1. Ali ZA, Yasseen AA, McAllister KA, Al-Dujailli A, Al-Karaqully AJ, Jumaah AS. SNP-PCR genotyping links alterations in the GABAA receptor (GABRG3: rs208129) and RELN (rs73670) genes to autism spectrum disorder among peadiatric Iraqi Arabs. Molecular biology reports. 2022.

INTRODUCTION: Autism spectrum disorder (ASD) is an increasing concern among the Iraqi Arab population. The genetic alterations that cause ASD are likely to converge at the synapse. This study investigated polymorphisms in the GABA(A) receptor subunit (GABRG3) and the RELN gene as putative biomarkers of ASD in a pediatric population in Iraq. METHODS: The case control study included 60 patients with a clinical diagnosis of ASD (mild, moderate, or severe) according to DSM-IV criteria and matched healthy controls (n = 60). Blood samples were collected for DNA genotyping of SNPs rs736707 and rs208129 for RELN and GABRG3 using allele specific PCR. Assessment of genotype and allele distributions in patient groups used odd ratios (OR) with 95% confidence intervals and the Chi-square test. All statistical analysis was performed used SPSS software. RESULT: The patient cohort was highly consanguineous, with increased ratio (p > 0.05) of males to females (3:1) in both ASD (mean age, 6.66 ± 3.05) and controls (mean age, 5.76 ± 2.3). Both GABRG3 rs208129 genotypes TT (OR 4.33, p = 0.0015) and TA (OR 0.259, P = 0.008), and the T and A alleles were significantly associated with ASD. The RELN rs736707 TC genotype (OR 2.626, P = 0.034) was the only significant association with ASD. CONCLUSION: GABRG3 SNP rs208129 is a leading biomarker to predict genetic vulnerability to ASD in Iraqi Arabs. Expanded SNP panels and increased sample sizes are required for future GABRG3 studies, and to reach a consensus on RELN utility. Future ASD screening programs in Iraq should include genetic metrics in addition to clinical phenotype assessments.

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2. Al-Mazidi S, Al-Ayadhi LY. Reply to « Plasma Levels of Alpha and Gamma Synucleins in Children with Autism Spectrum Disorder: Statistical Validity ». Medical principles and practice : international journal of the Kuwait University, Health Science Centre. 2022: 1.

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3. Araujo M, Mophosho M, Moonsamy S. Communication strategies used by adolescents with autism spectrum disorder and health professionals during treatment. African journal of disability. 2022; 11: 811.

BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder, which affects social communicative capabilities. The research study has shown that ASD studies are focused on young children, excluding adolescents and adults: and it is understudied in the context of South Africa. OBJECTIVE: This study examined the interactional communication strategies of adolescents with ASD and health professionals during different treatment consultations to identify the interactional styles and communication strategies utilised by adolescents with ASD and their respective healthcare professionals in a variety of scenarios in order to generate management strategies for future healthcare professional communication training. METHOD: A multi-case study design with a qualitative research approach has been used. Four adolescents with a moderate form of ASD and four health practitioners were interviewed. Participants were chosen by purpose and snowball sampling. Semi-structured, open-ended interviews were used for health professionals to collect information on the various interaction types and communication methods used, as well as their interpretations of these methods. Conversely, adapted face-to-face interviews were used to collect similar knowledge from adolescents themselves. The findings were qualitatively analysed on a case-by-case and cross-case basis by thematic analysis techniques. RESULTS: The findings indicated that ASD adolescents have interaction types that influence intervention to various degrees. In comparison to motor therapies such as occupational therapy and physiotherapy, interaction types have a greater impact on psychiatry and psychology, which depend mainly on verbal communication. Intuitively, to promote contact with these teens, all health practitioners changed their own interaction styles. They used techniques of clarification and repair. The therapists shared the intention to learn a range of successful ways to strengthen future experiences with ASD between themselves and adolescents. CONCLUSION: The findings indicate that practitioners can benefit from altering their interaction styles, and that approaches for promoting successful interactions and in establishing rapport could be shared with other professionals in the future.

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4. Bi XB, He HZ, Lin HY, Fan XZ. Influence of Social Support Network and Perceived Social Support on the Subjective Wellbeing of Mothers of Children With Autism Spectrum Disorder. Frontiers in psychology. 2022; 13: 835110.

This study explored the relations between the social support network of mothers of children with autism spectrum disorder (ASD), perceived social support, and their subjective wellbeing. The participants were mothers of children with ASD in Shanghai. Their social support network structure was explored via the nomination method. Perceived social support was measured using the Revised Social Provisions Scale for Autism (R-SPS-A), and the mothers’ subjective wellbeing was assessed using the Index of Wellbeing, Index of General Affect. A significant correlation was observed between the subjective wellbeing of mothers of children with ASD and perceived social support. Meanwhile, perceived social support was significantly correlated with the effectiveness of overall social support. Finally, perceived social support was also significantly correlated with the network size of social support. Moreover, the effectiveness of social support was significantly associated with the network size of social support and was highly significantly associated with the degree of intimacy of social support. Furthermore, the network size of instrumental support has a significant influence on all perceived social support subdimensions. Overall, social support effectiveness plays an important role in the social support network mechanism on perceived social support and subjective wellbeing in China.

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5. Buzhardt J, Wallisch A, Irvin D, Boyd B, Salley B, Jia F. Exploring Growth in Expressive Communication of Infants and Toddlers With Autism Spectrum Disorder. Journal of early intervention. 2022; 44(1): 3-22.

One of the earliest indicators of autism spectrum disorder (ASD) is delay in language and social communication. Despite consensus on the benefits of earlier diagnosis and intervention, our understanding of the language growth of children with ASD during the first years of life remains limited. Therefore, this study compared communication growth patterns of infants and toddlers with ASD to growth benchmarks of a standardized language assessment. We conducted a retrospective analysis of growth on the Early Communication Indicator (ECI) of 23 infants and toddlers who received an ASD diagnosis in the future. At 42 months of age, children with ASD had significantly lower rates of gestures, single words, and multiple words, but significantly higher rates of nonword vocalizations. Children with ASD had significantly slower growth of single and multiple words, but their rate of vocalization growth was significantly greater than benchmark. Although more research is needed with larger samples, because the ECI was designed for practitioners to monitor children’s response to intervention over time, these findings show promise for the ECI’s use as a progress monitoring measure for young children with ASD. Limitations and the need for future research are discussed.

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6. Ford TC, Hugrass LE, Jack BN. The Relationship Between Affective Visual Mismatch Negativity and Interpersonal Difficulties Across Autism and Schizotypal Traits. Frontiers in human neuroscience. 2022; 16: 846961.

Sensory deficits are a feature of autism and schizophrenia, as well as the upper end of their non-clinical spectra. The mismatch negativity (MMN), an index of pre-attentive auditory processing, is particularly sensitive in detecting such deficits; however, little is known about the relationship between the visual MMN (vMMN) to facial emotions and autism and schizophrenia spectrum symptom domains. We probed the vMMN to happy, sad, and neutral faces in 61 healthy adults (18-40 years, 32 female), and evaluated their degree of autism and schizophrenia spectrum traits using the Autism Spectrum Quotient (AQ) and Schizotypal Personality Questionnaire (SPQ). The vMMN to happy faces was significantly larger than the vMMNs to sad and neutral faces. The vMMN to happy faces was associated with interpersonal difficulties as indexed by AQ Communication and Attention to Detail subscales, and SPQ associated with more interpersonal difficulties. These data suggest that pre-attentive processing of positive affect might be more specific to the interpersonal features associated with autism and schizophrenia. These findings add valuable insights into the growing body of literature investigating symptom-specific neurobiological markers of autism and schizophrenia spectrum conditions.

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7. Gozes I, Shazman S. STOP Codon Mutations at Sites of Natural Caspase Cleavage Are Implicated in Autism and Alzheimer’s Disease: The Case of ADNP. Frontiers in endocrinology. 2022; 13: 867442.

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8. Iwasa M, Shimizu Y, Sasayama D, Imai M, Ohzono H, Ueda M, Hara I, Honda H. Twenty-year longitudinal birth cohort study of individuals diagnosed with autism spectrum disorder before seven years of age. Journal of child psychology and psychiatry, and allied disciplines. 2022.

BACKGROUND: Previous longitudinal studies have demonstrated that psychosocial outcomes for autistic adults are very limited. However, most studies are clinic-based and liable to selection bias and major methodological problems. METHODS: We conducted a long-term follow-up study with 278 autistic individuals from our previous birth cohort study comprising 31,426 individuals. All participants were born in northern Yokohama between 1988 and 1996, diagnosed with autism spectrum disorder (ASD) by age seven, and followed up over 20 years. A total of 170 consented to participate in the study. Outcome measures included overall social functioning based on work, independent living, and friendships. Moreover, the time-use data concerning social participation and activities of daily living were compared with the general population. RESULTS: Psychosocial outcomes in adulthood (average age 25) were very good in 13.7%, good in 25.0%, fair in 31.0%, poor in 25.6%, and very poor in 4.8% of the participants. The majority participated in major life areas of and work and education (96.4%), sports (82.1%), and recreational activities and/or hobbies (98.8%). The proportion of participants who engaged in housework and self-care was comparable to that of the general population. Participants with IQ < 50 at age five had significantly worse outcomes than those with higher IQ; however, for those with IQ ≥ 50, outcomes were not significantly associated with IQ levels. CONCLUSIONS: Although complete independence was difficult to accomplish, many autistic adults engaged in organized community activities and housework and self-care. Time-use survey could offer a variety of data in investigating psychosocial outcomes of ASD cross-culturally.

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9. Jia H, Wu X, Wang E. Aberrant dynamic functional connectivity features within default mode network in patients with autism spectrum disorder: evidence from dynamical conditional correlation. Cognitive neurodynamics. 2022; 16(2): 391-9.

Autism spectrum disorder (ASD) is characterized by aberrant functional connectivity (FC) within/between certain large-scale brain networks. Although relatively lower level of FC between default mode network (DMN) regions (i.e., DMN-FC) has been detected in many previous studies, they failed to capture the temporal dynamic features of DMN-FC and were limited by small sample size. Here, the dynamical conditional correlation, which could assess precise FC at each time point and has been proved to be a technique with high test-retest reliability, was applied to investigate the DMN-FC pattern of patients with ASD from the Autism Brain Imaging Data Exchange, which included functional and structural brain imaging data of more than 1000 participants. The data analysis here showed that compared to typical developing (TD) participants, patients with ASD exhibited significantly lower mean DMN-FC level across recording time, but significantly higher variance of DMN-FC level across recording time. Moreover, these alterations were significantly associated with symptom severity of patients, especially their impaired communication skills and repetitive behaviors. These results support the view that aberrant temporal dynamic of FC within DMN is an important neuropathological feature of ASD and is a potential biomarker for ASD diagnosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11571-021-09723-9.

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10. Li F, Wu D, Ren F, Shen L, Xue M, Yu J, Zhang L, Tang Y, Liu X, Tao M, Zhou L, Jiang L, Xu M, Li F. Effectiveness of Online-Delivered Project ImPACT for Children With ASD and Their Parents: A Pilot Study During the COVID-19 Pandemic. Frontiers in psychiatry. 2022; 13: 806149.

OBJECTIVE: During the COVID-19 pandemic, face-to-face intervention services for families of children with autism spectrum disorder (ASD) were limited. This study aimed to evaluate the effectiveness of an 8-week, online-delivered Project ImPACT program for children with ASD and their parents in China during the COVID-19 pandemic. METHODS: A pilot non-randomized study with a waitlist control group was conducted in 68 children with ASD and their parents in the Department of Developmental and Behavioral Pediatrics between April 15, 2020 and March 19, 2021. Participants were allocated to either the intervention (IG) or the waitlist group (WLG) according to their order of recruitment. Parents in the IG immediately received 8 weeks of the online-delivered Project ImPACT program, and the WLG received the same program with a delay when the IG had completed all sessions. Participants in both groups received treatment as usual during the research period. RESULTS: The online-delivered Project ImPACT program significantly improved the parent-reported social communication skills of children with ASD. Furthermore, parent’s involvement in the training program produced a collateral reduction in parenting stress and an increase in perceived competence in the parental role. Parents rated the program acceptable in terms of curriculum schedule, session content, homework assignments, and therapist feedback. CONCLUSIONS: The 8-week, online-delivered Project ImPACT program is a feasible and effective social skill training program for families of children with ASD in China during the COVID-19 pandemic. Due to the methodological limitations, randomized controlled studies with larger sample sizes are suggested to provide more solid evidence.

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11. Matteucci M, Lerman DC, Tsami L, Boyle S. Remote Training of Dental Students and Professionals to Promote Cooperative Behavior in Patients with Intellectual and Developmental Disabilities. Journal of developmental and physical disabilities. 2022: 1-21.

Many individuals diagnosed with intellectual and developmental disabilities (IDD) are uncooperative during routine dental exams, leading to poor oral health in this population. Few studies have evaluated methodologies for preparing dental students and professionals to work effectively with patients diagnosed with IDD. In this study, experimenters used remote behavioral skills training (BST) to train dental students and professionals how to implement a practical intervention that included tell-show-do, contingent praise, and noncontingent reinforcement. Results suggested that group training conducted via videoconferencing was effective for teaching six of seven participants to implement the intervention in the absence of post-training feedback. This approach appears useful for quickly and efficiently training current and future dental professionals to implement behavior techniques to promote patient compliance.

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12. McDaniel SL, Hall LJ, Kraemer BK. Exploring Extracurricular Clubs for Building Social Competence of Students With Autism. Frontiers in psychiatry. 2022; 13: 840294.

Individuals with autism experience challenges in social communication that directly impacts in-school and post-school performance. A growing number of these students are taught in general education settings in public high schools, where creating opportunities for practice of social communication skills is frequently a challenge. This exploratory, mixed methods pilot investigation explores existing and potential opportunities for high school students with autism to practice 21st century skills, including communication, in extracurricular club environments. Findings indicate that extracurricular club settings are rich environments in which all participating students, including those with autism, have opportunities to practice critical 21st century skills in a context related to their interests.

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13. Oredipe T, Kofner B, Riccio A, Cage E, Vincent J, Kapp SK, Dwyer P, Gillespie-Lynch K. Does learning you are autistic at a younger age lead to better adult outcomes? A participatory exploration of the perspectives of autistic university students. Autism : the international journal of research and practice. 2022: 13623613221086700.

People learn they are autistic at different ages. We wanted to know if telling kids they are autistic earlier helps them feel better about their lives when they grow up. We are a team of autistic and non-autistic students and professors. Seventy-eight autistic university students did our online survey. They shared how they found out they were autistic and how they felt about being autistic. They also shared how they feel about their lives now. Around the same number of students learned they were autistic from doctors and parents. Students who learned they were autistic when they were younger felt happier about their lives than people who learned they were autistic when they were older. Students who learned they were autistic when they were older felt happier about being autistic when they first found out than people who did not have to wait as long. Our study shows that it is probably best to tell people they are autistic as soon as possible. The students who did our study did not think it was a good idea to wait until children are adults to tell them they are autistic. They said that parents should tell their children they are autistic in ways that help them understand and feel good about who they are.

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14. Rech JP, Irwin JM, Rosen AB, Baldwin J, Schenkelberg M. Comparison of Physical Activity Between Children With and Without Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Adapted physical activity quarterly : APAQ. 2022: 1-26.

Lower levels of physical activity (PA) are often observed among children with autism spectrum disorder (ASD) compared to children without ASD; however, some studies have demonstrated few to no PA differences between the two groups. The purpose of this systematic review with meta-analysis was to compare the differences in PA between children (2-18 years) with and without ASD. An exhaustive search of five online databases was completed, and 31 studies met the inclusion criteria. A pooled random-effects Hedges’s g model was used to determine differences in PA between children with and without ASD. Children with ASD were found to be significantly less physically active than children without ASD (Δ = -0.62, p < .001). Subgroup analyses revealed significant moderate to large differences in PA by intensity level, age, setting, and measurement methods. Future studies are needed to further explore the underlying mechanisms associated with lower levels of PA among children with ASD.

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15. Sissons JH, Blakemore E, Shafi H, Skotny N, Lloyd DM. Calm with horses? A systematic review of animal-assisted interventions for improving social functioning in children with autism. Autism : the international journal of research and practice. 2022: 13623613221085338.

Children with autism typically experience difficulties interacting socially with others when compared to their non-autistic peers. Establishing how effective interventions are for improving social functioning is important to help inform what should be offered to children with autism. This study reviewed how effective interventions that involved interaction with a live animal, known as animal-assisted interventions, are in improving social functioning in children with autism. A systematic search of the evidence on this topic found nine studies, which were explored for the effectiveness of animal-assisted interventions and the quality of methods used. Overall, these studies showed improvements in social functioning following equine-assisted or therapeutic horse-riding interventions, with initial evidence showing improvements are sustained in the short and medium term. However, several issues were identified, which limit the strength of any conclusions that can be drawn from this evidence. For example, in many studies people assessing the children were aware that they received the intervention or were in a control group. There was also not enough evidence available to draw conclusions on the effectiveness of other animal-assisted interventions. Future research should address the limitations that were common in the designs of these studies and investigate the potential benefit of other animal populations, such as dogs and cats.

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16. Tagavi DM, Dick CC, Attar SM, Ibanez LV, Stone WL. The implementation of the screening tool for autism in toddlers in Part C early intervention programs: An 18-month follow-up. Autism : the international journal of research and practice. 2022: 13623613221086329.

The early detection of autism spectrum disorder can lead to access to autism spectrum disorder-specific services that have been shown to have a large impact on a child’s overall development. Although a stable diagnosis of autism spectrum disorder can be made by age 2 years, most children are not diagnosed until much later. To address this issue, this study examined the effectiveness of training Part C Early Intervention providers to use an interactive autism spectrum disorder screening tool, the Screening Tool for Autism in Toddlers. Sixty-nine providers attended a 1-day training workshop on the use of the Screening Tool for Autism in Toddlers. After the workshop, providers reported increased knowledge about recognizing the early signs of autism spectrum disorder, and about 45% of the providers reported using the Screening Tool for Autism in Toddlers with families in their caseloads 18 months after the training. These results suggest that the Screening Tool for Autism in Toddlers is feasible for use within Early Intervention settings. In addition, they suggest that specific providers might serve as a screening « point-person, » rather than expecting the Screening Tool for Autism in Toddlers to be used by all providers. Future research should aim to identify specific characteristics of agencies or providers that might be best suited for using the Screening Tool for Autism in Toddlers.

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17. Tsang B, Leung CNW, Chan RWS. A feasibility study on social competence intervention for Chinese adolescents and adults with comorbid autism spectrum disorder and intellectual disability. Journal of applied research in intellectual disabilities : JARID. 2022.

BACKGROUND: Social competence training for individuals with comorbid autistic spectrum disorder (ASD) and intellectual disability was scarce and had methodological limitations in sample sizes and outcome measures. AIMS: The current study addressed the limitations and reported a social competence intervention for adolescents and adults with ASD and intellectual disability in Hong Kong, the CBT-CSCA (Mild Intellectual Disability). MATERIALS & METHODS: Thirty-three participants (aged 14-44 years, with an FSIQ 55-70) completed the 15-session intervention in a community centre. A pre-post intervention design was employed. Outcome measures included proxy-ratings on participants’ social competence, autistic symptoms and behavioural problem, and participants’ weekly self-evaluation on knowledge acquisition and confidence in applying skills. RESULTS: Significant improvements were shown in proxy-reported negative social behaviours, autistic symptoms and overall behavioural problems. Participants also reported satisfactory knowledge gain and confidence in applying content learnt after each session. DISCUSSION: The CBT-CSCA (Mild Intellectual Disability) is based on an established model and validated studies on ASD population. It demonstrated its applicability and emerging effectiveness in individuals with ASD and mild intellectual disability. CONCLUSION: The study supports that social competence training remains a centrality intervention approach for individuals with ASD and intellectual disability.

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18. Wang X, Auyeung B, Pan N, Lin LZ, Chen Q, Chen JJ, Liu SY, Dai MX, Gong JH, Li XH, Jing J. Empathy, Theory of Mind, and Prosocial Behaviors in Autistic Children. Frontiers in psychiatry. 2022; 13: 844578.

BACKGROUND: Previous research has suggested that children with autism spectrum disorder (ASD) display fewer prosocial behaviors, and the role of empathy or Theory of Mind (ToM) in prosocial behaviors of autistic children remains unclear. METHODS: Data were obtained from an ongoing longitudinal study in Guangzhou, China. A total of 96 autistic children and 167 typically developing (TD) children were enrolled. Prosocial behaviors were assessed using a subscale of the Strength and Difficulties Questionnaire and Dictator Game (DG) paradigm with stickers as incentives. Empathic traits and ToM ability were measured using the children’s Empathy Quotient and the Chinese version of ToM toolkit. Generalized linear models were used to assess the differences of prosocial behaviors and empathic traits, ToM ability between the two groups and the associations between empathic traits, ToM ability and prosocial behaviors in autistic children. RESULTS: Compared with TD children, autistic children exhibited worse ToM ability and performed less pro-socially in the DG paradigm, while there were no differences regarding empathic traits. In autistic children, empathic traits especially affective empathy, were positively associated with parent-reported prosocial behaviors [β = 0.17, 95% confidence interval (CI): 0.07-0.27; β = 0.47, 95%CI: 0.33-0.60]. ToM ability was associated with DG paradigm (β = 1.03, 95%CI: 0.16-1.89). CONCLUSION: Autistic children showed less pro-sociality and ToM ability than TD children. In autistic children, empathic trait was associated with parent-reported prosocial behaviors while their ToM ability was associated with prosocial behaviors in experimental condition. Our findings indicated that better ToM ability and empathic trait might promote prosocial behaviors in autistic children.

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19. Williams ZJ, Cascio CJ, Woynaroski TG. Measuring subjective quality of life in autistic adults with the PROMIS global-10: Psychometric study and development of an autism-specific scoring method. Autism : the international journal of research and practice. 2022: 13623613221085364.

Quality of Life an outcome that both researchers and autistic advocates agree is extremely important to consider when implementing services, interventions, and supports for autistic people. However, there has been little research on the topic of how quality of life can best be measured in autistic people or whether existing quality of life questionnaires are appropriate for use in the autistic population. This study aimed to validate an established quality of life measure, the Patient-Reported Outcomes Measurement Information System Global-10, in a large sample of autistic adults recruited online. We created a new way to score the Patient-Reported Outcomes Measurement Information System Global-10 scale and generate a « General quality of life » score specific to autistic adults. This new score performed very well in this sample, showing very little measurement error and relating in expected ways to similar constructs, such as physical health and emotional distress. Exploratory analyses found that lower quality of life was associated with female sex and self-identification as a sexual or gender minority (i.e. LGBTQ + identity). These findings suggest that the new Patient-Reported Outcomes Measurement Information System Global-10 quality of life score is a reliable and valid measure of quality of life in autistic adults, although additional studies are necessary to further explore its measurement properties in other subsets of the autistic population, such as individuals with intellectual disabilities. This measure is freely available for use as an outcome in both research and clinical practice, and an online score calculator is available to support the use of this measure in real-world applications.

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20. Woodbury-Smith MR, Loftin R, Westphal A, Volkmar FR. Vulnerability to Ideologically-Motivated Violence Among Individuals With Autism Spectrum Disorder. Frontiers in psychiatry. 2022; 13: 873121.

People with autism spectrum disorder (ASD) are represented among those who espouse extremist thought and have committed violent acts associated with their beliefs. Media often highlight a perpetrator’s psychiatric diagnosis following acts of mass violence, which in some instances has included ASD. ASD may itself not provide useful information for understanding motivations. Instead, understanding specific traits and neuropsychological and other vulnerabilities may offer an opportunity to make sense of these very complex events.

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21. Xie X, Li L, Wu X, Hou F, Chen Y, Shi L, Liu Q, Zhu K, Jiang Q, Feng Y, Xiao P, Zhang J, Gong J, Song R. Alteration of the fecal microbiota in Chinese children with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2022.

Autism spectrum disorder (ASD) is associated with altered gut microbiota. However, there has been little consensus on the altered bacterial species and studies have had small sample sizes. We aimed to identify the taxonomic composition and evaluate the changes in the fecal microbiota in Chinese children with ASD by using a relatively large sample size. We conducted a case-control study of 101 children with ASD and 103 healthy controls in China. Demographic information and fecal samples were collected, and the V3-V4 hypervariable regions of the bacterial 16S ribosomal RNA (rRNA) gene were sequenced. The alpha and beta diversities between the two groups were significantly different. After correcting for multiple comparisons, at the phylum level the relative abundances of Actinobacteria and Proteobacteria in the case group were significantly higher than those in the control group. The relative abundance of the Escherichia-Shigella genus in the case group was significantly higher than that of the control group, and the relative abundance of Blautia and unclassified_f__Lachnospiraceae in the control group were higher than that of the case group. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis showed that children with ASD may have disturbed functional pathways, such as amino acid metabolism, cofactor and vitamin metabolism, and the AMP-activated protein kinase signaling pathway. This study revealed the characteristics of the intestinal flora of Chinese children with ASD and provided further evidence of gut microbial dysbiosis in ASD. LAY SUMMARY: This study characterized the gut microbiota composition of 101 children with ASD and 103 healthy controls in China. The altered gut microbiota may contribute significantly to the risk of ASD, including significant increases in the relative abundances of Actinobacteria, Proteobacteria and Escherichia-Shigella and significant decrease of Blautia and unclassified_f__Lachnospiraceae. This study provided further evidence of gut microbial dysbiosis in ASD.

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22. Zhang A, Liu L, Chang S, Shi L, Li P, Shi J, Lu L, Bao Y, Liu J. Connectivity-Based Brain Network Supports Restricted and Repetitive Behaviors in Autism Spectrum Disorder Across Development. Frontiers in psychiatry. 2022; 13: 874090.

INTRODUCTION: Autism spectrum disorder (ASD) is a lifelong condition. Autistic symptoms can persist into adulthood. Studies have reported that autistic symptoms generally improved in adulthood, especially restricted and repetitive behaviors and interests (RRBIs). We explored brain networks that are related to differences in RRBIs in individuals with ASDs among different ages. METHODS: We enrolled 147 ASD patients from the Autism Brain Imaging Data Exchange II (ABIDEII) database. The participants were divided into four age groups: children (6-9 years old), younger adolescents (10-14 years old), older adolescents (15-19 years old), and adults (≥20 years old). RRBIs were evaluated using the Repetitive Behaviors Scale-Revised 6. We first explored differences in RRBIs between age groups using the Kruskal-Wallis test. Associations between improvements in RRBIs and age were analyzed using a general linear model. We then analyzed RRBIs associated functional connectivity (FC) links using the network-based statistic method by adjusting covariates. The association of the identified FC with age group, and mediation function of the FC on the association of age-group and RRBI were further analyzed. RESULTS: Most subtypes of RRBIs improved with age, especially stereotyped behaviors, ritualistic behaviors, and restricted behaviors (p = 0.012, 0.014, and 0.012, respectively). Results showed that 12 FC links were closely related to overall RRBIs, 17 FC links were related to stereotyped behaviors. Among the identified 29 FC links, 15 were negatively related to age-groups. The mostly reported core brain regions included superior occipital gyrus, insula, rolandic operculum, angular, caudate, and cingulum. The decrease in FC between the left superior occipital lobe and right angular (effect = -0.125 and -0.693, respectively) and between the left insula and left caudate (effect = -0.116 and -0.664, respectively) might contribute to improvements in multiple RRBIs with age. CONCLUSION: We identified improvements in RRBIs with age in ASD patients, especially stereotyped behaviors, ritualistic behaviors, and restricted behaviors. The decrease in FC between left superior occipital lobe and right angular and between left insula and left caudate might contribute to these improvements. Our findings improve our understanding of the pathogenesis of RRBIs and suggest potential intervention targets to improve prognosis in adulthood.

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23. Zhao X, Zhu S, Cao Y, Cheng P, Lin Y, Sun Z, Jiang W, Du Y. Abnormalities of Gray Matter Volume and Its Correlation with Clinical Symptoms in Adolescents with High-Functioning Autism Spectrum Disorder. Neuropsychiatric disease and treatment. 2022; 18: 717-30.

BACKGROUND: Previous studies have indicated abnormal gray matter volume (GMV) in individuals with autism spectrum disorder (ASD); however, there is little consistency across the findings within these studies, partly due to small sample size and great heterogeneity among participants between studies. Additionally, few studies have explored the correlation between clinical symptoms and GMV abnormalities in individuals with ASD. Here, the current study examined GMV alterations in whole brain and their correlations with clinical symptoms in a relatively large and homogeneous sample of participants with ASD matched typically developing (TD) controls. METHODS: Forty-eight adolescents with high-functioning ASD and 29 group-matched TD controls underwent structural magnetic resonance images. Voxel-based morphometry was applied to investigate regional GMV alterations. The participants with ASD were examined for the severity of clinical symptoms with Autism Behavior Checklist (ABC). The relationship between GMV abnormalities and clinical symptoms was explored in ASD group using voxel-wise correlation analysis within brain regions that showed significant GMV alterations in individuals with ASD compared with TD controls. RESULTS: We found increased GMV in multiple brain regions, including the inferior frontal gyrus, medial frontal gyrus, superior frontal gyrus, superior temporal gyrus, occipital pole, anterior cingulate, cerebellum anterior lobe, cerebellum posterior lobe, and midbrain, as well as decreased GMV in cerebellum posterior lobe in individuals with ASD. The correlation analysis showed the GMV in the left fusiform was negatively associated with the scores of sensory factor, and the GMV in the right cerebellum anterior lobe was positively associated with the scores of social self-help factor. CONCLUSION: Our results indicated that widespread GMV abnormalities of brain regions occurred in individuals with ASD, suggesting a potential neural basis for the pathogenesis and symptomatology of ASD.

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24. Zhou B, Zheng X, Chen Y, Yan X, Peng J, Liu Y, Zhang Y, Tang L, Wen M. The Changes of Amygdala Transcriptome in Autism Rat Model After Arginine Vasopressin Treatment. Frontiers in neuroscience. 2022; 16: 838942.

BACKGROUND: Some studies have shown that arginine vasopressin (AVP) can significantly improve the social interaction disorder of autism, but the mechanism remains unclear. METHODS: Female Wistar rats were intraperitoneally injected with VPA or normal saline at embryonic day 12.5 to establish an autism model or normal control in their offspring. Male offspring prenatally exposed to VPA were randomly assigned to two groups: the VPA-induced autism model group and the AVP group. The rats in the AVP group were treated with intranasal AVP at postnatal day (PND) 21 and for 3 weeks. The VPA-induced autism model group was given the same dose of normal saline in the same way. Behavioral responses were evaluated in the open field and three-chambered social test apparatus; the expression levels of AVP in serum were detected by enzyme-linked immunosorbent assay kit, and the gene expression levels on the amygdala were measured by RNA-seq at PND42. RESULTS: Intranasal administration of AVP can significantly improve the social interaction disorder and elevate the levels of AVP in serum. Transcriptome sequencing results showed that 518 differently expressed genes (DEGs) were identified in the VPA-induced autism model group compared with the control in this study. Gene Ontology biological process enrichment analysis of DEGs showed that the VPA-induced autism model group had significant nervous system developmental impairments compared with the normal group, particularly in gliogenesis, glial cell differentiation, and oligodendrocyte differentiation. Gene Set Enrichment Analysis (GSEA) enrichment analysis also showed that biological process of oligodendrocyte differentiation, axoneme assembly, and axon ensheathment were inhibited in the VPA-induced autism model group. Pathway enrichment analysis of DEGs between the control and VPA-induced autism model group showed that the PI3K/AKT and Wnt pathways were significantly dysregulated in the VPA-induced autism model group. Few DEGs were found when compared with the transcriptome between the VPA-induced autism model group and the AVP treatment group. GSEA enrichment analysis showed deficits in oligodendrocyte development and function were significantly improved after AVP treatment; the pathways were mainly enriched in the NOTCH, mitogen-activated protein kinase, and focal adhesion signaling pathways, but not in the PI3K/AKT and Wnt pathways. The expression patterns analysis also showed the same results. CONCLUSION: AVP can significantly improve the social interaction disorder of VPA-induced autism model, and AVP may target behavioral symptoms in autism by modulating the vasopressin pathways, rather than primary disease mechanisms.

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