1. Boorom O, Alviar C, Zhang Y, Muñoz VA, Kello CT, Lense MD. Child language and autism diagnosis impact hierarchical temporal structure of parent-child vocal interactions in early childhood. Autism Res;2022 (Sep 3)

Timing is critical to successful social interactions. The temporal structure of dyadic vocal interactions emerges from the rhythm, timing, and frequency of each individuals’ vocalizations and reflects how the dyad dynamically organizes and adapts during an interaction. This study investigated the temporal structure of vocal interactions longitudinally in parent-child dyads of typically developing (TD) infants (n = 49; 9-18 months; 48% male) and toddlers with ASD (n = 23; 27.2 ± 5.0 months; 91.3% male) to identify how developing language and social skills impact the temporal dynamics of the interaction. Acoustic hierarchical temporal structure (HTS), a measure of the nested clustering of acoustic events across multiple timescales, was measured in free play interactions using Allan Factor. HTS reflects a signal’s temporal complexity and variability, with greater HTS indicating reduced flexibility of the dyadic system. Child expressive language significantly predicted HTS (ß = -0.2) longitudinally across TD infants, with greater dyadic HTS associated with lower child language skills. ASD dyads exhibited greater HTS (i.e., more rigid temporal structure) than nonverbal matched (d = 0.41) and expressive language matched TD dyads (d = 0.28). Increased HTS in ASD dyads occurred at timescales >1 s, suggesting greater structuring of pragmatic aspects of interaction. Results provide a new window into how language development and social reciprocity serve as constraints to shape parent-child interaction dynamics and showcase a novel automated approach to characterizing vocal interactions across multiple timescales during early childhood. LAY SUMMARY: Successful interactions involve conversational partners’ flexibly adapting the timing of their behaviors. We measured the temporal patterns of vocalizations in parent-child interactions of typically developing (TD) and autistic infants/toddlers. While language growth made vocal interaction timing more flexible for TD child-parent dyads, it did not for autistic child-parent dyads who exhibited increased clustering of vocal interactions. Both language and social reciprocity play a role in the timing structure and flexibility of smooth interactions.

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2. Carter SA, Lin JC, Chow T, Yu X, Rahman MM, Martinez MP, Feldman K, Eckel SP, Chen JC, Chen Z, Levitt P, Lurmann FW, McConnell R, Xiang AH. Maternal obesity, diabetes, preeclampsia, and asthma during pregnancy and likelihood of autism spectrum disorder with gastrointestinal disturbances in offspring. Autism;2022 (Sep 4):13623613221118430.

Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.

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3. Cooper K, Russell AJ, Lei J, Smith LG. The impact of a positive autism identity and autistic community solidarity on social anxiety and mental health in autistic young people. Autism;2022 (Sep 4):13623613221118351.

Autism is a diagnosis given to individuals by professionals but is also increasingly seen as an identity which an individual can choose for themselves. We wanted to explore how having autism as an identity affects autistic young people. There is evidence that autistic adults have better psychological well-being when they feel more solidarity with other autistic people and feel positively about being autistic. We know that autistic teenagers often feel anxious in social situations. Having a positive autism identity might help alleviate social anxiety associated with being autistic. We wanted to find out if autistic young people who felt more solidarity with other autistic people, and had more positive feelings about autism, had better psychological well-being and less social anxiety. We asked 121 autistic people aged 15-22 years to complete some questionnaires. These questionnaires asked about the young person’s autism traits, social anxiety, and psychological well-being. The questionnaires also asked how satisfied they felt to be autistic (satisfaction) and how much solidarity they felt with the autism community (solidarity). We found that autistic young people who had higher autism satisfaction had better psychological well-being and lower social anxiety. Young people who felt more solidarity with other autistic people had higher psychological well-being. There was no association between autism solidarity and social anxiety. We conclude that is important to support autistic young people to develop positive feelings about autism and to feel solidarity with other autistic people.

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4. Hsu TW, Chu CS, Tsai SJ, Hsu JW, Huang KL, Cheng CM, Su TP, Chen TJ, Bai YM, Liang CS, Chen MH. Diagnostic Progression to Schizophrenia: A Nationwide Cohort Study of 11,170 Adolescents and Young Adults with Autism Spectrum Disorder. Psychiatry Clin Neurosci;2022 (Sep 3)

AIMS: Previous studies have suggested an increased risk of developing schizophrenia later in life in children with ASD. This study aims to investigate the diagnosis stability and the potential predictors for progression to schizophrenia in autism spectrum disorder (ASD). METHODS: We recruited 11,170 adolescents (10-19 years) and young adults (20-29 years) with ASD between 2001 and 2010. They were followed up to the end of 2011 to identify newly diagnosed schizophrenia. The Kaplan-Meier method and Cox regression with age as a time scale were employed to estimate incidence rates and the significance of candidate predictors. RESULTS: The progression rate from ASD to schizophrenia was10.26%for 10 years of follow-up. Among 860 progressors, 580 (67.44%)occurred within the first 3 years after a diagnosis of ASD.The identified predictors were age (reported as hazard ratio with 95% confidence interval: 1.13; 1.11-1.15), depressive disorder (1.36; 1.09-1.69), alcohol use disorder (3.05; 2.14-4.35),substance use disorder (1.91; 1.18-3.09),cluster A personality disorder (2.95; 1.79-4.84), cluster B personality disorder (1.86; 1.05-3.28),and a family history of schizophrenia (2.12; 1.65-2.74). CONCLUSION: More than two-thirds of the progressors developed schizophrenia within the first 3 years. Demographic characteristics, physical and psychiatric comorbidities, and psychiatric family history were significant predictors of progression. This article is protected by copyright. All rights reserved.

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5. Jeon SJ, Kwon H, Bae HJ, Gonzales EL, Kim J, Chung HJ, Kim DH, Ryu JH, Shin CY. Agmatine relieves behavioral impairments in Fragile X mice model. Neuropharmacology;2022 (Aug 31);219:109234.

BACKGROUND: Fragile X syndrome (FXS) is the most common heritable form of neurodevelopmental disorder, which is caused by the loss of fragile X mental retardation protein (FMRP) expression. Despite the unceasing efforts to develop therapeutic agents against FXS based on the pathophysiological changes observed in animal models of FXS and human patients, therapeutic candidates including mGluR signaling modulators have failed to provide sufficient effects. Based on the recent successful demonstration of an endogenous polyamine, agmatine, to improve the autism-like symptoms in the valproic acid animal model of autism, we investigated the effects of agmatine against FXS symptoms using Fmr1 knockout (KO) mice. METHODS: We used male Fmr1 KO mice for behavioral tests such as marble burying, open-field test, memory tasks, social interaction tests and startle response to confirm the symptoms of FXS. We also checked the electrophysiological profile of neural activity in agmatine-treated Fmr1 KO mice. RESULTS: Agmatine reversed the compulsion, learning and memory deficits, hyperactivity, aberrant social interaction, and communication deficit in Fmr1 KO mice while it normalized the aberrant LTP and LTD in the hippocampus. CONCLUSIONS: The results highlight the potential of agmatine’s novel disease-ameliorating effects in FXS, which warrants further studies to ascertain whether these findings translate into clinical effects in FXS patients.

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6. Karaminis T, Stavrakaki S. The psychometric properties of the Greek version of the Social Communication Questionnaire. Autism Res;2022 (Sep);15(9):1768-1780.

There is a scarcity of diagnostic assessments and screening tools for autism spectrum disorders (ASD) in Greek. In this study, we examined the psychometric properties of the recently developed Greek version of the Social Communication Questionnaire (SCQ). We used parental responses for 311 children (mean age: 7.54 years old, SD = 1.92), 122 with a diagnosis of ASD (93 boys, 29 girls) and 189 neurotypical children (104 boys, 85 girls), with 167 responses referring to the Lifetime and 144 to the Current form of the SCQ. Both forms presented adequate construct validity based on the four-factor model, while in both forms, autistic children presented higher SCQ total and subscale scores (four factors) than typical children. The forms had excellent internal reliability. An item-response-theory analysis suggested that over 80% of test items fitted adequately a Rasch model, while a preliminary analysis of gender biases suggested that a small number of items (Lifetime: five; Current: six out of 39) were differentially sensitive to autistic symptomatology in boys and girls. A receiver-operating-characteristic analysis showed excellent diagnostic performance based on the SCQ total score (Lifetime: area-under-the-curve/AUC = 0.937, Current: AUC = 0.963), and acceptable to excellent discrimination for the four subscales (AUCs between 0.737 and 0.955). Our preliminary results suggest that the Greek SCQ presents satisfactory psychometric properties and can be used for differentiating children with ASD from typical children in initial assessments within clinical and research settings. LAY SUMMARY: Autism spectrum disorder (ASD or autism) is a lifelong neurodevelopmental condition with a prevalence of ~1.5%-2% and characterized by difficulties in social interaction and communication and repetitive and restricted behaviors. There is increasing concern that research in ASD has focused on a small number of languages and cultural settings and that this bias challenges the identification and diagnosis of the condition in other languages and cultures, which are underrepresented in autism research. One such language is Greek (spoken by ~13.5 million), for which there is a scarcity of standardized instruments for the diagnosis of autism. This study examines the psychometric properties of the recently published Greek version of the Social Communication Questionnaire (SCQ), a widely used screening tool for ASD. We conduct an in-depth psychometric analysis of the Greek SCQ, including both forms in which the instrument is available (Lifetime and Current). This analysis shows that the Greek SCQ can be used for differentiating children with ASD from typical children in initial assessments within clinical and research settings. The findings of this study have implications for clinicians, special educators and researchers working with Greek-speaking individuals with ASD and, more broadly, for cross-cultural autism research.

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7. Miot S, Chancel R, Peries M, Crepiat S, Couderc S, Pernon E, Picot MC, Gonnier V, Jeandel C, Blain H, Baghdadli A. Multimorbidity patterns and subgroups among autistic adults with intellectual disability: Results from the EFAAR study. Autism;2022 (Sep 2):13623613221121623.

Multimorbidity relates to having multiple chronic health conditions. It is a risk factor for poor health and reduces life expectancy. Autistic people have multiple chronic health conditions and die prematurely, especially if they have an intellectual disability (autism spectrum disorder and intellectual disability). Certain pathophysiological processes observed in autism spectrum disorder are common to those related to the genesis and/or maintenance of multimorbidity. Furthermore, multimorbidity could be helpful in better identifying patient subgroups in autism spectrum disorder. It is therefore essential to better characterize multimorbidity and its consequences in the subgroup of autism spectrum disorder + intellectual disability individuals to offer them personalized care. We conducted a preliminary study of 63 autism spectrum disorder + intellectual disability adults to classify them according to their multimorbidity and search for a specific combination of chronic health conditions. We observed high and early multimorbidity in this sample and identified four classes of participants, distinguished by their multimorbidity status, independence and number of treatments. In addition, we observed a dominant combination of multimorbidity in our sample, combining immune dysfunction and gastrointestinal disorders, neurological and joint diseases. These findings support the hypothesis that an altered gut-brain relationship is involved in the risk of autism spectrum disorder, its outcome, and its association with chronic health conditions. Although larger studies are needed, our results suggest that subgroups of autism spectrum disorder + intellectual disability individuals can be identified based on their multimorbidity and potentially different ageing trajectories. A more comprehensive and personalized approach is needed to reduce the burden of multimorbidity and increase the quality of life and life expectancy in autism spectrum disorder/ intellectual disability.

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8. Panayotis N, Ehinger Y, Felix MS, Roux JC. State-of-the-art therapies for Rett syndrome. Dev Med Child Neurol;2022 (Sep 3)

Rett syndrome (RTT) is an X-linked neurogenetic disorder caused by mutations of the MECP2 (methyl-CpG-binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re-express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome.

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9. Thompson-Hodgetts S. Reflections on my experiences as a non-autistic autism researcher. Autism;2022 (Sep 2):13623613221121432.

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10. Zhang Y, Maimaiti R, Lou S, Abula R, Abulaiti A, Kelimu A. Risk prediction of autism spectrum disorder behaviors among children based on blood elements by nomogram: A cross-sectional study in Xinjiang from 2018 to 2019. J Affect Disord;2022 (Aug 31);318:1-6.

BACKGROUND: Changes of toxic metals and essential elements during childhood may be the risk factor of autism spectrum disorder (ASD). This research established an accurate personalized predictive model of ASD behaviors among children by using the blood element detection index of children in Xinjiang, China. METHODS: A total of 1537 children (240 ASD behavior children and 1297 non-ASD behavior children) aged 0-7 were collected from September 2018 to September 2019 in Urumqi Children’s Hospital and the health management institute of Xinjiang Medical University. For measuring the copper (Cu), zinc (Zn), magnesium (Mg), iron (Fe), calcium (Ca), lead (Pb), and cadmium (Cd), 80 μL of blood was taken from each participant’s ring finger. Univariate logistic regression analysis was used to select predictors, then the multivariate logistic regression was used to establish the predictive model. The discriminability, calibration and clinical validity of the model were evaluated by the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test and decision curve analysis (DCA). RESULTS: Gender, concentrations of Pb, Ca and Zn in children’s blood specimens were found to be the independent risk factors of ASD behaviors and were used to develop the nomogram model. The area under the ROC curve (AUC) in the development group (AUC = 0.778) and the validation group (AUC = 0.775) showed the model had discrimination ability. The calibration curve indicated the model was accurate, and the DCA proved its clinical application value. CONCLUSION: The nomogram model can be used as a reliable tool to predict the risk of ASD behaviors among children.

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11. Zhang Y, Pang Y, Feng W, Jin Y, Chen S, Ding S, Wang Z, Zou Y, Li Y, Wang T, Sun P, Gao J, Zhu Y, Ke X, Marshall C, Huang H, Sheng C, Xiao M. miR-124 regulates early isolation-induced social abnormalities via inhibiting myelinogenesis in the medial prefrontal cortex. Cell Mol Life Sci;2022 (Sep 4);79(9):507.

Patients with autism spectrum disorder (ASD) typically experience substantial social isolation, which may cause secondary adverse effects on their brain development. miR-124 is the most abundant miRNA in the human brain, acting as a pivotal molecule regulating neuronal fate determination. Alterations of miR-124 maturation or expression are observed in various neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. In the present study, we analyzed a panel of brain-enriched microRNAs in serums from 2 to 6 year old boys diagnosed with ASD. The hsa-miR-124 level was found significantly elevated in ASD boys than in age and sex-matched healthy controls. In an isolation-reared weanling mouse model, we evidenced elevated mmu-miR-124 level in the serum and the medial prefrontal cortex (mPFC). These mice displayed significant sociability deficits, as well as myelin abnormality in the mPFC, which was partially rescued by expressing the miR-124 sponge in the bilateral mPFC, ubiquitously or specifically in oligodendroglia. In cultured mouse oligodendrocyte precursor cells, introducing a synthetic mmu-miR-124 inhibited the differentiation process through suppressing expression of nuclear receptor subfamily 4 group A member 1 (Nr4a1). Overexpressing Nr4a1 in the bilateral mPFC also corrected the social behavioral deficits and myelin impairments in the isolation-reared mice. This study revealed an unanticipated role of the miR-124/Nr4a1 signaling in regulating early social experience-dependent mPFC myelination, which may serve as a potential therapy target for social neglect or social isolation-related neuropsychiatric disorders.

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