1. Ding N, Fu L, Qian L, Sun B, Li C, Gao H, Lei T, Ke X. The correlation between brain structure characteristics and emotion regulation ability in children at high risk of autism spectrum disorder. Eur Child Adolesc Psychiatry;2024 (Feb 24)

As indicated by longitudinal observation, autism has difficulty controlling emotions to a certain extent in early childhood, and most children’s emotional and behavioral problems are further aggravated with the growth of age. This study aimed at exploring the correlation between white matter and white matter fiber bundle connectivity characteristics and their emotional regulation ability in children with autism using machine learning methods, which can lay an empirical basis for early clinical intervention of autism. Fifty-five high risk of autism spectrum disorder (HR-ASD) children and 52 typical development (TD) children were selected to complete the skull 3D-T1 structure and diffusion tensor imaging (DTI). The emotional regulation ability of the two groups was compared using the still-face paradigm (SFP). The classification and regression models of white matter characteristics and white matter fiber bundle connections of emotion regulation ability in the HR-ASD group were built based on the machine learning method. The volume of the right amygdala (R(2) = 0.245) and the volume of the right hippocampus (R(2) = 0.197) affected constructive emotion regulation strategies. FA (R(2) = 0.32) and MD (R(2) = 0.34) had the predictive effect on self-stimulating behaviour. White matter fiber bundle connection predicted constructive regulation strategies (positive edging R(2) = 0.333, negative edging R(2) = 0.334) and mother-seeking behaviors (positive edging R(2) = 0.667, negative edging R(2) = 0.363). The emotional regulation ability of HR-ASD children is significantly correlated with the connections of multiple white matter fiber bundles, which is a potential neuro-biomarker of emotional regulation ability.

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2. Fatta LM, Bianchi D, Laugeson EA, Veytsman E, Romano G, Laghi F, Scattoni ML. Enhancing social outcomes in autistic youth: Assessing the impact of PEERS® booster sessions. Res Dev Disabil;2024 (Feb 22);147:104698.

BACKGROUND: The Program for the Education and Enrichment of Relational Skills (PEERS®) is a social skills training program for autistic adolescents and those facing social challenges. Its efficacy has been established worldwide, including in Italy. Although booster interventions are a potentially valuable strategy to maintain improvements over time, there is currently no research on the efficacy of providing booster sessions of PEERS® following the traditional treatment. AIMS: This study aims to evaluate the efficacy of PEERS® Booster sessions in a sample who had previously participated in a traditional PEERS® Adolescent program. METHODS AND PROCEDURES: A longitudinal non-randomized study was conducted involving 21 autistic adolescents, divided into the treatment group undergoing PEERS® Booster sessions and the control group without it. OUTCOMES AND RESULTS: The study evaluated the primary outcomes (social abilities) and secondary outcomes (co-occurrences, executive functions) at two-time points (pre- and post-treatment). No significant differences were found between groups on baseline measures and primary outcomes. However, there were significant group differences between pre- and post-treatment on primary outcomes (social awareness and social communication) and secondary outcomes (externalizing problems). CONCLUSIONS AND IMPLICATIONS: The efficacy of the PEERS® Booster Sessions shows promise and clinical implications were also discussed.

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3. Fonteneau M, Brugoux A, Jaccaz D, Donello JE, Banerjee P, Le Merrer J, Becker JA. The NMDA receptor modulator zelquistinel durably relieves behavioral deficits in three mouse models of autism spectrum disorder. Neuropharmacology;2024 (Feb 22):109889.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders characterized by deficient social communication and interaction together with restricted, stereotyped behaviors. Currently approved treatments relieve comorbidities rather than core symptoms. Since excitation/inhibition balance and synaptic plasticity are disrupted in ASD, molecules targeting excitatory synaptic transmission appear as highly promising candidates to treat this pathology. Among glutamatergic receptors, the NMDA receptor has received particular attention through the last decade to develop novel allosteric modulators. Here, we show that positive NMDA receptor modulation by zelquistinel, a spirocyclic β-lactam platform chemical, relieves core symptoms in two genetic and one environmental mouse models of ASD. A single oral dose of zelquistinel rescued, in a dose-response manner, social deficits and stereotypic behavior in Shank3(Δex13-16-/-) mice while chronic intraperitoneal administration promoted a long-lasting relief of such autistic-like features in these mice. Subchronic oral mid-dose zelquistinel treatment demonstrated durable effects in Shank3(Δex13-16-/-), Fmr1(-/-) and in utero valproate-exposed mice. Carry-over effects were best maintained in the Fmr1 null mouse model, with social parameters being still fully recovered two weeks after treatment withdrawal. Among recently developed NMDA receptor subunit modulators, zelquistinel displays a promising therapeutic potential to relieve core symptoms in ASD patients, with oral bioavailability and long-lasting effects boding well for clinical applications. Efficacy in three mouse models with different etiologies supports high translational value. Further, this compound represents an innovative pharmacological tool to investigate plasticity mechanisms underlying behavioral deficits in animal models of ASD.

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4. Genovesi E, Yao YI, Mitchell E, Arad M, Diamant V, Panju A, Hanlon C, Tekola B, Hoekstra RA. Mapping awareness-raising and capacity-building materials on developmental disabilities for non-specialists: a review of the academic and grey literature. Int J Ment Health Syst;2024 (Feb 24);18(1):10.

Most children with developmental disabilities (DD), such as intellectual disabilities and autism, live in low- and middle-income countries (LMICs), where services are usually limited. Various governmental, non-governmental and research organisations in LMICs have developed awareness-raising campaigns and training and education resources on DD in childhood relevant to LMICs. This study aimed to comprehensively search and review freely available materials in the academic and grey literature, aimed at awareness raising, training and education on DD among non-specialist professionals and community members in LMICs. We consulted 183 experts, conducted key-word searches in five academic databases, four grey-literature databases and seventeen customised Google search engines. Following initial screening, we manually searched relevant systematic reviews and lists of resources and conducted forwards and backwards citation checks of included articles. We identified 7327 articles and resources after deduplication. We then used a rigorous multi-step screening process to select 78 training resources on DD relevant to LMICs, of which 43 aimed at informing and/or raising awareness DD, 16 highlighted specific strategies for staff in health settings and 19 in education settings. Our mapping analysis revealed that a wealth of materials is available for both global and local use, including comics, children’s books, flyers, posters, fact sheets, blogs, videos, websites pages, social media channels, handbooks and self-education guides, and training programmes or sessions. Twelve resources were developed for cross-continental or global use in LMICs, 19 were developed for and/or used in Africa, 23 in Asia, 24 in Latin America. Most resources were developed within the context where they were intended to be used. Identified gaps included a limited range of resources on intellectual disabilities, manuals for actively delivering training to staff in education settings and resources targeted at eastern European LMICs: future intervention development and adaptation efforts should address such gaps, to ensure capacity building materials exist for a sufficient variety of DD, settings and geographical areas. Beyond identifying these gaps, the value of the review lies in the compilation of summary tables of information on all freely available resources found, to support their selection and use in wider contexts. Information on the resource content, country of original development and copyright is provided to facilitate resource sharing and uptake.

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5. Khattab NA, El-Kadem AH, Elblehi SS, Ahmed El-Mahdy N, El-Shitany NA. The emerging role of α7nAChRs/caspase-3/Nrf-2 signaling pathway in citicoline improved autistic behavior induced by thimerosal in mice. Int Immunopharmacol;2024 (Feb 23);130:111736.

AIMS: Autism spectrum disorder (ASD) is a global concern,affecting around 75 million individuals.Various factors contribute to ASD,including mercury-containing preservatives like thimerosal (Thim) found in some vaccines.This study explored whether citicoline could be a therapeutic option for Thim-induced neuronal damage in a mouse model of ASD.Additionally,the study investigated the effects of citicoline on the α7nAChRs/Akt/Nrf2/caspase-3 pathway,which may be involved in the development of ASD. MATERIALS AND METHODS: The study separated newborn mice into four groups.The control group received saline injections,while the Thim group received intramuscular injections of 3000 μg Hg/kg Thim on days 7,9,11,and 15 after birth.The two citicoline groups were administered Thim followed by intraperitoneal injections of 250 mg/kg or 500 mg/kg citicoline for three weeks.Afterward,various parameters were assessed, including growth,behavior,brain histopathology,oxidative stress,apoptotic,and inflammatory markers. KEY FINDINGS: Untreated Thim-exposed mice exhibited significant brain damage,which was substantially alleviated by citicoline treatment.This beneficial effect was associated with increased expressions and concentrations of brain α7nAChRs and Akt, increased brain content of Nrf2, and the hippocampus contents of acetylcholine. Citicoline treatment decreased the brain levels of oxidative stress markers (MDA and NO),the apoptotic marker caspase-3,and pro-inflammatory markers (NF-κB,TNF-α,and IL-1β). The drug also increased the brain GPx activity. SIGNIFICANCE: Based on the results of this study,the α7nAChRs pathway appears to be essential for the therapeutic effectiveness of citicoline in treating Thim-induced ASD in mice.

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6. Li Y, Ma S, Zhang X, Gao L. ASD and ADHD: Divergent activating patterns of prefrontal cortex in executive function tasks?. J Psychiatr Res;2024 (Feb 10);172:187-196.

The functional Near-infrared Spectroscopy (fNIRS) has been more and more widely used to measure the activation state of prefrontal cortex when performing function-related tasks among children with various developmental disorders. Children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) have shown obvious executive function defects. We aimed to summarize the studies with fNIRS, to summarize the activation patterns of prefrontal cortex (PFC) of participants with ASD or ADHD in performing functional tasks. We selected 630 articles according to PRISMA guidelines, and the eligibility criteria were: 6-16 years old individuals diagnosed with ASD or ADHD by DSM-4 or 5, using fNIRS, having executive function (EF) task, typical development (TD) control, and between-group comparison of PFC activation. Eleven studies were finally included in the quantitative analysis, and compared to TD, ASD and ADHD showed the opposite PFC activation patterns during n-back tasks. We discussed the task-specific PFC activation in young participants with ASD and ADHD, and provided some new ideas on that issue.

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7. Restoy D, Oriol-Escudé M, Alonzo-Castillo T, Magán-Maganto M, Canal-Bedia R, Díez-Villoria E, Gisbert-Gustemps L, Setién-Ramos I, Martínez-Ramírez M, Ramos-Quiroga JA, Lugo-Marín J. Emotion regulation and emotion dysregulation in children and adolescents with Autism Spectrum Disorder: A meta-analysis of evaluation and intervention studies. Clin Psychol Rev;2024 (Feb 21);109:102410.

Children and adolescents with Autism Spectrum Disorder (ASD) often experience challenges in emotion regulation (ER) and emotion dysregulation (ED) which can interfere with their adaptive functioning. This study aimed to systematically review and meta-analyze the evidence on ER/ED in children and/or adolescents with ASD, examining its relationship with the following variables: internalizing and externalizing symptoms, cognitive function and social skills, and the effectiveness of non-pharmacological interventions addressing ER difficulties. Both electronic and manual searches were conducted to identify potential studies. Fifty-five studies were included in the meta-analysis. A statistically significant between-group difference was found, suggesting greater ER/ED challenges in the ASD group. Also, the ASD group showed more maladaptive ER strategies and fewer adaptive ER strategies compared to the non-ASD participants. Additionally, more severe ASD and poorer social skills were associated with greater ED and poorer ER skills, respectivelly. Furthermore, there was a significant correlation between internalizing symptomatology and both adaptive and maladaptive ER strategies. Studies of non-pharmacological interventions showed significant improvement in both ER and ED. These results imply that assessing ER/ED in children and adolescents with ASD should be part of the evaluation process, and it should also be a focal point for intervention in this population.

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8. Su PL, Yoo H, Ramsay G, Long HL, Bene ER, Klaiman C, Pulver SL, Richardson S, Pileggi ML, Brane N, Oller DK. Foundations of Vocal Category Development in Autistic Infants. J Autism Dev Disord;2024 (Feb 25)

The present study compared the infant’s tendency in the first year of life to produce clusters of particular vocal types (squeals, vocants, and growls) in typically developing (TD) and autistic infants. Vocal clustering provides evidence of vocal category formation and may establish a foundation for speech development. Specifically, we compared the extent of vocal clustering across outcome groups and age groups. We also examined the associations between the extent of vocal clustering and later outcomes at 2 years within the autistic group. Randomly selected 5-min segments (27,153 5-min segments total) from 1293 all-day home recordings from 103 TD infants and 44 autistic infants across the first year were humancoded (about 9.75 h of data coded per infant on average) to derive vocal clustering patterns. Fisher’s exact tests were used to compare the occurrence of squeals versus vocants, as well as growls versus vocants, across coded segments. Infants in both groups demonstrated clear clustering patterns of squeals and growls across all age groups. The extent of vocal clustering in the autistic group did not correlate significantly with later language, repetitive behavior, or autism severity outcomes. These findings highlight the robustness of the systematic production of vocal categories across the first year of life. The similarity of the clustering patterns in the TD and autistic groups suggests that vocal category formation through active infant vocal exploration is a robust feature of early speech development.

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9. Wilczyński KM, Auguściak-Duma A, Cichoń L, Stasik A, Janas-Kozik M. The role of selected polymorphisms in regulation of gene CD38 expression and their effect on the clinical picture of autism spectrum disorders – preliminary study. Psychiatr Pol;2023 (Sep 30):1-14.

OBJECTIVES: Clinical effects observed in cases of oxytocin deficiency can also manifest themselves in disorders of mechanisms responsible, for example, for its secretion. For oxytocin, this function is played by – among others – the cluster of differentiation antigen 38 (CD38). Existing literature along with the correlation between protein CD38 and oxytocin secretion raise interest in the context of their possible relation to the clinical picture and development of the autism spectrum disorders (ASD). The aim of the study was to analyze the correlations between polymorphisms rs3796863 and rs6449197 in gene CD38, the level of gene expression and the clinical picture and the risk of ASD diagnosis. METHODS: The study included 59 individuals with the mean age of 15.05 years with IQ > 90. The participants were divided into two groups: the studied group consisting of 37 persons with confirmed ASD diagnoses and the control group including 22 neurotypical individuals. Diagnosis verification was carried out via the ADOS-2 protocol. RESULTS: The comparative analysis with the standardized population based on the 1000Genomes database with the presence of clinically significant intensification of ASD traits showed the correlation of alleles « T » of polymorphisms rs3796863 and rs6449197, which are more frequent in the general population and are treated as « wild ». In the inter-group analysis, this type of dependency was weaker, and the genotype of the control group was somehow intermediate between the studied group and the standardized population. In the ΔΔCt analysis, the normalized value of the relative expression level of gene CD38 showed that in the studied group the expression level was around 1.1-1.2 times higher than in the control group. CONCLUSIONS: The obtained results show that a significant correlation with the severity of autism spectrum disorder traits is mainly observed in the carriers of wild variants of the studied polymorphisms, in which the related increase in the expression level of gene CD38 is also observed.

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