1. Abu Khait A, Menger A, Hamdan-Mansour AM, Aldalaykeh M, Hamaideh SH, Al-Mrayat YD, Nusair H. The Association Between Coping Strategies and Psychological and Emotional Distress Among Health Care Providers Caring for Autistic Children in Jordan. West J Nurs Res;2024 (Jun 3):1939459241254782.

BACKGROUND: Health care providers (HCPs) caring for autistic children report more perceived psychological and emotional distress related to their job. However, not much is known about what can be done to mitigate such distress, especially in countries with limited mental health resources, such as Jordan. OBJECTIVE: This study aimed to examine the association between coping strategies (problem-focused, emotion-focused, and avoidant) and perceived emotional and psychological distress among HCPs of autistic children in Jordan. METHODS: In this cross-sectional study, a convenience sample of 180 HCPs working with autistic children in Jordan were recruited through autism centers and social media using an online self-administered questionnaire. RESULTS: The multiple linear regression analysis revealed that 31% of the variability in perceived emotional distress was explained by its significant association with problem-focused coping, emotion-focused coping, and avoidant coping. Likewise, 39% of the variability in perceived psychological distress was explained by its significant association with gender, having an immediate family, area of specialty, problem-focused coping, emotion-focused coping, and avoidant coping. CONCLUSIONS: The study shows that problem-focused coping significantly decreases perceived emotional distress, whereas emotion-focused and avoidant coping significantly increase perceived emotional distress. Avoidant coping significantly increases perceived psychological distress. Understanding the association between coping strategies and perceived emotional and psychological distress among HCPs can assist mental health nurses in identifying at-risk providers and providing timely emotional and psychological support.

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2. Avrahami M, Ben-Dor DH, Ratzon R, Weizman A, Perlman Danieli P. Characterizing the clinical and sociodemographic profiles of hospitalized adolescents with autism spectrum disorder. Glob Ment Health (Camb);2024;11:e63.

The prevalence of autism spectrum disorder (ASD) is increasing worldwide. Youngsters with ASD demonstrate higher rates of intellectual disabilities (IDs), comorbid psychopathology and psychiatric hospitalizations, compared to children in the general population. This study characterizes the demographics and clinical parameters of adolescent psychiatric inpatients with ASD compared to inpatients without ASD, all hospitalized during the study period. Additionally, within the ASD group, those with ID were compared to those without. The rate of males among participants with ASD was significantly higher than among those without ASD, and the duration of hospitalization was longer. In contrast, the rate of cigarette smoking, major depressive disorder and suicidal thoughts among those with ASD was lower. One-third of those with ASD had moderate to severe ID, about 10% had comorbid epilepsy, and about half of them demonstrated aggressive behavior. Most ASD patients showed significant improvement upon discharge, although the extent of improvement was more prominent among ASD patients with no ID. Our findings, consistent with previous research, indicate that hospitalization is beneficial to youths with ASD, both those with and those without ID. Further studies that include long-term follow-up are needed.

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3. Brignell A, Williams KJ, Reilly S, Morgan AT. Language growth in verbal autistic children from 5 to 11 years. Autism Res;2024 (Jun 3)

To examine predictors and growth in language for verbal autistic and non-autistic children with/without low language from 4 to 11 years. Receptive and expressive language trajectories were compared in a community sample of 1026 children at ages 5, 7, and 11 years, across four groups: two autistic groups; one with and one without low language; and two non-autistic groups; one with and one without low language. Groups were delineated on baseline assessment at 4 years. Non-autistic and autistic children with low language had lower mean expressive language scores than the non-autistic typical language group (22.26 and 38.53 units lower, respectively, p < 0.001), yet demonstrated faster language growth across 5 to 11 years (p < 0.001 and p = 0.002, respectively). Both groups without low language had similar mean expressive language scores (p = 0.864) and a comparable rate of growth (p = 0.645). Language at 4 years was the only consistent predictor of language at 11 years for autistic children. Results were similar for receptive language in all analyses except there was no significant difference in rate of progress (slope) for the autistic with low language group compared with the typical language group (p = 0.272). Findings suggest early language ability, rather than a diagnosis of autism, is key to determining language growth and outcomes at 11 years in verbal children. Furthermore, children with low language showed developmental acceleration compared with same age peers.

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4. Brima T, Beker S, Prinsloo KD, Butler JS, Djukic A, Freedman EG, Molholm S, Foxe JJ. Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome. J Neurodev Disord;2024 (Jun 3);16(1):28.

BACKGROUND: In the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is « stationarity » of the underlying responses – i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary. METHODS: AEPs were recorded to simple 100 Hz tones from 18 RTT and 27 age-matched controls (Ages: 6-22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures. RESULTS: Substantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a « neural unreliability » account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident. CONCLUSIONS: To accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

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5. Bunce C, Gehdu BK, Press C, Gray KLH, Cook R. Autistic adults exhibit typical sensitivity to changes in interpersonal distance. Autism Res;2024 (Jun 3)

The visual processing differences seen in autism often impede individuals’ visual perception of the social world. In particular, many autistic people exhibit poor face recognition. Here, we sought to determine whether autistic adults also show impaired perception of dyadic social interactions-a class of stimulus thought to engage face-like visual processing. Our focus was the perception of interpersonal distance. Participants completed distance change detection tasks, in which they had to make perceptual decisions about the distance between two actors. On half of the trials, participants judged whether the actors moved closer together; on the other half, whether they moved further apart. In a nonsocial control task, participants made similar judgments about two grandfather clocks. We also assessed participants’ face recognition ability using standardized measures. The autistic and nonautistic observers showed similar levels of perceptual sensitivity to changes in interpersonal distance when viewing social interactions. As expected, however, the autistic observers showed clear signs of impaired face recognition. Despite putative similarities between the visual processing of faces and dyadic social interactions, our results suggest that these two facets of social vision may dissociate.

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6. Chau T, Tiego J, Brown LE, Mellahn OJ, Johnson BP, Arnatkeviciute A, Fulcher BD, Matthews N, Bellgrove MA. The distribution of parent-reported attention-deficit/hyperactivity disorder and subclinical autistic traits in children with and without an ADHD diagnosis. JCPP Adv;2024 (Jun);4(2):e12223.

BACKGROUND: Autistic traits are often reported to be elevated in children diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the distribution of subclinical autistic traits in children with ADHD has not yet been established; knowing this may have important implications for diagnostic and intervention processes. The present study proposes a preliminary model of the distribution of parent-reported ADHD and subclinical autistic traits in two independent samples of Australian children with and without an ADHD diagnosis. METHODS: Factor mixture modelling was applied to Autism Quotient and Conners’ Parent Rating Scale – Revised responses from parents of Australian children aged 6-15 years who participated in one of two independent studies. RESULTS: A 2-factor, 2-class factor mixture model with class varying factor variances and intercepts demonstrated the best fit to the data in both discovery and replication samples. The factors corresponded to the latent constructs of ‘autism’ and ‘ADHD’, respectively. Class 1 was characterised by low levels of both ADHD and autistic traits. Class 2 was characterised by high levels of ADHD traits and low-to-moderate levels of autistic traits. The classes were largely separated along diagnostic boundaries. The largest effect size for differences between classes on the Autism Quotient was on the Social Communication subscale. CONCLUSIONS: Our findings support the conceptualisation of ADHD as a continuum, whilst confirming the utility of current categorical diagnostic criteria. Results suggest that subclinical autistic traits, particularly in the social communication domain, are unevenly distributed across children with clinically significant levels of ADHD traits. These traits might be profitably screened for in assessments of children with high ADHD symptoms and may also represent useful targets for intervention.

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7. Chen YJ, Duku E, Szatmari P, Salt M, Smith I, Richard A, Zwaigenbaum L, Vaillancourt T, Zaidman-Zait A, Bennett T, Elsabbagh M, Kerns C, Georgiades S. Trajectories of adaptive functioning from early childhood to adolescence in autism: Identifying turning points and key correlates of chronogeneity. JCPP Adv;2024 (Jun);4(2):e12212.

BACKGROUND: Previous research has demonstrated heterogeneous adaptive outcomes across the autism spectrum; however, the current literature remains limited in elucidating turning points and associated factors for longitudinal variability (chronogeneity). To address these empirical gaps, we aimed to provide a finer-grained characterization of trajectories of adaptive functioning from early childhood to adolescence in autism. METHODS: Our sample (N = 406) was drawn from an inception cohort of children diagnosed Autistic at ages 2-5. Adaptive functioning was assessed with Vineland Adaptive Behavior Scales (VABS, 2(nd) Edition) across 6 visits from the time of diagnosis by age 18. Parallel-process latent growth curve modeling were used to estimate domain-level VABS trajectories, followed by latent class growth analysis to identify trajectory subgroups. Child characteristics at diagnosis, family demographics, and participation outcomes at adolescence were compared across subgroups. RESULTS: Piecewise latent growth models best described VABS trajectories with two turning points identified at around ages 5-6 and 9-10, respectively reflecting transitions into school age and early adolescence. We parsed four VABS trajectory subgroups that vary by level of functioning and change rate for certain domains and periods. Around 16% of the sample exhibited overall adequate functioning (standard score >85) with notable early growth and social adaptation during adolescence. About 21% showed low adaptive functioning (standard score ≤70), with decreasing slopes by age 6 followed by improvements in communication and daily-living skills by age 10. The other two subgroups (63% in total) were characterized by adaptive functioning between low and adequate levels, with relatively stable trajectories entering school age. These subgroups differed most in their cognitive ability at diagnosis, household income, and social participation in adolescence. CONCLUSIONS: We identified key individual and family characteristics and time windows associated with distinct adaptive functioning trajectories, which have important implications for providing timely and tailored supports to Autistic people across developmental stages.

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8. De Biase I, de Dios K, Brose SA, Hobert JA. Autism Spectrum Disorder and Mild Developmental Delay in a Patient with a Rare Inborn Error of Metabolism. Clin Chem;2024 (Jun 3);70(6):882-884.

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9. Denisova K. Neurobiology of cognitive abilities in early childhood autism. JCPP Adv;2024 (Jun);4(2):e12214.

This perspective considers complexities in the relationship between impaired cognitive abilities and autism from a maturational, developmental perspective, and aims to serve as a helpful guide for the complex and growing investigation of cognitive abilities and Autism Spectrum Disorder (ASD). Low Intelligence Quotient (IQ) and ASD are frequently co-occurring. About 37% of 8-year old children and 48% of 4-year old children diagnosed with ASD also have Intellectual Disability, with IQ below 70. And, low IQ in early infancy, including below 1 year of age, carries a 40% greater chance of receiving ASD diagnosis in early childhood. We consider the evidence that may explain this co-occurrence, including the possibility that high IQ may « rescue » the social communication issues, as well as the possible role of critical periods during growth and development. We consider how early low IQ may subsume a part of a subgroup of individuals with ASD, in particular, those diagnosed with autism in very early childhood, and we provide neurobiological evidence in support of this subtype. Moreover, we distinguish the concept of early low IQ from the delay in speech onset in preschool and school-aged children, based on (i) age and (ii) impairments in both verbal and non-verbal domains. The etiology of these early-diagnosed, early low IQ ASD cases is different from later-diagnosed, average or higher-IQ cases, and from children with speech delay onset. Given recent interest in formulating new subtypes of autism, rather than continuing to conceive of ASD as a spectrum, as well as new subtypes that vary in the degree of severity along the spectrum, we identify gaps in knowledge and directions for future work in this complex and growing area.

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10. Dias C, Mo A, Cai C, Sun L, Cabral K, Brownstein CA, Rockowitz S, Walsh CA. Cell-type-specific effects of autism-associated chromosome 15q11.2-13.1 duplications in human brain. bioRxiv;2024 (May 22)

Recurrent copy number variation represents one of the most well-established genetic drivers in neurodevelopmental disorders, including autism spectrum disorder (ASD). Duplication of 15q11.2-13.1 (dup15q) is a well-described neurodevelopmental syndrome that increases the risk of ASD by over 40-fold. However, the effects of this duplication on gene expression and chromatin accessibility in specific cell types in the human brain remain unknown. To identify the cell-type-specific transcriptional and epigenetic effects of dup15q in the human frontal cortex we conducted single-nucleus RNA-sequencing and multi-omic sequencing on dup15q cases (n=6) as well as non-dup15q ASD (n=7) and neurotypical controls (n=7). Cell-type-specific differential expression analysis identified significantly regulated genes, critical biological pathways, and differentially accessible genomic regions. Although there was overall increased gene expression across the duplicated genomic region, cellular identity represented an important factor mediating gene expression changes. Neuronal subtypes, showed greater upregulation of gene expression across a critical region within the duplication as compared to other cell types. Genes within the duplicated region that had high baseline expression in control individuals showed only modest changes in dup15q, regardless of cell type. Of note, dup15q and ASD had largely distinct signatures of chromatin accessibility, but shared the majority of transcriptional regulatory motifs, suggesting convergent biological pathways. However, the transcriptional binding factor motifs implicated in each condition implicated distinct biological mechanisms; neuronal JUN/FOS networks in ASD vs. an inflammatory transcriptional network in dup15q microglia. This work provides a cell-type-specific analysis of how dup15q changes gene expression and chromatin accessibility in the human brain and finds evidence of marked cell-type-specific effects of this genetic driver. These findings have implications for guiding therapeutic development in dup15q syndrome, as well as understanding the functional effects CNVs more broadly in neurodevelopmental disorders.

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11. Duan X, Peng X, Jia X, Tan S, Guo H, Tan J, Hu Z. CELF2 Deficiency Demonstrates Autism-Like Behaviors and Interferes with Late Development of Cortical Neurons in Mice. Mol Neurobiol;2024 (Jun 3)

CELF2 variants have been linked to neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD). However, the molecular mechanisms remain unclear. We generated Celf2 Nestin-Cre knockout mice.Our findings revealed that Celf2 Nestin-Cre heterozygous knockout mice exhibited social impairment and anxiety, an autism-like behavior, though no manifestations of repetitive stereotyped behavior, learning cognitive impairment, or depression were observed. Immunofluorescence assay showed an underdeveloped cerebral cortex with significantly reduced cortical thickness, albeit without abnormal cell density. Further in vitro neuronal culture demonstrated a significant reduction in dendritic spine density and affected synaptic maturation in Celf2 deficient mice, with no notable abnormalities in total neurite and axon length. RNA-seq and RIP-seq analysis of the cerebral cortex revealed differentially expressed genes post Celf2 gene knockout compared with the control group. Enrichment analysis highlighted significant enrichment in dendrite and synapse-related biological processes and pathways. Our study delineated the behavioral and neurodevelopmental phenotypes of Celf2, suggesting its potential involvement in autism through the regulation of target genes associated with dendritic spines and synapse development. Further research is needed to elucidate the specific mechanisms involved.

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12. Feller C, Ilen L, Eliez S, Schneider M. Loneliness in daily life: A comparison between youths with autism spectrum disorders and 22q11.2 deletion syndrome (22q11DS). Autism Res;2024 (Jun 3)

Loneliness is a negative emotional experience that can stem from a gap between desires and the reality of social relationships. It is also a predictor of mental health. Loneliness is therefore important to investigate in neurodevelopmental populations known for having difficulties in the social sphere. This co-registered study involved 48 youths with autism spectrum disorders (ASD), 54 youths with 22q11.2 deletion syndrome (22q11DS) and 65 typically developing youths (TD) aged 12-30. State loneliness was assessed with an ecological momentary assessment. Paper-pencil questionnaires assessing attitude toward aloneness, trait loneliness, and mental health, were completed by the youths and their caregivers. A comparable level of state loneliness between clinical groups and TD were found, with greater loneliness when alone than in a social context. Clinical groups showed a greater intra-individual variability. Both individuals with ASD and 22q11DS revealed a greater affinity toward being alone than TD, but only individuals with ASD reported greater trait loneliness. However, no significant association was found between attitude toward aloneness, trait and state loneliness. Emotional reactivity to loneliness was different between the clinical groups. Self-reported mental health only was associated with loneliness in the clinical groups. These results provide new insights into the understanding of loneliness in these clinical populations and have an impact on clinical care by highlighting the need to remain vigilant when encountering youths who report feeling lonely, and that these youths need to be supported in developing their social network, which appears to be a protective factor against loneliness.

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13. Fipp-Rosenfield H, Grauzer J, Roberts MY, Kaat AJ. Validity of the multidimensional assessment profile of disruptive behavior in autistic toddlers. JCPP Adv;2024 (Jun);4(2):e12233.

OBJECTIVE: Early measurement of atypical disruptive behavior within autistic children is critical for later referrals to behavioral screenings, diagnoses, and services. Disruptive behavior in autistic toddlers is often measured using a categorical approach and identifies the presence or absence of behavior. In contrast, dimensional approaches evaluate behavior on a spectrum of typical to atypical by measuring the clinical salience of disruptive behavior. We sought to assess the validity of the Infant/Toddler version of the multidimensional assessment profile of disruptive behavior (MAP-DB-IT), a dimensional approach measurement tool, in a sample of autistic toddlers. METHODS: Autistic toddlers (n = 82, M (age) = 33.2 months, SD = 6.28 months) and their mothers received 8 weeks of caregiver-mediated social communication intervention. Mothers completed the MAP-DB-IT and the Infant Toddler Social Emotional Assessment (ITSEA) across three timepoints: before intervention, immediately after intervention, and at 3 months post-intervention follow-up. The MAP-DB-IT provided scores for three subdomains: temper loss, noncompliance, and aggression (generically or specifically with siblings). Ratings on the MAP-DB-IT were compared to the ITSEA using several analytic strategies such as evaluating (a) the internal consistency of the MAP-DB-IT domain scores; (b) the convergent validity between the two measures; and (c) its convergent change due to intervention and if this varied by child characteristics. RESULTS: The MAP-DB-IT demonstrated excellent internal consistency across all four subdomains. We evaluated convergent validity and found positive correlations between the (a) ITSEA externalizing and MAP-DB-IT aggression domain, (b) ITSEA externalizing and MAP-DB-IT aggression with siblings domain, and (c) ITSEA dysregulation and MAP-DB-IT temper loss domain. CONCLUSION: The MAP-DB-IT is a valid measurement tool for disruptive behavior in autistic toddlers. Clinicians should consider the use of the MAP-DB-IT for young autistic clients presenting with disruptive behavior to (a) discriminate between early developmentally appropriate tantrums from clinically salient dysregulation, and (b) refer to additional behavioral evaluations and services.

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14. Gerdts J, Casagrande KA, Bateman KJ, Hudac CM, Bravo A, Mancini J, Mannheim J, Ogata B, Orville K, Stobbe GA. ECHO Autism Washington: Autism Diagnostic Evaluations in Primary Care. Clin Pediatr (Phila);2024 (Jun 3):99228241255866.

ECHO (Extensions for Community Healthcare Outcomes) Autism is a telementoring learning model to increase community capacity for autism-related health care. Seventy-seven pediatric providers (mostly primary care, seeing exclusively Medicaid patient populations) enrolled in 1 year of ECHO Autism Washington. Analysis of self-report surveys showed a significant increase in autism diagnoses made by ECHO providers after 1 year, F(1, 65) = 7.52, P = .008. Providers who attended more sessions reported making more diagnoses, F(2, 613.26), P = .045. Of note, autism diagnoses were not externally validated. The total number of reported barriers reduced, F(2, 61) = 13.5), P < .001, and confidence ratings increased F(2, 60) = 24.21, P < .001. The average number of diagnostic referrals from ECHO providers to the state's largest autism specialty clinic significantly reduced, t(43) = 4.23, P < .001, with significantly fewer diagnostic referrals made during and after ECHO training compared with a comparison group of 28 non-ECHO providers, t(58.77) = -3.36, P < .001. Overall, 1 year of ECHO Autism Washington participation led to significant changes in autism diagnostic practices.

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15. Giua G, Pereira-Silva J, Caceres-Rodriguez A, Lassalle O, Chavis P, Manzoni OJ. Cell- and pathway-specific disruptions in the accumbens of Fragile X mouse. J Neurosci;2024 (Jun 3)

Fragile X syndrome (FXS) is a genetic cause of intellectual disability and autism spectrum disorder (ASD), associated with social deficits. The mesocorticolimbic system, which includes the prefrontal cortex (PFC), basolateral amygdala (BLA), and nucleus accumbens core (NAcC), is essential for regulating socio-emotional behaviors. We employed optogenetics to compare the functional properties of the BLA→NAcC, PFC→NAcC, and reciprocal PFC↔BLA pathways in Fmr1-/y::Drd1a-tdTomato male mice. In FXS mice, the PFC↔BLA reciprocal pathway was unaffected, while significant synaptic modifications occurred in the BLA/PFC→NAcC pathways. We observed distinct changes in D1 striatal projection neurons (SPNs) and separate modifications in D2 SPNs. In FXS mice, the BLA/PFC→NAcC-D2 SPNs pathways demonstrated heightened synaptic strength. Focusing on the BLA→NAcC pathway, linked to autistic symptoms, we found increased AMPAR and NMDAR currents, and elevated spine density in D2 SPNs. Conversely, the amplified firing probability of BLA→NAcC-D1 SPNs was not accompanied by increased synaptic strength, AMPAR and NMDAR currents, or spine density. These pathway-specific alterations resulted in an overall enhancement of excitatory-to-spike coupling, a physiologically relevant index of how efficiently excitatory inputs drive neuronal firing, in both BLA→NAcC-D1 and BLA→NAcC-D2 pathways. Finally, the absence of FMRP led to impaired long-term depression specifically in BLA→D1 SPNs. These distinct alterations in synaptic transmission and plasticity within circuits targeting the NAcC highlight the potential role of postsynaptic mechanisms in selected SPNs in the observed circuit-level changes. This research underscores the heightened vulnerability of the NAcC in the context of FMRP deficiency, emphasizing its pivotal role in the pathophysiology of FXS.Significance Statement Fragile X Syndrome is a neurodevelopmental disorder characterized by significant emotional dysregulation and social challenges. The mesocorticolimbic system is a key socioemotional regulator. Nevertheless, its functioning in this condition is still poorly understood. Our study investigates connections between the basolateral amygdala (BLA), prefrontal cortex (PFC), and nucleus accumbens core (NAcC). We observed that while the PFC↔BLA reciprocal connections remained unaffected, their projections onto the NAcC showed target cell-specific changes. Specifically, D2 SPNs exhibited increased synaptic transmission and spine density, whereas D1 SPNs showed heightened firing probability and impaired long-term depression, alongside enhanced neuronal firing efficiency in both SPN types. These findings emphasize the NAcC’s crucial role as a neurobiological substrate in the pathophysiology of Fragile X Syndrome.

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16. Grönniger B, Fritschka E, Kimpe K, Singh A, Sadowski G. Simultaneous Water Sorption and Crystallization in ASDs 2: Modeling Long-Term Stabilities. Mol Pharm;2024 (Jun 3);21(6):2908-2921.

The physical stability of amorphous solid dispersions (ASDs) is a major topic in the formulation research of oral dosage forms. To minimize the effort of investigating the long-term stability using cost- and time-consuming experiments, we developed a thermodynamic and kinetic modeling framework to predict and understand the crystallization kinetics of ASDs during long-term storage below the glass transition. Since crystallization of the active phrarmaceutical ingredients (APIs) in ASDs largely depends on the amount of water absorbed by the ASDs, water-sorption kinetics and API-crystallization kinetics were considered simultaneously. The developed modeling approach allows prediction of the time evolution of viscosity, supersaturation, and crystallinity as a function of drug load, relative humidity, and temperature. It was applied and evaluated against two-year-lasting crystallization experiments of ASDs containing nifedipine and copovidone or HPMCAS measured in part I of this work. We could show that the proposed modeling approach is able to describe the interplay between water sorption and API crystallization and to predict long-term stabilities of ASDs just based on short-term measurements. Most importantly, it enables explaining and understanding the reasons for different and sometimes even unexpected crystallization behaviors of ASDs.

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17. Kasem A, Abuhammad S, Jamal N. Parents of children with autism spectrum disorder quality of life in Jordan: a comparative study. Future Sci OA;2024;10(1):Fso909.

Aim: This study aimed to assess the quality of life (QoL) of parents of children with autism spectrum disorder (ASD) in Jordan and its associated factors. Methods: This comparative study was conducted among parents of children with ASD and non-ASD. Data collection took four setting areas that include three centers for autism in three different municipalities and the control group was collected using social media. A convenience sample of 242 parents agreed to complete a QoL questionnaire. Results: Parents of children with ASD in Jordan have poor QoL across the five domains of QoL in compare with parents with non-ASD child. Factors such as gender, level of education, living condition and employment status were found impacting QoL.

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18. Li F, Zhang S, Jiang L, Duan K, Feng R, Zhang Y, Zhang G, Zhang Y, Li P, Yao D, Xie J, Xu W, Xu P. Recognition of autism spectrum disorder in children based on electroencephalogram network topology. Cogn Neurodyn;2024 (Jun);18(3):1033-1045.

Although our knowledge of autism spectrum disorder (ASD) has been deepened, the accurate diagnosis of ASD from normal individuals is still left behind. In this study, we proposed to apply the spatial pattern of the network topology (SPN) to identify children with ASD from normal ones. Based on two independent batches of electroencephalogram datasets collected separately, the accurate recognition of ASD from normal children was achieved by applying the proposed SPN features. Since decreased long-range connectivity was identified for children with ASD, the SPN features extracted from the distinctive topological architecture between two groups in the first dataset were used to validate the capacity of SPN in classifying ASD, and the SPN features achieved the highest accuracy of 92.31%, which outperformed the other features e.g., power spectrum density (84.62%), network properties (76.92%), and sample entropy (73.08%). Moreover, within the second dataset, by using the model trained in the first dataset, the SPN also acquired the highest sensitivity in recognizing ASD, when compared to the other features. These results consistently illustrated that the functional brain network, especially the intrinsic spatial network topology, might be the potential biomarker for the diagnosis of ASD.

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19. Li X, Hu C, Li W, Ruan M, Yu X, Paul L, Wang S. Exploiting ChatGPT for Diagnosing Autism-Associated Language Disorders and Identifying Distinct Features. Res Sq;2024 (May 21)

Diagnosing language disorders associated with autism is a complex and nuanced challenge, often hindered by the subjective nature and variability of traditional assessment methods. Traditional diagnostic methods not only require intensive human effort but also often result in delayed interventions due to their lack of speed and specificity. In this study, we explored the application of ChatGPT, a state-of-the-art large language model, to overcome these obstacles by enhancing diagnostic accuracy and profiling specific linguistic features indicative of autism. Leveraging ChatGPT’s advanced natural language processing capabilities, this research aims to streamline and refine the diagnostic process. Specifically, we compared ChatGPT’s performance with that of conventional supervised learning models, including BERT, a model acclaimed for its effectiveness in various natural language processing tasks. We showed that ChatGPT substantially outperformed these models, achieving over 13\% improvement in both accuracy and F1-score in a zero-shot learning configuration. This marked enhancement highlights the model’s potential as a superior tool for neurological diagnostics. Additionally, we identified ten distinct features of autism-associated language disorders that vary significantly across different experimental scenarios. These features, which included echolalia, pronoun reversal, and atypical language usage, were crucial for accurately diagnosing ASD and customizing treatment plans. Together, our findings advocate for adopting sophisticated AI tools like ChatGPT in clinical settings to assess and diagnose developmental disorders. Our approach not only promises greater diagnostic precision but also aligns with the goals of personalized medicine, potentially transforming the evaluation landscape for autism and similar neurological conditions.

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20. Ma J, Liu Y, Zhao K. Microcephaly type 22 and autism spectrum disorder: A case report and review of literature. Dialogues Clin Neurosci;2024;26(1):24-27.

INTRODUCTION: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with a multifaceted etiology. This case report explores the ischemic cryptogenic vascular dissection as a potential underlying cause of ASD. METHODS: A 9-year-old child presented with symptoms of ASD, including social interaction difficulties, repetitive behaviors, and cognitive challenges. Despite conventional ASD treatments, significant improvement was only observed after addressing an underlying ischemic cryptogenic vascular dissection identified through DCE-CT. RESULTS: Following a reconstructive treatment approach to the vascular dissection, the patient showed marked improvement in cognitive functions, social abilities, and a reduction in ASD-related symptoms whether during the perioperative period or during approximately 5-month follow-up. CONCLUSION: This case suggests that ischemic cryptogenic vascular dissection may contribute to the symptoms of ASD. Identifying and treating underlying vascular anomalies may offer a new avenue for mitigating ASD symptoms, emphasizing the need for comprehensive diagnostic estimations in ASD management.

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21. Mears K, Rai D, Shah P, Cooper K, Ashwin C. A Systematic Review of Gender Dysphoria Measures in Autistic Samples. Arch Sex Behav;2024 (Jun 3)

This systematic review investigated how studies have measured gender dysphoria (GD) in autistic samples and the impact of using different measures on study results. The literature search identified 339 relevant papers, with 12 of them meeting the inclusion criteria. Results showed that seven different measures of GD characteristics have been used with autistic samples and that the studies consistently reported a greater number of GD characteristics and a greater severity of GD in autistic compared to non-autistic samples. Methodological common practices were found in recruiting participants from clinical settings rather than the general population, having more autistic males than females in the samples, for studies being conducted in Europe, North America, and Oceania, and using single-item measures of GD for samples of autistic children. Issues were identified with study designs and measures of GD, suggesting a need for a more standardized multi-item self-report measure of GD for use in clinical and non-clinical samples across different ages and cultures.

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22. Olabumuyi OO, Uchendu OC, Green PA. Prevalence, Pattern and Factors Associated with Developmental Delay amongst Under-5 Children in Nigeria: Evidence from Multiple Indicator Cluster Survey 2011-2017. Niger Postgrad Med J;2024 (Apr 1);31(2):118-129.

BACKGROUND: Children develop dynamically, and when a child fails to reach age-appropriate developmental milestones compared to their peers, it is considered a developmental delay. In developing nations like Nigeria, several demographics, socioeconomic, childcare and external factors may influence the highly individualised process. This study assessed the prevalence and pattern of developmental delay, across Nigeria’s geopolitical zones including identified factors associated with developmental delay, providing insight for appropriate interventions to prevent disability in affected children. METHODS: This was a secondary analysis of data from the Multiple Indicator Cluster Survey (MICS), which was carried out in rounds 4 (2011) and 5 (2016/2017). Every 5 years, the UNICEF-supported MICS cross-sectional household survey is carried out using the cluster sampling method. A semi-structured, questionnaire administered by the interviewer was used to obtain individual and household-level data. This study comprised a weighted sample of 17,373 under-5 children who had complete data from both survey rounds on characteristics deemed significant for the study. Data were analysed using SPSS version 23. Using the Chi-square test and multivariate binomial logistic regression, factors linked to developmental delay were identified, with 95% confidence intervals (CIs) provided and the significance level set at 5%. RESULTS: The mean age and sex distribution of the children surveyed in both rounds was comparable, with a male preponderance of 51.2% in round 4 and 50.4% in round 5. In both round 4 (51.2%) and round 5 (49.0%), the Northeast zone had the highest prevalence of overall developmental delay while the least prevalence was seen in the Southwest zone (20.3%) and the Southeast zone (14.7%) in round 4 and round 5, respectively. Across all the zones, delay in the literacy-numeracy domain of development was the most prevalent, with the highest (91.3% and 86.7%, respectively) in the Northeast zone during both rounds of the survey. Delay in the physical domain was, however, the least prevalent form of developmental delay across the zones, with the least in South South (20.6%) and Southeast (5.4%) in rounds 4 and 5. The odds of developmental delay were 1.5 and 1.7 times higher amongst children 4 years old than 3 years old in both rounds of the survey. The likelihood of having developmental delay was found to increase with the severity of stunting amongst the children during both rounds of the survey (odds ratio [OR] =1.5; 95% CI = 1.20-1.78 in round 4 and OR = 1.4; 95% CI = 1.16-1.58 in round 5). Children from the poorest wealth index had higher odds of developmental delay (OR = 5.8; 95% CI = 4.92-6.82 in round 4 and OR = 2.5; 95% CI = 1.99-3.10 in round 5). CONCLUSION: The prevalence of developmental delay is high across all zones; however, the burden varies amongst them. The age of the child, nutritional status and wealth index were indicators of developmental delay in Nigerian under-5 children. This underscores the need for surveillance and interventions focussed on improving child literacy, nutritional status and household standard of living across the zones.

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23. Ross LF, Iltis AS. Medical Decision-Making for Children in Families with Siblings: parental discretion and its limits. Perspect Biol Med;2024;67(2):261-276.

This article examines how parents should make health decisions for one child when they may have a negative impact on the health interests or other interests of their siblings. The authors discuss three health decisions made by the parents of Alex Jones, a child with developmental disabilities with two older neurotypical siblings over the course of eight years. First, Alex’s parents must decide whether to conduct sequencing on his siblings to help determine if there is a genetic cause for Alex’s developmental disabilities. Second, Alex’s parents must decide whether to move to another town to maximize the therapy options for Alex. Third, Alex’s parents must decide whether to authorize the collection of stem cells from Alex for a bone marrow transplant for his sibling who developed leukemia. We examine whether the consensus recommendations by Salter and colleagues (2023) regarding pediatric decision-making apply in families with more than one child.

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24. Tan J, Zhan Y, Tang Y, Bao W, Tian Y. EEG decoding for effects of visual joint attention training on ASD patients with interpretable and lightweight convolutional neural network. Cogn Neurodyn;2024 (Jun);18(3):947-960.

Visual joint attention, the ability to track gaze and recognize intent, plays a key role in the development of social and language skills in health humans, which is performed abnormally hard in autism spectrum disorder (ASD). The traditional convolutional neural network, EEGnet, is an effective model for decoding technology, but few studies have utilized this model to address attentional training in ASD patients. In this study, EEGNet was used to decode the P300 signal elicited by training and the saliency map method was used to visualize the cognitive properties of ASD patients during visual attention. The results showed that in the spatial distribution, the parietal lobe was the main region of classification contribution, especially for Pz electrode. In the temporal information, the time period from 300 to 500 ms produced the greatest contribution to the electroencephalogram (EEG) classification, especially around 300 ms. After training for ASD patients, the gradient contribution was significantly enhanced at 300 ms, which was effective only in social scenarios. Meanwhile, with the increase of joint attention training, the P300 latency of ASD patients gradually shifted forward in social scenarios, but this phenomenon was not obvious in non-social scenarios. Our results indicated that joint attention training could improve the cognitive ability and responsiveness of social characteristics in ASD patients.

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25. Van Overwalle J, Geusens B, Van der Donck S, Boets B, Wagemans J. Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning. Mol Autism;2024 (Jun 3);15(1):23.

BACKGROUND: Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization. METHODS: The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures. RESULTS: Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results. LIMITATIONS: Data-collection occurred during the COVID-19 pandemic. CONCLUSIONS: Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC.

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26. Wang HI, Bell K, Blackwell J, Welch C, Mandefield L, Watson J, Standley E, McMillan D, Gilbody S, Wright B, Hewitt C, Parrott S. Cost-utility analysis of Social Stories™ for children with autism spectrum disorder in mainstream primary schools: results from a randomised controlled trial. BJPsych Open;2024 (Jun 3);10(4):e123.

BACKGROUND: One in 57 children are diagnosed with autism in the UK, and the estimated cost for supporting these children in education is substantial. Social Stories™ is a promising and widely used intervention for supporting children with autism in schools and families. It is believed that Social Stories™ can provide meaningful social information to children that can improve social understanding and may reduce anxiety. However, no economic evaluation of Social Stories has been conducted. AIMS: To assess the cost-effectiveness of Social Stories through Autism Spectrum Social Stories in Schools Trial 2, a multi-site, pragmatic, cluster-randomised controlled trial. METHOD: Children with autism who were aged 4-11 years were recruited and randomised (N = 249). Costs measured from the societal perspective and quality-adjusted life-years (QALYs) measured by the EQ-5D-Y-3L proxy were collected at baseline and at 6-month follow-up for primary analysis. The incremental cost-effectiveness ratio was calculated, and the uncertainty around incremental cost-effectiveness ratios was captured by non-parametric bootstrapping. Sensitivity analyses were performed to evaluate the robustness of the primary findings. RESULTS: Social Stories is likely to result in a small cost savings (-£191 per child, 95% CI -767.7 to 337.7) and maintain similar QALY improvements compared with usual care. The probability of Social Stories being a preferred option is 75% if society is willing to pay £20 000 per QALY gained. The sensitivity analysis results aligned with the main study outcomes. CONCLUSIONS: Compared with usual care, Social Stories did not lead to an increase in costs and maintained similar QALY improvements for primary-aged children with autism.

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27. Watts G, Crompton C, Grainger C, Long J, Botha M, Somerville M, Cage E. ‘A certain magic’ – autistic adults’ experiences of interacting with other autistic people and its relation to Quality of Life: A systematic review and thematic meta-synthesis. Autism;2024 (Jun 3):13623613241255811.

Research has suggested that autistic people enjoy spending time with other autistic people and find them easier to talk to. We wanted to find out what autistic people say about spending time with other autistic people and whether this makes their life better. We found 52 papers which described this and reviewed what they found. We found that many autistic people had positive experiences of spending time with other autistic people and these experiences had positive impact on their lives in a range of different ways. The papers did not tell us whether this also happens for autistic people with a learning disability. More research is needed to find out more about why spending time with other autistic people helps some autistic people.

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28. Xiaoyan H, Zhaoxi Y, Lingli Z, Jinyuan C, Wen Q. Taurine Improved Autism-Like Behaviours and Defective Neurogenesis of the Hippocampus in BTBR Mice through the PTEN/mTOR/AKT Signalling Pathway. Folia Biol (Praha);2024;70(1):45-52.

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.

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29. Yang Y, Song P, Wang Y. Assessing the impact of repetitive transcranial magnetic stimulation on effective connectivity in autism spectrum disorder: An initial exploration using TMS-EEG analysis. Heliyon;2024 (Jun 15);10(11):e31746.

Initial indications propose that repetitive transcranial magnetic stimulation (rTMS) could mitigate clinical manifestations in patients with autism spectrum disorder (ASD). Nevertheless, the precise mechanisms responsible for these therapeutic and behavioral outcomes remain elusive. We examined alterations in effective connectivity induced by rTMS using concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in children with ASD. TMS-EEG data were acquired from 12 children diagnosed with ASD both before and following rTMS treatment. The rTMS intervention regimen included delivering 5-s trains at a frequency of 15 Hz, with 10-min intervals between trains, targeting the left parietal lobe. This was conducted on each consecutive weekday over 3 weeks, totaling 15 sessions. The dynamic EEG network analysis revealed that following the rTMS intervention, long-range feedback connections within the brains of ASD patients were strengthened (e.g., frontal to parietal regions, frontal to occipital regions, and frontal to posterior temporal regions), and short-range connections were weakened (e.g., between the bilateral occipital regions, and between the occipital and posterior temporal regions). In alignment with alterations in network connectivity, there was a corresponding amelioration in fundamental ASD symptoms, as assessed through clinical scales post-treatment. According to our findings, people with ASD may have increased long-range frontal-posterior feedback connection on application of rTMS to the parietal lobe.

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30. Yu Y, Yang X, Hu G, Yin Y, Yu R. Causal effects of 731 immune cell phenotypes on autism spectrum disorder: a Mendelian randomization study. Front Psychiatry;2024;15:1397006.

OBJECTIVE: The role of different immune cells in autism spectrum disorders (ASD) is still controversial. The purpose of this study was to evaluate the causal effects of different immune cell phenotypes on ASD via Mendelian randomization (MR). METHODS: Datasets of immune cell phenotypes were obtained from the European Bioinformatics Institute, and datasets of ASD were obtained from the IEU Open GWAS project. Single nucleotide polymorphisms were selected based on the assumptions of association, independence, and exclusivity. Inverse variance weighted was utilized as the main method for MR analysis. MR-Egger was employed to assess the horizontal pleiotropy of the results. Cochran’s Q and leave-one-out method were used for heterogeneity analysis and sensitivity analysis of the results, respectively. RESULTS: MR analysis showed that TD CD8br AC [odds ratio (OR), 1.137; 95% confidence interval (CI), 1.031-1.254; p = 0.010], CD8br %leukocyte (OR, 1.142; 95% CI, 1.067-1.223; p < 0.001), CD8br and CD8dim %leukocyte (OR, 1.117; 95% CI, 1.032-1.210; p = 0.006), naive CD8br %T cell (OR, 1.052; 95% CI, 1.004-1.104; p = 0.035), CD28- CD8dim %T cell (OR, 1.097; 95% CI, 1.038-1.158; p < 0.001), CD127- CD8br AC (OR, 1.086; 95% CI, 1.006-1.171; p = 0.034), CD45 on CD8br (OR, 1.059; 95% CI, 1.021-1.099; p = 0.002), CD3 on HLA DR+ CD8br (OR, 1.098; 95% CI, 1.041-1.158; p < 0.001), CD4 on activated Treg (OR, 1.048; 95% CI, 1.001-1.096; p = 0.046), CD3 on CD39+ resting Treg (OR, 1.070; 95% CI, 1.012-1.131; p = 0.018), IgD+ CD38- %lymphocyte (OR, 1.103; 95% CI, 1.023-1.190; p = 0.011), CD62L- plasmacytoid DC %DC (OR, 1.046; 95% CI, 1.001-1.093; p = 0.046), and FSC-A on plasmacytoid DC (OR, 1.075; 95% CI, 1.003-1.153; p = 0.042) were associated with increased genetic susceptibility to ASD. MR-Egger displayed no horizontal pleiotropy (p ≥ 0.05). Cochran's Q revealed no heterogeneity of results (p ≥ 0.05). Sensitivity analysis indicated that the results were robust. CONCLUSION: This MR analysis revealed 13 immune cell phenotypes associated with increased genetic susceptibility to ASD and emphasized the importance of CD8 T cells and Tregs, which provides new directions for the pathogenesis and drug research of ASD.

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31. Zhang J, Xu Y, Liu Y, Yue L, Jin H, Chen Y, Wang D, Wang M, Chen G, Yang L, Zhang G, Zhang X, Li S, Zhao H, Zhao Y, Niu G, Gao Y, Cai Z, Yang F, Zhu C, Zhu D. Genetic Testing for Global Developmental Delay in Early Childhood. JAMA Netw Open;2024 (Jun 3);7(6):e2415084.

IMPORTANCE: Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited. OBJECTIVES: To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets. MAIN OUTCOMES AND MEASURES: The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale. RESULTS: The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment. CONCLUSIONS AND RELEVANCE: In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.

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32. Zhao M, You Y, Gao X, Li L, Li J, Cao M. The effects of a web-based 24-hour movement behavior lifestyle education program on mental health and psychological well-being in parents of children with autism spectrum disorder: A randomized controlled trial. Complement Ther Clin Pract;2024 (May 31);56:101865.

BACKGROUND AND PURPOSE: Compared with parents of neurotypical children or children diagnosed with other disabilities, parents of children with autism spectrum disorder (ASD) often experience poorer mental health, greater stress, and more depression and anxiety symptoms. This study aimed to assess the effects of a web-based 24-h movement behavior lifestyle education program on mental health and psychological well-being in parents of children with ASD. METHODS: This study employed a randomized controlled trial utilizing the Health Action Process Approach (HAPA) as a theoretical framework. A total of 318 parents of children with ASD were enrolled and randomly assigned to the experimental or control group. The experimental group received an 8-week web-based 24-h movement behavior lifestyle education program, while the control group followed their usual routine. Two instruments, the Depression Anxiety and Stress Scale (DASS-21) and the Satisfaction With Life Scale (SWLS), were used to measure mental health and psychological well-being, respectively. The data were collected at two time points-at the beginning and the end of the intervention. RESULTS: Compared with the baseline and control groups, the experimental group demonstrated significant improvements in all outcome measures (p < 0.01). There were significant differences in the DASS-21 and SWLS scores between the two groups before and after the intervention (p ≤ 0.01). CONCLUSION: This study represents the first randomized controlled trial involving a web-based 24-h movement behavior lifestyle education program specifically designed to address the mental health and psychological well-being of parents of children with ASD. The findings confirm the potential impact of 24-h movement behavior lifestyle education as a functional and effective strategy for parents of children with ASD.

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