1. Afif IY, Farkhan M, Kurdi O, Maula MI, Ammarullah MI, Setiyana B, Jamari J, Winarni TI. Effect of Short-Term Deep-Pressure Portable Seat on Behavioral and Biological Stress in Children with Autism Spectrum Disorders: A Pilot Study. Bioengineering (Basel, Switzerland). 2022; 9(2).

Children with autism spectrum disorder (ASD) have challenging behaviors, which are associated with difficulties in parenting. Deep pressure is a therapeutic modality in occupational therapy, and it was reported to produce a calming effect. This study aimed to determine whether the short-term use of an autism hug machine portable seat (AHMPS) improves behavioral and neurobiological stress in children with ASD, and to determine whether AHMPS with an inflatable wrap or manual pull is more effective. This study enrolled children with ASD who were administered with the inflatable wrap (group I) and manual pull (group II) for 20 min twice a week for 3 weeks. Conners’ Parent Rating Scale-48 (CPRS-48) was used to rate behavioral improvements, and galvanic skin response (GSR) was used to measure sympathetic stress response. A total of 20 children with ASD (14 boys and 6 girls; aged 7-13 years) were included. CPRS-48 presented conduct problems: behavior was significantly decreased in the inflatable group (p = 0.007) compared to the manual pull group. The GSR captured a significant reduction in sympathetic response (p = 0.01) only in group I. Neurobiological stress was reduced in children who were wearing the AHMPS inflatable wrap; therefore, AHMPS inflatable wrap is an effective method to reduce emotional arousal.

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2. Beqiraj L, Denne LD, Hastings RP, Paris A. Positive behavioural support for children and young people with developmental disabilities in special education settings: A systematic review. Journal of applied research in intellectual disabilities : JARID. 2022; 35(3): 719-35.

BACKGROUND: Positive behavioural support (PBS) can be effective in supporting children and young people (CYP) with developmental disabilities. This systematic review focused on describing the components and nine characteristics of PBS that have been used with CYP with developmental disabilities in special education settings, and the evidence for PBS effectiveness in these settings. Additionally, facilitators and barriers to PBS implementation, and experiences of stakeholders, were investigated. METHOD: Systematic searches followed a registered protocol, and 30 studies were identified, narratively synthesised, and critically appraised. RESULTS: From the 30 studies included, 10 reported the presence of all 9 PBS characteristics, 17 reported on 8 PBS characteristics, and 3 reported on 7 characteristics. Overall, 28 studies demonstrated significant decreases in behaviours that challenge and increases in alternative behaviours, if increasing alternative behaviours was part of the interventions. CONCLUSIONS: There was a lack of evidence on facilitators and barriers, and a lack of qualitative studies exploring experiences of stakeholders with PBS in special education settings. The available evidence suggested that not all studies reported on all PBS characteristics when describing the approach followed. In addition, available evidence suggested that most studies demonstrated effectiveness of PBS regarding the measured outcomes. Implications and future directions are discussed.

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3. Cola M, Zampella CJ, Yankowitz LD, Plate S, Petrulla V, Tena K, Russell A, Pandey J, Schultz RT, Parish-Morris J. Conversational adaptation in children and teens with autism: Differences in talkativeness across contexts. Autism research : official journal of the International Society for Autism Research. 2022.

Successful social communication is complex; it relies on effectively deploying and continuously revising one’s behavior to fit the needs of a given conversation, partner, and context. For example, a skilled conversationalist may instinctively become less talkative with a quiet partner and more talkative with a chattier one. Prior research suggests that behavioral flexibility across social contexts can be a particular challenge for individuals with autism spectrum condition (ASC), and that difficulty adapting to the changing needs of a conversation contributes to communicative breakdowns and poor social outcomes. In this study, we examine whether reduced conversational adaptation, as measured by talkativeness, differentiates 48 verbally fluent children and teens with ASC from 50 neurotypical (NT) peers matched on age, intelligence quotient, and sex ratio. Participants completed the Contextual Assessment of Social Skills with two novel conversation partners. The first acted interested in the conversation and talked more (Interested condition), while the second acted bored and talked less (Bored condition). Results revealed that NT participants emulated their conversation partner’s behavior by being more talkative in the Interested condition as compared to the Bored condition (z = 9.92, p < 0.001). In contrast, the ASC group did not differentially adapt their behavior to the Bored versus Interested context, instead remaining consistently talkative in both (p = 0.88). The results of this study have implications for understanding social communication and behavioral adaptation in ASC, and may be valuable for clinicians interested in improving conversational competence in verbally fluent individuals with autism. LAY SUMMARY: Social communication-including everyday conversations-can be challenging for individuals on the autism spectrum. In successful conversations, people tend to adjust aspects of their language to be more similar to their partners'. In this study, we found that children and teens with autism did not change their own talkativeness in response to a social partner who was more or less talkative, whereas neurotypical peers did. These findings have clinical implications for improving conversational competence in verbally fluent individuals with autism.

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4. Coughlan B, van IMH, Woolgar M, Weisblatt EJL, Duschinsky R. Differentiating « Attachment Difficulties » From Autism Spectrum Disorders and Attention Deficit Hyperactivity Disorder: Qualitative Interviews With Experienced Health Care Professionals. Frontiers in psychology. 2021; 12: 780128.

OBJECTIVES: « Attachment difficulties » is an umbrella term often used to describe various forms of non-secure attachment. Differentiating « attachment difficulties » from autism spectrum disorder (hereafter autism) and attention deficit hyperactivity disorder (ADHD) has been characterized as challenging. Few studies have explored how this happens in practice, from the perspective of professionals. DESIGN: Qualitative study. METHODS: We conducted in-depth semi-structured interviews with (n = 17) healthcare professionals from five NHS Foundation Trusts in the United Kingdom. Participants were recruited using a combination of snowballing, convenience and purposive sampling. Data were analyzed using a thematic approach. RESULTS: We identified six interrelated themes that might reflect difficulties with differential conceptualization. These include: a clinical lexicon of attachment; approaching attachment with caution; contextual factors; perceived characteristic behaviors; assessing attachment and adjacent supports; spotlighting intervention and dual conceptualization. CONCLUSION: Our results indicate some of the ways suspicions around attachment are raised in practice. We advocate for more dialogue between research and practice communities on issues of differential conceptualization. We call for collaboration between a panel of experts consisting of attachment and neurodevelopmental orientated practitioners and researchers, to clarify issues around differentiating between attachment difficulties, ASD, and ADHD.

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5. Donahoe JW, Palmer DC. Acquired reinforcement: Implications for autism. The American psychologist. 2022.

Integration of experimental analyses of behavior and neuroscience provides an interpretation of a substantial number of the diverse behavioral deficits observed within the autism spectrum. To that end, the behavioral and neural conditions under which experience changes the environmental guidance of behavior are first described, that is, the conditions under which learning occurs. These findings lead to the conclusion that acquired reinforcers-events that function as reinforcers as the result of individual experience-satisfy the same requirements and ultimately engage the same neural system as unconditioned reinforcers. Acquired reinforcers are critical to the development of complex behavior and some of the behavioral problems seen in autism may be due to these deficits. Specific consequences of these deficits are described-including effects on automatic reinforcement, joint control, and joint attention. Environmental as well as genetic factors can produce neurodevelopmental errors that impair acquired reinforcement and a possible such factor is identified. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

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6. Hertz-Picciotto I, Korrick SA, Ladd-Acosta C, Karagas MR, Lyall K, Schmidt RJ, Dunlop AL, Croen LA, Dabelea D, Daniels JL, Duarte CS, Fallin MD, Karr CJ, Lester B, Leve LD, Li Y, McGrath M, Ning X, Oken E, Sagiv SK, Sathyanaraya S, Tylavsky F, Volk HE, Wakschlag LS, Zhang M, O’Shea TM, Musci RJ. Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts. Autism research : official journal of the International Society for Autism Research. 2022; 15(3): 551-69.

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child’s risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results.

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7. Limbu B, Deb S, Roy M, Lee R, Roy A, Taiwo O. Randomised controlled trials of mood stabilisers for people with autism spectrum disorder: systematic review and meta-analysis. BJPsych open. 2022; 8(2): e52.

BACKGROUND: Despite the widespread use of psychotropic medications in people with autism spectrum disorder (ASD), there is limited evidence to suggest that psychotropic medications including mood stabilisers are effective in individuals with ASD. AIMS: To carry out a systematic review and meta-analysis of randomised controlled trials (RCTs) that assessed the effectiveness of mood stabilisers in people with ASD. METHOD: We searched the following databases: Cochrane Library, MEDLINE, Embase, CINAHL, PsycINFO, ERIC, DARE, and ClinicalTrials.gov. In addition, we hand-searched 12 relevant journals. We used the Cochrane Risk of Bias and Jadad scores to assess the quality of included RCTs. We carried out a meta-analysis using a random-effects model. RESULTS: We included eight RCTs (four on valproate, two on levetiracetam, and one each on lamotrigine and topiramate) that included a total of 310 people with ASD, primarily children. Outcomes were based on core and associated ASD symptoms including irritability and aggression but not bipolar disorder. Only two small studies (25%) from the same group showed definite superiority over placebo and one over psychoeducation alone. Meta-analysis of pooled data on the Aberrant Behaviour Checklist-irritability, Clinical Global Impression Scale-improvement, and Overt Aggression Scale (OAS)/OAS-modified did not show any significant inter-group difference. The rates of adverse effects did not show any significant inter-group difference. CONCLUSIONS: Given the methodological flaws in the included studies and the contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of mood stabilisers to treat either ASD core symptoms or associated behaviours. Robust large-scale RCTs are needed in the future to address this issue.PROSPERO registration: CRD42021255467 on 18 May 2021.

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8. Liu G, Shi L, Qiu J, Lu W. Two neuroanatomical subtypes of males with autism spectrum disorder revealed using semi-supervised machine learning. Molecular autism. 2022; 13(1): 9.

BACKGROUND: Clinical and etiological varieties remain major obstacles to decompose heterogeneity in autism spectrum disorders (ASD). Recently, neuroimaging raised new hope to identify neurosubtypes of ASD for further understanding the biological mechanisms behind the disorder. METHODS: In this study, brain structural MRI data and clinical measures of 221 male subjects with ASD and 257 healthy controls were selected from 7 independent sites from the Autism Brain Image Data Exchange database (ABIDE). Heterogeneity through discriminative analysis (HYDRA), a recently-proposed semi-supervised clustering method was utilized to divide individuals with ASD into several neurosubtypes by regional volumetric measures of gray matter, white matter, and cerebrospinal fluid. Voxel-wise volume, clinical measures, dynamic resting-state functional magnetic resonance imaging (R-fMRI) measures among different neurosubtypes of ASD were explored. In addition, support vector machine (SVM) model was applied to test whether the neurosubtyping of ASD could improve diagnostic accuracy of ASD. RESULTS: Two neurosubtypes of ASD with different voxel-wise volumetric patterns were revealed. The full-scale intelligence quotient (IQ), verbal IQ, Autism Diagnostic Observation Schedule (ADOS) total scores and ADOS severity scores were significantly different between the two neurosubtypes, the total intracranial volume was correlated with performance IQ in Subtype 1 and was correlated with ADOS communication score and ADOS social score in Subtype 2. Compared with Subtype 2, Subtype 1 showed lower dynamic R-fMRI measures, lower dynamic functional architecture stability, higher mean and lower standard deviation (SD) of concordance among dynamic R-fMRI measures in cerebellum. In addition, classification accuracies between ASD neurosubtypes and healthy controls were significantly improved compared with classification accuracy between entire ASD group and healthy controls. LIMITATIONS: The present study excluded female subjects and left-handed subjects, which limited the ability to investigate the associations between these factors and the heterogeneity of ASD. CONCLUSIONS: The two distinct neuroanatomical subtypes of ASD validated by other data modalities not only adds reliability of the result, but also bridges from brain phenomenology to clinical behavior. The current neurosubtypes of ASD could facilitate understanding the neuropathology of this disorder and could be potentially used to improve clinical decision-making process and optimize treatment.

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9. Lucas R, Cage E, James AI. Supporting Effective Transitions From University to Post-graduation for Autistic Students. Frontiers in psychology. 2021; 12: 768429.

BACKGROUND: The number of autistic students graduating is increasing; however, little is known regarding their transition out of university. Understanding this transition is particularly pertinent with regard to the employment of autistic graduates. It is vital that we understand autistic people’s experiences of the transition and identify what support would be beneficial during this time. METHOD: Thirty-four autistic graduates from the United Kingdom took part in a mixed-methods study exploring their transition experience. Both quantitative and qualitative questions were used to obtain in-depth information concerning participants’ experiences. Participants completed questions regarding their experiences and emotions in relation to the transition, the support they received for the transition, and their career and post-graduation plans. RESULTS: Participants reported high levels of fear and low preparedness for the transition. They did not feel well supported in preparing for the transition or for their future career. In the 6 months pre-graduation, 59% of participants had accessed emotion-related transition support and 70% accessed career-related support. Post-graduation, one-third accessed emotion-related or career-related support. Perspectives on this accessed support were mixed, as were transition experiences. Additional support desired included preparation for life changes, career planning, employment accessibility, and autism-specific support. Advice for future students centered on forward planning. CONCLUSION: These results highlight the importance of supporting autistic students with the transition out of university. Service provision should be tailored to autistic students’ needs and support early planning for the transition.

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10. Lucibello S, Bertè G, Verdolotti T, Lucignani M, Napolitano A, D’Abronzo R, Cicala MG, Pede E, Chieffo D, Mariotti P, Colosimo C, Mercuri E, Battini R. Cortical Thickness and Clinical Findings in Prescholar Children With Autism Spectrum Disorder. Frontiers in neuroscience. 2021; 15: 776860.

The term autism spectrum disorder (ASD) includes a wide variability of clinical presentation, and this clinical heterogeneity seems to reflect a still unclear multifactorial etiopathogenesis, encompassing different genetic risk factors and susceptibility to environmental factors. Several studies and many theories recognize as mechanisms of autism a disruption of brain development and maturation time course, suggesting the existence of common neurobiological substrates, such as defective synaptic structure and aberrant brain connectivity. Magnetic resonance imaging (MRI) plays an important role in both assessment of region-specific structural changes and quantification of specific alterations in gray or white matter, which could lead to the identification of an MRI biomarker. In this study, we performed measurement of cortical thickness in a selected well-known group of preschool ASD subjects with the aim of finding correlation between cortical metrics and clinical scores to understand the underlying mechanism of symptoms and to support early clinical diagnosis. Our results confirm that recent brain MRI techniques combined with clinical data can provide some useful information in defining the cerebral regions involved in ASD although large sample studies with homogeneous analytical and multisite approaches are needed.

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11. Mellema CJ, Nguyen KP, Treacher A, Montillo A. Reproducible neuroimaging features for diagnosis of autism spectrum disorder with machine learning. Scientific reports. 2022; 12(1): 3057.

Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD.

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12. Pabian-Jewuła S, Bragiel-Pieczonka A, Rylski M. Ying Yang 1 engagement in brain pathology. Journal of neurochemistry. 2022; 161(3): 236-53.

Herein, we discuss data concerning the involvement of transcription factor Yin Yang 1 (YY1) in the development of brain diseases, highlighting mechanisms of its pathological actions. YY1 plays an important role in the developmental and adult pathology of the nervous system. YY1 is essential for neurulation as well as maintenance and differentiation of neuronal progenitor cells and oligodendrocytes regulating both neural and glial tissues of the brain. Lack of a YY1 gene causes many developmental abnormalities and anatomical malformations of the central nervous system (CNS). Once dysregulated, YY1 exerts multiple neuropathological actions being involved in the induction of many brain disorders like stroke, epilepsy, Alzheimer’s and Parkinson’s diseases, autism spectrum disorder, dystonia, and brain tumors. A better understanding of YY1’s dysfunction in the nervous system may lead to the development of novel therapeutic strategies related to YY1’s actions.

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13. Raeisy H, Bayati P, Noorbakhsh F, Hakim Shooshtari M, Eftekhar Ardebili M, Shekarabi M, Mojtabavi N. C1q/TNF-related protein-1: Potential biomarker for early diagnosis of autism spectrum disorder. International journal of immunopathology and pharmacology. 2022; 36: 3946320221079471.

INTRODUCTION: Autism spectrum disorders (ASDs) are neurodevelopmental diseases characterized by communication inabilities, social interaction impairment, repetitive behavior, as well as learning problems. Although the exact mechanism underlying this disease is still obscure, researchers believe that several factors play a significant role in its development and pathogenesis. Some authors have reported an association between adipokines family and autism. C1q/TNF-related protein-1 (CTRP1) is a member of the adipokines family, and we hypothesized that this adipokine might have an influential role in the pathogenesis of ASDs. Since there is no specific marker for screening the disease, we evaluated CTRP1 as a potential marker for achieving this purpose. METHODS: Blood samples were collected from 82 (41 ASDs boys, 41 healthy boys as controls) children aged 5-7 years old. CTRP1 gene expression and CTRP1 serum level were measured by quantitative realtime-PCR and enzyme-linked immunosorbent assay methods, respectively. RESULTS: It was found that CTRP1 is significantly elevated in autistic children in comparison to healthy controls, both at the gene expression level, as well as at the serum level; demonstrating a good diagnostic value with a good range of sensitivity and specificity for detecting ASDs. CONCLUSION: CTRP1 expression is elevated in ASDs boys aged 5-7 years old, suggesting a role for this adipokine in ASDs pathophysiology. Also, receiver operating characteristic curve analyses revealed that this adipokine could be utilized as a diagnostic biomarker for differentiating ASDs patients from healthy individuals along with other recently proposed biomarkers.

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14. Rigby MJ, Orefice NS, Lawton AJ, Ma M, Shapiro SL, Yi SY, Dieterich IA, Frelka A, Miles HN, Pearce RA, Yu JPJ, Li L, Denu JM, Puglielli L. Increased expression of SLC25A1/CIC causes an autistic-like phenotype with altered neuron morphology. Brain : a journal of neurology. 2022; 145(2): 500-16.

N ε-lysine acetylation within the lumen of the endoplasmic reticulum is a recently characterized protein quality control system that positively selects properly folded glycoproteins in the early secretory pathway. Overexpression of the endoplasmic reticulum acetyl-CoA transporter AT-1 in mouse forebrain neurons results in increased dendritic branching, spine formation and an autistic-like phenotype that is attributed to altered glycoprotein flux through the secretory pathway. AT-1 overexpressing neurons maintain the cytosolic pool of acetyl-CoA by upregulation of SLC25A1, the mitochondrial citrate/malate antiporter and ATP citrate lyase, which converts cytosolic citrate into acetyl-CoA. All three genes have been associated with autism spectrum disorder, suggesting that aberrant cytosolic-to-endoplasmic reticulum flux of acetyl-CoA can be a mechanistic driver for the development of autism spectrum disorder. We therefore generated a SLC25A1 neuron transgenic mouse with overexpression specifically in the forebrain neurons. The mice displayed autistic-like behaviours with a jumping stereotypy. They exhibited increased steady-state levels of citrate and acetyl-CoA, disrupted white matter integrity with activated microglia and altered synaptic plasticity and morphology. Finally, quantitative proteomic and acetyl-proteomic analyses revealed differential adaptations in the hippocampus and cortex. Overall, our study reinforces the connection between aberrant cytosolic-to-endoplasmic reticulum acetyl-CoA flux and the development of an autistic-like phenotype.

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15. Santhanam SP, Bellon-Harn ML. Speech-Language Pathologist’s Role in Understanding and Promoting Self-Advocacy in Autistic Adults. American journal of speech-language pathology. 2022; 31(2): 649-63.

PURPOSE: This tutorial introduces speech-language pathologists (SLPs) to strategies that promote and support self-advocacy among autistic college students. The discussion for this tutorial is grounded within the framework of the social model of disability and the need for addressing environmental barriers to communication and self-advocacy. METHOD: We provide a self-advocacy framework to guide SLPs in developing programs for autistic adults. We describe factors that impact self-advocacy in autistic college students and the role of university-based SLPs and speech-language pathology graduate students in program implementation. Scenarios and examples are included to aid SLPs in implementing the recommendations. CONCLUSIONS: Self-advocacy is a predictor of retention, adaptation, and graduation of autistic postsecondary students. Prior research on autistic self-advocacy is minimal, and guidance for SLPs on promoting and supporting self-advocacy of their autistic clients is limited. SLPs play a very important role as they can increase understanding and appreciation for autistic social communication differences among nonautistic peers and professors and address autistic stigma through meaningful engagement of autistic individuals in planning and program development.

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16. Schendel D, Roux AM, McGhee Hassrick E, Lyall K, Shea L, Vivanti G, Wieckowski AT, Newschaffer C, Robins DL. Applying a public health approach to autism research: A framework for action. Autism research : official journal of the International Society for Autism Research. 2022; 15(4): 592-601.

Most published autism research, and the funding that supports it, remains focused on basic and clinical science. However, the public health impact of autism drives a compelling argument for utilizing a public health approach to autism research. Fundamental to the public health perspective is a focus on health determinants to improve quality of life and to reduce the potential for adverse outcomes across the general population, including in vulnerable subgroups. While the public health research process can be conceptualized as a linear, 3-stage path consisting of discovery – testing – translation/dissemination/implementation, in this paper we propose an integrated, cyclical research framework to advance autism public health objectives in a more comprehensive manner. This involves discovery of primary, secondary and tertiary determinants of health in autism; and use of this evidence base to develop and test detection, intervention, and dissemination strategies and the means to implement them in ‘real world’ settings. The proposed framework serves to facilitate identification of knowledge gaps, translational barriers, and shortfalls in implementation; guides an iterative research cycle; facilitates purposeful integration of stakeholders and interdisciplinary researchers; and may yield more efficient achievement of improved health and well-being among persons on the autism spectrum at the population-level. LAY SUMMARY: Scientists need better ways to identify and address gaps in autism research, conduct research with stakeholders, and use findings to improve the lives of autistic people. We recommend an approach, based in public health science, to guide research in ways that might impact lives more quickly.

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17. Starke EL, Zius K, Barbee SA. FXS causing missense mutations disrupt FMRP granule formation, dynamics, and function. PLoS genetics. 2022; 18(2): e1010084.

Fragile X Syndrome (FXS) is the most prevalent cause of inherited mental deficiency and is the most common monogenetic cause of autism spectral disorder (ASD). Here, we demonstrate that disease-causing missense mutations in the conserved K homology (KH) RNA binding domains (RBDs) of FMRP cause defects in its ability to form RNA transport granules in neurons. Using molecular, genetic, and imaging approaches in the Drosophila FXS model system, we show that the KH1 and KH2 domains of FMRP regulate distinct aspects of neuronal FMRP granule formation, dynamics, and transport. Furthermore, mutations in the KH domains disrupt translational repression in cells and the localization of known FMRP target mRNAs in neurons. These results suggest that the KH domains play an essential role in neuronal FMRP granule formation and function which may be linked to the molecular pathogenesis of FXS.

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18. Zhang L, Xu Y, Li H, Li B, Duan G, Zhu C. The role of probiotics in children with autism spectrum disorders: A study protocol for a randomised controlled trial. PloS one. 2022; 17(2): e0263109.

BACKGROUND: Autism spectrum disorder (ASD) is a neurological and developmental condition that begins in infancy or earlier and lasts through the individual’s lifetime. The aetiology and mechanisms of ASD are not yet fully understood, and current treatment comprises mainly education and rehabilitation, without significant improvement in the core symptoms. Recent studies suggest that microbiota change in children with ASD after the ingestion of probiotics may improve the balance of microbiota and thus ASD symptoms. OBJECTIVE: The objectives of this study are to evaluate the efficacy of probiotics on the symptoms of children with ASD and the possible mechanisms involved. METHODS: This is a prospective controlled trial. A total of 160 children with ASD will be stratified and allocated to placebo and probiotics groups randomised according to the severity of their ASD symptoms. The probiotics group will be given probiotics supplements orally twice a day for 3 months and the control group will be given a placebo at the same amount, in addition to the baseline therapy of education and rehabilitation. All the children will be evaluated systematically by using different scales, questionnaires before, during, and after 3 months’ treatment, as well as 3 months after discontinuation. The potential impact of probiotics on immunity and inflammation, metabolism, and metagenome will also be investigated. DISCUSSION: Our previous study showed that the abundance of intestinal flora was greatly different in children with ASD, and that Bifidobacterium was associated with the severity of ASD. In the present study, we will investigate the impact of probiotics supplementation on the symptoms of Children with ASD, with the purpose of evaluating the possible therapeutic effects of additives on ASD and of providing a reference for clinical treatment. The results will help to disclose as yet unknown relationship between probiotics and ASD. TRIAL REGISTRATION: This study has been registered with Chinese Clinical Trial Registry (ChiCTR-2000037941).

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19. Zhao H, Mao X, Zhu C, Zou X, Peng F, Yang W, Li B, Li G, Ge T, Cui R. GABAergic System Dysfunction in Autism Spectrum Disorders. Frontiers in cell and developmental biology. 2021; 9: 781327.

Autism spectrum disorder (ASD) refers to a series of neurodevelopmental diseases characterized by two hallmark symptoms, social communication deficits and repetitive behaviors. Gamma-aminobutyric acid (GABA) is one of the most important inhibitory neurotransmitters in the central nervous system (CNS). GABAergic inhibitory neurotransmission is critical for the regulation of brain rhythm and spontaneous neuronal activities during neurodevelopment. Genetic evidence has identified some variations of genes associated with the GABA system, indicating an abnormal excitatory/inhibitory (E/I) neurotransmission ratio implicated in the pathogenesis of ASD. However, the specific molecular mechanism by which GABA and GABAergic synaptic transmission affect ASD remains unclear. Transgenic technology enables translating genetic variations into rodent models to further investigate the structural and functional synaptic dysregulation related to ASD. In this review, we summarized evidence from human neuroimaging, postmortem, and genetic and pharmacological studies, and put emphasis on the GABAergic synaptic dysregulation and consequent E/I imbalance. We attempt to illuminate the pathophysiological role of structural and functional synaptic dysregulation in ASD and provide insights for future investigation.

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