1. Al-Mazroua HA, Nadeem A, Ansari MA, Attia SM, Albekairi TH, Bakheet SA, Alobaidi AF, Alhosaini K, Alqarni SA, Ibrahim KE, Alsaad AMS, Ahmad SF. Methylmercury chloride exposure exacerbates existing neurobehavioral and immune dysfunctions in the BTBR T(+) Itpr3(tf)/J mouse model of autism. Immunology letters. 2022; 244: 19-27.

Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by impaired communication, impaired reciprocal social interaction, restricted sociability deficits, and the presence of stereotyped patterns of behaviors. Immune dysregulation has been suggested to play a possible etiological role in ASD. Recent studies have demonstrated that exposure to methylmercury chloride (MeHgCl) leads to abnormal gait, motor deficits, impaired hearing, and memory deficits; however, its effects on behavioral and immunological responses have not been adequately investigated in ASD. In this study, we investigated the effects of MeHgCl exposure on marble burying, self-grooming behaviors, sociability tests, and locomotor activities in BTBR T(+) Itpr3tf/J (BTBR) mice. We also explored the possible molecular mechanism underlying the effects of MeHgCl administration on IFN-γ-, T-bet-, IL-9-, and IL-17A-producing CD4(+), CXCR5(+), CXCR6(+), and CCR9(+) cells isolated from spleens. Furthermore, the effects of MeHgCl exposure on the mRNA expression and levels of pro-inflammatory cytokines in the brain tissue and serum samples were also assessed. Our results demonstrated that MeHgCl exposure caused a significant increase in marble burying, self-grooming behaviors and a decrease in social interactions and adverse effects on locomotor activity in BTBR mice. MeHgCl exposure also significantly increased the production of CD4(+)IFN-γ(+), CD4(+)T-bet(+), CCR9(+)T-bet(+), CXCR5(+)IL-9(+), CD4(+)IL-9(+), CXCR6(+)IL-17A(+), and CD4(+)IL-17A(+) cells in the spleen. Furthermore, MeHgCl exposure increased mRNA and protein levels of pro-inflammatory cytokines in the brain and serum respectively in BTBR mice. In conclusion, MeHgCl administration aggravated existing behavioral and immune abnormalities in BTBR mice.

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2. Chen T, Wen R, Liu H, Zhong X, Jiang C. Dance intervention for negative symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis. Complementary therapies in clinical practice. 2022; 47: 101565.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopment disorder, marked by deficits in social communication and social interaction as well as by a restricted, repetitive patterns of behaviors, interests and activities. There is an increasing interest in the use of dance as part of rehabilitation for individuals with ASD. However, it is not clear how dance can influence on ASD symptoms. And few studies have measured and compared the outcomes of multiple studies. This study was aimed to provide a more comprehensive perspective of the efficacy of dance practice on ASD symptoms by conducting a systematic review with meta-analysis. METHODS: The electronic databases PubMed, EBSCO, MEDLINE, Cochrane and PsycINFO were searched for relevant studies reporting on the effects of dance on ASD symptoms. Only randomized controlled trials (RCTs) and non-randomized controlled studies were included in this review. Two review authors independently performed literature search, data extraction, and study quality assessment. Effect sizes for ASD symptoms were expressed as standardized mean differences (SMD) with 95% confidence intervals. RESULTS: Seven eligible studies were included for meta-analysis. Dance interventions varied in frequency (1-2 sessions/week), time (40 – 90 min), duration (7 – 17 weeks) and type. As compared to control groups, dance practice showed significant alleviation of overall symptoms of ASD (-1.48 points, CI -2.55 to – 0.42 points, p = 0.006, I(2) = 75%) and improvement in social interaction (0.88, CI 0.46 to 1.30, p < 0.0001, I(2) = 0%), but no significant effect on empathy (0.09, CI - 0.25 to 0.42, p = 0.61, I(2) = 2%). CONCLUSIONS: Dance probably alleviate the negative symptoms and social deficits of individuals with ASD. However, little difference is found in empathy. Further research and studies are needed to determine the optimal dose and if dance results in greater benefits than other types of physical activity.

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3. Chen YS, Zhang SM, Yue CX, Xiang P, Li JQ, Wei Z, Xu L, Zeng Y. Early environmental enrichment for autism spectrum disorder Fmr1 mice models has positive behavioral and molecular effects. Experimental neurology. 2022; 352: 114033.

Autism spectrum disorder is a complex neurodevelopmental condition with genetic and phenotypic heterogeneity characterized by hallmark impairments in social functioning and repetitive behaviors. Fragile X syndrome (FXS), the leading single-gene form of autism spectrum disorder, is the most common form of inherited intellectual disability. Environmental enrichment has been shown to improve several aspects of brain development and affect histopathological, cognitive, and behavioral outcomes. However, the optimal time window to initiate it and improve cognitive and emotional development is largely unexplored. In the current study, we determined the longitudinal trends of BDNF-TrkB expression and dendritic development in FXS mice. Additionally, FXS mice were housed in an enriched environment when they showed significantly different BDNF-TrkB pathways and the phenotype of dendritic spines on postnatal day 10 (P10) until P60. The environmental enrichment delayed and attenuated some neurological alterations in FXS mice and prevented the development of cognitive and anxiety-related abnormalities and repetitive stereotyped behaviors. The correlation between neurotrophin-related pathways and multiple autistic-like behaviors was confirmed. Transcriptional profiling indicates that environmental enrichment increases the differences in the prefrontal cortex and hippocampal gene expression associated with the neural system and behavioral development. Our results provide novel evidence on the usefulness of early intervention for neurodevelopmental disorders as a strategy to facilitate positive effects on neural development and behaviors by acting on the BDNF/TrkB-PLCγ1-CaMKII pathway.

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4. Guzmán-Salas S, Weber A, Malci A, Lin X, Herrera-Molina R, Cerpa W, Dorador C, Signorelli J, Zamorano P. The metabolite p-cresol impairs dendritic development, synaptogenesis, and synapse function in hippocampal neurons: Implications for autism spectrum disorder. Journal of neurochemistry. 2022.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopment disorder resulting from different etiological factors, both genetic and/or environmental. These factors can lead to abnormal neuronal development on dendrite and synaptic function at the central nervous system. Recent studies have shown that a subset of ASD patients display increased circulation levels of the tyrosine metabolite, p-cresol, related to chronic intestinal disorders because of dysbiosis of the intestinal microbiota. In particular, abnormal presence of intestinal Clostridium sp. has been linked to high levels of p-cresol in ASD children younger than 8 years. However, the role of p-cresol during development of the central nervous system is unknown. Here, we evaluated in vitro the effect of p-cresol on neurite outgrowth in N2a and PC12 cell lines and dendritic morphology, synaptic density, neuronal activity, and calcium responses in primary rat hippocampal neurons. p-cresol inhibits neural differentiation and neurites outgrowth in N2a and PC12 neuronal cell lines. In hippocampal neuronal cultures, Sholl’s analysis shows a decrease in the dendritic arborization of neurons treated with p-cresol. Synaptic density analyzed with the synaptic markers Piccolo and Shank2 is diminished in hippocampal neurons treated with p-cresol. Electrically evoked intracellular calcium rise was drastically, but reversely, blocked by p-cresol, whereas that spontaneous neuronal activity was severely affected by early addition of the metabolite. These findings show that p-cresol alters dendrite development, synaptogenesis, and synapse function of neurons in culture, therefore, neuronal alterations occurring in ASD children may be related to this metabolite and dysbiosis of the intestinal microbiota.

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5. Le Goff L, Mamimoue É, Pelluet A, Des Portes V, Fourneret P. [Psychomotor development of infants and children…]. La Revue du praticien. 2022; 72(1): 101-4.

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6. Rattaz C, Loubersac J, Michelon C, Geoffray MM, Picot MC, Munir K, Baghdadli A. Factors associated with age of diagnosis in children with autism spectrum disorders: Report from a French cohort. Autism : the international journal of research and practice. 2022: 13623613221077724.

Autism spectrum disorder is an early onset neurodevelopmental disorder and diagnosis can be made as early as 18 months of age. Early diagnosis of autism spectrum disorder is critical as it leads to early intervention. Age of autism spectrum disorder diagnosis has been linked to the child profile as autism spectrum disorder is characterized by strong heterogeneity, but is also influenced by socio-economic factors. There is paucity of data on age of diagnosis of autism spectrum disorder in France. We therefore examined the age of autism spectrum disorder diagnosis in 554 children and adolescents enrolled in the ELENA cohort study with respect to the influences of child profile, family antecedents, and socio-economic factors. The mean age of diagnosis was 4.9 years (±2.8 years). Early diagnosis, before 3 years of age, was related to the co-occurrence of intellectual disability, higher autism spectrum disorder symptom severity, and lower communicative abilities. Children in low socio-economic status families tended to have an earlier diagnosis, but these children also had greater degree of intellectual impairment compared to children in high socio-economic status families. The age of autism spectrum disorder diagnosis was not associated with the presence of an older sibling with autism spectrum disorder. The observed current trend of an inverse relationship between socio-economic status and age of diagnosis of autism spectrum disorder suggests equitable access to autism spectrum disorder services in France where health coverage is universal and free. Better screening of more subtle/less severe forms of autism spectrum disorder is needed, as well as further assessment of the link between the co-occurrence of autism spectrum disorder and intellectual impairment in children in lower socio-economic status families.

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7. Saito A, Matsumoto S, Sato M, Sakata Y, Haraguchi H. Relationship between parental autistic traits and parenting difficulties in a Japanese community sample. Research in developmental disabilities. 2022; 124: 104210.

BACKGROUND: Previous studies have suggested an association between higher levels of parental autistic traits and negative aspects of parenting; however, the domain of autistic traits specifically associated with parenting difficulties has not been investigated yet. Moreover, it remains to be determined whether this association exists even after controlling for children’s characteristics. AIMS: This study examined the relationship between each domain of parental autistic traits and parenting difficulties after controlling for children’s characteristics in a Japanese community sample. METHODS AND PROCEDURES: Surveys were administered to 1373 Japanese adults who were parents to children in kindergartens, nursery schools, and elementary schools. OUTCOMES AND RESULTS: The results showed that parents with higher levels of autistic traits had more parenting difficulties. Even after controlling for children’s sex, age, and emotional/behavioral problems, paternal impaired communication and maternal poor attention switching, impaired communication, and lack of imagination were related to higher parenting difficulties, while a higher maternal level of attention to detail was associated with lower difficulties in parenting. CONCLUSIONS AND IMPLICATIONS: The findings of this study highlight the importance of focusing on parental autistic traits and providing appropriate parenting support considering these traits.

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8. Shanmugarajah K, Rosenbaum P, Di Rezze B. Exploring Autism, Culture, and Immigrant Experiences: Lessons from Sri Lankan Tamil Mothers. Canadian journal of occupational therapy Revue canadienne d’ergotherapie. 2022: 84174221085433.

Canada is home to a mosaic of cultures with immigrant communities from a wide range of countries, but there are significant variations in how autism spectrum disorder (ASD) may be understood across different immigrant groups, including Sri Lankan Tamils. Such gaps in knowledge may present challenges for immigrant families that are trying to access appropriate care for their child, including occupational therapy services. This descriptive qualitative study aimed to better understand the experiences of immigrant Sri Lankan Tamil parents of children diagnosed with ASD in Southern Ontario, Canada. Interviews were analyzed using an in-depth content analysis. Results demonstrated parents’ perceived supports and barriers towards ASD intervention planning, and indicated that parents were generally satisfied by the level of cultural competence in current ASD systems. However, families may still experience significant immigrant-related barriers that are not fully addressed. Recommendations to improve cultural awareness among occupational therapists utilizing ASD interventions are suggested.

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9. Stroth S, Tauscher J, Wolff N, Küpper C, Poustka L, Roepke S, Roessner V, Heider D, Kamp-Becker I. Phenotypic differences between female and male individuals with suspicion of autism spectrum disorder. Molecular autism. 2022; 13(1): 11.

BACKGROUND: Although autism spectrum disorder (ASD) is a common developmental disorder, our knowledge about a behavioral and neurobiological female phenotype is still scarce. As the conceptualization and understanding of ASD are mainly based on the investigation of male individuals, females with ASD may not be adequately identified by routine clinical diagnostics. The present machine learning approach aimed to identify diagnostic information from the Autism Diagnostic Observation Schedule (ADOS) that discriminates best between ASD and non-ASD in females and males. METHODS: Random forests (RF) were used to discover patterns of symptoms in diagnostic data from the ADOS (modules 3 and 4) in 1057 participants with ASD (18.1% female) and 1230 participants with non-ASD (17.9% % female). Predictive performances of reduced feature models were explored and compared between females and males without intellectual disabilities. RESULTS: Reduced feature models relied on considerably fewer features from the ADOS in females compared to males, while still yielding similar classification performance (e.g., sensitivity, specificity). LIMITATIONS: As in previous studies, the current sample of females with ASD is smaller than the male sample and thus, females may still be underrepresented, limiting the statistical power to detect small to moderate effects. CONCLUSION: Our results do not suggest the need for new or altered diagnostic algorithms for females with ASD. Although we identified some phenotypic differences between females and males, the existing diagnostic tools seem to sufficiently capture the core autistic features in both groups.

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10. Umagami K, Remington A, Lloyd-Evans B, Davies J, Crane L. Loneliness in autistic adults: A systematic review. Autism : the international journal of research and practice. 2022: 13623613221077721.

Recently, researchers have been interested in how autistic people experience loneliness. Yet, most of this research has focused on loneliness in autistic children and young people. We present the results of a systematic review on loneliness in autistic adults. A systematic review is a rigorous way of searching for all existing research on a topic and summarizing the findings about specific questions. We searched for all research published on this topic until 9 April 2021. We found 34 articles that investigated loneliness in autistic adults. This research showed that (1) there is fairly little research that has involved directly asking autistic adults about their first-hand experiences of loneliness (e.g. what loneliness feels like for them); (2) few research studies have used loneliness questionnaires specifically developed for autistic adults (this was attempted in just one research study); (3) collective loneliness (i.e. loneliness associated with how much an autistic person feels they ‘fit in’ to society) seems important to autistic adults but has not been investigated as commonly as other aspects of loneliness (e.g. loneliness associated with romantic relationships or friendships); (4) things that might increase loneliness in autistic adults include anxiety and depression, and a lack of autism understanding and acceptance, for example; and (5) things that might reduce loneliness in autistic adults include having relationships and self-acceptance, for example. In our article, we discuss the kinds of future research on loneliness in autistic adults that might be useful.

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