Pubmed du 10/06/22

Pubmed du jour

1. Armstrong K, Duvall SW. Introductory editorial to the special issue: Assessment and diagnosis of autism spectrum disorder (ASD) and related clinical decision making in neuropsychological practice. Clin Neuropsychol;2022 (Jun 9):1-5.

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2. Atherton G, Edisbury E, Piovesan A, Cross L. ‘They ask no questions and pass no criticism’: A mixed-methods study exploring pet ownership in autism. J Autism Dev Disord;2022 (Jun 9)

Many autistic people cite a strong attachment to animals, and some studies suggest they may even show a bias towards animals over people. This mixed-methods study explored companion animal attachment in the adult autistic community. In a quantitative study with 735 people, we found that autistic adults were equally attached to their pets as neurotypicals but were less likely to own them, even though pet ownership corresponded with better mental health outcomes. Substituting pets for people also served as a compensatory mechanism for social contact in the autistic sample. In a second qualitative study, we explored the lived experiences of 16 autistic pet owners. The interpretive phenomenological analysis highlighted the benefits and the barriers to animal companionship. Together these mixed methods findings underline how pets improve the lives of their autistic owners. We conclude with specific recommendations for increasing animal companionship opportunities for autistic adults.

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3. Boudewyn MA. Insights Into the Temporal Dynamics of Cognitive Control in Kindergarteners With Autism Spectrum Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging;2022 (Jun);7(6):532-533.

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4. Byiers B. Integrated biopsychosocial pain research in intellectual and developmental disability. Dev Med Child Neurol;2022 (Jun 10)

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5. Cameron LA, Tonge BJ, Howlin P, Einfeld SL, Stancliffe RJ, Gray KM. Social and community inclusion outcomes for adults with autism with and without intellectual disability in Australia. J Intellect Disabil Res;2022 (Jun 8)

BACKGROUND: Research suggests that adults with autism tend to have poor outcomes. Outcomes have mostly been defined using summary outcome ratings, with less focus on specific outcomes such as employment, living situation, social satisfaction, loneliness, and friendships. This study aimed to explore social and community outcomes, including employment, education, living arrangements, friendships, and social satisfaction, for autistic adults with and without intellectual disability. METHOD: Eighty-four adults with autism (mean age 34.2 years, SD = 4.5; 67% with co-occurring intellectual disability), recruited as children and adolescents, participated in the current study. Adult social and community inclusion outcomes were explored through interview and questionnaire, both parent/carer-report and self-report. RESULTS: Participants predominantly lived with family or in supported accommodation, did not pursue higher education, and mostly participated in day activity programmes. Most had limited friendships as reported by parents/carers; however, self-report data (n = 28) indicated that adults were largely satisfied with their social relationships. Overall outcome was poor for 57%, and good/very good for 34%. Adults with intellectual disability generally had poorer outcomes. CONCLUSION: Autistic adults encountered numerous difficulties in leading an independent life. Adults with co-occurring intellectual disability were most likely to experience difficulties; however, outcomes ranged from poor to very good for adults without intellectual disability. Discrepancies in parent/carer-report and self-reported experiences of friendships highlight the need to ensure individual experiences are captured in addition to parent/carer-report. Appropriate resources and programmes are crucial for adults with autism to support them to have the choice to live independently.

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6. Carey ME, Rando J, Melnyk S, James SJ, Snyder N, Salafia C, Croen LA, Fallin MD, Hertz-Picciotto I, Volk H, Newschaffer C, Lyall K. Examining associations between prenatal biomarkers of oxidative stress and ASD-related outcomes using quantile regression. J Autism Dev Disord;2022 (Jun 9)

We examined associations between prenatal oxidative stress (OS) and child autism-related outcomes. Women with an autistic child were followed through a subsequent pregnancy and that younger sibling’s childhood. Associations between glutathione (GSH), glutathione disulfide (GSSG), 8-oxo-deoxyguanine (8-OHdG), and nitrotyrosine and younger sibling Social Responsiveness Scale (SRS) scores were examined using quantile regression. Increasing GSH:GSSG (suggesting decreasing OS) was associated with minor increases in SRS scores (50th percentile β: 1.78, 95% CI: 0.67, 3.06); no other associations were observed. Results from this cohort with increased risk for autism do not support a strong relationship between OS in late pregnancy and autism-related outcomes. Results may be specific to those with enriched autism risk; future work should consider other timepoints and biomarkers.

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7. Chong PF, Torio M, Fujii F, Hirata Y, Matsuoka W, Sonoda Y, Ichimiya Y, Yada Y, Kaku N, Ishimura M, Sasazuki M, Koga Y, Sanefuji M, Sakai Y, Ohga S. Critical vitamin deficiencies in autism spectrum disorder: Reversible and irreversible outcomes. Eur J Clin Nutr;2022 (Jun 10)

Vitamin deficiencies are an emerging concern in the management of children with autism spectrum disorder (ASD). Particular attention is required for recognizing the variable signs caused by unbalanced food intakes. We herein report two patients with multiple vitamin deficiencies who needed critical care showing different prognoses. Patient 1 with ‘Shoshin’ beriberi presenting with cardiac arrest had thiamine deficiency developed severe neurological sequelae despite rapid vitamin supplementation. Patient 2, who had leg pain and a limping gait, showed a rapid recovery with intravenous infusion and tube feeding after being diagnosed with scurvy. A literature search revealed several children with ASD with critically ill thiamine deficiency, but few reports documented a life-threatening condition in the form of cardiac arrest at the onset. Considering the high observation rate of food selectivity in children with ASD, early intervention is required to prevent the exacerbation of vitamin deficiencies to severe neurological disabilities.

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8. Davis SA, Howard K, Ellis AR, Jonas DE, Carey TS, Morrissey JP, Thomas KC. Feasibility of a best-worst scaling exercise to set priorities for autism research. Health Expect;2022 (Jun 8)

BACKGROUND: The preferences of autism stakeholders regarding the top priorities for future autism research are largely unknown. OBJECTIVE: This study had two objectives: First, to examine what autism stakeholders think new research investments should be and the attributes of investment that they consider important, and second, to explore the feasibility, acceptability and outcomes of two prioritization exercises among autism stakeholders regarding their priorities for future research in autism. DESIGN: This was a prospective stakeholder-engaged iterative study consisting of best-worst scaling (BWS) and direct prioritization exercise. SETTING AND PARTICIPANTS: A national snowball sample of 219 stakeholders was included: adults with autism, caregivers, service providers and researchers. MAIN OUTCOME MEASURES: The main outcomes measures were attributes that participants value in future research investments, and priority research investments for future research. RESULTS: Two hundred and nineteen participants completed the exercises, of whom 11% were adults with autism, 58% were parents/family members, 37% were service providers and 21% were researchers. Among stakeholders, the BWS exercises were easier to understand than the direct prioritization, less frequently skipped and yielded more consistent results. The proportion of children with autism affected by the research was the most important attribute for all types of stakeholders. The top three priorities among future research investments were (1) evidence on which child, family and intervention characteristics lead to the best/worst outcomes; (2) evidence on how changes in one area of a child’s life are related to changes in other areas; and (3) evidence on dietary interventions. Priorities were similar for all stakeholder types. CONCLUSIONS: The values and priorities examined here provide a road map for investigators and funders to pursue autism research that matters to stakeholders. PATIENT OR PUBLIC CONTRIBUTION: Stakeholders completed a BWS and direct prioritization exercise to inform us about their priorities for future autism research.

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9. Deserno MK, Bathelt J, Groenman AP, Geurts HM. Probing the overarching continuum theory: data-driven phenotypic clustering of children with ASD or ADHD. Eur Child Adolesc Psychiatry;2022 (Jun 10)

The clinical validity of the distinction between ADHD and ASD is a longstanding discussion. Recent advances in the realm of data-driven analytic techniques now enable us to formally investigate theories aiming to explain the frequent co-occurrence of these neurodevelopmental conditions. In this study, we probe different theoretical positions by means of a pre-registered integrative approach of novel classification, subgrouping, and taxometric techniques in a representative sample (N = 434), and replicate the results in an independent sample (N = 219) of children (ADHD, ASD, and typically developing) aged 7-14 years. First, Random Forest Classification could predict diagnostic groups based on questionnaire data with limited accuracy-suggesting some remaining overlap in behavioral symptoms between them. Second, community detection identified four distinct groups, but none of them showed a symptom profile clearly related to either ADHD or ASD in neither the original sample nor the replication sample. Third, taxometric analyses showed evidence for a categorical distinction between ASD and typically developing children, a dimensional characterization of the difference between ADHD and typically developing children, and mixed results for the distinction between the diagnostic groups. We present a novel framework of cutting-edge statistical techniques which represent recent advances in both the models and the data used for research in psychiatric nosology. Our results suggest that ASD and ADHD cannot be unambiguously characterized as either two separate clinical entities or opposite ends of a spectrum, and highlight the need to study ADHD and ASD traits in tandem.

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10. DeVries L, Pickard K, Boles R, Blakeley-Smith A, Duncan A, Keefer A, Klinger L, Meyer A, Reaven J. The Role of Maternal Anxiety in Treatment Response for Youth with ASD and Co-occurring Anxiety. Child Psychiatry Hum Dev;2022 (Jun 9)

Anxiety disorders occur at higher rates in youth with ASD than in neurotypical youth. Although the efficacy of CBT for anxiety in children with ASD is widely supported, factors that influence treatment outcomes are not well understood. This study examined the role of maternal anxiety in treatment outcomes for youth with ASD. Youth with ASD and anxiety (ages 8 to 14), along with their mothers (n = 87), participated in a group CBT intervention. Results indicated that maternal anxiety did not improve over the course of treatment. However, findings suggest that high levels of maternal anxiety at pre-treatment predicted higher levels of youth anxiety post-treatment. Importantly, the relationship between parent anxiety and youth outcomes was moderated by child age. The findings of the present study may provide initial insight into the role that maternal anxiety plays in treatment outcomes for children with ASD and co-occurring anxiety, particularly when considering child age.

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11. Feng H, Mahoor MH, Dino F. A Music-Therapy Robotic Platform for Children With Autism: A Pilot Study. Front Robot AI;2022;9:855819.

Children with Autism Spectrum Disorder (ASD) experience deficits in verbal and nonverbal communication skills including motor control, turn-taking, and emotion recognition. Innovative technology, such as socially assistive robots, has shown to be a viable method for Autism therapy. This paper presents a novel robot-based music-therapy platform for modeling and improving the social responses and behaviors of children with ASD. Our autonomous social interactive system consists of three modules. Module one provides an autonomous initiative positioning system for the robot, NAO, to properly localize and play the instrument (Xylophone) using the robot’s arms. Module two allows NAO to play customized songs composed by individuals. Module three provides a real-life music therapy experience to the users. We adopted Short-time Fourier Transform and Levenshtein distance to fulfill the design requirements: 1) « music detection » and 2) « smart scoring and feedback », which allows NAO to understand music and provide additional practice and oral feedback to the users as applicable. We designed and implemented six Human-Robot-Interaction (HRI) sessions including four intervention sessions. Nine children with ASD and seven Typically Developing participated in a total of fifty HRI experimental sessions. Using our platform, we collected and analyzed data on social behavioral changes and emotion recognition using Electrodermal Activity (EDA) signals. The results of our experiments demonstrate most of the participants were able to complete motor control tasks with 70% accuracy. Six out of the nine ASD participants showed stable turn-taking behavior when playing music. The results of automated emotion classification using Support Vector Machines illustrates that emotional arousal in the ASD group can be detected and well recognized via EDA bio-signals. In summary, the results of our data analyses, including emotion classification using EDA signals, indicate that the proposed robot-music based therapy platform is an attractive and promising assistive tool to facilitate the improvement of fine motor control and turn-taking skills in children with ASD.

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12. Fredrick SS, Nickerson AB, Sun L, Rodgers JD, Thomeer ML, Lopata C, Todd F. ASD Symptoms, Social Skills, and Comorbidity: Predictors of Bullying Perpetration. J Autism Dev Disord;2022 (Jun 9)

Children with ASD are more likely to be involved in bullying compared to typically developing peers; however, studies rarely examine bullying perpetration and the contributing factors among this population. The primary aim of this study was to examine the extent to which parent-reported ASD symptoms, social skills, and comorbid externalizing and internalizing symptoms predicted bullying perpetration in a sample of 390 children with ASD without intellectual disability. Findings from hierarchical regression analyses indicated that social skill deficits, externalizing symptoms (i.e., hyperactivity, aggression, and conduct problems), and depressive symptoms were associated with higher likelihood of bullying perpetration, while severity of ASD symptoms and anxiety were not significant predictors. Further research is needed to better understand bullying perpetration among children with ASD.

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13. Huashuang Z, Yang L, Chensheng H, Jing X, Bo C, Dongming Z, Kangfu L, Shi-Bin W. Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis. Front Psychiatry;2022;13:875591.

BACKGROUND: A growing number of studies have suggested that transcranial magnetic stimulation (TMS) may represent a novel technique with both investigative and therapeutic potential for autism spectrum disorder (ASD). However, a full spectrum of the adverse effects (AEs) of TMS used in ASD has not been specifically and systematically evaluated. OBJECTIVE: This systematic review and meta-analysis was to assess the prevalence of AEs related to TMS in ASD and to further explore the potentially related factors on the AEs. METHODS: A systematic literature research of articles published before 31 December 2020 was conducted in the databases of PubMed, Embase, Cochrane Library, Ovid, PsycINFO, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP, and WANFANG DATA. AEs reported in the studies were carefully examined and synthesized to understand the safety and tolerability of TMS among ASD. Then, subgroup and sensitivity analyses were performed to examine the potentially related factors on the AEs. PROSPERO registration number: CRD42021239827. RESULTS: Eleven studies were included in the meta-analysis. The pooled prevalence with 95% confidence interval (CI) of AEs was calculated (overall AEs: 25%, 95% CI 18-33%; headache: 10%, 95% CI 3-19%; facial discomfort: 15%, 95% CI 4-29%; irritability 21%, 95% CI 8-37%; pain at the application site: 6%, 95% CI 0-19%; headedness or dizziness: 8%, 95% CI 0-23%). All reported AEs were mild and transient with relatively few serious AEs and can be resolved after having a rest or medication. In addition, the following variables showed no significant change in overall prevalence of AEs: the purpose of using TMS, mean age of participants, whether the stimulation site was dorsolateral pre-frontal cortex (DLPFC), intensity of TMS, and the number of stimulation sessions. CONCLUSION: The overall prevalence of reported AEs of TMS among ASD was 25%. No identified ASD-specific risk factors for TMS-induced AEs were found. Further studies are needed to clarify the variation in the prevalence. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=239827, PROSPERO, identifier: CRD42021239827.

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14. Kiyono T, Ando S, Morishima R, Fujikawa S, Kanata S, Morimoto Y, Endo K, Yamasaki S, Usami S, Hiraiwa-Hasegawa M, Nishida A, Kasai K. Sex-based differences in the longitudinal association between autistic traits and positive psychotic experiences in adolescents: A population-based cohort study. Schizophr Res;2022 (Jun 10);246:1-6.

Previous reports have suggested a cross-sectional association between autistic traits and psychotic experiences (PEs) in adolescents. However, while both autistic traits and PEs show sex-related differences, no studies have directly assessed whether such differences exist in the longitudinal association between autistic traits and PEs. Using a population-based adolescent cohort sample (n = 3007), we tested whether the longitudinal association between autistic traits and positive PEs was affected by sex-based differences using regression analyses. Autistic traits were assessed at 12 years old (timepoint 1 [T1]), and PEs were assessed at 12 and 14 years old (T1 and T2). Subsequently, we tested whether subdomains of autistic traits (difficulties in social interaction, communication, imagination, attention to detail, and attention switching) were associated with subtypes of PEs (auditory hallucinations, visual hallucinations, and delusions) using structural equation modeling, after controlling for PEs at T1, socio-economic status, school performance and parents’ psychiatric disorders. After controlling for PEs at T1, we did not find any associations between autistic traits at T1 and PEs at T2 in both sexes. There was no significant positive or negative association between all subdomains of autistic traits and subtypes of PEs in both sexes. Autistic traits do not seem to predict future PEs in general adolescents regardless of sex.

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15. Kumar NS, Malhi P, Bharti B, Saini L. Restricted and Repetitive Behaviors and Interests in Young Children with Autism: A Comparative Study. Indian J Pediatr;2022 (Jun 9)

OBJECTIVES: To examine the frequency of repetitive behaviors among children with autism spectrum disorder (ASD) and compare it to age-matched developmentally delayed (DD) and typically developing children (TD). METHODS: Twenty-five children (3-8 y) with a diagnosis of ASD were compared to two age-matched control groups namely the DD and TD groups. The Repetitive Behaviors Scale-Revised (RBS-R) was administered to the parents to assess the frequency, severity, and impairment associated with restricted, repetitive behaviors, and interests (RRBIs) displayed. The study was cleared by the institute ethics committee. RESULTS: The three groups were well matched on age and sex distribution and comparisons on the RBS-R showed that the ASD group had a significantly higher total score (F = 51.52, p = 0.0001) and number of items endorsed on the scale (F = 37.91, p = 0.0001). Stepwise multiple regression analysis revealed that 35.8% of the variance in the total RRBI score of the ASD children was explained by the age and severity of autism (F = 6.12. p = .008). Older children with severe ASD features had significantly higher total RRBI scores. CONCLUSIONS: RRBIs are not just specific to autism and should not be used in isolation to identify children with autism. Gaining a complete understanding of the complexity and variability of the restricted interests would help in improving the diagnostic procedures and in the development of a comprehensive therapeutic plan.

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16. Lim ET, Chan Y, Dawes P, Guo X, Erdin S, Tai DJC, Liu S, Reichert JM, Burns MJ, Chan YK, Chiang JJ, Meyer K, Zhang X, Walsh CA, Yankner BA, Raychaudhuri S, Hirschhorn JN, Gusella JF, Talkowski ME, Church GM. Orgo-Seq integrates single-cell and bulk transcriptomic data to identify cell type specific-driver genes associated with autism spectrum disorder. Nat Commun;2022 (Jun 10);13(1):3243.

Cerebral organoids can be used to gain insights into cell type specific processes perturbed by genetic variants associated with neuropsychiatric disorders. However, robust and scalable phenotyping of organoids remains challenging. Here, we perform RNA sequencing on 71 samples comprising 1,420 cerebral organoids from 25 donors, and describe a framework (Orgo-Seq) to integrate bulk RNA and single-cell RNA sequence data. We apply Orgo-Seq to 16p11.2 deletions and 15q11-13 duplications, two loci associated with autism spectrum disorder, to identify immature neurons and intermediate progenitor cells as critical cell types for 16p11.2 deletions. We further applied Orgo-Seq to identify cell type-specific driver genes. Our work presents a quantitative phenotyping framework to integrate multi-transcriptomic datasets for the identification of cell types and cell type-specific co-expressed driver genes associated with neuropsychiatric disorders.

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17. Liu X, Wang Z, Zhang X, Zhang D, Yang Q, Hu P, Li F. LncRNA MEG3 activates CDH2 expression by recruitment of EP300 in valproic acid-induced autism spectrum disorder. Neurosci Lett;2022 (Jun 10):136726.

LncRNAs partake in the biological processes contributing to development of autism spectrum disorder (ASD). The aim of the present study is to investigate the effects of lncRNA maternally expressed gene 3 (MEG3) on viability and apoptosis of hippocampal neurons from ASD rats. Mice with ASD were induced using valproic acid (VPA) with normal saline (NS) as control. We performed microarray analysis on hippocampal tissues of NS rats and ASD rats to screen the differentially expressed lncRNAs. MEG3 loss in rats alleviated the impairment of learning and memory abilities induced by VPA, and promoted neuronal viability and inhibited apoptosis. MEG3 could recruit the transcription factor E1A binding protein p300 (EP300) in the nucleus and promote the cadherin 2 (CDH2) expression. CDH2 depletion in rats ameliorated the impairment of learning and memory capacities in ASD rats. After upregulation of CDH2 in neurons with sh-MEG3, we found diminished viability and increased apoptosis in hippocampal neurons of ASD rats. Taken together, MEG3 supports activation of CDH2 via EP300, thus repressing the viability of hippocampal neurons. Therefore, MEG3 upregulation may be partially responsible for the pathogenesis of ASD.

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18. Movaghar A, Page D, Brilliant M, Mailick M. Advancing artificial intelligence-assisted pre-screening for fragile X syndrome. BMC Med Inform Decis Mak;2022 (Jun 10);22(1):152.

BACKGROUND: Fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism, is significantly underdiagnosed in the general population. Diagnosing FXS is challenging due to the heterogeneity of the condition, subtle physical characteristics at the time of birth and similarity of phenotypes to other conditions. The medical complexity of FXS underscores an urgent need to develop more efficient and effective screening methods to identify individuals with FXS. In this study, we evaluate the effectiveness of using artificial intelligence (AI) and electronic health records (EHRs) to accelerate FXS diagnosis. METHODS: The EHRs of 2.1 million patients served by the University of Wisconsin Health System (UW Health) were the main data source for this retrospective study. UW Health includes patients from south central Wisconsin, with approximately 33 years (1988-2021) of digitized health data. We identified all participants who received a code for FXS in the form of International Classification of Diseases (ICD), Ninth or Tenth Revision (ICD9 = 759.83, ICD10 = Q99.2). Only individuals who received the FXS code on at least two occasions (« Rule of 2 ») were classified as clinically diagnosed cases. To ensure the availability of sufficient data prior to clinical diagnosis to test the model, only individuals who were diagnosed after age 10 were included in the analysis. A supervised random forest classifier was used to create an AI-assisted pre-screening tool to identify cases with FXS, 5 years earlier than the time of clinical diagnosis based on their medical records. The area under receiver operating characteristic curve (AUROC) was reported. The AUROC shows the level of success in identification of cases and controls (AUROC = 1 represents perfect classification). RESULTS: 52 individuals were identified as target cases and matched with 5200 controls. AI-assisted pre-screening tool successfully identified cases with FXS, 5 years earlier than the time of clinical diagnosis with an AUROC of 0.717. A separate model trained and tested on UW Health cases achieved the AUROC of 0.798. CONCLUSIONS: This result shows the potential utility of our tool in accelerating FXS diagnosis in real clinical settings. Earlier diagnosis can lead to more timely intervention and access to services with the goal of improving patients’ health outcomes.

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19. Schrott R, Greeson KW, King D, Symosko Crow KM, Easley CAt, Murphy SK. Cannabis alters DNA methylation at maternally imprinted and autism candidate genes in spermatogenic cells. Syst Biol Reprod Med;2022 (Jun 10):1-13.

Cannabis use in the United States is increasing, with highest consumption among men at their peak reproductive years. We previously demonstrated widespread changes in sperm DNA methylation with cannabis exposure in humans and rats, including genes important in neurodevelopment. Here, we use an in vitro human spermatogenesis model to recapitulate chronic cannabis use and assess DNA methylation at imprinted and autism spectrum disorder (ASD) candidate genes in spermatogonial stem cell (SSC)- and spermatid-like cells. Methylation at maternally imprinted genes SGCE and GRB10 was significantly altered in SSC- and spermatid-like cells, respectively, while PEG3 was significantly differentially methylated in spermatid-like cells. Two of ten randomly selected ASD candidate genes, HCN1 and NR4A2, had significantly altered methylation with cannabis exposure in SSC-like cells. These results support our findings in human cohorts and provide a new tool with which to gain mechanistic insights into the association between paternal cannabis use and risk of ASD in offspring.

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20. Seo SS, Louros SR, Anstey N, Gonzalez-Lozano MA, Harper CB, Verity NC, Dando O, Thomson SR, Darnell JC, Kind PC, Li KW, Osterweil EK. Excess ribosomal protein production unbalances translation in a model of Fragile X Syndrome. Nat Commun;2022 (Jun 10);13(1):3236.

Dysregulated protein synthesis is a core pathogenic mechanism in Fragile X Syndrome (FX). The mGluR Theory of FX predicts that pathological synaptic changes arise from the excessive translation of mRNAs downstream of mGlu(1/5) activation. Here, we use a combination of CA1 pyramidal neuron-specific TRAP-seq and proteomics to identify the overtranslating mRNAs supporting exaggerated mGlu(1/5) -induced long-term synaptic depression (mGluR-LTD) in the FX mouse model (Fmr1(-/y)). Our results identify a significant increase in the translation of ribosomal proteins (RPs) upon mGlu(1/5) stimulation that coincides with a reduced translation of long mRNAs encoding synaptic proteins. These changes are mimicked and occluded in Fmr1(-/y) neurons. Inhibiting RP translation significantly impairs mGluR-LTD and prevents the length-dependent shift in the translating population. Together, these results suggest that pathological changes in FX result from a length-dependent alteration in the translating population that is supported by excessive RP translation.

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21. Sharma A, Bhalla S, Mehan S. PI3K/AKT/mTOR signalling inhibitor chrysophanol ameliorates neurobehavioural and neurochemical defects in propionic acid-induced experimental model of autism in adult rats. Metab Brain Dis;2022 (Jun 10)

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder marked by social and communication deficits as well as repetitive behaviour. Several studies have found that overactivation of the PI3K/AKT/mTOR signalling pathways during brain development plays a significant role in autism pathogenesis. Overexpression of the PI3K/AKT/mTOR signalling pathway causes neurological disorders by increasing cell death, neuroinflammation, and oxidative stress. Chrysophanol, also known as chrysophanic acid, is a naturally occurring chemical obtained from the plant Rheum palmatum. This study aimed to examine the neuroprotective effect of CPH on neurobehavioral, molecular, neurochemical, and gross pathological alterations in ICV-PPA induced experimental model of autism in adult rats. The effects of ICV-PPA on PI3K/AKT/mTOR downregulation in the brain were studied in autism-like rats. Furthermore, we investigated how CPH affected myelin basic protein (MBP) levels in rat brain homogenate and apoptotic biomarkers such as caspase-3, Bax, and Bcl-2 levels in rat brain homogenate and blood plasma samples. Rats were tested for behavioural abnormalities such as neuromuscular dysfunction using an actophotometer, motor coordination using a beam crossing task (BCT), depressive behaviour using a forced swim test (FST), cognitive deficiency, and memory consolidation using a Morris water maze (MWM) task. In PPA-treated rats, prolonged oral CPH administration from day 12 to day 44 of the experimental schedule reduces autistic-like symptoms. Furthermore, in rat brain homogenates, blood plasma, and CSF samples, cellular, molecular, and cell death markers, neuroinflammatory cytokines, neurotransmitter levels, and oxidative stress indicators were investigated. The recent findings imply that CPH also restores abnormal neurochemical levels and may prevent autism-like gross pathological alterations, such as demyelination volume, in the rat brain.

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22. Sterrett K, Magaña MT, Gulsrud A, Paparella T, Kasari C. Predictors of Attrition in a Randomized Trial of a Social Communication Intervention for Infant-Toddlers at Risk for Autism. J Autism Dev Disord;2022 (Jun 9)

Addressing factors that make it more likely for families to attrite from early intervention trials will allow researchers to ensure that families reap the full benefits of participation. This study was an analysis of 78 children (Mage = 18.38 months, SD = 5.78) at risk for autism participating in a university-based randomized controlled trial of two 8-week long early intervention programs. Overall, attrition through 8-weeks was low, approximately 13%, however by the one-year follow-up attrition rates were approximately 50%. The most consistent predictor of attrition was the distance that families had to travel to the university. These data highlight the importance of providing services and support (e.g., financial and logistic) during follow-up to families to maximize their participation. Clincaltrials.gov Identifier: NCT01874327, 6/11/2013.

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23. Wang JE, Tsai SJ, Chen TJ, Wang TJ, Chen MH. Risk of Retinal Disease in Patients with Autism Spectrum Disorder. CNS Spectr;2022 (Jun 9):1-27.

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24. Yang YJ, Chung KM. Pilot Randomized Control Trial of an App-Based CBT Program for Reducing Anxiety in Individuals with ASD without Intellectual Disability. J Autism Dev Disord;2022 (Jun 10)

This study developed and tested the effectiveness of an app-based cognitive behavioral therapy (CBT) program in alleviating anxiety among adolescents and adults with autism without co-occurring intellectual disability. Thirty participants from 15 to 35 years old were randomly assigned to either the intervention or waitlist control group, and self- and caregiver proxy report questionnaires were administered, accompanied by direct behavior observation before and after the intervention period. There was a significant decrease in anxiety level, an increase in positive affect, and a decline in stereotypic behaviors, hyperactivity, noncompliance, and inappropriate speech in proxy reports for the intervention group, compared to the control group. A significant rise in passive response in the direct observation was also seen in the intervention group.

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25. Yarımkaya E, Esentürk OK, İlhan EL, Kurtipek S, Işım AT. Zoom-delivered Physical Activities Can Increase Perceived Physical Activity Level in Children with Autism Spectrum Disorder: a Pilot Study. J Dev Phys Disabil;2022 (Jun 3):1-19.

Although the benefits of regular physical activity are clearly expressed, children with Autism Spectrum Disorder (ASD) are less physically active than their typically developing peers. Recent empirical studies have revealed that the level of physical activity of children with ASD has further decreased during the novel coronavirus (COVID-19) pandemic, which has adversely affected the whole world. The aim of this study was to evaluate the potential efficacy of a Zoom-delivered physical activities for children with Autism Spectrum Disorder (ASD). Twenty-two families (parent and child dyads) participated in the study. Families were assigned randomly to an experimental group (n = 11) and a control group (n = 11). Families in the experimental group were engaged in 10 weeks of the Zoom-delivered physical activities. Data were collected using multiple data collection strategies (Personal Information Form- Leisure Time Exercise Questionnaire-Semi-Structured Interview). After the Zoom-delivered physical activities, a significant increase was observed in the physical activity level of children with ASD in the experimental group (F = 95.396, p = 0.000, Ƞ (2)  = 0.834). Parents reported that Zoom-delivered physical activities are a viable and useful intervention to increase the level of physical activity of children with ASD. The findings suggest that Zoom-delivered physical activities merit further investigation as an intervention to increase physical activity in children with ASD.

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