1. Alomar HA, Ansari MA, Nadeem A, Attia SM, Bakheet SA, Al-Mazroua HA, Hussein MH, Alqarni SA, Ahmad SF. A potent and selective CXCR2 antagonist improves neuroimmune dysregulation through the inhibition of NF-κB and notch inflammatory signaling in the BTBR mouse model of autism. Journal of neuroimmunology. 2023; 377: 578069.

Autism comprises a broad range of neurodevelopmental disorders characterized by social communication deficits and repetitive and stereotyped behaviors. Chemokine receptor CXCR2 is expressed on neurons and is upregulated in neurological disorders. BTBR T+ Itpr3tf/J (BTBR) mice, a model for autism that shows the core features of ASD. Here, we studied the anti-inflammatory effect of a potent and selective CXCR2 antagonist SB332235 in the BTBR mice. The CXCR2 antagonist represents a promising therapeutic agent for several neuroinflammatory disorders. In this study, we investigated the effects of SB332235 administration on NF-κB-, Notch-1-, Notch-3-, GM-CSF-, MCP-1-, IL-6-, and IL-2- and TGF-β1-expressing CD40+ cells in BTBR and C57BL/6 (C57) mice in the spleen cells by flow cytometry. We further assessed the effect of SB332235 treatment on NF-κB, Notch-1, GM-CSF, MCP-1, IL-6, and IL-2 mRNA expression levels in the brain tissue by RT-PCR. We also explored the effect of SB332235 administration on NF-κB, GM-CSF, IL-6, and TGF-β1 protein expression levels in the brain tissue by western blotting. The SB332235-treated BTBR mice significantly decreases in CD40 + NF-κB+, CD40 + Notch-1+, CD40 + Notch-3+, CD40 + GM-CSF+, CD40 + MCP-1+, CD40 + IL-6+, and CD40 + IL-2+, and increases in CD40 + TGF-β1+ in the spleen cells. Our results further demonstrated that BTBR mice treated with SB332235 effectively decreased NF-κB, Notch-1, GM-CSF, MCP-1, IL-6, and IL-2, increasing TGF-β1 mRNA and protein expression levels in the brain tissue. In conclusion, these results indicate that SB332235 elicits an anti-inflammatory response by downregulating the inflammatory mediators and NF-κB/Notch inflammatory signaling in BTBR mice. This could represent a promising novel therapeutic target for autism treatment.

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2. Brito A, Franco F, Brentani H, Beltrão-Braga PCB. Assessment of vulnerability dimensions considering Family History and environmental interplay in Autism Spectrum Disorder. BMC psychiatry. 2023; 23(1): 254.

BACKGROUND: Despite previous studies have recently shown Autism Spectrum Disorders (ASD) as having a strong genetics background, over a minimum environmental background, no study up to date has investigated the interplay between genetics and environment. METHODS: We have collected data regarding Family History (FH) and Environmental Factors (EF) from 2,141 individuals with ASD and their caretakers throughout Brazil, based on an online questionnaire. Most of the ASD individuals were males (81%) and the average age was 02 years minimum for males and females, and the maximum age was 41 years for males and 54 for females. People from all states in Brazil have answered the questionnaire. Genetic inheritance was obtained based on the declared FH of Psychiatric and Neurological diagnosis. As for EF, exposure to risk factors during pregnancy was considered, like infections, diabetes, drugs/chemicals exposure, socioeconomic, and psychological factors. Respondents were invited to answer the questionnaire in lectures given throughout Brazil, and by the social networks of the NGO « The Tooth Fairy Project ». A Multiple Correspondence Analysis (MCA) was conducted to search vulnerability dimensions, and a Cluster Analysis was conducted to classify and identify the subgroups. RESULTS: Regarding EF, social and psychological exposures contributed to the first two dimensions. Concerning FH, the first dimension represented psychiatric FH, while the second represented neurological FH. When analyzed together, EF and FH contributed to two new dimensions: 1. psychiatric FH, and 2. a psychosocial component. Using Cluster Analysis, it was not possible to isolate subgroups by genetic vulnerability or environmental exposure. Instead, a gradient of psychiatric FH with similar contributions of EF was observed. CONCLUSION: In this study, it was not possible to isolate groups of patients that correspond to only one component, but rather a continuum with different compositions of genetic and environmental interplay.

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3. Choi JE, Kaang BK. Increased social interaction in Shank2-deficient mice following acute social isolation. Molecular brain. 2023; 16(1): 35.

Autism spectrum disorder (ASD) is neuropsychiatric disorder with a gender specific risk. Although social impairment in ASD is one of the well characterized phenotypes, loneliness issue resides in patients with ASD and emerging reports show gender distribution in symptoms. Acute social isolation increases the motivation to socially interact in a gender-dependent manner, as only the male mice show increase in sociability following isolation. However, it remains to be explored whether the effects of loneliness in ASD differ between genders. Here, we used Shank2-deficient (Shank2(-/-)) mice, one of the animal models of ASD, to examine the sociability changes after acute social isolation. While only the male wild-type (WT) mice display increased sociability following 24-h isolation, both sexes of Shank2(-/-) mice show an increase in social interaction following isolation. These observations provide evidence that animal models of ASD have the sensitivity to acute social isolation and further show the motivation to socially interact.

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4. Cong J, Zhuang W, Liu Y, Yin S, Jia H, Yi C, Chen K, Xue K, Li F, Yao D, Xu P, Zhang T. Altered default mode network causal connectivity patterns in autism spectrum disorder revealed by Liang information flow analysis. Human brain mapping. 2023; 44(6): 2279-93.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with severe cognitive impairment in social communication and interaction. Previous studies have reported that abnormal functional connectivity patterns within the default mode network (DMN) were associated with social dysfunction in ASD. However, how the altered causal connectivity pattern within the DMN affects the social functioning in ASD remains largely unclear. Here, we introduced the Liang information flow method, widely applied to climate science and quantum mechanics, to uncover the brain causal network patterns in ASD. Compared with the healthy controls (HC), we observed that the interactions among the dorsal medial prefrontal cortex (dMPFC), ventral medial prefrontal cortex (vMPFC), hippocampal formation, and temporo-parietal junction showed more inter-regional causal connectivity differences in ASD. For the topological property analysis, we also found the clustering coefficient of DMN and the In-Out degree of anterior medial prefrontal cortex were significantly decreased in ASD. Furthermore, we found that the causal connectivity from dMPFC to vMPFC was correlated with the clinical symptoms of ASD. These altered causal connectivity patterns indicated that the DMN inter-regions information processing was perturbed in ASD. In particular, we found that the dMPFC acts as a causal source in the DMN in HC, whereas it plays a causal target in ASD. Overall, our findings indicated that the Liang information flow method could serve as an important way to explore the DMN causal connectivity patterns, and it also can provide novel insights into the nueromechanisms underlying DMN dysfunction in ASD.

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5. Gallo C, Scarpis A, Mucignat-Caretta C. Oral health status and management of autistic patients in the dental setting. European journal of paediatric dentistry. 2023: 1.

AIM: Dental treatment of patients with Autism Spectrum Disorders (ASD) is challenging due to difficulties in social interactions, hypersensitivity to sensory stimuli, various degrees of cognitive and developmental issues, poor collaboration, limited capacity to manage emotions, stereotyped movements, hyperactivity, limited adaptation to new situations and environments. Data on the type of treatment required are scarce. This study investigates the oral health status of ASD patients, the possibilities of chair treatment and the need for dental treatments under general anaesthesia (GA). METHODS: One hundred sixty-nine medical records, from 2005 to 2018, of patients with ASD were examined. Patients undergoing chair or general anaesthesia were assigned to two groups according age (younger or older than 14 years old). The level of cooperation was classified into four categories: none, poor, fair, good. CONCLUSION: Primary prevention, setting up a routine oral hygiene at home and regular dental examinations, internalised like a habit by patients, are the main instruments to maintain oral health in ASD patients. When non-cooperative patients need urgent treatment, safe and high-level dental therapies should be performed under GA.

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6. Hase A, Haynes M, Hasler G. Using simple economic games to assess social orienting and prosocial behavior in adolescents with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2023.

Deficits in socio-emotional reciprocity, in prosocial behavior and in developing social relationships are diagnostic criteria of autism spectrum disorder (ASD), usually assessed by self-report or observation. Simple social experiments developed by behavioral economists allow for quantification of ASD-related social behavior. In this study, we used such experiments to compare social-economic decision-making between ASD adolescents and neurotypical controls. Precisely, we analyzed social orienting and prosocial behavior in 17 adolescents with ASD (Asperger syndrome) and 24 matched neurotypical adolescents. We used a two-condition distribution game (possibility of punishment by fellow player versus no such possibility) and an impunity game to examine social orienting (distribution game) and prosocial behavior (both games). Participants with ASD exhibited less social orienting in the distribution game (p = 0.03, d = -0.61). In addition, there was a trend for ASD participants to behave in a more prosocial way than neurotypical participants in the impunity game (p = 0.08, d = 0.60), which was not the case in the no-punishment condition of the distribution game (p = 0.35, r = 0.17). These results demonstrate the potential of simple economic games to capture reduced social orienting in ASD. The unexpected finding of more prosocial behavior in adolescents with autism spectrum disorder than in neurotypical controls adds to the complexity of previously published results. We recommend meta-analytic efforts to determine average effect sizes across studies and elucidate the conditions for prosocial behavior in ASD to occur.

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7. Kildal ESM, Quintana DS, Szabo A, Tronstad C, Andreassen O, Nærland T, Hassel B. Heart rate monitoring to detect acute pain in non-verbal patients: a study protocol for a randomized controlled clinical trial. BMC psychiatry. 2023; 23(1): 252.

BACKGROUND: Autism entails reduced communicative abilities. Approximately 30% of individuals with autism have intellectual disability (ID). Some people with autism and ID are virtually non-communicative and unable to notify their caregivers when they are in pain. In a pilot study, we showed that heart rate (HR) monitoring may identify painful situations in this patient group, as HR increases in acutely painful situations. OBJECTIVES: This study aims to generate knowledge to reduce the number of painful episodes in non-communicative patients’ everyday lives. We will 1) assess the effectiveness of HR as a tool for identifying potentially painful care procedures, 2) test the effect of HR-informed changes in potentially painful care procedures on biomarkers of pain, and 3) assess how six weeks of communication through HR affects the quality of communication between patient and caregiver. METHODS: We will recruit 38 non-communicative patients with autism and ID residing in care homes. ASSESSMENTS: HR is measured continuously to identify acutely painful situations. HR variability and pain-related cytokines (MCP-1, IL-1RA, IL-8, TGFβ1, and IL-17) are collected as measures of long-term pain. Caregivers will be asked to what degree they observe pain in their patients and how well they believe they understand their patient’s expressions of emotion and pain. Pre-intervention: HR is measured 8 h/day over 2 weeks to identify potentially painful situations across four settings: physiotherapy, cast use, lifting, and personal hygiene. INTERVENTION: Changes in procedures for identified painful situations are in the form of changes in 1) physiotherapy techniques, 2) preparations for putting on casts, 3) lifting techniques or 4) personal hygiene procedures. DESIGN: Nineteen patients will start intervention in week 3 while 19 patients will continue data collection for another 2 weeks before procedure changes are introduced. This is done to distinguish between specific effects of changes in procedures and non-specific effects, such as caregivers increased attention. DISCUSSION: This study will advance the field of wearable physiological sensor use in patient care. TRIAL REGISTRATION: Registered prospectively at ClinicalTrials.gov (NCT05738278).

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8. Marquis S, Lunsky Y, McGrail KM, Baumbusch J. Population level administrative data evidence of visits to the emergency department by youth with intellectual/developmental disabilities in BC, Canada. The American journal of emergency medicine. 2023; 69: 52-7.

INTRODUCTION: The literature indicates that youth with intellectual/developmental disabilities (IDD) have poor health and that access to health services decreases as they transition from pediatric to adult services. At the same time their use of emergency department services increases. The objective of this study was to compare use of emergency department services by youth with IDD to youth without IDD, with particular emphasis on the transition period from pediatric to adult health care services. METHODS: This research used a population level administrative health data base for the province of British Columbia Canada for 2010-2019 to examine the use of emergency departments by youth with IDD (N = 20,591) compared to a population group of youth without IDD (N = 1,293,791). Using the ten years of data, odds ratios for visits to the emergency department were calculated adjusting for sex, income and geographical area within the Province. In addition, difference-in-differences analyses were calculated for age matched subsets of the two cohorts. RESULTS: Over the ten year period, 40.60% of youth with IDD visited an emergency department at least once, compared to 29.10% of youth without IDD. Youth with IDD had an odds ratio of visiting an emergency department 1.697 (1.649, 1.747) times that of youth without IDD. However, when odds were adjusted for a diagnosis of either psychotic illness or anxiety/depression, the odds for youth with IDD visiting emergency compared to youth without IDD were reduced to 1.063 (1.031, 1.096). Use of emergency services increased as youth aged. Type of IDD also affected use of emergency services. Youth with Fetal Alcohol Syndrome had the greatest odds of using emergency services compared to youth with other types of IDD. DISCUSSION: The findings from this study indicate that youth with IDD have higher odds of using emergency services than youth without IDD although these increased odds appear to be largely driven by mental illness. In addition, use of emergency services increases as the youth age and transition from pediatric to adult health services. Better treatment of mental health issues within this population may reduce their use of emergency services.

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9. Muller K. Exploring the Clinical Feasibility of Alternative Word-Understanding Measures for Autistic Children With Minimal Spoken Language. American journal of speech-language pathology. 2023: 1-14.

PURPOSE: The primary aim of this study was to explore the clinical feasibility of using alternate word-understanding assessment modalities for autistic children who have minimal verbal skills. Specifically, assessment duration, occurrence of disruptive behavior, and no-response trials were examined across three word-understanding assessment conditions: a low-tech condition, a touchscreen condition, and a condition that used real-object stimuli. A secondary aim was to examine the relationship between disruptive behavior and assessment outcomes. METHOD: Twenty-seven autistic children between the ages of 3 and 12 years who had minimal verbal skills completed 12 test items on the three assessment conditions. Repeated-measures analyses of variance with post hoc Bonferroni procedures were used to describe and compare assessment duration, occurrence of disruptive behavior, and no-response trials across conditions. A Spearman rank-order correlation coefficient was used to examine the relationship between disruptive behavior and assessment outcomes. RESULTS: The real-object assessment condition took significantly longer than the low-tech and touchscreen conditions. Participants engaged in disruptive behavior most frequently during the low-tech condition; however, differences among conditions were not significant. There were significantly more no-response trials in the low-tech condition than in the touchscreen condition. There was a significant, weak negative correlation between disruptive behavior and experimental assessment outcomes. CONCLUSION: Results show there is promise in using real objects and touchscreen devices to assess word understanding in autistic children who have minimal verbal skills.

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10. Qu A, Duan B, Wang Y, Cui Z, Zhang N, Wu D. Children with autism show differences in the gut DNA virome compared to non-autistic children: a case control study. BMC pediatrics. 2023; 23(1): 174.

BACKGROUND: Several previous studies have identified a potential role that the gut microbiome can play in autism spectrum disorder (ASD) in children, but little is known about how variations in the virome may be involved in ASD. We aimed to understand the changes in the gut DNA virome of children with ASD. METHODS: A case-control study was presented, in which 13 two-children families were observed while considering the age, mode of birth, history of antibiotic use, and vaccination history to minimize the influence of confounding factors. DNA viral metagenomic sequencing was successfully performed on stool samples from 11 children with ASD and 12 healthy non-ASD children. The basic composition and gene function of the participants’ fecal DNA virome were detected and analyzed. Finally, the abundance and diversity of the DNA virome of children with ASD and their healthy siblings were compared. RESULTS: The gut DNA virome in children aged 3-11 years was found to be dominated by the Siphoviridae family of Caudovirales. The proteins encoded by the DNA genes mainly carry out the functions of genetic information transmission and metabolism. Compared the gut DNA virome of ASD and healthy non-ASD children, their abundance of Caudovirales and Petitvirales both showed a significant negative correlation (r = -0.902, P < 0.01), there was no statistically significant difference in the relative abundance of viruses at the order and family levels, and a difference in the relative abundance at the genus level for Skunavirus (Ζ = -2.157, P = 0.031). Viral α diversity was reduced in children with ASD, but α diversity and β diversity did not differ statistically between groups. CONCLUSIONS: This study indicates that elevated Skunavirus abundance and decreased α diversity in the gut DNA virulence group of children with ASD, but no statistically significant difference in the change in alpha and beta diversity. This provides preliminary cumulative information on virological aspects of the relationship between the microbiome and ASD, and should benefit future multi-omics and large sample studies on the gut microbes in children with ASD.

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11. Stoieva TV, Bratkova LB, Fedin MV, Godlevska TL, Titkova OV, Dzhagiashvili OV, Papinko RM. PECULIARITIES OF EATING BEHAVIOR IN CHILDREN WITH AUTISTIC SPECTRUM DISORDERS. Wiadomosci lekarskie (Warsaw, Poland : 1960). 2023; 76(3): 508-14.

OBJECTIVE: The aim: To determine of the nutrition peculiarities in children with ASD. PATIENTS AND METHODS: Materials and methods: The study involved 37 children with ASD from 2 -12 years and thier mothers, in according to reveal its disorder effect on the clinical course of ASD in children. RESULTS: Results: It was shown role of irrational nutrition of the mother during pregnancy, peculiarities of family food traditions, problems of breastfeeding and com-plementary feeding. Eating behavior of mothers during pregnancy were: monotonous nutrition and an inadequate diet. The family food preferences were: varied and included both traditional and specific food preferences ( vegan, vegeterian, monotony diet). CONCLUSION: Conclusions: The analysis of the eating behavior in the ASD children, taking into account the age peculiarities, was carried out. Intolerance to certain products was noted. Also effectiveness of the elimination diet was shown. Elimination from the diet of the white flour products within 6 months has a positive result which evaluated by digestive and cognitive signs.

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12. Wójcik M, Eikeseth S, Eikeseth FF, Budzinska E, Budzinska A. A Comparison Controlled Study Examining Outcome for Children With Autism Receiving Intensive Behavioral Intervention (IBI). Behavior modification. 2023: 1454455231165934.

This study evaluated the effects of a center-based Intensive Behavioral Intervention (IBI) model for preschool aged children with autism. Outcomes of 25 children receiving IBI was compared to the outcomes of 14 children receiving autism specific, eclectic, special education. Both provisions were described as appropriate treatment options by the professional agency who diagnosed the children, and the decision of where to enroll the child was made by the parents after consultations with the specialists. After 14 months of treatment, children from the IBI group improved significantly on standard scores in intellectual functioning and adaptive behavior and had a significant reduction in autism severity compared to the children in the autism specific, eclectic, special education group. Results suggest that preschool aged children with autism may make large gains in intellectual and adaptive functioning and improvement in autism severity with IBI, and that effects of IBI may be similar to that of EIBI. These findings must be interpreted with caution due to the limitations inherent in the present comparison-controlled design.

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13. Zhou H, Feng XL. Autism Spectrum Disorders: Advances in Proteomics. Protein and peptide letters. 2023.

Autism is a class of developmental disorders with extremely high rates of disability affecting patients throughout their lives. There is no cure to date clinically, and early rehabilitation interventions can improve some of the behavioral problems of autistic patients, but these are limited by age and often have minimal effects in older adults with autism. Early diagnosis is also necessary while developing effective autism therapies. At present, the early diagnosis of autism is dependent on the search for effective markers in an attempt to screen differentially expressed proteins in autistic patients using high-throughput assays, such as synaptic scaffolding proteins, microtubule-associated proteins, apolipoproteins, immunoglobulin G complement factor-related proteins, etc. It would also be a big step forward for mechanistic studies of autism if a valid biomarker for autism could be found.

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