1. Arai T, Kamagata K, Uchida W, Andica C, Takabayashi K, Saito Y, Tuerxun R, Mahemuti Z, Morita Y, Irie R, Kirino E, Aoki S. Reduced neurite density index in the prefrontal cortex of adults with autism assessed using neurite orientation dispersion and density imaging. Front Neurol;2023;14:1110883.

BACKGROUND: Core symptoms of autism-spectrum disorder (ASD) have been associated with prefrontal cortex abnormalities. However, the mechanisms behind the observation remain incomplete, partially due to the challenges of modeling complex gray matter (GM) structures. This study aimed to identify GM microstructural alterations in adults with ASD using neurite orientation dispersion and density imaging (NODDI) and voxel-wise GM-based spatial statistics (GBSS) to reduce the partial volume effects from the white matter and cerebrospinal fluid. MATERIALS AND METHODS: A total of 48 right-handed participants were included, of which 22 had ASD (17 men; mean age, 34.42 ± 8.27 years) and 26 were typically developing (TD) individuals (14 men; mean age, 32.57 ± 9.62 years). The metrics of NODDI (neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISOVF]) were compared between groups using GBSS. Diffusion tensor imaging (DTI) metrics and surface-based cortical thickness were also compared. The associations between magnetic resonance imaging-based measures and ASD-related scores, including ASD-spectrum quotient, empathizing quotient, and systemizing quotient were also assessed in the region of interest (ROI) analysis. RESULTS: After controlling for age, sex, and intracranial volume, GBSS demonstrated significantly lower NDI in the ASD group than in the TD group in the left prefrontal cortex (caudal middle frontal, lateral orbitofrontal, pars orbitalis, pars triangularis, rostral middle frontal, and superior frontal region). In the ROI analysis of individuals with ASD, a significantly positive correlation was observed between the NDI in the left rostral middle frontal, superior frontal, and left frontal pole and empathizing quotient score. No significant between-group differences were observed in all DTI metrics, other NODDI (i.e., ODI and ISOVF) metrics, and cortical thickness. CONCLUSION: GBSS analysis was used to demonstrate the ability of NODDI metrics to detect GM microstructural alterations in adults with ASD, while no changes were detected using DTI and cortical thickness evaluation. Specifically, we observed a reduced neurite density index in the left prefrontal cortices associated with reduced empathic abilities.

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2. Barbaro J, Winata T, Gilbert M, Nair R, Khan F, Lucien A, Islam R, Masi A, Diaz AM, Dissanayake C, Karlov L, Descallar J, Eastwood J, Hasan I, Jalaludin B, Kohlhoff J, Liaw ST, Lingam R, Ong N, Tam CWM, Woolfenden S, Eapen V. General practitioners’ perspectives regarding early developmental surveillance for autism within the australian primary healthcare setting: a qualitative study. BMC Prim Care;2023 (Aug 10);24(1):159.

BACKGROUND: Significant challenges remain in the early identification of child developmental disabilities in the community. Implementing supports and services early in the life course has been shown to promote positive developmental outcomes for children at high likelihood of developmental disabilities, including autism. As part of a cluster randomised controlled trial, this study seeks to examine and compare the perspectives and experiences of Australian general practitioners (GPs) in relation to a digital developmental surveillance program for autism and usual care pathway, in general practice clinics. METHODS: A qualitative research methodology with semi-structured interviews and thematic inductive analysis underpinned by grounded theory was utilised. All GPs from South Western Sydney (NSW) and Melbourne (Victoria) who participated in the main program (« GP Surveillance for Autism ») were invited to the interview. GPs who provided consent were interviewed either over online or in-person meeting. Interviews were audio-recorded, transcribed, and coded using NVivo12 software. Inductive interpretive approach was adopted and data were analysed thematically. RESULTS: Twenty-three GPs across the two sites (NSW: n = 11; Victoria: n = 12) agreed to be interviewed; data saturation had reached following this number of participants. Inductive thematic coding and analysis yielded eight major themes and highlighted common enablers such as the role of GPs in early identification and subsequent supports, enhanced communication between clinicians/professionals, relationship-building with patients, and having standardised screening tools. Specific facilitators to the feasibility and acceptability of a digital screening program for the early identification of developmental disabilities, including the early signs of autism, and encouraging research and education for GPs. However, several practical and socioeconomic barriers were identified, in addition to limited knowledge and uptake of child developmental screening tools as well as COVID-19 lockdown impacts. Common and specific recommendations involve supporting GPs in developmental/paediatrics training, streamlined screening process, and funding and resources in the primary healthcare services. CONCLUSIONS: The study highlighted the need for practice and policy changes, including further training of GPs alongside sufficient time to complete developmental checks and appropriate financial remuneration through a Medicare billing item. Further research is needed on implementation and scale up of a national surveillance program for early identification of developmental disabilities, including autism.

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3. Chen HB, Warrington R, Mandy W, Yang F, Tang Y, Yang JJ, Li A, Lin YQ, Xu MZ, Jia FJ, Hou CL. Validation of the developmental, dimensional and diagnostic interview -short version (3Di-sv) for diagnosis of autism spectrum disorder in Chinese children. Asian J Psychiatr;2023 (Aug 11);88:103733.

The purpose of this study was to evaluate the psychometric features of the Chinese version of the developmental dimensional diagnostic interview-short version (3Di-sv). A total sample of 138 children including 79 children with autism spectrum disorder (ASD) and 59 typically developing children completed the 3Di-sv interview. The Chinese version of the 3Di-sv has a good internal consistency (0.94). Test-retest analysis confirmed the instrument’s time stability (0.89). The instrument’s concurrent validity with the Autism Behavior Checklist (ABC), the Childhood Autism Rating Scale (CARS) and clinical diagnosis was verified; the correlation between total scores was 0.72, 0.82 and 0.90, respectively. The 3Di-sv significantly distinguished between autistic children and non-autistic children in every area of autism symptoms. Optimal cutoffs were derived using receiver operating characteristics curves. Using clinical diagnosis as criterion, overall sensitivity was 98 % and specificity was 90 %. The study determined that the Chinese version of 3Di-sv can well distinguish autistic children from typically developing children.

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4. Gan H, Su Y, Zhang L, Huang G, Lai C, Lv Y, Li Y. Questionnaire-based analysis of autism spectrum disorders and gastrointestinal symptoms in children and adolescents: a systematic review and meta-analysis. Front Pediatr;2023;11:1120728.

BACKGROUND: Gastrointestinal (GI) symptoms are frequently experienced by children with autism spectrum disorder (ASD), and these symptoms cause difficulties for these children and their families. However, studies of GI symptom prevalence differ significantly. This meta-analysis aimed to analyze the prevalence of GI symptoms in children with ASD. METHODS AND FINDINGS: PubMed, Scopus, Web of Science, EMBASE were electronically searched to collect all literature on gastrointestinal symptoms of children with ASD collected through questionnaires or scales from January 2012 to May 2021. Four researchers independently scanned the literature and extracted information on general characteristics. First author name, year of publication, geographical location, type of study, sample sizes of ASD and control (if any) children, sex and average age, number of GI cases, number of GI symptoms, GI assessment tools (gastrointestinal symptoms scale), autism diagnosis methods, and other necessary data were collected and analyzed using Stata V16. The questionnaires included the Rome, 6-GSI, GIQ, GSRS, GSIQ, ADI-R, PedsQL-GI, parent-report, GI-related, and self-administered questionnaires. Compared with typically developing (TD) children, the odds ratio for In children with ASD with at least one GI symptom was 3.64, and the total prevalence was 55%. The cumulative prevalence rates of various symptoms were summarized, showing that 37% of children with ASD had constipation, 21% had abdominal pain, 19% had diarrhea, 8% had vomiting, and 23% had abdominal distension. CONCLUSIONS: The results of this meta-analysis on GI symptoms in ASD show that patients with ASD are more likely to develop symptoms than TD children. The prevalence of GI symptoms in In children with ASD was 55%. SYSTEMATIC REVIEW REGISTRATION: www.crd.york.ac.uk/PROSPERO, identifier, #CRD42017080579.

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5. Hawthorne K, Loveall SJ. The Effects of Syntactic, Semantic, and Pragmatic Prominence on Pronoun Interpretation in Adults With Intellectual and Developmental Disabilities. J Speech Lang Hear Res;2023 (Aug 10):1-16.

PURPOSE: Pronouns are referentially ambiguous: For example, « she » could refer to any female. Nonetheless, errors in pronoun interpretation rarely occur for adults with typical development (TD) due to several strategies implicitly shared between the talker and listener. The purpose of this study was to test the impacts of syntactic, semantic, and prosodic prominence on pronoun interpretation for adults with intellectual and developmental disabilities (IDD) and TD. METHOD: Adults with IDD (n = 28) and TD (n = 27) listened to ministories involving a pronoun with two potential antecedents that varied in syntactic, semantic, and pragmatic prominence. Subject/first-mentioned antecedents are more syntactically prominent than object antecedents. Semantic prominence was manipulated via verb transitivity: Subjects are more semantically prominent when the verb is highly transitive (e.g., « hit » vs. « see, » a low-transitivity verb for which the subject is merely experiencing the action). Pragmatic prominence was manipulated by placing prosodic focus on one of the two potential antecedents. Eye gaze to images representing the potential antecedents was tracked as a measure of online processing. Responses to a follow-up pronoun interpretation question were also recorded. RESULTS: Adults with TD used syntactic, semantic, and-in early processing-pragmatic prominence when interpreting ambiguous pronouns. Adults with IDD were sensitive to syntactic prominence but to a significantly lesser extent than their peers with TD. CONCLUSIONS: Pronouns are an integral part of everyday conversation, and when the conversational partners do not share common strategies to link ambiguous pronouns with their antecedents, misunderstandings will occur. Results show that adults with IDD only weakly share pronoun interpretation strategies with adults with TD, suggesting that pronouns may be an important focus for intervention for this population. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23875809.

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6. Healthcare Engineering JO. Retracted: Intelligent Somatosensory Interactive Activities Restore Motor Function to Children with Autism. J Healthc Eng;2023;2023:9857376.

[This retracts the article DOI: 10.1155/2022/4516005.].

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7. Ivanova DV, Ziganshin AU. Comparative Assessment of Disturbances of Contractions of the Isolated Uterus in 3- and 9-Month-Old Rats with a Model of Autism. Bull Exp Biol Med;2023 (Jul);175(3):341-344.

We performed a comparative study of the effects of carbachol, α,β-methylene-ATP, β,γ-methylene-ATP, and electric field stimulation on the contractile activity of the isolated uterus from rats aged 3 and 9 months with valproic model of autism. The contractile responses of isolated rat uterine preparations induced by P2X-receptor agonists α,β-methylene-ATP and β,γ-methylene-ATP were significantly lower than in the control. In addition, the contractions of the isolated uterus of 9-month-old rats induced by carbachol were significantly lower than in controls. No significant differences in uterine smooth muscle contractions in both age groups of rats induced by electric field stimulation in comparison with the control were found. Thus, significant impairment of uterine contractile activity was revealed in rats with valproic model of autism, which persisted up to the age of 9 months. The absence of changes in the contractions induced by electric field stimulation suggests that the changes in the contractile activity of the uterus of the rats with modeled autism spectrum disorder are caused by the disorders occurring at the postsynaptic level.

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8. Jourdon A, Wu F, Mariani J, Capauto D, Norton S, Tomasini L, Amiri A, Suvakov M, Schreiner JD, Jang Y, Panda A, Nguyen CK, Cummings EM, Han G, Powell K, Szekely A, McPartland JC, Pelphrey K, Chawarska K, Ventola P, Abyzov A, Vaccarino FM. Modeling idiopathic autism in forebrain organoids reveals an imbalance of excitatory cortical neuron subtypes during early neurogenesis. Nat Neurosci;2023 (Aug 10)

Idiopathic autism spectrum disorder (ASD) is highly heterogeneous, and it remains unclear how convergent biological processes in affected individuals may give rise to symptoms. Here, using cortical organoids and single-cell transcriptomics, we modeled alterations in the forebrain development between boys with idiopathic ASD and their unaffected fathers in 13 families. Transcriptomic changes suggest that ASD pathogenesis in macrocephalic and normocephalic probands involves an opposite disruption of the balance between excitatory neurons of the dorsal cortical plate and other lineages such as early-generated neurons from the putative preplate. The imbalance stemmed from divergent expression of transcription factors driving cell fate during early cortical development. While we did not find genomic variants in probands that explained the observed transcriptomic alterations, a significant overlap between altered transcripts and reported ASD risk genes affected by rare variants suggests a degree of gene convergence between rare forms of ASD and the developmental transcriptome in idiopathic ASD.

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9. Kahveci G, Güneyli A. Examining Conjoint Behavioral Consultation to Support 2e-Autism Spectrum Disorder and Gifted Students in Preschool with Academic and Behavior Concerns. Behav Sci (Basel);2023 (Aug 11);13(8)

Conjoint behavioral consultation (CBC), as adjusted for 2e children with academic and behavioral difficulties, was the focus of this single-subject design study. Three young children from a preschool participated, together with their parents and teachers. Academic enablers for students-intervention, maintenance, and generalization phases; academic and behavioral competencies-intervention, maintenance, and generalization phases; and teachers’, parents’, and students’ perceptions of the intervention’s social validity data were collected among the outcome measures. Findings from multiple participant-related probes pointed to constructive improvements in the phases of intervention, maintenance for listening behavior, and improved on-task skill in intervention, maintenance, and generalization. Additionally, during the consultation, parents and teachers noted improvements in the outcomes of the target behavior such as rhythm keeping, picture-word matching, writing the pictured concept in Turkish, writing the pictured concept in English, short personal story writing, short personal story telling, and verbal math problem solving, and each stakeholder gave the intervention a grade for its social validity. Limitations, potential routes for future study, and implications for preschool CBC intervention are highlighted.

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10. Li C, Li T, Chen Y, Zhang C, Ning M, Qin R, Li L, Wang X, Chen L. Sex differences of the triple network model in children with autism: A resting-state fMRI investigation of effective connectivity. Autism Res;2023 (Aug 10)

Autism spectrum disorder (ASD) has a pronounced male predominance, but the underlying neurobiological basis of this sex bias remains unclear. Gender incoherence (GI) theory suggests that ASD is more neurally androgynous than same-sex controls. Given its central role, altered structures and functions, and sex-dependent network differences in ASD, the triple network model, including the central executive network (CEN), default mode network (DMN), and salience network (SN), has emerged as a candidate for characterizing this sex difference. Here, we measured the sex-related effective connectivity (EC) differences within and between these three networks in 72 children with ASD (36 females, 8-14 years) and 72 typically developing controls (TCs) (36 females, 8-14 years) from 5 sites of the Autism Brain Imaging Data Exchange repositories using a 2 × 2 analysis of covariance factorial design. We also assessed brain-behavior relationships and the effects of age on EC. We found significant diagnosis-by-sex interactions on EC: females with ASD had significantly higher EC than their male counterparts within the DMN and between the SN and CEN. The interaction pattern supported the GI theory by showing that the higher EC observed in females with ASD reflected a shift towards the higher level of EC displayed in male TCs (neural masculinization), and the lower EC seen in males with ASD reflected a shift towards the lower level of EC displayed in female TCs (neural feminization). We also found significant brain-behavior correlations and significant effects of age on EC.

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11. Lin F, Huang W, Lu S, Li J. Cerebral blood flow measured by diffuse correlation spectroscopy in children with autism spectrum disorder. J Biophotonics;2023 (Aug 10):e202300151.

Diffuse correlation spectroscopy (DCS) was used to measure resting-state cerebral blood flow (CBF) in temporal lobes of children with autism spectrum disorder (ASD) and typically developing (TD) children. Twenty-two children with ASD and 34 age-matched TD children were recruited to participate in the experiment. DCS signals were recorded with 3 long source-detector (SD) channels (SD distance = 22.0 mm) and 1 short SD channel (SD distance = 10.5 mm) from each side of the temporal lobe. Significant difference in CBF between left and right hemispheres was observed in ASD group, but not in TD group. With the degree of CBF lateralization as a discrimination feature, a leave-one-out ROC curve was plotted with the area-under-curve (AUC) value of 0.731 ± 0.010, indicating children with ASD could be discriminated from TD children. This suggested CBF lateralization in temporal lobes measured with DCS might serve as a discriminative feature for ASD.

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12. Little LM, Cohen SR, Tomchek S, Baker A, Wallisch A, Dean E. Interventions to Support Participation in Play for Autistic Children and Youth (Dates of Review: 2013-2021). Am J Occup Ther;2023 (Mar 1);77(Suppl 1)

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association’s Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings to support participation in play for autistic1 children and adolescents (birth to 18 yr).

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13. Pace F, Callaghan G. [Are there verbal hallucinations in autism? Review from a historical and transparadigmatic perspective]. Vertex;2023 (Jul 10);34(160, abr.-jun.):87-99.

The differential diagnosis between autism and schizophrenia in childhood has been the subject of numerous controversies. Because verbal hallucinations could be one of the main clinical phenomena when establishing a differential diagnosis, the objective was to investigate the presence or absence of verbal hallucinations in autism. For this, a selective and unsystematic review of the current scientific evidence was carried out. Added to this, the phenomenon of hallucination, and mainly verbal hallucination, was conceptualized from a historical perspective; the relevance given to hallucinations in the delimitation of the mentioned nosographic constructs was broached; and verbal hallucinations in autism were analyzed comparing different paradigms, including contributions from psychoanalysis. We observe that from the side of scientific evidence it is not possible to state strong conclusions regarding the presence or absence of verbal hallucinations in autism. In turn, the historical review of the concept of verbal hallucination from classical psychiatry together with contributions from psychoanalysis, invite us to think that one of the differential characteristics between autism and psychosis is the absence of verbal hallucinations in the first diagnosis, and that if there were hallucinations in autism, these would present different qualities from those of psychosis. We consider it highly relevant to be able to establish this differentiation in the hallucinatory phenomenon in autism, not only in order to establish a differential diagnosis between the two conditions, but also because of the implications that this could have in pharmacotherapy.

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14. Patten K, Murthi K, Chen YL, Onwumere D, Shore S. Interventions for Developing Positive Mental Health in Autistic Individuals (2013-2021). Am J Occup Ther;2023 (Mar 1);77(Suppl 1)

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association’s Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings to support or improve positive mental health for autistic1 individuals.

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15. Pomè A, Tyralla S, Zimmermann E. Altered oculomotor flexibility is linked to high autistic traits. Sci Rep;2023 (Aug 10);13(1):13032.

Autism is a multifaced disorder comprising sensory abnormalities and a general inflexibility in the motor domain. The sensorimotor system is continuously challenged to answer whether motion-contingent errors result from own movements or whether they are due to external motion. Disturbances in this decision could lead to the perception of motion when there is none and to an inflexibility with regard to motor learning. Here, we test the hypothesis that altered processing of gaze-contingent sensations are responsible for both the motor inflexibility and the sensory overload in autism. We measured motor flexibility by testing how strong participants adapted in a classical saccade adaptation task. We asked healthy participants, scored for autistic traits, to make saccades to a target that was displaced either in inward or in outward direction during saccade execution. The amount of saccade adaptation, that requires to shift the internal target representation, varied with the autistic symptom severity. The higher participants scored for autistic traits, the less they adapted. In order to test for visual stability, we asked participants to localize the position of the saccade target after they completed their saccade. We found the often-reported saccade-induced mis-localization in low Autistic Quotient (AQ) participants. However, we also found mislocalization in high AQ participants despite the absence of saccade adaptation. Our data suggest that high autistic traits are associated with an oculomotor inflexibility that might produce altered processing of trans-saccadic vision which might increase the perceptual overstimulation that is experienced in autism spectrum disorders (ASD).

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16. Premoli M, Fyke W, Bellocchio L, Lemaire V, Wolley-Roberts M, Bontempi B, Pietropaolo S. Early Administration of the Phytocannabinoid Cannabidivarin Prevents the Neurobehavioral Abnormalities Associated with the Fmr1-KO Mouse Model of Fragile X Syndrome. Cells;2023 (Jul 25);12(15)

Phytocannabinoids, including the non-addictive cannabis component cannabidivarin (CBDV), have been reported to hold therapeutic potential in several neurodevelopmental disorders (NDDs). Nonetheless, the therapeutic value of phytocannabinoids for treating Fragile X syndrome (FXS), a major NDD, remains unexplored. Here, we characterized the neurobehavioral effects of CBDV at doses of 20 or 100 mg/kg in the Fmr1-knockout (Fmr1-KO) mouse model of FXS using two temporally different intraperitoneal regimens: subchronic 10-day delivery during adulthood (Study 1: rescue treatment) or chronic 5-week delivery at adolescence (Study 2: preventive treatment). Behavioral tests assessing FXS-like abnormalities included anxiety, locomotor, cognitive, social and sensory alterations. Expression of inflammatory and plasticity markers was investigated in the hippocampus and prefrontal cortex. When administered during adulthood (Study 1), the effects of CBDV were marginal, rescuing at the lower dose only the acoustic hyper-responsiveness of Fmr1-KO mice and at both doses their altered hippocampal expression of neurotrophins. When administered during adolescence (Study 2), CBDV at both doses prevented the cognitive, social and acoustic alterations of adult Fmr1-KO mice and modified the expression of several inflammatory brain markers in both wild-type littermates and mutants. These findings warrant the therapeutic potential of CBDV for preventing neurobehavioral alterations associated with FXS, highlighting the relevance of its early administration.

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17. Seyedinia SA, Tarahomi P, Abbarin D, Sedaghat K, Rashidy-Pour A, Yaribeygi H, Vafaei AA, Raise-Abdullahi P. Saffron and crocin ameliorate prenatal valproic acid-induced autistic-like behaviors and brain oxidative stress in the male offspring rats. Metab Brain Dis;2023 (Aug 11)

Autism is a neurobehavioral disease that induces cognitive and behavioral alterations, usually accompanied by oxidative stress in the brain. Crocus sativus (saffron) and its active ingredient, crocin, have potent antioxidative effects that may benefit autistic behaviors. This study aimed to determine the effects of saffron extract and crocin against brain oxidative stress and behavioral, motor, and cognitive deficits in an animal model of autism in male offspring rats. 14 female rats were randomly divided into the saline and valproic acid (VPA) groups. Then, they were placed with mature male rats to mate and produce offspring. VPA (500 mg/kg, i.p.) was injected on day 12.5 of pregnancy (gestational day, GD 12.5) to induce an experimental model of autism. 48 male pups were left undisturbed for 29 days. First-round behavioral tests (before treatments) were performed on 30-33 post-natal days (PND), followed by 28 days of treatment (PND 34-61) with saffron (30 mg/kg, IP), crocin (15 or 30 mg/kg, i.p.), or saline (2 ml/kg, i.p.). The second round of behavioral tests (after treatments) was performed on PND 62-65 to assess the effects of the treatments on behavioral and cognitive features. In the end, animals were sacrificed under deep anesthesia, and their brains were dissected to evaluate the brain oxidative stress parameters, including malondialdehyde (MDA), glutathione (GSH), and catalase (CAT). VPA injection into female rats increased anxiety-like behaviors, enhanced pain threshold, impaired motor functions, disturbed balance power, increased MDA, and decreased GSH and CAT in their male offspring. 28 days of treatment with saffron or crocin significantly ameliorated behavioral abnormalities, reduced MDA, and increased GSH and CAT levels. Brain oxidative stress has been implicated in the pathophysiology of autistic-like behaviors. Saffron and crocin ameliorate anxiety-like behaviors, pain responses, motor functions, and brain oxidative stress parameters in an experimental model of autism. Saffron and crocin may hold promise as herbal-based pharmacological treatments for individuals with autism. However, further histological evidence is needed to confirm their efficacy.

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18. Townes P, Liu C, Panesar P, Devoe D, Lee SY, Taylor G, Arnold PD, Crosbie J, Schachar R. Do ASD and ADHD Have Distinct Executive Function Deficits? A Systematic Review and Meta-Analysis of Direct Comparison Studies. J Atten Disord;2023 (Aug 11):10870547231190494.

OBJECTIVE: To evaluate if children and adolescents with a diagnosis of ASD or ADHD have distinct executive function (EF) profiles. METHODS: Peer-reviewed articles comparing ASD, ADHD, and typically developing individuals under 19 years of age were identified. The domains evaluated were: working memory, response inhibition, planning, cognitive flexibility, attention, processing speed, and visuospatial abilities. RESULTS: Fifty-eight articles met inclusion criteria. Analyses were performed on 45 performance metrics from 24 individual tasks. No differences in EF were found between individuals diagnosed with ASD and ADHD. Individuals diagnosed with ASD and ADHD exhibited worse performance in attention, flexibility, visuospatial abilities, working memory, processing speed, and response inhibition than typically developing individuals. Groups did not differ in planning abilities. CONCLUSION: Children and adolescents with ASD and ADHD have similar EF profiles. Further research is needed to determine if comorbidity accounts for the commonality in executive dysfunction between each disorder.

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19. Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C. Multidisciplinary Management of Rett Syndrome: Twenty Years’ Experience. Genes (Basel);2023 (Aug 11);14(8)

Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. This study provides a comprehensive review of the clinical features, comorbidities and multidisciplinary management of a well-characterized cohort of females with classical Rett syndrome. We aim to improve awareness and understanding of Rett syndrome amongst pediatricians, pediatric subspecialists and allied health professionals to enable early diagnosis and a streamlined enrolment approach for future clinical trials. Rett syndrome, a complex X-linked condition, affecting mainly females, is due to pathogenic variants of the MECP2 gene in most affected individuals. The Rett syndrome Multidisciplinary Management clinic at The Children’s Hospital at Westmead, Sydney, Australia, was established in 2000. This retrospective analysis of individuals who attended the clinic from 2000 to 2020 was performed to identify the incidence and predicted age of onset of Rett syndrome related comorbidities, disease progression and to review management principles. Data collected included age of Rett syndrome diagnosis, MECP2 genotype, clinical features and medical comorbidities, such as sleep disturbance, seizures, breathing irregularities, scoliosis, mobility, hand stereotypies, hand function, constipation, feeding ability, use of gastrostomy, communication skills, QTc prolongation, anthropometry, and bruxism. Analysis of 103 girls who fulfilled the clinical diagnostic criteria for classical Rett syndrome with a pathogenic variant of the MECP2 gene showed a median age of diagnosis of 3 years. The most frequent MECP2 variant was c.502 C>T.

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20. Wormwood KL, Charette L, Ryan JP, Darie CC, Woods AG. A Proteomics Investigation of Salivary Profiles as Potential Biomarkers for Autism Spectrum Disorder (ASD). Protein J;2023 (Aug 11)

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects approximately 1/68 children, with a more recent study suggesting numbers as high as 1/36. According to Diagnostic and Statistical Manual of Mental Disorders, the etiology of ASD is unknown and diagnosis of this disorder is behavioral. There is currently no biomarker signature for ASD, however, identifying a biomarker signature is crucial as it would aid in diagnosis, identifying treatment targets, monitoring treatments, and identifying the etiology of the disorder. Here we used nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) to investigate the saliva from individuals with ASD and matched controls in a 14 vs 14 study. We found numerous proteins to have statistically significant dysregulations, including lactotransferrin, transferrin, polymeric immunoglobulin receptor, Ig A L, Ig J chain, mucin 5 AC, and lipocalin 1 isoform X1. These findings are consistent with previous studies by our lab, and others, and point to dysregulations in the immune system, lipid metabolism and/or transport, and gastrointestinal disturbances, which are common and reoccurring topics in ASD research.

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21. Yang Y, Wang H, Xu H, Yao M, Yu D. Randomized, controlled trial of a mixed early start Denver model for toddlers and preschoolers with autism. Autism Res;2023 (Aug);16(8):1640-1649.

The early start Denver model (ESDM) has been extensively studied as a promising early intervention approach for young children with autism spectrum disorder (ASD). Various methodological drawbacks from earlier ESDM investigations must be rectified to expand the application scopes. For this purpose, the present study recruited a very large sample of 249 autistic children (aged 24-47 months), and used a randomized controlled design to compare outcomes from a mixed ESDM (M-ESDM) intervention with a mixed discrete trial teaching (M-DTT) intervention which remains one of the most commonly-used programming for early intervention. Over the course of a 12-week period, both groups (i.e., M-ESDM and M-DTT groups) received 25 h of intensive intervention per week using individual, group, and parent coaching techniques. Findings showed that: (i) the M-ESDM significantly outperformed the M-DTT in enhancing children’s developmental abilities in gross motor and personal-social skills for toddlers and preschoolers, as well as in language for preschoolers with mild/moderate ASD and toddlers; and (ii) the M-ESDM dramatically reduced the severity of autistic symptoms in toddlers with severe ASD only, when compared to the M-DTT. However, the M-ESDM did not outperform the M-DTT in terms of improving children’s developmental abilities in adaptability and fine motor for toddlers and preschoolers, as well as in language for preschoolers with severe ASD. In addition, when compared to the M-DTT, the M-ESDM did not show an advantage in reducing the severity of autistic symptoms in toddlers with mild/moderate ASD and preschoolers. Clinical Trial Registration: Chinese Clinical Trial Registry. Registration number ChiCTR200039492.

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22. Zhan XL, Pan N, Karatela S, Shi L, Wang X, Liu ZY, Jing J, Li XH, Cai L, Lin LZ. Infant feeding practices and autism spectrum disorder in US children aged 2-5 years: the national survey of children’s health (NSCH) 2016-2020. Int Breastfeed J;2023 (Aug 11);18(1):41.

OBJECTIVE: To investigate the relationship between infant feeding practices and autism spectrum disorder (ASD) among children aged 2-5 years in the United States (US). METHODS: Data from the 2016-2020 National Survey of Children’s Health, a nationally representative cross-sectional survey, were utilized for this study. Questionnaires were administered to parents of children aged 2-5 years to gather information on ASD diagnosis, infant feeding practices, and demographic factors (e.g., child sex, ethnic group, and maternal age at birth). Logistic regression with sample weights was employed to assess the association between infant feeding practices and ASD, while controlling for demographic variables. Polynomial regression models were used to examine trends in exclusive breastfeeding and ever breastfeeding rates among children with and without ASD. RESULTS: A total of 35,050 children aged 2-5 years were analyzed, including 616 diagnosed with ASD, after excluding participants with missing information on breastfeeding and ASD diagnosis. Of these children with ASD, 76.6% (n = 472) had a breastfeeding history, with 67.5% (n = 416) engaged in partial breastfeeding and 9.1% (n = 56) exclusively breastfed. Adjusted odds ratios for each additional month of breastfeeding compared to never being breastfed were 0.98 (95% CI, 0.96-1.01). The adjusted odds ratios for breastfeeding durations of > 0-6 months, > 6-12 months, > 12-24 months, and > 24 months were 0.81 (95% CI, 0.50-1.31), 0.65 (95% CI, 0.36-1.18), 0.81 (95% CI, 0.44-1.49), and 0.48 (95% CI, 0.23-1.01), respectively. Compared to children who were never breastfed, the adjusted odds ratio for children who were ever breastfed was 0.74 (95% CI, 0.47-1.18). Among children with ASD, the proportion of ever breastfeeding declined from 82.0% in 2017 to 64.3% in 2020, while exclusive breastfeeding decreased from 12.0% in 2016 to 4.2% in 2020. CONCLUSIONS AND RELEVANCE: Although no significant association was found between infant feeding practices and ASD among US children aged 2-5 years, the rates of breastfeeding, particularly exclusive breastfeeding, were suboptimal among children with ASD. This highlights the need for specific policies and practices to promote and support breastfeeding among parents of children with ASD or those at high risk of having a child with ASD.

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