1. Arpone M, Bretherton L, Amor DJ, Hearps SJC, Rogers C, Field MJ, Hunter MF, Santa Maria L, Alliende AM, Slee J, Godler DE, Baker EK. Agreement between parents’ and clinical researchers’ ratings of behavioral problems in children with fragile X syndrome and chromosome 15 imprinting disorders. Res Dev Disabil;2022 (Sep 28);131:104338.

BACKGROUND: Despite the increasing number of clinical trials involving children with neurodevelopmental disorders, appropriate and objective outcome measures for behavioral symptoms are still required. AIM: This study assessed the agreement between parents’ and clinical researchers’ ratings of behavioral problem severity in children with fragile X syndrome (FXS) and chromosome 15 imprinting disorders. METHODS AND PROCEDURES: The cohort comprised 123 children (64% males), aged 3-17 years, with FXS (n = 79), Prader-Willi (PWS; n = 19), Angelman (AS; n = 15), and Chromosome 15q duplication (n = 10) syndromes. Specific items from the Autism Diagnostic Observation Schedule-Second Edition and Aberrant Behavior Checklist-Community Edition mapping to corresponding behavioral domains were selected ad-hoc, to assess behavioral problems. OUTCOMES AND RESULTS: Inter-rater agreement for the cohort was slight for self-injury (Intraclass Correlation Coefficient (ICC) = 0.12), fair for tantrums/aggression (0.24) and mannerisms/stereotypies (0.25), and moderate for hyperactivity (0.48). When stratified by diagnosis, ICC ranged from poor (0; self-injury, AS and PWS) to substantial (0.48; hyperactivity, females with FXS). CONCLUSIONS AND IMPLICATIONS: The high level of inter-rater disagreement across most domains suggests that parents’ and researchers’ assessments led to discrepant appraisal of behavioral problem severity. These findings have implications for treatment targets and outcome measure selection in clinical trials, supporting a multi-informant approach.

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2. Bamgboye MA, Herold KG, Vieira DCO, Traficante MK, Rogers PJ, Ben-Johny M, Dick IE. CaV1.2 channelopathic mutations evoke diverse pathophysiological mechanisms. J Gen Physiol;2022 (Nov 7);154(11)

The first pathogenic mutation in CaV1.2 was identified in 2004 and was shown to cause a severe multisystem disorder known as Timothy syndrome (TS). The mutation was localized to the distal S6 region of the channel, a region known to play a major role in channel activation. TS patients suffer from life-threatening cardiac symptoms as well as significant neurodevelopmental deficits, including autism spectrum disorder (ASD). Since this discovery, the number and variety of mutations identified in CaV1.2 have grown tremendously, and the distal S6 regions remain a frequent locus for many of these mutations. While the majority of patients harboring these mutations exhibit cardiac symptoms that can be well explained by known pathogenic mechanisms, the same cannot be said for the ASD or neurodevelopmental phenotypes seen in some patients, indicating a gap in our understanding of the pathogenesis of CaV1.2 channelopathies. Here, we use whole-cell patch clamp, quantitative Ca2+ imaging, and single channel recordings to expand the known mechanisms underlying the pathogenesis of CaV1.2 channelopathies. Specifically, we find that mutations within the S6 region can exert independent and separable effects on activation, voltage-dependent inactivation (VDI), and Ca2+-dependent inactivation (CDI). Moreover, the mechanisms underlying the CDI effects of these mutations are varied and include altered channel opening and possible disruption of CDI transduction. Overall, these results provide a structure-function framework to conceptualize the role of S6 mutations in pathophysiology and offer insight into the biophysical defects associated with distinct clinical manifestations.

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3. Bloor D, Ballantyne C, Gillespie-Smith K, Wilson C, Hendry G. Investigating the challenges of teaching sex education to autistic learners: A qualitative exploration of teachers’ experiences. Res Dev Disabil;2022 (Sep 28);131:104344.

BACKGROUND: Sex education is essential as it equips individuals with the knowledge to live independent and safe sex lives. However, in the United Kingdom, sex education is not particularly accessible for autistic learners which may lead to a lack of knowledge around appropriate sexual behaviours. AIMS: The current study focusses on the challenges of teaching sex education to autistic learners. METHODS AND PROCEDURES: The data was produced through one-to-one interviews with thirteen educational practitioners that have experienced delivering sex education to autistic learners. OUTCOMES AND RESULTS: Reflexive thematic analysis (Braun & Clarke, 2006) was used to interpret the data, producing themes of (1) Pedagogical Restrictions, and (2) Sexual Impulses. CONCLUSIONS AND IMPLICATIONS: These findings demonstrated that the main challenges of teaching sex education to autistic learners pertained to Pedagogical Restrictions in the classroom, and learners’ own sexual impulses. These findings are a positive step towards understanding how to adapt sex education lessons to make them more inclusive and accessible for learners with autism. This study contributes to developing understanding around how to support autistic learners, highlighting gaps in the current sex education curriculum for policy makers, and enabling those surrounding autistic individuals to best support them with body transformations.

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4. Brignell A, Harwood RC, May T, Woolfenden S, Montgomery A, Iorio A, Williams K. Overall prognosis of preschool autism spectrum disorder diagnoses. Cochrane Database Syst Rev;2022 (Sep 28);9(9):CD012749.

BACKGROUND: Autism spectrum disorder is a neurodevelopmental disorder characterised by social communication difficulties, restricted interests and repetitive behaviours. The clinical pathway for children with a diagnosis of autism spectrum disorder is varied, and current research suggests some children may not continue to meet diagnostic criteria over time. OBJECTIVES: The primary objective of this review was to synthesise the available evidence on the proportion of preschool children who have a diagnosis of autism spectrum disorder at baseline (diagnosed before six years of age) who continue to meet diagnostic criteria at follow-up one or more years later (up to 19 years of age). SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO, and eight other databases in October 2017 and ran top-up searches up to July 2021. We also searched reference lists of relevant systematic reviews. SELECTION CRITERIA: Two review authors independently assessed prospective and retrospective follow-up studies that used the same measure and process within studies to diagnose autism spectrum disorder at baseline and follow-up. Studies were required to have at least one year of follow-up and contain at least 10 participants. Participants were all aged less than six years at baseline assessment and followed up before 19 years of age. DATA COLLECTION AND ANALYSIS: We extracted data on study characteristics and the proportion of children diagnosed with autism spectrum disorder at baseline and follow-up. We also collected information on change in scores on measures that assess the dimensions of autism spectrum disorder (i.e. social communication and restricted interests and repetitive behaviours). Two review authors independently extracted data on study characteristics and assessed risk of bias using a modified quality in prognosis studies (QUIPS) tool. We conducted a random-effects meta-analysis or narrative synthesis, depending on the type of data available. We also conducted prognostic factor analyses to explore factors that may predict diagnostic outcome. MAIN RESULTS: In total, 49 studies met our inclusion criteria and 42 of these (11,740 participants) had data that could be extracted. Of the 42 studies, 25 (60%) were conducted in North America, 13 (31%) were conducted in Europe and the UK, and four (10%) in Asia. Most (52%) studies were published before 2014. The mean age of the participants was 3.19 years (range 1.13 to 5.0 years) at baseline and 6.12 years (range 3.0 to 12.14 years) at follow-up. The mean length of follow-up was 2.86 years (range 1.0 to 12.41 years). The majority of the children were boys (81%), and just over half (60%) of the studies primarily included participants with intellectual disability (intelligence quotient < 70). The mean sample size was 272 (range 10 to 8564). Sixty-nine per cent of studies used one diagnostic assessment tool, 24% used two tools and 7% used three or more tools. Diagnosis was decided by a multidisciplinary team in 41% of studies. No data were available for the outcomes of social communication and restricted and repetitive behaviours and interests. Of the 42 studies with available data, we were able to synthesise data from 34 studies (69% of all included studies; n = 11,129) in a meta-analysis. In summary, 92% (95% confidence interval 89% to 95%) of participants continued to meet diagnostic criteria for autism spectrum disorder from baseline to follow-up one or more years later; however, the quality of the evidence was judged as low due to study limitations and inconsistency. The majority of the included studies (95%) were rated at high risk of bias. We were unable to explore the outcomes of change in social communication and restricted and repetitive behaviour and interests between baseline and follow-up as none of the included studies provided separate domain scores at baseline and follow-up. Details on conflict of interest were reported in 24 studies. Funding support was reported by 30 studies, 12 studies omitted details on funding sources and two studies reported no funding support. Declared funding sources were categorised as government, university or non-government organisation or charity groups. We considered it unlikely funding sources would have significantly influenced the outcomes, given the nature of prognosis studies. AUTHORS' CONCLUSIONS: Overall, we found that nine out of 10 children who were diagnosed with autism spectrum disorder before six years of age continued to meet diagnostic criteria for autism spectrum disorder a year or more later, however the evidence was uncertain. Confidence in the evidence was rated low using GRADE, due to heterogeneity and risk of bias, and there were few studies that included children diagnosed using a current classification system, such as the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the eleventh revision of the International Classification of Diseases (ICD-11). Future studies that are well-designed, prospective and specifically assess prognosis of autism spectrum disorder diagnoses are needed. These studies should also include contemporary diagnostic assessment methods across a broad range of participants and investigate a range of relevant prognostic factors.

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5. Byrne K, Zheng S, Bishop S, Boucher J, Ghods S, Kim SH, Lord C. Behavioral responses to fevers and other medical events in children with and without ASD. Autism Res;2022 (Sep 26)

Anecdotal reports and a small number of research studies suggest possible behavioral improvements in children with autism spectrum disorders (ASD) during a fever. However, previous studies rely largely on retrospective reports of this phenomenon. Establishing a robust association between fever and reduction of ASD-related symptoms would promote opportunities for the development of innovative therapeutic interventions for children with ASD. In the current study, prospective data were collected from 141 children with ASD and 103 typically developing (TD) controls using parent responses to an 11-item behavioral survey. Behaviors when no illness was present, during a fever, the week after a fever, and during non-febrile illnesses for TD and ASD children were compared. Profiles of cases in which caregivers reported consistent behavioral improvements during fever are described. Data indicated worsening social, emotional/behavioral, and somatic symptoms during a fever regardless of diagnosis, with children with ASD demonstrating greater worsening of behaviors during a fever than TD children. Only three out of 141 children with ASD demonstrated consistent behavioral improvements during a fever; these children had a range of cognitive and adaptive skills. Children with ASD had stronger negative responses to fever than TD children. These findings contradict previous literature suggesting behavioral improvements for children with ASD. While improvements may occur for some children, it does not appear to be a common phenomenon. Additional research is needed to elucidate the nature of behavioral improvements in the subset of children with ASD who may respond positively to fever. LAY SUMMARY: This study examines behavioral changes during fever and other medical events in children with autism compared to behavioral changes in a typically developing control group. Previous research and consistent subjective reports from parents and pediatricians suggest the possibility of behavioral improvements for children with autism during a fever. There is a lack of methodically collected data examining these effects. In the current study, children with autism consistently had stronger and more frequent negative behavior changes during fever than typically developing children (who also primarily showed worsening of behavior during fevers). Three out of 141 autistic children, and no typical children, showed improvements in varied areas during fevers.

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6. Chen Y, Ma K, Si H, Duan Y, Zhai H. Network pharmacology integrated molecular docking to reveals the autism and mechanism of Baohewan Heshiwei Wen Dan Tang. Curr Pharm Des;2022 (Sep 26)

BACKGROUND: In recent years, the prevalence and mortality of autism spectrum disorder (ASD) have been increasing. The clinical clinical features are different with different cases, so the treatment ways are necessary for each one. OBJECTIVE: Baohewan Heshiwei Wen Dan Tang (BHWDT) has been recommended for treating autistic spectrum disorder. To investigate the mechanism of action and how the compounds interact with ASD targets, network pharmacology and molecular docking methods were used in this study. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the active components according to index of oral bio-activity and drug likeness. Then, TCMSP and Swiss Target Prediction databases were used to screen potential target genes of active components. The related target genes of ASD were obtained from the Gene Cards database. Matescape database was utilized to get gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation of gene targets. Composition-target-pathway (C-T-P) and a protein-protein interaction (PPI) networks were built with Cytoscape 3.8.2 software. RESULTS: Interaction of the main active components of BHWDT were verified by the molecular docking. The key targets of MAPK1, IL6, CXCL8 and TP53 of BHWDT for were obtained. The key active components Quercetin, Kaempferol and Iuteolin of BHWDT could bind with MAPK1, IL6, CXCL8 and TP53 of BHWDT, respectively. CONCLUSION: BHWDT can be higher effectively for treating ASD and which can help us to understand multiple targets and multiple pathways mechanism.

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7. Cheng L, Zhan L, Huang L, Zhang H, Sun J, Huang G, Wang Y, Li M, Li H, Gao Y, Jia X. The atypical functional connectivity of Broca’s area at multiple frequency bands in autism spectrum disorder. Brain Imaging Behav;2022 (Sep 26)

As a developmental disorder, autism spectrum disorder (ASD) has drawn much attention due to its severe impacts on one’s language capacity. Broca’s area, an important brain region of the language network, is largely involved in language-related functions. Using the Autism Brain Image Data Exchange (ABIDE) dataset, a mega-analysis was performed involving a total of 1454 participants (including 618 individuals with ASD and 836 healthy controls (HCs). To detect the neural pathophysiological mechanism of ASD from the perspective of language, we conducted a functional connectivity (FC) analysis with Broca’s area as the seed in multiple frequency bands (conventional: 0.01-0.08 Hz; slow-4: 0.027-0.073 Hz; slow-5: 0.01-0.027 Hz). We found that compared with HC, ASD patients demonstrated increased FC in the left thalamus, left precuneus, left anterior cingulate and paracingulate gyri, and left medial orbital of the superior frontal gyrus in the conventional frequency band (0.01-0.08 Hz). The results of the slow-5 frequency band (0.01-0.027 Hz) presented increased FC values of the left precuneus, left medial orbital of the superior frontal gyrus, right medial orbital of the superior frontal gyrus and right thalamus. No significant cluster was detected in the slow-4 frequency band (0.027-0.073 Hz). In conclusion, the abnormal functional connectivity in patients with ASD has frequency-specific properties. Furthermore, the slow-5 frequency band (0.01-0.027 Hz) mainly contributed to the findings of the conventional frequency band (0.01-0.08 Hz). The current study might shed new light on the neural pathophysiological mechanism of language impairments in people with ASD.

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8. Ebrahimi P, Seyedmirzaei H, Moradi K, Bagheri S, Moeini M, Mohammadi MR, Akhondzadeh S. Cilostazol as adjunctive therapy in treatment of children with autism spectrum disorders: a double-blind and placebo-controlled randomized trial. Int Clin Psychopharmacol;2022 (Sep 15)

We aimed to evaluate cilostazol therapeutic effects on aberrant behaviors of autism spectrum disorder (ASD) children and its safety profile in a double-blind, randomized clinical trial. Sixty-six children with confirmed ASD were allocated to receive either daily 50-mg cilostazol (increased to 100 mg/day after 2 weeks) or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and a checklist of probable adverse effects were used to assess the behavioral outcomes and safety profile at weeks 0, 5, and 10 of the study. Sixty-one participants, with comparable baseline characteristics, completed the trial. Unlike other ABC-C subscales, repeated-measures analysis showed significant effect for time × treatment interaction in the hyperactivity subscale (P = 0.047; partial eta squared = 0.06). We used the median value for the baseline score hyperactivity subscale [median (interquartile range) = 31 (24-37)] to stratify participants to higher hyperactivity and lower hyperactivity subgroups and found that only participants with higher hyperactivity benefit from cilostazol adjunctive therapy (P = 0.028; partial eta squared = 0.14). Cilostazol could be considered as a safe agent with beneficial effects on hyperactivity in children with ASD and higher levels of hyperactivity.

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9. Hayward SM, Flower RL, Denney KE, Bury S, Richdale AL, Dissanayake C, Hedley D. The Efficacy of Disability Employment Service (DES) Providers Working with Autistic Clients. J Autism Dev Disord;2022 (Sep 28):1-14.

The efficacy of the Australian Disability Employment Services (DES) for autistic jobseekers has not been examined and is currently undergoing Government reform. To help inform the new DES strategy, we sought the views of: 24 autistic individuals; seven family members of autistic individuals, and; 46 DES employees. Data were collected using surveys and interviews. Data were analysed using Mann Whitney tests plus deductive thematic analysis based on Nicholas and colleagues’ ecosystems model. Participants highlighted a need to adapt existing policies to enhance flexibility of the DES model. There was participant consensus that DES staff require specific education and training to meet the needs of autistic people. Suggestions to inform the new model of DES for autistic people are made.

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10. Hsieh MY, Tuan LH, Chang HC, Wang YC, Chen CH, Shy HT, Lee LJ, Gau SS. Altered synaptic protein expression, aberrant spine morphology, and impaired spatial memory in Dlgap2 mutant mice, a genetic model of autism spectrum disorder. Cereb Cortex;2022 (Sep 28)

A microdeletion of approximately 2.4 Mb at the 8p23 terminal region has been identified in a Taiwanese autistic boy. Among the products transcribed/translated from genes mapped in this region, the reduction of DLGAP2, a postsynaptic scaffold protein, might be involved in the pathogenesis of autism spectrum disorder (ASD). DLGAP2 protein was detected in the hippocampus yet abolished in homozygous Dlgap2 knockout (Dlgap2 KO) mice. In this study, we characterized the hippocampal phenotypes in Dlgap2 mutant mice. Dlgap2 KO mice exhibited impaired spatial memory, indicating poor hippocampal function in the absence of DLGAP2. Aberrant expressions of postsynaptic proteins, including PSD95, SHANK3, HOMER1, GluN2A, GluR2, mGluR1, mGluR5, βCAMKII, ERK1/2, ARC, BDNF, were noticed in Dlgap2 mutant mice. Further, the spine density was increased in Dlgap2 KO mice, while the ratio of mushroom-type spines was decreased. We also observed a thinner postsynaptic density thickness in Dlgap2 KO mice at the ultrastructural level. These structural changes found in the hippocampus of Dlgap2 KO mice might be linked to impaired hippocampus-related cognitive functions such as spatial memory. Mice with Dlgap2 deficiency, showing signs of intellectual disability, a common co-occurring condition in patients with ASD, could be a promising animal model which may advance our understanding of ASD.

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11. Jameson C, Boulton KA, Silove N, Guastella AJ. Eczema and related atopic diseases are associated with increased symptom severity in children with autism spectrum disorder. Transl Psychiatry;2022 (Sep 28);12(1):415.

Growing evidence indicates that autism spectrum disorder (ASD) has diverse genetic, neurological, and environmental factors that contribute to its neurodevelopmental course. Interestingly, childhood ASD is often accompanied by skin disorders, such as eczema, and other related atopic manifestations. This link may be due to the shared embryonic origin of epidermal and neural tissue. Accordingly, we consider the potential influence of a skin-brain co-vulnerability and ensuing atopic cascade on ASD symptomatology by investigating whether atopic disorders (asthma, allergies, eczema and hay fever) are associated with increased symptom severity in children with ASD. Overall, 45 atopic and 93 non-atopic children with ASD were assessed using the ADOS-2 on scores of total, social and non-social symptoms. Differences in ASD symptom severity were further evaluated as a function of atopic disease type. Atopic children displayed greater symptom severity overall and in the social domain, relative to non-atopic participants. Atopic children were 2.4 times more likely to experience overall impairments classified within the ADOS-2 highest-level severity bracket and 2.7 times more likely to show social difficulties in this range. Moreover, those reporting comorbid eczema displayed increased symptom severity relative to both their non-atopic peers and those reporting asthma and allergies. Taken together, findings indicate that atopic disorders, and particularly comorbid eczema, are associated with increases in ASD symptom severity. Findings provide grounds for future investigations into this link between childhood skin diseases and ASD symptom severity to advance our understanding of neurodevelopment and to develop targeted assessment and intervention opportunities.

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12. Jonak CR, Pedapati EV, Schmitt LM, Assad SA, Sandhu MS, DeStefano L, Ethridge L, Razak KA, Sweeney JA, Binder DK, Erickson CA. Baclofen-associated neurophysiologic target engagement across species in fragile X syndrome. J Neurodev Disord;2022 (Sep 27);14(1):52.

BACKGROUND: Fragile X syndrome (FXS) is the most common inherited form of neurodevelopmental disability. It is often characterized, especially in males, by intellectual disability, anxiety, repetitive behavior, social communication deficits, delayed language development, and abnormal sensory processing. Recently, we identified electroencephalographic (EEG) biomarkers that are conserved between the mouse model of FXS (Fmr1 KO mice) and humans with FXS. METHODS: In this report, we evaluate small molecule target engagement utilizing multielectrode array electrophysiology in the Fmr1 KO mouse and in humans with FXS. Neurophysiologic target engagement was evaluated using single doses of the GABA(B) selective agonist racemic baclofen (RBAC). RESULTS: In Fmr1 KO mice and in humans with FXS, baclofen use was associated with suppression of elevated gamma power and increase in low-frequency power at rest. In the Fmr1 KO mice, a baclofen-associated improvement in auditory chirp synchronization was also noted. CONCLUSIONS: Overall, we noted synchronized target engagement of RBAC on resting state electrophysiology, in particular the reduction of aberrant high frequency gamma activity, across species in FXS. This finding holds promise for translational medicine approaches to drug development for FXS, synchronizing treatment study across species using well-established EEG biological markers in this field. TRIAL REGISTRATION: The human experiments are registered under NCT02998151.

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13. Kim Y, Kadlaskar G, Keehn RM, Keehn B. Measures of tonic and phasic activity of the locus coeruleus-norepinephrine system in children with autism spectrum disorder: An event-related potential and pupillometry study. Autism Res;2022 (Sep 26)

A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event-related potential [ERP]) indices may provide meaningful insights about the nature of LC-NE function in ASD. Twenty-four children with ASD and 27 age- and nonverbal-IQ matched typically developing (TD) children completed two experiments: (1) a resting eye-tracking task to measure tonic pupil diameter, and (2) a three-stimulus oddball paradigm to measure phasic responsivity using PDR and ERP. Consistent with prior reports, our results indicate that children with ASD exhibit increased tonic (resting pupil diameter) and reduced phasic (PDR and ERP) activity of the LC-NE system compared to their TD peers. For both groups, decreased phasic responsivity was associated with increased resting pupil diameter. Lastly, tonic and phasic LC-NE indices were primarily related to measures of attention-deficit/hyperactivity disorder (ADHD), and not ASD, symptomatology. These findings expand our understanding of neurophysiological differences present in ASD and demonstrate that aberrant LC-NE activation may be associated with atypical arousal and decreased responsivity to behaviorally-relevant information in ASD. LAY SUMMARY: The locus coeruleus (LC), a small brain stem nucleus, is the primary source of norepinephrine (NE), plays an important role in attention and arousal, and may function differently in autism spectrum disorder (ASD). Using pupillometry and event-related potentials, we found that children with ASD show increased tonic and reduced phasic LC-NE activation compared to their typically developing peers. These differences in LC-NE function may be associated with impairments in attention and arousal regulation in ASD.

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14. Mishra A, Singla R, Kumar R, Sharma A, Joshi R, Sarma P, Kaur G, Prajapat M, Bhatia A, Medhi B. Granulocyte Colony-Stimulating Factor Improved Core Symptoms of Autism Spectrum Disorder via Modulating Glutamatergic Receptors in the Prefrontal Cortex and Hippocampus of Rat Brains. ACS Chem Neurosci;2022 (Sep 27)

Chronic neuroinflammation-induced anomalous glutamate receptor activation has been identified as one of the important factors in the pathogenesis of autism spectrum disorder (ASD). Thus, the current study was designed to elucidate the neuroprotective effect of the granulocyte colony-stimulating factor (G-CSF), a haemopoietic growth factor, an anti-inflammatory, and a neuroprotectant to decipher the underlying mechanism(s) in the valproic acid (VPA)-induced experimental model of ASD. Experimentally, the ASD rat model was induced by a single dose of VPA (600 mg/kg; i.p.) on gestation day 12.5 to the pregnant female rats. After birth, pups were treated with vehicle, that is, normal saline 0.9% i.p., risperidone (2.5 mg/kg; i.p.), and G-CSF (10, 35, and 70 μg/kg; i.p.) from postnatal day (PND) 23 to 43. All the groups were subjected to various developmental and behavior (???) tests from birth. The rats were sacrificed on PND 55, and their brain was excised and processed for biochemical parameters (oxidative stress, inflammatory markers, BDNF), histological examination (H&E, Nissl staining), NMDA, and AMPA receptor expression by immunohistochemistry, western blot, and real-time polymerase chain reaction evaluation. Also, the possible interaction of the G-CSF with NMDA and AMPA receptors was evaluated using the in silico method. The results of the study showed that in VPA-exposed rats, postnatal treatment of the G-CSF rescued all the behavioral abnormalities, oxidative stress, and inflammatory parameters in a dose-dependent manner while risperidone did not show any significant results. The in silico analysis showed the direct interaction of the G-CSF with NMDA and AMPA receptors. The upregulated expression of NMDA and AMPA both in the prefrontal cortex as well as hippocampus was alleviated by the G-CSF thereby validating its anti-inflammatory and excitoprotective properties. Thus, the G-CSF demonstrated neuroprotection against the core symptoms of autism in the VPA-induced rodent model, making it a potential candidate for the treatment of ASD.

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15. O’Donnell S, Palmeter S, Laverty M, Lagacé C. Accuracy of administrative database algorithms for autism spectrum disorder, attention-deficit/hyperactivity disorder and fetal alcohol spectrum disorder case ascertainment: a systematic review. Health Promot Chronic Dis Prev Can;2022 (Sep);42(9):355-383.

INTRODUCTION: The purpose of this study was to perform a systematic review to assess the validity of administrative database algorithms used to identify cases of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorder (FASD). METHODS: MEDLINE, Embase, Global Health and PsycInfo were searched for studies that validated algorithms for the identification of ASD, ADHD and FASD in administrative databases published between 1995 and 2021 in English or French. The grey literature and reference lists of included studies were also searched. Two reviewers independently screened the literature, extracted relevant information, conducted reporting quality, risk of bias and applicability assessments, and synthesized the evidence qualitatively. PROSPERO CRD42019146941. RESULTS: Out of 48 articles assessed at full-text level, 14 were included in the review. No studies were found for FASD. Despite potential sources of bias and significant between-study heterogeneity, results suggested that increasing the number of ASD diagnostic codes required from a single data source increased specificity and positive predictive value at the expense of sensitivity. The best-performing algorithms for the identification of ASD were based on a combination of data sources, with physician claims database being the single best source. One study found that education data might improve the identification of ASD (i.e. higher sensitivity) in school-aged children when combined with physician claims data; however, additional studies including cases without ASD are required to fully evaluate the diagnostic accuracy of such algorithms. For ADHD, there was not enough information to assess the impact of number of diagnostic codes or additional data sources on algorithm accuracy. CONCLUSION: There is some evidence to suggest that cases of ASD and ADHD can be identified using administrative data; however, studies that assessed the ability of algorithms to discriminate reliably between cases with and without the condition of interest were lacking. No evidence exists for FASD. Methodologically higher-quality studies are needed to understand the full potential of using administrative data for the identification of these conditions.

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16. Szlamka Z, Hanlon C, Tekola B, Pacione L, Salomone E, Servili C, Hoekstra RA. Exploring contextual adaptations in caregiver interventions for families raising children with developmental disabilities. PLoS One;2022;17(9):e0272077.

There are increasing efforts to scale up services globally for families raising children with developmental disabilities (DDs). Existing interventions, often developed in high income, Western settings, need substantial adaptation before they can be implemented in different contexts. The aim of this study was to explore perspectives on the role that context plays in the adaptation and implementation of interventions targeting caregivers of children with DDs across settings. The study question was applied to the Caregiver Skills Training (CST) programme of the World Health Organization specifically, as well as to stakeholder experiences with caregiver interventions more broadly. Two focus group discussions (FGDs; n = 15 participants) and 25 individual semi-structured interviews were conducted. Participants were caregivers of children with DDs and professionals involved in adapting or implementing the CST across five continents and different income settings. Data were analysed thematically. Four main themes were developed: 1) Setting the scene for adaptations; 2) Integrating an intervention into local public services; 3) Understanding the reality of caregivers; 4) Challenges of sustaining an intervention. Informants thought that contextual adaptations were key for the intervention to fit in locally, even more so than cultural factors. The socio-economic context of caregivers, including poverty, was highlighted as heavily affecting service access and engagement with the intervention. Competing health priorities other than DDs, financial constraints, and management of long-term collaborations were identified as barriers. This study validates the notion that attention to contextual factors is an essential part of the adaptation of caregiver interventions for children with DDs, by providing perspectives from different geographical regions. We recommend a stronger policy and research focus on contextual adaptations of interventions and addressing unmet socio-economic needs of caregivers.

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17. Tomas V, Kingsnorth S, Kirsh B, Anagnostou E, Lindsay S. Using the COM-B Model and Theoretical Domains Framework to Understand Workplace Disclosure Experiences, Influencers, and Needs Among Autistic Young Adults. J Autism Dev Disord;2022 (Sep 28):1-15.

For autistic young adults, deciding whether to disclose their autism at work is complex. Minimal research explores what they need to support disclosure and what influences decisions. To understand disclosure needs and influencers, we explored (i) disclosure decision-making experiences and (ii) perceptions of the disclosure process among autistic young adults. We conducted focus groups using the Capability, Opportunity, Motivation, Behaviour Model and Theoretical Domains Framework (TDF). We analyzed data from 23 participants and mapped onto the TDF to develop five themes: (1) workplace environment, (2) perceptions of disclosure outcomes, (3) personal factors and identity, (4) disclosure-related ambitions and determination, and (5) know-hows of disclosure. Future work should prioritize developing disclosure decision-making supports and investigate employer roles in fostering inclusive workplaces.

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18. Yamazaki M, Arai T, Yarimizu J, Matsumoto M. 5-HT5A Receptor Antagonist ASP5736 Ameliorates Several Abnormal Behaviors in an Fmr1-Targeted Transgenic Male Rat Model of Fragile X Syndrome. Int J Neuropsychopharmacol;2022 (Sep 28);25(9):786-793.

BACKGROUND: Fragile X syndrome (FXS) is a genetic condition that causes a range of developmental problems, including intellectual disability, aggressive behavior, anxiety, abnormal sensory processing, and cognitive impairment. Despite intensive preclinical research in Fmr1-targeted transgenic mice, an effective treatment for FXS has yet to be developed. We previously demonstrated that ASP5736, a 5-Hydroxytryptamine (serotonin) receptor 5A receptor antagonist, ameliorated scopolamine-induced working memory deficits in mice, reference memory impairment in aged rats, and methamphetamine-induced positive symptoms and phencyclidine-induced cognitive impairment in animal models of schizophrenia. We hypothesized that ASP5736 may be effective for ameliorating similar behavior deficits in male Fmr1-targeted transgenic rats as a preclinical model of FXS. METHODS: We evaluated the effect of acute oral administration of ASP5736 on the abnormal behavior of hyperactivity (0.01, 0.1 mg/kg), prepulse inhibition (0.01, 0.03, 0.1 mg/kg), and the novel object recognition task (0.1 mg/kg) in Frmr1-knockout (KO) rats. RESULTS: Fmr1-KO rats showed body weight gain, hyperactivity, abnormal sensory motor gating, and cognitive impairment. ASP5736 (0.1 mg/kg) reversed the hyperactivity and ameliorated the sensory motor gating deficits (0.03-0.1 mg/kg). ASP5736 (0.01 mg/kg) also improved cognitive impairment. CONCLUSIONS: ASP5736 is a potential drug candidate for FXS. Further studies are needed to confirm its clinical efficacy.

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