1. Aithal S, Moula Z, Karkou V, Karaminis T, Powell J, Makris S. A Systematic Review of the Contribution of Dance Movement Psychotherapy Towards the Well-Being of Children With Autism Spectrum Disorders. Frontiers in psychology. 2021; 12: 719673.

Background: The present review provides an original examination of published literature on the use of Dance Movement Psychotherapy (DMP) as an intervention for children with an Autism Spectrum Disorder (ASD). Method: The review was systematically conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. A protocol consisting of four phases: identification; screening and selection; data extraction and synthesis; quality assurance was developed and registered with the PROSPERO. A search strategy was developed using population and intervention as the key concepts and ten databases were searched between 6.1.2018 to 4.4.2018 and 10.07.2021 to 20.07.2021. The intervention characteristics were extracted based on the TIDieR template for intervention description and replication checklist. Quality assessment and level of evidence of all the included studies were evaluated using the Mixed Methods Appraisal Tool (MMAT) and the Centre for Evidence-Based Medicine (CEBM) for treatment criteria. Results: Nine research studies with a total of 133 participants were identified through a systematic search process. There was only one mixed-methods study with the component of randomisation found during the literature search. Collected information was synthesised in relation to (a) ways in which dance movement psychotherapists work with children; (b) data collection methods and findings. Results from the reviewed literature suggest that DMP can potentially promote various aspects of well-being in children with ASD. Eight out of nine studies mentioned the effects of DMP on improving different social and communication skills. However, results from quality assessments and synthesised outcomes indicate that research in DMP is still in its infancy. Conclusions: We conclude that further large-scale, high-quality studies are required to generate further evidence that explains the processes involved in DMP, the effectiveness of DMP, the relationship between therapeutic factors of DMP, and research findings for children on the autism spectrum. Systematic Review Protocol Registration: PROSPERO, identifier: CRD42018087912.

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2. Baizer JS. Functional and Neuropathological Evidence for a Role of the Brainstem in Autism. Frontiers in integrative neuroscience. 2021; 15: 748977.

The brainstem includes many nuclei and fiber tracts that mediate a wide range of functions. Data from two parallel approaches to the study of autistic spectrum disorder (ASD) implicate many brainstem structures. The first approach is to identify the functions affected in ASD and then trace the neural systems mediating those functions. While not included as core symptoms, three areas of function are frequently impaired in ASD: (1) Motor control both of the limbs and body and the control of eye movements; (2) Sensory information processing in vestibular and auditory systems; (3) Control of affect. There are critical brainstem nuclei mediating each of those functions. There are many nuclei critical for eye movement control including the superior colliculus. Vestibular information is first processed in the four nuclei of the vestibular nuclear complex. Auditory information is relayed to the dorsal and ventral cochlear nuclei and subsequently processed in multiple other brainstem nuclei. Critical structures in affect regulation are the brainstem sources of serotonin and norepinephrine, the raphe nuclei and the locus ceruleus. The second approach is the analysis of abnormalities from direct study of ASD brains. The structure most commonly identified as abnormal in neuropathological studies is the cerebellum. It is classically a major component of the motor system, critical for coordination. It has also been implicated in cognitive and language functions, among the core symptoms of ASD. This structure works very closely with the cerebral cortex; the cortex and the cerebellum show parallel enlargement over evolution. The cerebellum receives input from cortex via relays in the pontine nuclei. In addition, climbing fiber input to cerebellum comes from the inferior olive of the medulla. Mossy fiber input comes from the arcuate nucleus of the medulla as well as the pontine nuclei. The cerebellum projects to several brainstem nuclei including the vestibular nuclear complex and the red nucleus. There are thus multiple brainstem nuclei distributed at all levels of the brainstem, medulla, pons, and midbrain, that participate in functions affected in ASD. There is direct evidence that the cerebellum may be abnormal in ASD. The evidence strongly indicates that analysis of these structures could add to our understanding of the neural basis of ASD.

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3. Cheriyan C, Shevchuk-Hill S, Riccio A, Vincent J, Kapp SK, Cage E, Dwyer P, Kofner B, Attwood H, Gillespie-Lynch K. Exploring the Career Motivations, Strengths, and Challenges of Autistic and Non-autistic University Students: Insights From a Participatory Study. Frontiers in psychology. 2021; 12: 719827.

Supports for the growing number of autistic university students often focus on helping them succeed in university. However, even educated autistic people experience discrimination and other challenges which can make it very difficult for them to obtain meaningful jobs. Little remains known about how universities can better support their autistic students and alumni in overcoming barriers to meaningful employment. In this participatory study, a team of autistic and non-autistic researchers asked autistic (n = 92) and non-autistic (n = 774) university students about their career aspirations, strengths they believe will help them succeed in their « dream jobs, » and obstacles they expect to encounter. Autistic participants’ top goal in attending college was to improve their career prospects. However, relatively few autistic students reported learning career-specific skills at university. Autistic students were more likely to seek an academic job and less likely to seek a career in healthcare than non-autistic students. Autistic students highlighted writing skills and detail orientation as strengths that could help them succeed in their dream jobs more often than non-autistic students. However, they were also more likely to expect discrimination, social, and psychological difficulties to stand in the way of their dream jobs. These findings suggest that universities should prioritize experiential learning opportunities to help autistic (and non-autistic) students develop employment-related skills while providing mental health supports. Universities should demonstrate their commitment to supporting diverse learners by seeking out and hiring autistic professionals and by teaching their own staff and employers how to appreciate and support autistic colleagues.

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4. Francese R, Risi M, Tortora G, Di Salle F. Thea: empowering the therapeutic alliance of children with ASD by multimedia interaction. Multimedia tools and applications. 2021; 80(26-27): 34875-907.

The Therapeutic Alliance (TA) between patient and health provider (therapist or clinician) is one of the most relevant factors for the success of a therapy. In the case of people suffering from Autism Spectrum Disorder (ASD), the alliance is extended to all the people involved in their care (i.e., teachers, therapists, clinicians, relatives). In this paper, we propose a multimedia application named Thea for empowering the TA of children with ASD by improving the communication among the TA members, sharing guidelines, multimedia contents, and strategies to comply with challenging behaviors and progress with particular attention towards end-users who are occasional smart-users. A detailed process for empowering the TA members by enhancing the informed interaction among all of them is proposed and implemented. A vocal assistant also supports patients/caregivers and therapists in documenting their activity with the person with ASD by recording videos in a free-hand modality. After a contextual analysis based on Thematic Analysis Template, Thea has been implemented using a user-centered development approach. We performed three iterations involving the end-users. A user study is performed at the third iteration. Results of the user study revealed a positive attitude towards the application. In particular, the perception of empowerment of participants increased after the tool had been used. We also highlighted the guidelines and tools that may be adopted for empowering different kinds of patients. The first results seem to suggest that the use of Thea may increase the belief of the caregivers of a person with ASD to be able to better take care of her, in a more controlled and informed way.

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5. Ha J, McClain MB, Covington B, Golson ME. Brief Report: A Brief Video Intervention for Increasing Autism Knowledge in a General Population Sample. Journal of autism and developmental disorders. 2021.

As many individuals in the general population will likely interact with autistic persons in various contexts, ensuring adequate autism knowledge and awareness is important. Increased knowledge of autism has been linked to positive outcomes such as a reduction in explicit bias against autism by non-autistic adults and an increase in service quality for autistic individuals provided by indirect professionals. For this study we developed an informational video about autism and employed a randomized control trial to evaluate its effectiveness at increasing autism awareness in a general population sample. Participants were randomly assigned to the intervention (n = 80) or active control group (n = 72). Results from a repeated measures analysis of variance indicated that the video intervention was effective at increasing knowledge about autism. Results from this study can be applied to future educational efforts aimed at increasing awareness about autism among the general population.

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6. Huang M, Liu J, Liu K, Chen J, Wei Z, Feng Z, Wu Y, Fong M, Tian R, Wang B, Budjan C, Zhuang P, Wan G, Kong XJ. Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study. Frontiers in psychiatry. 2021; 12: 682454.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear mechanisms of pathogenesis. Gastrointestinal microbiome alterations were found to correlate with ASD core symptoms, but its specific role in ASD pathogenesis has not been determined. In this study, we used a case-control strategy that simultaneously compared the ASD gastrointestinal microbiome with that from age-sex matched controls and first-degree relative controls, using a statistical framework accounting for confounders such as age. Enterobacteriaceae (including Escherichia/Shigella) and Phyllobacterium were significantly enriched in the ASD group, with their relative abundances all following a pattern of ASD > first degree relative control > healthy control, consistent with our hypothesis of living environment and shared microbial and immunological exposures as key drivers of ASD gastrointestinal microbiome dysbiosis. Using multivariable omnibus testing, we identified clinical factors including ADOS scores, dietary habits, and gastrointestinal symptoms that covary with overall microbiome structure within the ASD cohort. A microbiome-specific multivariate modeling approach (MaAsLin2) demonstrated microbial taxa, such as Lachnoclostridium and Tyzzerella, are significantly associated with ASD core symptoms measured by ADOS. Finally, we identified alterations in predicted biological functions, including tryptophan and tyrosine biosynthesis/metabolism potentially relevant to the pathophysiology of the gut-brain-axis. Overall, our results identified gastrointestinal microbiome signature changes in patients with ASD, highlighted associations between gastrointestinal microbiome and clinical characteristics related to the gut-brain axis and identified contributors to the heterogeneity of gastrointestinal microbiome within the ASD population.

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7. Huang ZX, Chen Y, Guo HR, Chen GF. Systematic Review and Bioinformatic Analysis of microRNA Expression in Autism Spectrum Disorder Identifies Pathways Associated With Cancer, Metabolism, Cell Signaling, and Cell Adhesion. Frontiers in psychiatry. 2021; 12: 630876.

Background: Previous studies have identified differentially expressed microRNAs in autism spectrum disorder (ASD), however, results are discrepant. We aimed to systematically review this topic and perform bioinformatic analysis to identify genes and pathways associated with ASD miRNAs. Methods: Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses, we searched the Web of Science, PubMed, Embase, Scopus, and OVID databases to identify all studies comparing microRNA expressions between ASD persons and non-ASD controls on May 11, 2020. We obtained ASD miRNA targets validated by experimental assays from miRTarBase and performed pathway enrichment analysis using Metascape and DIANA-miRPath v3. 0. Results: Thirty-four studies were included in the systematic review. Among 285 altered miRNAs reported in these studies, 15 were consistently upregulated, 14 were consistently downregulated, and 39 were inconsistently dysregulated. The most frequently altered miRNAs including miR-23a-3p, miR-106b-5p, miR-146a-5p, miR-7-5p, miR-27a-3p, miR-181b-5p, miR-486-3p, and miR-451a. Subgroup analysis of tissues showed that miR-146a-5p, miR-155-5p, miR-1277-3p, miR-21-3p, miR-106b-5p, and miR-451a were consistently upregulated in brain tissues, while miR-4742-3p was consistently downregulated; miR-23b-3p, miR-483-5p, and miR-23a-3p were consistently upregulated in blood samples, while miR-15a-5p, miR-193a-5p, miR-20a-5p, miR-574-3p, miR-92a-3p, miR-3135a, and miR-103a-3p were consistently downregulated; miR-7-5p was consistently upregulated in saliva, miR-23a-3p and miR-32-5p were consistently downregulated. The altered ASD miRNAs identified in at least two independent studies were validated to target many autism risk genes. TNRC6B, PTEN, AGO1, SKI, and SMAD4 were the most frequent targets, and miR-92a-3p had the most target autism risk genes. Pathway enrichment analysis showed that ASD miRNAs are significantly involved in pathways associated with cancer, metabolism (notably Steroid biosynthesis, Fatty acid metabolism, Fatty acid biosynthesis, Lysine degradation, Biotin metabolism), cell cycle, cell signaling (especially Hippo, FoxO, TGF-beta, p53, Thyroid hormone, and Estrogen signaling pathway), adherens junction, extracellular matrix-receptor interaction, and Prion diseases. Conclusions: Altered miRNAs in ASD target autism risk genes and are involved in various ASD-related pathways, some of which are understudied and require further investigation.

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8. Leussis MP, Thanos JM, Powers A, Peterson E, Head JP, McGovern NJ, Malarkey FJ, Drake A. Sex differences in long-term behavioral alterations, especially anxiety, following prenatal fluoxetine exposure in C57BL/6 mice. Pharmacology, biochemistry, and behavior. 2021; 211: 173293.

Evidence demonstrates that psychiatric disorders during pregnancy are detrimental to the offspring. Many disorders are treated with SSRIs and increasing numbers of pregnant women now receive these drugs during gestation. The long-term neurobehavioral consequences of prenatal SSRI exposure require further evaluation. This study examined the effects of prenatal fluoxetine exposure in mice in an extensive battery of behaviors related to neurodevelopment, mood, social, and repetitive behaviors. C57BL/6J dams were administered fluoxetine at a low (0.6 mg/kg/day) or high (6 mg/kg/day) dose or saline from embryonic days 8 to 18. Juvenile mice were tested for changes in ultrasonic vocalizations and neuromotor development. In adulthood, offspring were tested for changes in behaviors related to anxiety, depression, social, and repetitive behaviors. Prenatal exposure to fluoxetine impaired surface righting reflex at P5, and sex-dependently reduced the frequency of ultrasonic vocalizations in juvenile males but not females. In adulthood, both males and females prenatally exposed to high, but not low, doses of fluoxetine exhibited an increase in repetitive behaviors in the marble burying task and a decrease in sucrose preference. Males, but not females, exposed to fluoxetine exhibited increased anxiety-related behaviors in the elevated plus maze. Prenatal fluoxetine exposure did not affect other adult behaviors including social preference, self-grooming, passive avoidance and open field activity. These findings suggest males are more sensitive than females to disruptions in serotonin balance during prenatal development and highlight the need for additional systematic and mechanistic studies to evaluate the impact of fluoxetine exposure during other periods of gestation.

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9. Li J, Rubini P, Tang Y, Illes P. Astrocyte-derived ATP: A New Etiological Factor for Autism Spectrum Disorder. Neuroscience bulletin. 2022; 38(1): 104-6.

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10. Li J, Wang F, Pan J, Wen Z. Identification of Autism Spectrum Disorder With Functional Graph Discriminative Network. Frontiers in neuroscience. 2021; 15: 729937.

Autism spectrum disorder (ASD) is a specific brain disease that causes communication impairments and restricted interests. Functional connectivity analysis methodology is widely used in neuroscience research and shows much potential in discriminating ASD patients from healthy controls. However, due to heterogeneity of ASD patients, the performance of conventional functional connectivity classification methods is relatively poor. Graph neural network is an effective graph representation method to model structured data like functional connectivity. In this paper, we proposed a functional graph discriminative network (FGDN) for ASD classification. On the basis of pre-built graph templates, the proposed FGDN is able to effectively distinguish ASD patient from health controls. Moreover, we studied the size of training set for effective training, inter-site predictions, and discriminative brain regions. Discriminative brain regions were determined by the proposed model to investigate its applicability and biomarkers for ASD identification. For functional connectivity classification and analysis, FGDN is not only an effective tool for ASD identification but also a potential technique in neuroscience research.

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11. Sabaie H, Dehghani H, Shiva S, Asadi MR, Rezaei O, Taheri M, Rezazadeh M. Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder. Frontiers in molecular biosciences. 2021; 8: 754296.

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the « JAK-STAT signaling pathway » and « Adipocytokine signaling pathway. » An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.

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12. Soranzo A, Bertamini M, Cassidy S. How Do Children Reason About Mirrors? A Comparison Between Adults, Typically Developed Children, and Children With Autism Spectrum Disorder. Frontiers in psychology. 2021; 12: 722213.

The information about what one can see and what other people can see from different viewpoints is important. There are circumstances in which adults and children make systematic errors when predicting what is visible from their own or others’ viewpoints. This happens for example when reasoning about mirrors. We explored differences among three developmental groups: young adults (N=60) typically developing children (N=30); and children with autism spectrum disorder (ASD, N=30). We used an illustration of a top-down view of a room with a mirror on a wall (Room Observer and Mirror Perspective test: ROMP). Participants selected (circled on paper) which objects behind the observer in the room were visible, reflected from the mirror and from a given position (viewpoint). For half of each group, the observer in the room was described as a teddy bear; for the other half, it was described as a child. Overall, there were many errors in all groups, which we separate in errors of ignoring the viewpoint (same response to all three locations) and inversion errors (choosing objects on the left instead of the right or vice versa). In addition to the overall task difficulty, the ASD group made relatively more mistakes of ignoring the viewpoint compared to the other groups and underestimated how many objects were visible in the teddy bear condition that is when the viewpoint was an inanimate object. We suggest that this is related to a delay in theory of mind (ToM) development.

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13. Su T, Yan Y, Li Q, Ye J, Pei L. Endocannabinoid System Unlocks the Puzzle of Autism Treatment via Microglia. Frontiers in psychiatry. 2021; 12: 734837.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder and characterized by early childhood-onset impairments in social interaction and communication, restricted and repetitive patterns of behavior or interests. So far there is no effective treatment for ASD, and the pathogenesis of ASD remains unclear. Genetic and epigenetic factors have been considered to be the main cause of ASD. It is known that endocannabinoid and its receptors are widely distributed in the central nervous system, and provide a positive and irreversible change toward a more physiological neurodevelopment. Recently, the endocannabinoid system (ECS) has been found to participate in the regulation of social reward behavior, which has attracted considerable attention from neuroscientists and neurologists. Both animal models and clinical studies have shown that the ECS is a potential target for the treatment of autism, but the mechanism is still unknown. In the brain, microglia express a complete ECS signaling system. Studies also have shown that modulating ECS signaling can regulate the functions of microglia. By comprehensively reviewing previous studies and combining with our recent work, this review addresses the effects of targeting ECS on microglia, and how this can contribute to maintain the positivity of the central nervous system, and thus improve the symptoms of autism. This will provide insights for revealing the mechanism and developing new treatment strategies for autism.

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14. Vaiouli P, Panayiotou G. Alexithymia and Autistic Traits: Associations With Social and Emotional Challenges Among College Students. Frontiers in neuroscience. 2021; 15: 733775.

Background: Alexithymia is a multifaceted personality construct defined by marked difficulties in identifying and describing feelings and in externally oriented thinking. Given its intrinsic role in social-emotional processing, alexithymia is now recognized as a trans-diagnostic trait in a range of neurodevelopmental disorders, including autism. Research has pinpointed to the co-occurrence of autism with characteristics typical of alexithymic normative samples, such as social-communication difficulties and decreased emotion regulation abilities. Nonetheless, the role of individual facets of alexithymia in predicting challenges in social communication functioning is still understudied. Methods: In total, 275 young adults completed the Toronto Alexithymia Scale, the Autism Spectrum Quotient (short form), the Interpersonal Competence Questionnaire, and the Difficulties in Emotion Regulation Scale self-reported questionnaires for assessing alexithymic and autistic traits, social-communication abilities, and emotion regulation difficulties. We used regression models to establish cross-sectional associations between autism, alexithymia, and social-emotional difficulties. Also, we ran a parallel mediation analysis to determine whether the relationship between autistic traits and emotion regulations challenges are mediated by Alexithymia facets. Results: Analysis showed a significant positive association between autistic traits and alexithymic traits and between autistic traits and emotion regulation difficulties while, as expected, autistic traits were negatively correlated with social skills. A significant relationship was found among the participants’ levels of alexithymia and their interpersonal skills with two of three alexithymic subscales significantly contributing to the model. Similarly, a significant relationship was found among alexithymia subscales and emotion regulation difficulties with all three alexithymia subscales being statistically significant. Finally, analysis on two mediator models indicated a significant effect of autistic traits on social skills mediated by alexithymic traits as well as a significant indirect effect of autistic traits on emotion regulation difficulties mediated by alexithymic traits. Conclusion: The results of this study provide evidence of the influence of different alexithymic facets on the relationship between autistic traits and social-emotional challenges in young adults. Longitudinal studies may explore further alexithymia and its associations with social-emotional difficulties in autism as well as the potential implications of these findings in intervention and treatment programs.

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15. Waddington H, Shepherd D, van der Meer L, Powell-Hector N, Wilson E, Barbaro J. Brief Report: Training New Zealand Well Child/Tamariki Ora Nurses on Early Autism Signs Using the Social Attention and Communication Surveillance-Revised. Journal of autism and developmental disorders. 2021: 1-8.

Universal developmental surveillance is considered best practice for early identification of autism. We analysed data from 175 New Zealand Well-Child/Tamariki Ora nurses who attended a 1-day training in developmental surveillance for autism using the social attention and communication surveillance-revised (SACS-R) tool. We used a survey to measure nurses’ knowledge of typical development, knowledge of early signs of autism, general autism knowledge, and confidence in identifying and discussing early signs, prior to the workshop, after the workshop, and at follow-up. We measured perceived acceptability of the SACS-R after the workshop and at follow-up. Nurses showed improvements on all measures from pre-workshop to post-workshop and pre-workshop to follow-up. Implementation of the SACS-R across different contexts appears feasible and acceptable.

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16. Xie MJ, Iwata K, Ishikawa Y, Nomura Y, Tani T, Murata K, Fukazawa Y, Matsuzaki H. Autistic-Like Behavior and Impairment of Serotonin Transporter and AMPA Receptor Trafficking in N-Ethylmaleimide Sensitive Factor Gene-Deficient Mice. Frontiers in genetics. 2021; 12: 748627.

Autism spectrum disorder (ASD), characterized by profound impairment in social interactions and communication skills, is the most common neurodevelopmental disorder. Many studies on the mechanisms underlying the development of ASD have focused on the serotonergic system; however, these studies have failed to completely elucidate the mechanisms. We previously identified N-ethylmaleimide-sensitive factor (NSF) as a new serotonin transporter (SERT)-binding protein and described its importance in SERT membrane trafficking and uptake in vitro. In the present study, we generated Nsf (+/-) mice and investigated their behavioral, neurotransmitter, and neurophysiological phenotypes in vivo. Nsf (+/-) mice exhibited abnormalities in sociability, communication, repetitiveness, and anxiety. Additionally, Nsf loss led to a decrease in membrane SERT expression in the raphe and accumulation of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors at the synaptic membrane surface in the hippocampal CA1 region. We found that postsynaptic density and long-term depression were impaired in the hippocampal CA1 region of Nsf (+/-) mice. Taken together, these findings demonstrate that NSF plays a role in synaptic plasticity and glutamatergic and serotonergic systems, suggesting a possible mechanism by which the gene is linked to the pathophysiology of autistic behaviors.

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17. Zheng Y, Bek MK, Prince NZ, Peralta Marzal LN, Garssen J, Perez Pardo P, Kraneveld AD. The Role of Bacterial-Derived Aromatic Amino Acids Metabolites Relevant in Autism Spectrum Disorders: A Comprehensive Review. Frontiers in neuroscience. 2021; 15: 738220.

In recent years, the idea of the gut microbiota being involved in the pathogenesis of autism spectrum disorders (ASD) has attracted attention through numerous studies. Many of these studies report microbial dysregulation in the gut and feces of autistic patients and in ASD animal models. The host microbiota plays a large role in metabolism of ingested foods, and through the production of a range of metabolites it may be involved in neurodevelopmental disorders such as ASD. Two specific microbiota-derived host metabolites, p-cresol sulfate and 4-ethylphenyl sulfate, have been associated with ASD in both patients and animal models. These metabolites originate from bacterially produced p-cresol and 4-ethylphenol, respectively. p-Cresol and 4-ethylphenol are produced through aromatic amino acid fermentation by a range of commensal bacteria, most notably bacteria from the Clostridioides genus, which are among the dysregulated bacteria frequently detected in ASD patients. Once produced, these metabolites are suggested to enter the bloodstream, pass the blood-brain-barrier and affect microglial cells in the central nervous system, possibly affecting processes like neuroinflammation and microglial phagocytosis. This review describes the current knowledge of microbial dysbiosis in ASD and elaborates on the relevance and synthesis pathways of two specific ASD-associated metabolites that may form a link between the microbiota and the brain in autism. While the two discussed metabolites are promising candidates for biomarkers and (nutritional) intervention targets, more research into the role of these metabolites in ASD is required to causally connect these metabolites to ASD pathophysiology.

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