hum Genet;2024 (Aug 8);111(8):1544-1558.

Recurrent copy-number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder. Duplication of 15q11-q13 (dup15q) is a well-described neurodevelopmental syndrome that increases the risk of autism more than 40-fold. However, the effects of this duplication on gene expression and chromatin accessibility in specific cell types in the human brain remain unknown. To identify the cell-type-specific transcriptional and epigenetic effects of dup15q in the human frontal cortex, we conducted single-nucleus RNA sequencing and multi-omic sequencing on dup15q-affected individuals (n = 6) as well as individuals with non-dup15q autism (n = 7) and neurotypical control individuals (n = 7). Cell-type-specific differential expression analysis identified significantly regulated genes, critical biological pathways, and differentially accessible genomic regions. Although there was overall increased gene expression across the duplicated genomic region, cellular identity represented an important factor mediating gene-expression changes. As compared to other cell types, neuronal subtypes showed greater upregulation of gene expression across a critical region within the duplication. Genes that fell within the duplicated region and had high baseline expression in control individuals showed only modest changes in dup15q, regardless of cell type. Of note, dup15q and autism had largely distinct signatures of chromatin accessibility but shared the majority of transcriptional regulatory motifs, suggesting convergent biological pathways. However, the transcriptional binding-factor motifs implicated in each condition implicated distinct biological mechanisms: neuronal JUN and FOS networks in autism vs. an inflammatory transcriptional network in dup15q microglia. This work provides a cell-type-specific analysis of how dup15q changes gene expression and chromatin accessibility in the human brain, and it finds evidence of marked cell-type-specific effects of this genetic driver. These findings have implications for guiding therapeutic development in dup15q syndrome, as well as understanding the functional effects of copy-number variants more broadly in neurodevelopmental disorders.

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8. Dvir T, Rabinowitch TC, Elefant C. The effectiveness of group interpersonal synchrony in young autistic adults’ work environment: A mixed methods RCT study protocol. PLoS One;2024;19(7):e0307956.

INTRODUCTION: Few autistic adults are able to integrate successfully into the world of work given their difficulties adapting to the social and stressful aspects of work environments. Interpersonal synchrony, when two or more individuals share body movements or sensations, is a powerful force that consolidates human groups while promoting the ability to self-regulate and cooperate with others. The abilities to self-regulate and cooperate are crucial for maintaining a calm and productive work environment. This study protocol outlines research that aims to assess the effects of group interpersonal synchrony on prosociality and work-related stress of young autistic adults in their work environment. METHODS AND ANALYSIS: This mixed-methods randomized controlled trial will investigate two movement-based group synchronous and non-synchronous intervention conditions. The sample will be composed of young adults enrolled in an innovative Israeli program designed to integrate cognitively-abled 18- to 25-year-old autistic adults into the Israeli army work force. The movement-based intervention sessions will take place in groups of 10-14 participants, once a week for 10 weeks. Questionnaires, behavioral collaborative tasks and semi-structured interviews will be conducted. Quantitative data will be collected for each participant at three points of time: before and after the intervention period, and 17 weeks after the end of the intervention. Qualitative data will be collected after the intervention period in interviews with the participants. DISCUSSION: Little is known about interventions that promote successful integration into social and stressful work environments. The findings are likely to shed new light on the use of group interpersonal synchrony in autistic individuals at work. TRIAL REGISTRATION: NCT05846308.

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9. Faghani P, Nikpeyma N, Haghani S, Amrollah Majdabadi Z, Pashaeypoor S. Relationship of nutritional behaviors and parent-child interactions with developmental domains of Iranian toddlers: a cross-sectional study. BMC Pediatr;2024 (Jul 31);24(1):488.

BACKGROUND: Health service providers closely monitor the developmental state of toddlers to identify the factors affecting this process because any defect during this period will cause irreversible damage. Therefore, this study investigated the relationship of nutritional behaviors and parent-child interactions with the developmental domains of Iranian toddlers. METHODS: This cross-sectional, descriptive-analytical study was conducted on 341 toddlers aged 12-36 months covered by comprehensive health centers in the south of Tehran in 2021-2022. The participants were selected through single-stage cluster sampling. To this end, 16 comprehensive health centers were randomly selected, and then some of the clients from each center were randomly selected as the sample. The required data were collected through the Ages and Stages Questionnaire (ASQ), the Children’s Eating Behavior Questionnaire (CEBQ), the Child-Parent Relationship Scale (CPRS), and a demographics form. They were then analyzed statistically using descriptive and inferential statistics in SPSS-21, considering a significance level of p < 0.05. RESULTS: The results showed that most participants were normal in all developmental domains (communication, gross motor, fine motor, personal-social, and problem-solving), with a mean developmental delay ranging from 1.8 to 7%. The most serious problem of participants requiring medical referral was related to gross motor (7%) with a mean of 54.35 ± 7.28 followed by communication (6.5%) with a mean of 49.41 ± 9.67. The mean nutritional behavior of participants was 77.9 ± 21.7. A significant relationship was found between the nutritional behaviors of participants and the problem-solving domain of development (p = 0.018). The results also indicated a mean parent-child interaction score of 94.26 ± 12.63. There was a significant relationship between parent-child interactions and the communication area of development (p = 0.04). CONCLUSION: Since some areas of toddler development are influenced by children's nutritional behavior and parent-child interactions, it is necessary to train families to identify, monitor, and correct the factors affecting the development of their children. Health system officials and planners are also recommended to develop interventions to improve the nutritional behaviors of children and parent-child interactions.

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10. Farmer AL, Febo M, Wilkes BJ, Lewis MH. Environmental enrichment reduces restricted repetitive behavior by altering gray matter microstructure. PLoS One;2024;19(7):e0307290.

Restricted, repetitive behaviors are common symptoms in neurodevelopmental disorders including autism spectrum disorder. Despite being associated with poor developmental outcomes, repetitive behaviors remain poorly understood and have limited treatment options. Environmental enrichment attenuates the development of repetitive behaviors, but the exact mechanisms remain obscure. Using the C58 mouse model of repetitive behavior, we performed diffusion tensor imaging to examine microstructural alterations associated with the development of repetitive behavior and its attenuation by environmental enrichment. The C57BL/6 mouse strain, which displays little or no repetitive behavior, was used as a control group. We observed widespread differences in diffusion metrics between C58 mice and C57BL/6 mice. In juvenile C58 mice, repetitive motor behavior displayed strong negative correlations with fractional anisotropy in multiple gray matter regions, whereas in young adult C58 mice, high repetitive motor behavior was most strongly associated with lower fractional anisotropy and higher radial diffusivity in the striatum. Environmental enrichment increased fractional anisotropy and axial diffusivity throughout gray matter regions in the brains of juvenile C58 mice and overlapped predominantly with cerebellar and sensory regions associated with repetitive behavior. Our results suggest environmental enrichment reduces repetitive behavior development by altering gray matter microstructure in the cerebellum, medial entorhinal cortex, and sensory processing regions in juvenile C58 mice. Under standard laboratory conditions, early pathology in these regions appears to contribute to later striatal and white matter dysfunction in adult C58 mice. Future studies should examine the role these regions play in the development of repetitive behavior and the relationship between sensory processing and cerebellar deficits and repetitive behavior.

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11. Franco M, Costa AP. Correction: Should Parents Only Use One Language with Their Autistic Children? The Relations between Multilingualism, Children’s Social Skills, and Parent-Child Communication. J Autism Dev Disord;2024 (Sep);54(9):3574.

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12. Hazan-Liran B, Walter O. Psychological Capital, Self-Advocacy, and Future Orientation among Adults on the Autism Spectrum. J Autism Dev Disord;2024 (Jul 30)

The paper offers an innovative exploration of the mediating role of psychological capital (PsyCap) in the relations between future orientation and self-advocacy among high-functioning adults on the autism spectrum. We posited that PsyCap, a composite of hope, self-efficacy, resilience, and optimism, serves as a crucial mediator of future orientation and self-advocacy. The sample comprised 40 high-functioning adults on the autism spectrum. Future orientation, self-advocacy, and PsyCap were significantly correlated among young adults with ASD. PsyCap was a mediator of the relations between future orientation and self-advocacy. The findings contribute to the understanding of psychological factors influencing self-advocacy and future orientation and have practical implications for interventions aimed at enhancing PsyCap to improve self-advocacy and future orientation in individuals with autism spectrum disorder.

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13. Herrera-Pino J, Benedetti-Isaac J, Ripoll-Córdoba D, Camargo L, Castillo-Tamara EE, Morales-Asencio B, Perea-Castro E, Torres Zambrano M, Ducassou A, Flórez Y, Porto MF, Gargiulo PA, Zurita-Cueva B, Caldichoury N, Coronado JC, Castellanos C, Ramírez-Penso C, López N. Effectiveness of deep brain stimulation on refractory aggression in pediatric patients with autism and severe intellectual disability: meta-analytic review. BMC Pediatr;2024 (Jul 30);24(1):487.

Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator’s bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies’ quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.

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14. Ismail R, Negm WA, Basha EH, Rizk FH, Attallah NGM, Altwaijry N, Ibrahim HA, Eltantawy AF, Elkordy A, Osama A, Magdeldin S, Azzam AR. The potential neuroprotective effects of Spirulina platensis in a valproic acid-induced experimental model of autism in the siblings of albino rats: targeting PIk3/AKT/mTOR signalling pathway. Nutr Neurosci;2024 (Jul 31):1-23.

Introduction: Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders with poor social interaction, communication issues, aberrant motor movements, and limited repetitive interests and behaviour. Spirulina platensis (SP) contains several multi-nutrients and has a wide range of neuroprotective properties.Aim: The target of the current experiment is to detect the protective effects of S. platensis on valproic-induced autism in adult female albino rats’ siblings for the first time.Materials and Methods: Twelve Pregnant rats were separated into four main groups; Group I (control); Group II (S. platensis); Group III (autistic group); and Group IV (autistic SP-treated group). Fifteen offspring pups from each group were sacrificed, brain was divided for biochemical analysis as superoxide dismutase and malondialdehyde were evaluated spectrophotometrically while interleukin-6, interleukin-12, Bcl-2-associated X protein, B-cell lymphoma-2, Beclin-1, brain-derived neurotrophic factor were assessed by ELISA, other division of brain were used for gene expression of PI3k, Akt and mTOR pathway, last division of brain were stained using (H&E) and Giemsa stains. Tumour necrosis factor alpha (TNF-α) and Synaptophysin (SYN) markers were used for immunohistochemical staining.Results: Autistic Group (III) showed an increment in levels of MDA, IL-6, IL12 and BAX while showing a decrement in SOD, Bcl-2 and Beclin-1 as well as increased PI3k, Akt and mTOR gene expression. Autistic Group (III) also exhibited hypocellularity and disorganization of hippocampal and prefrontal cortex cells. The autistic SP-treated group (IV) showed improvement in these biochemical markers and pathological changes. Our findings suggest that Spirulina platensis will be significant in managing autism.

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15. Jiang C, Huang W, Zhou Y, Wang J, Lei H, Niu Y, Zhou R, Zhang Y. Generating a human induced pluripotent stem cell line (XACHi018-A) from a Timothy syndrome infant carrying heterozygous CACNA1C c.1216G>A (p.G406R) mutation. Stem Cell Res;2024 (Oct);80:103513.

Timothy syndrome, an extremely rare disease, is closely associated with a mutation in CACNA1C gene, which encodes the cardiac L-type voltage-gated calcium channel (Cav1.2). In this study, we generated a human induced pluripotent stem cell (iPSC) line from a Timothy syndrome infant carrying heterozygous CACNA1C mutation (transcript variant NM_000719.7c.1216G>A: p.G406R). The generated iPSC line showed typical stem cell morphology, positively expressed pluripotency and proliferation markers, normal karyotype, and trilineage differentiation potential. Therefore, this patient-specific iPSC can be of great significance in investigating the mechanisms underlying Timothy syndrome, and hence establishing effective intervention strategies.

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16. Kaplan-Kahn EA, Benecke RM, Guthrie W, Yerys BE, Holmes LG, Miller JS. Measurement invariance of the PROMIS emotional distress and subjective well-being domains among autistic and General Population adolescents. Qual Life Res;2024 (Jul 30)

PURPOSE: Quality of life (QoL) is identified as a clinical and research priority by the autistic community. Researchers have the responsibility to ensure that instruments used to measure QoL do so reliably and accurately among autistic participants. METHODS: Our study evaluated measurement invariance of Emotional Distress (Depression, Anxiety, Anger, Psychological Stress) and Subjective Well-Being (Life Satisfaction, Positive Affect, and Meaning & Purpose) scales of the Patient-Reported Outcomes Measurement Information System (PROMIS) among groups of autistic (N=140, n per scale=132-140) and general population (N=1,224, n per scale=406-411) teenagers (14-17 years). These scales were included in the PROMIS Autism Battery-Lifespan, which uses PROMIS scales to measure QoL domains most relevant for autistic people. RESULTS: Multi-group confirmatory factor analyses using permutation tests demonstrated that Depression and Positive Affect scales exhibited scalar invariance between groups, indicating that scores can be meaningfully compared across autistic and general population teens. Anger and Psychological Stress scales demonstrated metric invariance between groups, indicating that these scales measure the same latent trait in both groups, but group comparisons are not supported. CONCLUSION: We provide guidance as to how these scales can be used in psychometrically supported ways to capture constructs relevant for understanding QoL among autistic teens.

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17. Maeda T, Tanahashi Y, Asada H, Kidokoro H, Takahashi Y, Sato Y. High threshold of total developmental quotient at 3 years for follow-up in extremely preterm infants. Early Hum Dev;2024 (Sep);196:106098.

AIM: To investigate the relationship between the developmental quotient (DQ) at age 3 years and the need for educational support at school age in extremely preterm infants. METHODS: A total of 176 infants with a gestational age of <28 weeks were analyzed. The total DQ and subscales were evaluated using the Kyoto Scale of Psychological Development (KSPD) test. Neurodevelopment at age 3 years was stratified using total DQ in a conventional (DQ < 70 as developmental delay, DQ 70- <85 as subnormal, DQ ≥85 as normal) and a modified way (subdividing normal into DQ 85- <93 as low-normal and DQ ≥93 as high-normal). The prevalence of future educational support was compared for each stratum. Additionally, subscales were compared between those with and without educational support in each total DQ stratum. RESULTS: In conventional stratification, the prevalence of educational support was 32 (63 %) for developmental delay, 14 (24 %) for subnormal, and 10 (15 %) for normal. In modified stratification, the prevalence was 8 (26 %) for low-normal and 2 (5 %) for high-normal. While there was no significant difference in the odds of educational support between the normal and subnormal, the low-normal had significantly higher odds compared to the high-normal (OR 6.00; 95 % CI, 1.16-30.95, p = 0.03). Among the low-normal stratum, the language-social subscale was significantly lower in those with educational support. CONCLUSION: Setting high thresholds for total DQ and evaluating detailed subscales at age 3 years may be useful for developmental follow-up in extremely preterm infants.

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18. Marocchini E, Baldin I. Cross-neurotype communication from an autistic point of view: Insights on autistic Theory of Mind from a focus group study. Int J Lang Commun Disord;2024 (Jul 31)

BACKGROUND: The conceptualisation of autism as a disorder where Theory of Mind (ToM) and pragmatics are fundamentally impaired has prompted a wealth of research on autistic deficits, most of which is characterised by two main assumptions: first, that autistic people would display said deficits, if present, with any conversation partner and in any situation; second, that neurotypical people do not present these deficits, regardless of the conversation partner. However, this is not necessarily reflected in autistic accounts of the way they experience social cognition and pragmatics. AIMS: The present paper aims to investigate the autistic experience of communication with both autistic and neurotypical people, with a particular focus on their perception of the ability of autistic and neurotypical people to understand their communicative intentions. METHODS & PROCEDURES: Participants, 23 adult Italian autistic people without intellectual disability or language disorders, were recruited online. Two virtual focus groups of 2 hours each were conducted, transcribed and analysed through thematic analysis with a descriptive phenomenological approach by two independent researchers. OUTCOMES & RESULTS: Six themes were developed from the analysis, the most relevant being Autistic-Autistic communication and Autistic ToM. The results, in line with the Double Empathy theory, suggest there seem to be important differences between neurotypical and autistic people’s ToM. These appear to make it easier for autistic people to communicate with one another, as well as to create difficulties for neurotypical people to understand autistic people, not just the other way around. CONCLUSIONS & IMPLICATIONS: These results seem to confirm that challenges in cross-neurotype communication are better interpreted as mutual miscomprehension and reciprocal differences in ToM rather than deficits on the autistic part. This calls for a reframing of ToM and/or the need for autistic ToM as a construct, of which neurotypical people seem to be lacking. Moreover, these insights should be taken into account for speech and language therapy and clinical practice in general, advocating for a neurodiversity-informed view of co-constructed communication as well as for a broader societal change in which therapists can play a crucial role, through participatory approaches or raising awareness in their daily practice. WHAT THIS PAPER ADDS: What is already known on the subject Autism is conceived as characterised by social cognition and communication difficulties, often linked to Theory of Mind (ToM) deficits. However, recent research suggested variations in ToM abilities within the autistic population and proposed alternative theories like the Double Empathy theory. Nevertheless, only a few studies examined how autistic individuals perceive communication across neurotypes. What this study adds Autistic individuals seem to find it easier to communicate with other autistic people, and they identify specific characteristics of neurotypical communication that hinder successful communication. Moreover, neurotypical people are perceived as having difficulties in autistic ToM, which seems to emerge as a relevant and needed construct in light of the Double Empathy problem. What are the clinical implications of this work? These findings can inform speech and language therapy and clinical practice about the potential gains of raising awareness on the Double Empathy problem and the higher communication ease inside the autistic community, alongside individualised support. Participatory approaches and closer collaboration with the autistic community also seem to be crucial for therapists to help improve communication experiences for autistic individuals.

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19. McDonald RG, Cargill MI, Khawar S, Kang E. Emotion dysregulation in autism: A meta-analysis. Autism;2024 (Jul 30):13623613241257605.

Autistic people often experience other mental health challenges, which makes it particularly important to understand factors that may contribute to the development of these conditions. Emotion dysregulation, or difficulties in effectively regulating one’s own emotions in response to a changing environment, is one factor that is experienced frequently by autistic and non-autistic people and is commonly related to a wide range of mental health conditions. This article represents a quantitative synthesis of the current state of the literature on emotion dysregulation, with a specific focus on how the severity of emotion dysregulation differs across autistic and non-autistic people across the lifespan. The findings suggest elevated emotion dysregulation in autistic individuals compared to both neurotypical and other clinical populations and provide insights into the experiences of emotion dysregulation in autistic people. Overall, this article underscores the importance of more research into emotion dysregulation in autistic people to inform areas of challenges related to emotion dysregulation that can be used to better inform treatment targets.

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20. Miles KD, Barker CM, Russell KP, Appel BH, Doll CA. Electrical Synapses Mediate Embryonic Hyperactivity in a Zebrafish Model of Fragile X Syndrome. J Neurosci;2024 (Jul 31);44(31)

Although hyperactivity is associated with a wide variety of neurodevelopmental disorders, the early embryonic origins of locomotion have hindered investigation of pathogenesis of these debilitating behaviors. The earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons (MNs) that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Gap junction electrical synapses drive early spontaneous behavior in zebrafish, prior to the emergence of chemical neurotransmitter networks. We use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show altered sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 34/35. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. We also use functional imaging to examine MN and interneuron (IN) activity in early embryogenesis, finding genetic disruption of electrical gap junctions uncouples activity between mnx1 (+) MNs and INs. Taken together, our work highlights the importance of electrical synapses in motor development and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initial formation of locomotive circuits.

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21. Mohammed MA, Abdalkhalig EM, Ali IA, Hassan SS, Osman H. Pattern of sleep disorders among children with autism spectrum disorder. BMC Psychiatry;2024 (Jul 30);24(1):539.

BACKGROUND: Sleep disorders (SDs) are among many co-morbid medical conditions that affect children with autism spectrum disorder (ASD). Raising awareness and improving the standard of care for children diagnosed with ASD may result from identifying SDs among them. This study aims to evaluate patterns of SDs among Sudanese children diagnosed with ASD. METHOD: Using the Childhood Sleep Habit Questionnaire (CSHQ) to gather data on sleep disorders and SPSS version 26.0 for data analysis, a descriptive cross-sectional study was carried out in the five main autistic centres in Khartoum state covering all registered patients with ASD between April and June 2022. Ninety-two children diagnosed with ASD were enrolled in this study after the purpose of the research was explained and consent was obtained from their guardians. A p-value < 0.05 was considered to indicate statistical significance. RESULTS: The mean age was 6.90 (± 2.6) years with a boys-to-girls ratio of 2.17:1. The prevalence of SDs (at least one sleep condition almost daily) was 95.65%. Sleep onset 71 (77.2%), limit setting 32 (32.6%), resistant onset to sleep 48 (52.2%), and combined 52 (56.5%) insomnia affected the majority of children. Additionally, there were significant associations between sex and Limit-setting insomnia, advanced sleep phase disorder, and narcolepsy type 2 (P values = 0.033, 0.009, and 0.037, respectively). Additionally, there was a significant association between age and sleep-related breathing disorders-snoring (p value = 0.031). CONCLUSION: The frequency of SDs is significant among children diagnosed with ASD from Sudan, and certain SDs are associated with age and sex. Subsequent studies are required to develop national guidelines for the prevalence, presentation, screening, and treatment of SDs in children diagnosed with ASD.

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22. Moon HJ, Cho SB. Exploring Implicit Biological Heterogeneity in ASD Diagnosis Using a Multi-Head Attention Graph Neural Network. J Integr Neurosci;2024 (Jul 17);23(7):135.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder exhibiting heterogeneous characteristics in patients, including variability in developmental progression and distinct neuroanatomical features influenced by sex and age. Recent advances in deep learning models based on functional connectivity (FC) graphs have produced promising results, but they have focused on generalized global activation patterns and failed to capture specialized regional characteristics and accurately assess disease indications. METHODS: To overcome these limitations, we propose a novel deep learning method that models FC with multi-head attention, which enables simultaneous modeling of the intricate and variable patterns of brain connectivity associated with ASD, effectively extracting abnormal patterns of brain connectivity. The proposed method not only identifies region-specific correlations but also emphasizes connections at specific, transient time points from diverse perspectives. The extracted FC is transformed into a graph, assigning weighted labels to the edges to reflect the degree of correlation, which is then processed using a graph neural network capable of handling edge labels. RESULTS: Experiments on the autism brain imaging data exchange (ABIDE) I and II datasets, which include a heterogeneous cohort, showed superior performance over the state-of-the-art methods, improving accuracy by up to 3.7%p. The incorporation of multi-head attention in FC analysis markedly improved the distinction between typical brains and those affected by ASD. Additionally, the ablation study validated diverse brain characteristics in ASD patients across different ages and sexes, offering insightful interpretations. CONCLUSION: These results emphasize the effectiveness of the method in enhancing diagnostic accuracy and its potential in advancing neurological research for ASD diagnosis.

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23. Oz M, Kury LA, Sadek B, Mahgoub MO. The role of nicotinic acetylcholine receptors in the pathophysiology and pharmacotherapy of autism spectrum disorder: Focus on α7 nicotinic receptors. Int J Biochem Cell Biol;2024 (Sep);174:106634.

Postmortem studies have revealed that brains of individuals with autism spectrum disorder (ASD) exhibit abnormalities in various components of the cholinergic system including cholinergic receptors, projections, and nuclei. Deletions in the 15q13.3 region which encompasses CHRNA7, the gene that encodes the α7-nACh receptor, have been linked to various neurodevelopmental disorders, including ASD. In addition, the involvement of α7-nACh receptors in biological phenomena known to play a role in the pathophysiology of ASD such as cognitive functions, learning, memory, neuroinflammation, and oxidative stress, as well as the excitation-inhibition balance in neuronal circuits and maternal immune activation have been reported in previous studies. Furthermore, evolving preclinical and clinical literature supports the potential therapeutic benefits of using selectively acting cholinergic compounds, particularly those targeting the α7-nACh receptor subtype, in the treatment of ASD. This study reviews the previous literature on the involvement of nACh receptors in the pathophysiology of ASD and focuses on the α7-nACh receptor as a potential therapeutic target.

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24. Schwartz AE, McDonald K. Research ethics for all: Development of a social-behavioral research ethics education program for community research partners with developmental disabilities. Disabil Health J;2024 (Jul 31):101675.

BACKGROUND: People with developmental disabilities make important contributions to research. However, inaccessible research ethics trainings present a barrier to them taking on some research roles. OBJECTIVES: We developed a social-behavioral research ethics training that leads to certification tailored to the accessibility needs and roles of community research partners with developmental disabilities. METHODS: We collaborated with diverse partners (people with developmental disabilities, a disability service provider, health researchers, human research participant protections experts) to develop the research ethics training. To identify potential training content, we conducted a rapid scoping review of ethical, legal, and social issues in social-behavioral research with adults with developmental disabilities and reviewed national research ethics curricula. Through discussions and a modified Delphi process, we worked with partners to identify content to teach; partners also provided guidance on accessibility. RESULTS: The training and rapid scoping reviews and input from partners resulted in 93 potential educational content elements to include. After completing the modified Delphi process, partners recommended inclusion of 83 of these content elements in the educational training and provided input on depth and approach to teaching this content. Research Ethics for All is a freely available training that includes 5 units, delivered via didactic and active learning, and assessment activities to verify understanding. Research Ethics for All should be facilitated by an experienced researcher. CONCLUSIONS: Research Ethics for All includes foundational social-behavioral research ethics content designed to support community research partners with developmental disabilities to take on new research responsibilities.

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25. Teerikorpi N, Lasser MC, Wang S, Kostyanovskaya E, Bader E, Sun N, Dea J, Nowakowski TJ, Willsey AJ, Willsey HR. Ciliary biology intersects autism and congenital heart disease. bioRxiv;2024 (Jul 31)

Autism spectrum disorder (ASD) commonly co-occurs with congenital heart disease (CHD), but the molecular mechanisms underlying this comorbidity remain unknown. Given that children with CHD come to clinical attention by the newborn period, understanding which CHD variants carry ASD risk could provide an opportunity to identify and treat individuals at high risk for developing ASD far before the typical age of diagnosis. Therefore, it is critical to delineate the subset of CHD genes most likely to increase the risk of ASD. However, to date there is relatively limited overlap between high confidence ASD and CHD genes, suggesting that alternative strategies for prioritizing CHD genes are necessary. Recent studies have shown that ASD gene perturbations commonly dysregulate neural progenitor cell (NPC) biology. Thus, we hypothesized that CHD genes that disrupt neurogenesis are more likely to carry risk for ASD. Hence, we performed an in vitro pooled CRISPR interference (CRISPRi) screen to identify CHD genes that disrupt NPC biology similarly to ASD genes. Overall, we identified 45 CHD genes that strongly impact proliferation and/or survival of NPCs. Moreover, we observed that a cluster of physically interacting ASD and CHD genes are enriched for ciliary biology. Studying seven of these genes with evidence of shared risk (CEP290, CHD4, KMT2E, NSD1, OFD1, RFX3, TAOK1), we observe that perturbation significantly impacts primary cilia formation in vitro. While in vivo investigation of TAOK1 reveals a previously unappreciated role for the gene in motile cilia formation and heart development, supporting its prediction as a CHD risk gene. Together, our findings highlight a set of CHD risk genes that may carry risk for ASD and underscore the role of cilia in shared ASD and CHD biology.

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26. Tu G, Jiang N, Chen W, Liu L, Hu M, Liao B. The neurobiological mechanisms underlying the effects of exercise interventions in autistic individuals. Rev Neurosci;2024 (Jul 31)

Autism spectrum disorder is a pervasive and heterogeneous neurodevelopmental condition characterized by social communication difficulties and rigid, repetitive behaviors. Owing to the complex pathogenesis of autism, effective drugs for treating its core features are lacking. Nonpharmacological approaches, including education, social-communication, behavioral and psychological methods, and exercise interventions, play important roles in supporting the needs of autistic individuals. The advantages of exercise intervention, such as its low cost, easy implementation, and high acceptance, have garnered increasing attention. Exercise interventions can effectively improve the core features and co-occurring conditions of autism, but the underlying neurobiological mechanisms are unclear. Abnormal changes in the gut microbiome, neuroinflammation, neurogenesis, and synaptic plasticity may individually or interactively be responsible for atypical brain structure and connectivity, leading to specific autistic experiences and characteristics. Interestingly, exercise can affect these biological processes and reshape brain network connections, which may explain how exercise alleviates core features and co-occurring conditions in autistic individuals. In this review, we describe the definition, diagnostic approach, epidemiology, and current support strategies for autism; highlight the benefits of exercise interventions; and call for individualized programs for different subtypes of autistic individuals. Finally, the possible neurobiological mechanisms by which exercise improves autistic features are comprehensively summarized to inform the development of optimal exercise interventions and specific targets to meet the needs of autistic individuals.

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27. Valderrama A, Nikièma B, Forgeot d’Arc B, Guerrero L, Giroux M. Revealing the Most Vulnerable Groups: Courtesy Stigma in Caregivers of Autistic Persons in Quebec. Front Psychol;2024;15:1320816.

INTRODUCTION: Caregivers of autistic persons often face « courtesy stigma, » a phenomenon by which caregivers experience stigma because of their association with a person whose disability may be stigmatized. Understanding the repercussions of this stigma is crucial not only for caregivers’ mental health but also for the quality of care provided to their dependent. This study aimed to explore courtesy stigma among caregivers of autistic persons in Quebec, examining its prevalence and impact in order to identify groups that are particularly susceptible to negative outcomes. METHODS: This study used a cross-sectional online survey methodology employing quota sampling to collect responses from 194 participants. Data were collected using a computer-assisted web interview (CAWI) platform. The impact of courtesy stigma was measured in terms of care burden, mental health, and overall well-being of caregivers. RESULTS: The findings revealed that caregivers frequently experience rejection, isolation, and work-related challenges. Notably, caregivers’ health was below average with the lowest reported health outcomes in Quebec. The caregivers who are the most vulnerable to negative outcomes included female caregivers, those aged 45 or older, financially strained households, caregivers of children requiring elevated levels of support, caregivers who isolated due to their autistic dependents, and those who experienced stigmatization directed at themselves or their children in the form of rejection.Interestingly, 60% of respondents reported that the caregiving burden was « not at all » to « somewhat » difficult, raising questions about factors that may mitigate caregiving challenges over time. CONCLUSION: Negative outcomes from courtesy stigma vary depending on certain risk factors and individual characteristic. This study underscores the need for targeted public policies and interventions, particularly for those at a higher risk of experiencing the negative effects of courtesy stigma on the burden of care, overall health, and mental health. By tailoring resources and support for these priority groups, we can better address the challenges faced by families of autistic persons.

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28. Willfors C, Borg J, Kleberg JL, Hallman A, Van Der Poll M, Lundin Remnélius K, Björlin Avdic H, Bölte S, Nordgren A. Symptoms of autism in Williams syndrome: a transdiagnostic approach. Sci Rep;2024 (Jul 30);14(1):17583.

Williams syndrome (WS) is associated with atypical social communication and cognition reminiscent of the behaviours observed in autism. Nonetheless, WS also differs significantly from autism, such as regarding social motivation, which is typically enhanced in WS and reduced in autism. This study sought to examine the conditions’ transdiagnostic similarities and differences for autistic symptoms and social functioning, and their developmental trajectories, by comparing individuals with WS (n = 24) and those diagnosed with idiopathic autism (n = 24) and attention deficit hyperactivity disorder (ADHD; n = 24), aged 9 to 53 years, on measures of autism, social functioning, IQ and cooccurring psychiatric conditions. Although only 12.5% in the WS group met the criteria for an autism diagnosis, a majority exhibited distinct difficulties within social communication, social cognition, repetitive behaviours, and atypical sensory reactivity resembling autism. Conversely, elevated social motivation and a high number of social initiatives accompany these characteristics. No group differences in the developmental trajectories of autism symptoms were found. Our results demonstrate that autistic behaviours are more frequent in individuals with WS, than in individuals with idiopathic ADHD, and emphasize the need for clinical management of these behaviours.

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29. Wu R, Lim JT, Ahmed Z, Berger R, Acem E, Chowdhury I, White SJ. Do autistic adults spontaneously reason about belief? A detailed exploration of alternative explanations. R Soc Open Sci;2024 (Jul);11(7):231889.

Southgate et al.’s (Southgate 2007 Psychol. Sci. 18, 587-92 (doi:10.1111/j.1467-9280.2007.01944.x)) anticipatory-looking paradigm has presented exciting yet inconclusive evidence surrounding spontaneous mentalizing in autism. The present study aimed to develop this paradigm to address alternative explanations for the lack of predictive eye movements on false-belief tasks by autistic adults. This was achieved through implementing a multi-trial design with matched true-belief conditions, and both high and low inhibitory demand false-belief conditions. We also sought to inspect if any group differences were related to group-specific patterns of attention on key events. Autistic adults were compared with non-autistic adults on this adapted implicit mentalizing task and an established explicit task. The two groups performed equally well in the explicit task; however, autistic adults did not show anticipatory-looking behaviour in the false-belief trials of the implicit task. Critically, both groups showed the same attentional distribution in the implicit task prior to action prediction, indicating that autistic adults process information from social cues in the same way as non-autistic adults, but this information is not then used to update mental representations. Our findings further document that many autistic people struggle to spontaneously mentalize others’ beliefs, and this non-verbal paradigm holds promise for use with a wide range of ages and abilities.

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30. Yost RT, Scott AM, Kurbaj JM, Walshe-Roussel B, Dukas R, Simon AF. Recovery from social isolation requires dopamine in males, but not the autism-related gene nlg3 in either sex. R Soc Open Sci;2024 (Jul);11(7):240604.

Social isolation causes profound changes in social behaviour in a variety of species. However, the genetic and molecular mechanisms modulating behavioural responses to social isolation and social recovery remain to be elucidated. Here, we quantified the behavioural response of vinegar flies to social isolation using two distinct protocols (social space preference and sociability, the spontaneous tendencies to form groups). We found that social isolation increased social space and reduced sociability. These effects of social isolation were reversible and could be reduced after 3 days of group housing. Flies with a loss of function of neuroligin3 (orthologue of autism-related neuroligin genes) with known increased social space in a socially enriched environment were still able to recover from social isolation. We also show that dopamine (DA) is needed for a response to social isolation and recovery in males but not in females. Furthermore, only in males, DA levels are reduced after isolation and are not recovered after group housing. Finally, in socially enriched flies mutant for neuroligin3, DA levels are reduced in males, but not in females. We propose a model to explain how DA and neuroligin3 are involved in the behavioural response to social isolation and its recovery in a dynamic and sex-specific manner.

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31. Zupin L, Sahyoun C, Krauss B, Dagri A, Rocco EM, Barbi E, Celsi F. Effectiveness of pharmacological procedural sedation in children with autism spectrum disorder: A systematic review and meta-analysis. Acta Paediatr;2024 (Jul 31)

AIM: Management of primary healthcare and routine minor procedures for children with autism spectrum disorder (ASD) can be challenging; therefore, when behavioural strategies fail, sedative medications are often employed. We evaluated the effectiveness of the current pharmacological strategies for managing children with ASD. METHODS: We performed a systematic review and meta-analysis of the current approaches for procedural sedation in children with ASD. RESULTS: Twenty studies met inclusion criteria. Dexmedetomidine, midazolam, propofol and chloral hydrate were the most efficient agents for successful procedures, while propofol had the highest number of adverse events. The most frequently used agents were dexmedetomidine and midazolam or a combination of the two, and the effectiveness of dexmedetomidine plus midazolam was superior to dexmedetomidine alone. CONCLUSION: Multiple effective drug regimens exist for procedural sedation in children with ASD. These results could support the development of specific guidelines for procedural sedation in children with ASD.

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