1. Adibsaber F, Ansari S, Elmieh A, Barkadehi B. Vitamin D3 Supplementation and Aquatic Exercise Combination as a Safe- Efficient Therapeutic Strategy to Ameliorate Interleukin-6 and 10, and Social Interaction in Children with Autism. Iran J Child Neurol;2024 (Summer);18(3):91-102.

OBJECTIVES: Increasing evidence demonstrated that there are altered levels of both pro-and anti-inflammatory cytokines in autism spectrum disorder (ASD) and pointed out that immune dysfunction may also relate to social deficits. This study aimed to investigate the effect of aquatic exercise combined with vitamin D supplementation on social interaction and two related cytokines (Interleukin-6 and Interleukin-10) in children with ASD. MATERIALS & METHODS: Forty boys with ASD (mean age: 10.90; age range: 6-14 years) were randomly assigned to the three interventions (groups 1, 2, and 3) and one control group (each 10 participants). Participants in the group 1 and 3 received a 10-week aquatic exercise program. Subjects in groups 2 and 3 took orally 50,000 IU of vitamin D3/week. This study evaluated the serum levels of IL-6 and IL-10, as well as the participants’ social interaction at baseline and post-intervention. RESULTS: Compared to the control group, all three interventions improved social skills scores (p< 0.001). Surprisingly, the combination strategy could significantly reduce IL-6 and increase IL-10 serum levels in children with ASD. CONCLUSION: Aqua-based exercise programs combined with vitamin D supplementation are recommended to benefit children with ASD and improve social and communication dysfunction.

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2. Bailey CA, Christiansen A, Augustyn M. Challenging Case: A Toddler with Autism and Concerns About Release of Information in Medical Record. J Dev Behav Pediatr;2024 (Jul 10)

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3. Bakken TL, Hellerud JMA, Kildahl AN, Solheim-Inderberg AM, Hove O, Helverschou SB. Correction To: Schizophrenia in Autistic People with Intellectual Disabilities. Treatment and Interventions. J Autism Dev Disord;2024 (Jul 11)

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4. Barokova MD, Tager-Flusberg H. Exploring cross-linguistic differences in parental input and their associations with child expressive language in ASD: Bulgarian versus English comparison. Int J Lang Commun Disord;2024 (Jul 11)

BACKGROUND: Parental input plays a central role in typical language acquisition and development. In autism spectrum disorder (ASD), characterized by social communicative and language difficulties, parental input presents an important avenue for investigation as a target for intervention. A rich body of literature has identified which aspects of grammatical complexity and lexical diversity are most associated with child language ability in both typical development and autism. Yet, the majority of these studies are conducted with English-speaking children, thus potentially overlooking nuances in parental input derived from cross-linguistic variation. AIMS: To examine the differences in verbal parental input to Bulgarian- and English-speaking children with ASD. To examine whether aspects of verbal parental input found to be concurrent predictors of English-speaking children’s expressive language ability are also predictors of the expressive language of Bulgarian-speaking children with ASD. METHODS & PROCEDURES: We compared parental input to Bulgarian-speaking (N = 37; 2;7-9;10 years) and English-speaking (N = 37; 1;8-4;9 years) children with ASD matched on expressive language. Parent-child interactions were collected during free play with developmentally appropriate toys. These interactions were transcribed, and key measures of parental input were extracted. OUTCOMES & RESULTS: English-speaking parents produced more word tokens and word types than Bulgarian-speaking parents. However, Bulgarian parents produced more verbs in relation to nouns and used more statements and exclamations but asked fewer questions than English-speaking parents. In addition, child age and parents’ use of questions were significant concurrent predictors of child expressive vocabulary. CONCLUSIONS & IMPLICATIONS: This is one of the first studies to conduct a cross-linguistic comparison of parental input in ASD. The differences found emphasize the need to further study parental input to Bulgarian children and adapt naturalistic parent-mediated interventions to the local language and its specific characteristics. WHAT THIS PAPER ADDS: What is already known on the subject A rich body of literature has identified the specific aspects of grammatical complexity, lexical diversity, and question-asking that are concurrently and longitudinally associated with the language ability of children with typical development and of children with ASD. Yet, the majority of these studies are conducted with English-speaking children. What this paper adds to the existing knowledge The present study finds that there are specific differences in verbal parental input to Bulgarian- and English-speaking children with autism in terms of lexical composition and question-asking. Bulgarian parents used more verbs than nouns, and the opposite pattern was found for English-speaking parents. In addition, Bulgarian parents asked fewer questions but used more statements and exclamations. Nevertheless, parental question use was significantly correlated with children’s language ability across both groups, suggesting that question-asking should be further examined as a potential target for parent-mediated language interventions for Bulgarian children with autism. What are the potential or actual clinical implications of this work? Most language and social communication interventions for autism are designed and piloted with English-speaking children. These interventions are often simply translated and used in different countries, with different populations and in different contexts. However, considering that one of the defining characteristics of autism is language difficulty, more studies should examine (1) how these language difficulties manifest in languages other than English, and (2) what characterizes verbal parental input in these other contexts. Such research investigations should inform future language and social communication interventions. The present study emphasizes the cross-linguistic differences between Bulgarian- and English-speaking parents’ verbal input to their children with autism.

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5. Berg J, Sideridis GD, DePillis R, Harstad E. Types and Predictors of Service use Among Young Children Recommended to Receive Intensive Services After Initial Autism Spectrum Disorder Diagnosis. J Autism Dev Disord;2024 (Jul 11)

Intensive services are recommended for young children with autism spectrum disorder (ASD). Limited research on service receipt in states with mandated ASD-specific service coverage suggests that it remains low, and factors associated with intensity are unclear. Participants were 206 children from the Boston Outcomes of Autism in Toddlers study living in states with autism mandates, diagnosed with ASD through a multidisciplinary consultation at 12-36 months, and recommended to receive at least 20 h of services weekly. Outcome measures were caregiver-reported receipt of total and ASD-specific services within 18 months of ASD diagnosis. Separate negative binomial regression models were run for each outcome, with covariates of child adaptive and cognitive functioning, age, gender, household income, primary insurance, and maternal educational level. The sample was 83% male with a mean age of 24.5 months at ASD diagnosis. Mean Vineland adaptive behavior composite and Bayley cognitive standard scores were 73 and 81, respectively. 90% of children received ASD-specific services. The median intensities for total and ASD-specific services were 22 and 17 h weekly respectively, with 44% of the participants receiving at least 20 h of ASD-specific services weekly. Adjusted regression models found significant associations between lower adaptive scores and increased total and ASD-specific service receipt. Children in insurance-mandated states received a high intensity of intervention after clinical ASD diagnosis. Lower child adaptive functioning was associated with increased service receipt, while socioeconomic factors were not associated. Additional research in other regions and mandate-ineligible populations is needed.

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6. Birtwell K, Goldin R, Saro H, McDougle C, Horick N, Ravichandran C, Nowinski L. Using Restricted Interests in Cognitive Behavioral Therapy for Children With Autism Spectrum Disorder: Results From a Preliminary Randomized Controlled Trial. J Cogn Psychother;2024 (Jul 11);38(3):186-202.

Children with autism spectrum disorder (ASD) exhibit significant deficits in social communication and emotion regulation skills. While cognitive behavioral therapy (CBT) applications appear promising, trials to date have largely excluded social communication skill development and have not been designed to include a wider range of emotional challenges. To our knowledge, the present study is the first to pilot a uniquely modified CBT program targeting emotion regulation, including social communication training, and explicitly focusing on the child’s areas of circumscribed interest in order to teach skills and promote generalization. Forty participants were randomly assigned to either the CBT group or a waitlist control (WLC) group, resulting in 20 school-aged children in each group. The treatment approach was determined to be feasible and acceptable, and therapy engagement and attendance were reasonably high. Caregivers expressed high satisfaction with the program, qualitatively citing gains in skills such as social problem-solving, emotion identification, and identifying and processing cognitive distortions. The primary outcome of postintervention changes was not significantly different between the groups (CBT vs. WLC). The mean Social Skills Improvement System score decreased by 0.44 points (95% confidence interval [CI]: -5.04, 4.15) in the CBT group and increased by 0.41 points (95% CI: -4.23, 5.04) in the WLC group, and the postintervention changes were not significantly different between the groups (difference: -0.85; 95% CI: -7.29, 5.60; p = .79). The estimated rate of emotional dysregulation episodes decreased by a factor of 0.94 (95% CI: 0.57, 1.56) in the CBT group and increased by a factor of 1.07 (95% CI: 0.51, 2.24) for WLC (p = .74). Among those who reported emotional dysregulation episodes, the mean duration decreased by 1.39 minutes (95% CI: -3.90, 6.67) less for CBT than waitlist (p = .60). Although satisfaction, acceptability, and emotional dysregulation outcome results from this preliminary CBT treatment for ASD are promising, sample size and measurement limitations will be important considerations to inform future trials.

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7. Bled C, Guillon Q, Mottron L, Soulieres I, Bouvet L. Visual mental imagery abilities in autism. Autism Res;2024 (Jul 11)

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8. Cohen TD, Koller J, Duku E, Kata A, Anderson C, Bennett T, Cauwenbergs A, Dekker K, DiRezze B, Drmic I, Eerkes J, Gentles SJ, Georgiades K, Hoult L, De Camargo OK, Mahoney B, Mesterman R, Ng O, Robertson S, Roncadin C, Georgiades S. The Association Between Autism Symptomatology and Adaptive Functioning Over Six Months: Findings from the Pilot Phase of the PARC Study. J Autism Dev Disord;2024 (Jul 11)

PURPOSE: In the context of developmental trajectories, the association between adaptive functioning and core autism symptomatology remains unclear. The current study examines the associations of adaptive behavior with autism symptom sub-domains and with different facets of symptom expression. METHODS: Participants include 36 children with a recent diagnosis of autism (33 males; mean age = 56.4 months; SD = 9 months). Families were recruited in the context of the Pediatric Autism Research Cohort (PARC) project. Parents filled out questionnaires at two time points, six months apart, regarding their child’s autism symptoms and adaptive functioning. The longitudinal relationship between adaptive functioning and autism symptoms was investigated using Mixed Linear Model analyses: one assessing the relationship between general symptom levels and adaptive functioning, and another examining the associations between symptom frequency and impact with adaptive functioning. We conducted Pearson correlation tests at both time points to assess the associations between symptom sub-domains and adaptive functioning. RESULTS: Findings showed that higher autism symptoms associated with lower adaptive behavior skills, and that this association remained stable over time. Autism impact scores did not significantly relate to adaptive skills, as opposed to frequency scores. Associations between adaptive functioning and autism symptom sub-domains strengthened over time. CONCLUSION: These findings suggest that adaptive functioning is associated with parent-report autism symptomatology, and that this association changes and, on average, becomes stronger over time. Findings may indicate that frequency and impact of symptoms have differential roles in the development of adaptive skills and are worthy of further exploration.

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9. den Boer JC, Klip H, Blonk A, Lenselink M, Kaijdoe SPT, Tielkes M, van Zandbeek A, Bres G, Herinx M, Staal WG, Rommelse N. Study Protocol: Pegasus: psychotherapy incorporating horses for ‘therapy-resistant’ adolescents with autism spectrum disorders, a study with series of randomised, baseline controlled n-of-1 trials. BMC Psychiatry;2024 (Jul 10);24(1):499.

BACKGROUND: For people with autism spectrum disorder (ASD), daily life can be highly stressful with many unpredictable events that can evoke emotion dysregulation (ED): a strong difficulty with appropriately negative affect regulation. For some of the patients with ASD, treatment as usual does not prove to be effective for ED. They may be at risk of life-long impairment, development of other disorders and loss of motivation for most regular forms of therapy. A highly promising method that may prove effective for therapy-resistant individuals with ASD is Psychotherapy incorporating horses (PIH). PIH uses the interactions of the horse and the patients on the ground and does not include horseriding. While often met with prejudgment and scepticism, reports from parents and therapists as well as a recent systematic review suggest that PIH may have beneficial effects on youths with ASD. Therefore, we examine clinical outcomes both in the short and in the long terms of PIH offered to adolescents with ASD and severe ED despite regular therapy. METHODS: A total of 35 adolescents aged 11-18 years with ASD will receive PIH during 15 sessions once a week with randomization to five different groups differentiating in baseline phase from 2 to 6 weeks. PIH uses horses to promote social awareness and self-awareness as well as relationship management and self-management. The primary outcome is the response to treatment on the Emotion Dysregulation Index (EDI). The secondary outcome measures include ASD symptom severity, quality of life, self-esteem, global and family functioning, and goal attainment. Assessments take place at the baseline (T0), at the end of baseline phase A (T1), after completion of intervention phase B (T2), after the end of post-measurement phase C (T3) and after one year (T4). Qualitative interviews of participants, parents and therapists will be held to reveal facilitators and barriers of PIH and a cost-effectiveness study will be performed. DISCUSSION: This study aims at contributing to clinical practice for adolescents with ASD and persistent emotion regulation problems despite 1.5 year of treatment by offering Psychotherapy incorporating horses in a study with series of randomised, baseline controlled n-of-1 trials. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05200351, December 10th 2021.

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10. Grindle H, Sassu KA, Dooley JM, Farmer EB, Volkmar FR. Facilitating Interaction with Police During Routine Traffic Stops for Persons with ASD. J Autism Dev Disord;2024 (Jul 11)

A product of ASD socio-communicative-deficits and insufficient police training related to autism, ASD-police interactions have the potential to become problematic, with negative outcomes for ASD individuals and police alike. Thus, the combination of police acclimation, simulatory experience for drivers with ASD and the introduction of Connecticut’s recent Blue Envelope could improve overall experiences for drivers. A simulated routine traffic stop practice event, utilising pre- and post- measures was conducted in an effort to quantify drivers’ feelings about current and future interactions with police. Our prediction that participants would experience a statistically significant improvement in anxiety, comfort and self-perceived knowledge levels about future ASD-police interactions immediately following the intervention was confirmed. Our prediction that initially significant disparities between participants with and without police experience – those with previous police encounters versus those that don’t – would become not significant immediately following the intervention was disconfirmed. While the longitudinal data suggested that improved post-intervention ASD psychological measures remained statistically significant in the long-term, the sample responses to our long-term questionnaire were too few in number to make any definitive conclusions. It is suggested that practice traffic stops such as these could benefit both drivers with ASD and law enforcement nationwide. It is further suggested that police officer curriculums should include additional training regarding special populations.

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11. Karayol R, Borroto MC, Haghshenas S, Namasivayam A, Reilly J, Levy MA, Relator R, Kerkhof J, McConkey H, Shvedunova M, Petersen AK, Magnussen K, Zweier C, Vasileiou G, Reis A, Savatt JM, Mulligan MR, Bicknell LS, Poke G, Abu-El-Haija A, Duis J, Hannig V, Srivastava S, Barkoudah E, Hauser NS, van den Born M, Hamiel U, Henig N, Baris Feldman H, McKee S, Krapels IPC, Lei Y, Todorova A, Yordanova R, Atemin S, Rogac M, McConnell V, Chassevent A, Barañano KW, Shashi V, Sullivan JA, Peron A, Iascone M, Canevini MP, Friedman J, Reyes IA, Kierstein J, Shen JJ, Ahmed FN, Mao X, Almoguera B, Blanco-Kelly F, Platzer K, Treu AB, Quilichini J, Bourgois A, Chatron N, Januel L, Rougeot C, Carere DA, Monaghan KG, Rousseau J, Myers KA, Sadikovic B, Akhtar A, Campeau PM. MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature. Am J Hum Genet;2024 (Jul 11);111(7):1330-1351.

Epigenetic dysregulation has emerged as an important etiological mechanism of neurodevelopmental disorders (NDDs). Pathogenic variation in epigenetic regulators can impair deposition of histone post-translational modifications leading to aberrant spatiotemporal gene expression during neurodevelopment. The male-specific lethal (MSL) complex is a prominent multi-subunit epigenetic regulator of gene expression and is responsible for histone 4 lysine 16 acetylation (H4K16ac). Using exome sequencing, here we identify a cohort of 25 individuals with heterozygous de novo variants in MSL complex member MSL2. MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues such as coordination problems, feeding difficulties, and gait disturbance. Dysmorphisms and behavioral and/or psychiatric conditions, including autism spectrum disorder, and to a lesser extent, seizures, connective tissue disease signs, sleep disturbance, vision problems, and other organ anomalies, were observed in affected individuals. As a molecular biomarker, a sensitive and specific DNA methylation episignature has been established. Induced pluripotent stem cells (iPSCs) derived from three members of our cohort exhibited reduced MSL2 levels. Remarkably, while NDD-associated variants in two other members of the MSL complex (MOF and MSL3) result in reduced H4K16ac, global H4K16ac levels are unchanged in iPSCs with MSL2 variants. Regardless, MSL2 variants altered the expression of MSL2 targets in iPSCs and upon their differentiation to early germ layers. Our study defines an MSL2-related disorder as an NDD with distinguishable clinical features, a specific blood DNA episignature, and a distinct, MSL2-specific molecular etiology compared to other MSL complex-related disorders.

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12. Le Belle JE, Condro M, Cepeda C, Oikonomou KD, Tessema K, Dudley L, Schoenfield J, Kawaguchi R, Geschwind D, Silva AJ, Zhang Z, Shokat K, Harris NG, Kornblum HI. Acute rapamycin treatment reveals novel mechanisms of behavioral, physiological, and functional dysfunction in a maternal inflammation mouse model of autism and sensory over-responsivity. bioRxiv;2024 (Jul 11)

Maternal inflammatory response (MIR) during early gestation in mice induces a cascade of physiological and behavioral changes that have been associated with autism spectrum disorder (ASD). In a prior study and the current one, we find that mild MIR results in chronic systemic and neuro-inflammation, mTOR pathway activation, mild brain overgrowth followed by regionally specific volumetric changes, sensory processing dysregulation, and social and repetitive behavior abnormalities. Prior studies of rapamycin treatment in autism models have focused on chronic treatments that might be expected to alter or prevent physical brain changes. Here, we have focused on the acute effects of rapamycin to uncover novel mechanisms of dysfunction and related to mTOR pathway signaling. We find that within 2 hours, rapamycin treatment could rapidly rescue neuronal hyper-excitability, seizure susceptibility, functional network connectivity and brain community structure, and repetitive behaviors and sensory over-responsivity in adult offspring with persistent brain overgrowth. These CNS-mediated effects are also associated with alteration of the expression of several ASD-,ion channel-, and epilepsy-associated genes, in the same time frame. Our findings suggest that mTOR dysregulation in MIR offspring is a key contributor to various levels of brain dysfunction, including neuronal excitability, altered gene expression in multiple cell types, sensory functional network connectivity, and modulation of information flow. However, we demonstrate that the adult MIR brain is also amenable to rapid normalization of these functional changes which results in the rescue of both core and comorbid ASD behaviors in adult animals without requiring long-term physical alterations to the brain. Thus, restoring excitatory/inhibitory imbalance and sensory functional network modularity may be important targets for therapeutically addressing both primary sensory and social behavior phenotypes, and compensatory repetitive behavior phenotypes.

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13. Narzisi A, Sesso G, Fabbri-Destro M, Berloffa S, Fantozzi P, Muccio R, Bruzzi G, Scatigna S, Valente E, Viglione V, Milone A, Cortese S, Masi G. Social Skills Interventions for Adolescents with Level 1 Autism Spectrum Disorder: A Systematic Review with Meta-Analysis of Randomized Controlled Trials. Clin Neuropsychiatry;2024 (Jun);21(3):169-181.

OBJECTIVE: Evidence on the efficacy of social skills training for adolescents with Level 1 Autism Spectrum Disorder (ASD) is unclear. METHOD: 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. RESULTS: 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. CONCLUSIONS: 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.

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14. Ömercioğlu E, Mert Karakaya EN, Özdemir G, Şencan Karakuş B, Kılınç Ş, İskender HC, Cihan Çam E, Mete Yeşil A, Çelik HT, Karahan S, Özmert EN. Has the COVID-19 pandemic negatively impacted children’s development? An assessment of the neurodevelopment of premature babies born during the pandemic. Turk J Pediatr;2024 (Jul 11);66(3):275-286.

BACKGROUND: Pandemics, such as COVID-19, have the potential to adversely affect children’s development due to a variety of negative factors at the level of children, families, and services. In this study the effect of the pandemic on the cognitive, language and motor development of premature babies who are among the most vulnerable group, were evaluated. METHODS: The study included 236 premature infants who were followed at Hacettepe University Department of Developmental Pediatrics. The Bayley-Third Edition Developmental Assessment (Bayley III) was used to evaluate the neurodevelopment of 152 premature infants from the pre-pandemic group and 84 from the post-pandemic group at the corrected age of 18-24 months. The perinatal and sociodemographic risks were also evaluated. RESULTS: No difference in Bayley III scores (cognitive, language, and motor) was found between the pre- and post-pandemic groups. Furthermore, the multivariate covariance analysis displayed that regardless of the pandemic, infants with higher maternal education consistently scored higher in the cognitive, language, and motor domains; and the motor area scores of infants with moderate perinatal risk were also significantly higher than infants with high perinatal risk. CONCLUSIONS: It is crucial to monitor the development of vulnerable children who encounter developmental risks, such as premature babies. Fortunately, no significant effect was encountered during the COVID-19 pandemic. However, this does not underweigh the need for close supervision in extraordinary circumstances. Additionally, it should be noted that severe postnatal comorbidities, perinatal risks, and social factors, such as maternal education level, interact to influence the neurodevelopmental outcomes of preterm infants.

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15. Osman H, Ashwood P. Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders. Neural Regen Res;2025 (Apr 1);20(4):1101-1102.

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16. Salerno C, Allam A, Cirio S, Malerba A, Ionescu AC, Tartaglia GM, Campus G, Cagetti MG. Survival of different caries managements in children with autism and unaffected peers: a retrospective cohort study. Eur J Paediatr Dent;2024 (Jul 1):1.

AIM: Dental caries is a common oral disease in children with special needs such as those with autism spectrum disorders (ASDs). The aim is to assess whether the type and survival of three caries management, conventional resin restorations (CR), ART technique (ART) and SDF application without caries removal (SDF), in primary teeth carried out at the Pediatric Dentistry Department of San Paolo Hospital (University of Milan) differed between children with ASDs and unaffected peers. METHODS: Data from a convenience sample of children with and without ASDs, who have received dental care for caries in primary teeth from January 2019 to June 2022, were analysed. Medical history, age, sex, teeth treated, and type of treatment were collected from dental charts. Data on success and minor and major failures of each treatment were also collected. Two survival analysis were performed, one considering both major and minor failures, a second considering only major failures. Cox Proportional Hazards multivariate logistic models were run to assess factors associated with failures. The statistical significance was set at 5% (p< 0.05). CONCLUSION: In children with autism, the different techniques for approaching caries lesions seem to have the same probability of success. Therefore, the choice of treatment should be patient-oriented rather than lesion-oriented. In unaffected children, the gold standard always seems to be traditional restorative treatment.

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17. Terroux A, Mello C, Morin D, Rivard M. Everyday Executive Function in Preschoolers with Autism and Links with Intellectual Functioning, Adaptive Behavior, and Autism Symptoms. J Autism Dev Disord;2024 (Jul 11)

Impairments in executive function (EF) among individuals with autism spectrum disorder and their association with negative academic, adaptive, and social functioning outcomes have been widely reported over the past 20 years. However, there remains a lack of understanding of EF in autism during the preschool period, an age at which several crucial abilities (including EF) emerge. The present study therefore sought to document everyday EF in preschool-aged children with autism and its associations with other clinical characteristics. Parents rated the EF of their preschool-aged child with autism (M = 30-65 months, N = 288) using the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P; Gioia, G. A., Espy, K. A., & Isquith, P. K. (2003). Behavior Rating Inventory of Executive Function-Preschool Version. Psychological Assessment Resources.). Intellectual quotient, adaptive behavior, and autism symptom severity were also assessed. Preschoolers with ASD displayed impairments in everyday EF, particularly in relation with inhibition and working memory. Greater challenges in EF were strongly associated with lower levels of adaptive behavior and a higher severity of autistic symptoms. To a lesser extent, EF challenges were also associated with lower levels of intellectual functioning. The early assessment and detection of EF difficulties in preschoolers with ASD may assist in developing and integrating specific intervention targets to improve these essential abilities within existing early intervention programs for ASD. This could help to maximize their effectiveness and limit the extent of difficulties these children may face growing up.

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18. Torty C, Eyong K, Asindi AA, Usun E. Autism Spectrum Disorders in Calabar, Nigeria. Iran J Child Neurol;2024 (Summer);18(3):75-81.

OBJECTIVES: Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is prevalent worldwide. The incidence of autism has increased worldwide. However, there is a dearth of data in sub-Saharan Africa. The study is aimed at determining the clinical and socio-developmental profile of children with ASD in a tertiary hospital in Nigeria. MATERIALS & METHODS: This study is a six-year retrospective review of the medical records of children who presented with clinical autism diagnoses at the Department of Pediatrics, University of Calabar Teaching Hospital. Relevant data were extracted from the medical records of those who met the diagnostic criteria. Descriptive statistics were presented in proportions, percentages, and tables. RESULTS: Of the 1806 children with neurological disorders seen in the clinic within the study period, twenty-eight were found to have symptoms of autism based on the American Psychiatric Association›s Diagnostic and Statistical Manual V (DSM -5) criteria, giving a prevalence of 1.6%. The mean age at diagnosis was 3.8 ±1.4 (range 2 to 10) years, with a male-to-female ratio of 3:1. About two-thirds of the children diagnosed were older than three years. Seven percent of the children had siblings with autism, 53.5% of children with autism in the study had hyperactivity as comorbidity, while seizures were found in 7% of cases. CONCLUSION: The prevalence of ASD among children seen in Calabar is 1.6%. Hyperactivity, mental retardation, and seizure disorders are associated comorbidities in the study. Late presentation is a common feature in this facility. Thus, increasing awareness is essential to enhance early recognition, timely diagnosis, and appropriate intervention.

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19. Wan Y, Su Q, Ng SC. New insights on gut microbiome and autism. Trends Mol Med;2024 (Jul 9)

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that often coincides with gut dysbiosis. Studies show that alterations in gut microbiota influence brain function and could serve as diagnostic biomarkers and therapeutic targets. This forum article discusses the role of gut microbiota in ASD pathogenesis and its diagnostic and therapeutic potential.

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20. Wu Y, Ding L, Zhang Q, Dong Y, Tao C, Li Z, Li Z, Lu L. The effect of physical exercise therapy on autism spectrum disorder:a systematic review and meta-analysis. Psychiatry Res;2024 (Jul 6);339:116074.

BACKGROUND: Physical Exercise Therapy (PET) is increasingly applied in the treatment of Autism Spectrum Disorders (ASD), yet the empirical evidence supporting its efficacy remains ambiguous. This systematic review and meta-analysis aimed to investigate the effectiveness of PET for individuals with ASD, providing evidence-based support for clinical and scientific research. METHODS: We systematically searched four international databases (Medline via PubMed, Embase, Cochrane Libraries, and Web of Science) and three Chinese databases (CNKI, Wanfang, and VIP Libraries) up to July 31, 2023. The search was conducted in both English and Chinese for original research articles employing randomized-controlled-trial (RCT) designs to study PET’s effects on individuals diagnosed with ASD according to DSM or other established criteria. Co-primary outcomes focused on the overall severity of autism, while secondary outcomes included measures of stereotyped behaviors, social deficits, social skills, and executive functioning. Data from the included studies were synthesized and analyzed using RevMan 5.4. This systematic review is registered with PROSPERO (CRD42023443951). RESULTS: A total of 28 RCTs comprising 1081 participants were analyzed. Of these, only three studies met high-quality standards. Compared to control groups, PET showed improvement in at least one core symptom of autism, including Motor Performance (SMD=1.72, 95%CI[1.01, 2.44], I(2)=90%), Restricted Repetitive Behaviors (SMD=-0.81, 95%CI[-1.00, -0.62], I(2)=0%), Social Dysfunction (SMD=-0.76, 95%CI[-1.06, -0.46], I(2)=47%). CONCLUSIONS: PET may offer benefits in reducing the overall severity and associated symptoms in individuals with ASD. However, given the high overall risk of bias in the included studies, these findings should be interpreted with caution.

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21. Yang F, Tian J, Yuan P, Liu C, Zhang X, Yang L, Jiang Y. Unconscious and Conscious Gaze-Triggered Attentional Orienting: Distinguishing Innate and Acquired Components of Social Attention in Children and Adults with Autistic Traits and Autism Spectrum Disorders. Research (Wash D C);2024;7:0417.

Typically developing (TD) individuals can readily orient attention according to others’ eye-gaze direction, an ability known as social attention, which involves both innate and acquired components. To distinguish between these two components, we used a critical flicker fusion technique to render gaze cues invisible to participants, thereby largely reducing influences from consciously acquired strategies. Results revealed that both visible and invisible gaze cues could trigger attentional orienting in TD adults (aged 20 to 30 years) and children (aged 6 to 12 years). Intriguingly, only the ability to involuntarily respond to invisible gaze cues was negatively correlated with autistic traits among all TD participants. This ability was substantially impaired in adults with autism spectrum disorder (ASD) and in children with high autistic traits. No such association or reduction was observed with visible gaze cues. These findings provide compelling evidence for the functional demarcation of conscious and unconscious gaze-triggered attentional orienting that emerges early in life and develops into adulthood, shedding new light on the differentiation of the innate and acquired aspects of social attention. Moreover, they contribute to a comprehensive understanding of social endophenotypes of ASD.

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22. Yang KL, Yen TA, Lin FJ, Hsu CN, Wang CC. Antibiotic use and risk of autism spectrum disorder and attention-deficit/hyperactivity disorder: a population-based cohort study. Child Adolesc Psychiatry Ment Health;2024 (Jul 11);18(1):82.

BACKGROUND: The gut microbiota is believed to influence neurodevelopment through the gut-brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. METHODS: This was a retrospective cohort study using 2003-2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. RESULTS: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04-1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01-1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90-0.94). CONCLUSIONS: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use.

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23. Yang Y, Wang Q, Wang C, Buxbaum J, Ionita-Laza I. KnockoffHybrid: A knockoff framework for hybrid analysis of trio and population designs in genome-wide association studies. Am J Hum Genet;2024 (Jul 11);111(7):1448-1461.

Both trio and population designs are popular study designs for identifying risk genetic variants in genome-wide association studies (GWASs). The trio design, as a family-based design, is robust to confounding due to population structure, whereas the population design is often more powerful due to larger sample sizes. Here, we propose KnockoffHybrid, a knockoff-based statistical method for hybrid analysis of both the trio and population designs. KnockoffHybrid provides a unified framework that brings together the advantages of both designs and produces powerful hybrid analysis while controlling the false discovery rate (FDR) in the presence of linkage disequilibrium and population structure. Furthermore, KnockoffHybrid has the flexibility to leverage different types of summary statistics for hybrid analyses, including expression quantitative trait loci (eQTL) and GWAS summary statistics. We demonstrate in simulations that KnockoffHybrid offers power gains over non-hybrid methods for the trio and population designs with the same number of cases while controlling the FDR with complex correlation among variants and population structure among subjects. In hybrid analyses of three trio cohorts for autism spectrum disorders (ASDs) from the Autism Speaks MSSNG, Autism Sequencing Consortium, and Autism Genome Project with GWAS summary statistics from the iPSYCH project and eQTL summary statistics from the MetaBrain project, KnockoffHybrid outperforms conventional methods by replicating several known risk genes for ASDs and identifying additional associations with variants in other genes, including the PRAME family genes involved in axon guidance and which may act as common targets for human speech/language evolution and related disorders.

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