1. Balathay D, Narasimhan U, Belo D, Anandan K. Quantitative assessment of cognitive profile and brain asymmetry in the characterization of autism spectrum in children: A task-based EEG study. Proceedings of the Institution of Mechanical Engineers Part H, Journal of engineering in medicine. 2023: 9544119231170683.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by learning, attention, social, communication, and behavioral impairments. Each person with Autism has a different severity and level of brain functioning, ranging from high functioning (HF) to low functioning (LF), depending on their intellectual/developmental abilities. Identifying the level of functionality remains crucial in understanding the cognitive abilities of Autistic children. Assessment of EEG signals acquired during specific cognitive tasks is more appropriate in identifying brain functional and cognitive load variations. The spectral power of EEG sub-band frequency and parameters related to brain asymmetry has the potential to be employed as indices to characterize brain functioning. Thus, the objective of this work is to analyze the cognitive task-based electrophysiological variations in autistic and control groups, using EEG acquired during two well-defined protocols. Theta to Alpha ratio (TAR) and Theta to Beta ratio (TBR) of absolute powers of the respective sub-band frequencies have been estimated to quantify the cognitive load. The variations in interhemispheric cortical power measured by EEG were studied using the brain asymmetry index. For the arithmetic task, the TBR of the LF group was found to be considerably higher than the HF group. The findings reveal that the spectral powers of EEG sub-bands can be a key indicator in the assessment of high and low-functioning ASD to facilitate appropriate training strategies. Instead of depending solely on behavioral tests to diagnose autism, it could be a beneficial approach to use task-based EEG characteristics to differentiate between the LF and HF groups.

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2. Carruthers S, Pickles A, Charman T, McConachie H, Le Couteur A, Slonims V, Howlin P, Collum R, Salomone E, Tobin H, Gammer I, Maxwell J, Aldred C, Parr J, Leadbitter K, Green J. Mediation of 6-year mid-childhood follow-up outcomes after pre-school social communication (PACT) therapy for autistic children: randomised controlled trial. Journal of child psychology and psychiatry, and allied disciplines. 2023.

BACKGROUND: There are very few mechanistic studies of the long-term impact of psychosocial interventions in childhood. The parent-mediated Paediatric Autism Communication Therapy (PACT) RCT showed sustained effects on autistic child outcomes from pre-school to mid-childhood. We investigated the mechanism by which the PACT intervention achieved these effects. METHODS: Of 152 children randomised to receive PACT or treatment as usual between 2 and 5 years of age, 121 (79.6%) were followed 5-6 years after the endpoint at a mean age of 10.5 years. Assessors, blind to the intervention group, measured Autism Diagnostic Observation Scale Calibrated Severity Score (ADOS CSS) for child autistic behaviours and Teacher Vineland (TVABS) for adaptive behaviour in school. Hypothesised mediators were child communication initiations with caregivers in a standard play observation (Dyadic Communication Measure for Autism, DCMA). Hypothesised moderators of mediation were baseline child non-verbal age equivalent scores (AE), communication and symbolic development (CSBS) and ‘insistence on sameness’ (IS). Structural equation modelling was used in a repeated measures mediation design. RESULTS: Good model fits were obtained. The treatment effect on child dyadic initiation with the caregiver was sustained through the follow-up period. Increased child initiation at treatment midpoint mediated the majority (73%) of the treatment effect on follow-up ADOS CSS. A combination of partial mediation from midpoint child initiations and the direct effect of treatment also contributed to a near-significant total effect on follow-up TVABS. No moderation of this mediation was found for AE, CSBS or IS. CONCLUSIONS: Early sustained increase in an autistic child’s communication initiation with their caregiver is largely responsible for the long-term effects from PACT therapy on autistic and adaptive behaviour outcomes. This supports the theoretical logic model of PACT therapy but also illuminates fundamental causal processes of social and adaptive development in autism over time: early social engagement in autism can be improved and this can have long-term generalised outcome effects.

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3. Chen S, Huang L, Liu G, Kang J, Qian Q, Wang J, Wang R, Zheng L, Wang H, Ou P. Acupuncture Ameliorated Behavioral Abnormalities in the Autism Rat Model via Pathways for Hippocampal Serotonin. Neuropsychiatric disease and treatment. 2023; 19: 951-72.

PURPOSE: Acupuncture can improve symptoms of autism spectrum disorder (ASD), but the potential mechanisms remain undefined. So, we aimed to explore the behavioral improvement of autism rat model after acupuncture and to describe the potential molecular mechanism underlying these changes. PATIENTS AND METHODS: Wistar rats were intraperitoneally injected with VPA 12.5 days after conception, and their offspring were considered as good models of autism. Experimental rats were divided into three groups (wild-type (WT), n = 10; VPA, n = 10; and VPA_acupuncture, n = 10). VPA_acupuncture group rat received 4 weeks of acupuncture treatment (Shéntíng (GV24), and Bilateral Běnshén (GB13)) on the 23rd day after birth. All rats were subjected to behavioral tests, including social interaction, open field, and Morris water maze tests. Afterwards, hippocampal tissues (left side) were removed and subjected to RNA sequencing (RNA-seq) analysis; ELISA was also used to detect the associated serotonin levels in the hippocampus. RESULTS: Behavioral tests showed that acupuncture treatment improved spontaneous activity, aberrant social interaction, and alleviated impaired learning and memory in the VPA-induced rat model. Differentially expressed genes (DGEs) analysis showed 142 significantly differentially expressed genes between WT and VPA groups, and 282 between VPA and VPA_acupuncture rats. Htr2c and Htr1a, 5-HT receptor genes, were up-regulated in the VPA group compared with WT group. Additionally, Tph1, a rate-limiting enzyme gene of 5-HT synthesis, was up-regulated after acupuncture. These genes were confirmed to have the same trend of expression obtained by RT-qPCR and RNA seq. Furthermore, the concentration of serotonin in the hippocampus in the VPA group was significantly lower than the WT and VPA_acupuncture groups. CONCLUSION: Acupuncture improved abnormal behavioral symptoms in the VPA-induced rat model. Further experiments showed that the improvement of the serotonin system may be one of the main regulatory mechanisms of acupuncture for treating ASD.

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4. Chin WC, Chang HL, Chao KY. Exploring Coping Strategies of Parents of Children With Autism Spectrum Disorder in Taiwan: A Qualitative Study. The journal of nursing research : JNR. 2023.

BACKGROUND: Children with autism spectrum disorder (ASD) experience impairments in their social interactions, language communication, and stereotypical patterns of behavior. Parents of children with ASD experience higher levels of stress and more depression and anxiety than parents of children with other disabilities or typically developing children. Parents of children with disabilities develop coping strategies to counteract the stresses associated with raising a child with special needs. Understanding coping strategies to help counteract the stresses associated with parenting a child with ASD may enhance well-being in parents of children with ASD, improve the quality of care provided to these children, and foster better parent-child relationships. PURPOSE: The purpose of this study was to explore the coping strategies used by parents in Taiwan parenting a child with ASD. METHODS: In this descriptive qualitative study, thematic analysis was conducted on data collected during face-to-face interviews. Fourteen parents of children with ASD were recruited using purposive sampling. Researchers employed a teamwork approach for data analysis to increase the dependability and consistency of the transcribed interviews. Team members discussed coding and identified the themes collaboratively. RESULTS: Taiwanese parents of children with ASD coped with the psychological impacts of parenting by employing problem-focused and emotion-focused strategies. Problem-focused strategies included communication, support, and management, whereas emotion-focused strategies included acceptance and adaptation. Findings showed that both coping strategies were useful in addressing specific situations and circumstances. Social and clinical support improved parents’ mental health and children’s external behaviors. CONCLUSIONS/IMPLICATION FOR PRACTICE: Healthcare providers should evaluate how parents are coping with the stresses related to raising a child with ASD and consider the cultural factors that might influence how they accept and adapt to parenting children with ASD. Understanding these variables may be used to tailor strategies appropriate to reducing stress and improving the well-being of parents and their children. Support and resource referrals should be considered, including parent support groups, books, web-based services, and recommendations for professional consultations with social workers or therapists.

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5. Falkovich R, Danielson EW, Perez de Arce K, Wamhoff EC, Strother J, Lapteva AP, Sheng M, Cottrell JR, Bathe M. A synaptic molecular dependency network in knockdown of autism- and schizophrenia-associated genes revealed by multiplexed imaging. Cell reports. 2023; 42(5): 112430.

The complex functions of neuronal synapses depend on their tightly interconnected protein network, and their dysregulation is implicated in the pathogenesis of autism spectrum disorders and schizophrenia. However, it remains unclear how synaptic molecular networks are altered biochemically in these disorders. Here, we apply multiplexed imaging to probe the effects of RNAi knockdown of 16 autism- and schizophrenia-associated genes on the simultaneous joint distribution of 10 synaptic proteins, observing several protein composition phenotypes associated with these risk genes. We apply Bayesian network analysis to infer hierarchical dependencies among eight excitatory synaptic proteins, yielding predictive relationships that can only be accessed with single-synapse, multiprotein measurements performed simultaneously in situ. Finally, we find that central features of the network are affected similarly across several distinct gene knockdowns. These results offer insight into the convergent molecular etiology of these widespread disorders and provide a general framework to probe subcellular molecular networks.

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6. Guo X, Cao Y, Liu J, Zhang X, Zhai G, Chen H, Gao L. Dysregulated dynamic time-varying triple-network segregation in children with autism spectrum disorder. Cerebral cortex (New York, NY : 1991). 2023; 33(9): 5717-26.

One of the remarkable characteristics of autism spectrum disorder (ASD) is the dysregulation of functional connectivity of the triple-network, which includes the salience network (SN), default mode network (DMN), and central executive network (CEN). However, there is little known about the segregation of the triple-network dynamics in ASD. This study used resting-state functional magnetic resonance imaging data including 105 ASD and 102 demographically-matched typical developing control (TC) children. We compared the dynamic time-varying triple-network segregation and triple-network functional connectivity states between ASD and TC groups, and examined the relationship between dynamic triple-network segregation alterations and clinical symptoms of ASD. The average dynamic network segregation value of the DMN with SN and the DMN with CEN in ASD was lower but the coefficient of variation (CV) of dynamic network segregation of the DMN with CEN was higher in ASD. Furthermore, partially reduced triple-network segregation associated with the DMN was found in connectivity states analysis of ASD. These abnormal average values and CV of dynamic network segregation predicted social communication deficits and restricted and repetitive behaviors in ASD. Our findings indicate abnormal dynamic time-varying triple-network segregation of ASD and highlight the crucial role of the triple-network in the neural mechanisms underlying ASD.

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7. Hall A, Maw R, Iles-Caven Y, Gregory S, Rai D, Golding J. Associations between autistic traits and early ear and upper respiratory signs: a prospective observational study of the Avon Longitudinal Study of Parents and Children (ALSPAC) geographically defined childhood population. BMJ open. 2023; 13(3): e067682.

OBJECTIVE: To determine whether early ear and upper respiratory signs are associated with the development of high levels of autistic traits or diagnosed autism. DESIGN: Longitudinal birth cohort: Avon Longitudinal Study of Parents and Children (ALSPAC). SETTING: Area centred on the city of Bristol in Southwest England. Eligible pregnant women resident in the area with expected date of delivery between April 1991 and December 1992 inclusive. PARTICIPANTS: 10 000+ young children followed throughout their first 4 years. Their mothers completed three questionnaires between 18-42 months recording the frequency of nine different signs and symptoms relating to the upper respiratory system, as well as ear and hearing problems. OUTCOME MEASURES: Primary-high levels of autism traits (social communication, coherent speech, sociability, and repetitive behaviour); secondary-diagnosed autism. RESULTS: Early evidence of mouth breathing, snoring, pulling/poking ears, ears going red, hearing worse during a cold, and rarely listening were associated with high scores on each autism trait and with a diagnosis of autism. There was also evidence of associations of pus or sticky mucus discharge from ears, especially with autism and with poor coherent speech. Adjustment for 10 environmental characteristics made little difference to the results, and substantially more adjusted associations were at p<0.001 than expected by chance (41 observed; 0.01 expected). For example, for discharge of pus or sticky mucus from ears the adjusted odds ratio (aOR) for autism at 30 months was 3.29 (95% CI 1.85 to 5.86, p<0.001), and for impaired hearing during a cold the aOR was 2.18 (95% CI 1.43 to 3.31, p<0.001). CONCLUSIONS: Very young children exhibiting common ear and upper respiratory signs appear to have an increased risk of a subsequent diagnosis of autism or demonstrated high levels of autism traits. Results suggest the need for identification and management of ear, nose and throat conditions in autistic children and may provide possible indicators of causal mechanisms.

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8. Hong T, McBride E, Dufour BD, Falcone C, Doan M, Noctor SG, Martínez-Cerdeño V. Synaptic boutons are smaller in chandelier cell cartridges in autism. PloS one. 2023; 18(4): e0281477.

Chandelier (Ch) cells are cortical interneurons with axon terminal structures known as cartridges that synapse on the axon initial segment of excitatory pyramidal neurons. Previous studies indicate that the number of Ch cells is decreased in autism, and that GABA receptors are decreased in the Ch cell synaptic target in the prefrontal cortex. To further identify Ch cell alterations, we examined whether the length of cartridges, and the number, density, and size of Ch cell synaptic boutons, differed in the prefrontal cortex of cases with autism versus control cases. We collected samples of postmortem human prefrontal cortex (Brodmann Area (BA) 9, 46, and 47) from 20 cases with autism and 20 age- and sex-matched control cases. Ch cells were labeled using an antibody against parvalbumin, a marker that labeles soma, cartridges, and synaptic boutons. We found no significant difference in the average length of cartridges, or in the total number or density of boutons in control subjects vs. subjects with autism. However, we found a significant decrease in the size of Ch cell boutons in those with autism. The reduced size of Ch cell boutons may result in reduced inhibitory signal transmission and impact the balance of excitation to inhibition in the prefrontal cortex in autism.

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9. Lee CM, Green Snyder L, Carpenter LA, Harris J, Kanne S, Taylor CM, Sarver DE, Stephenson KG, Shulman LH, Wodka EL, Esler A. Agreement of parent-reported cognitive level with standardized measures among children with autism spectrum disorder. Autism research : official journal of the International Society for Autism Research. 2023.

Assessing cognitive development is critical in clinical research of autism spectrum disorder (ASD). However, collecting cognitive data from clinically administered assessments can add a significant burden to clinical research in ASD due to the substantial cost and time required, and it is often prohibitive in large-scale studies. There is a need for more efficient, but reliable, methods to estimate cognitive functioning for researchers, clinicians, and families. To examine the degree to which caregiver estimates of cognitive level agree with actual measured intelligence/developmental scores and understand factors that may impact that agreement, 1,555 autistic individuals (81.74% male; age 18 months-18 years) were selected from a large cohort (Simons Foundation Powering Autism Research for Knowledge, SPARK). Results suggest that querying parents about recent testing results and developmental diagnoses can provide valid and useful information on cognitive ability. The agreement of parental estimates varied with age, measured cognitive ability, autistic traits, and adaptive skills. In the context of large-scale research efforts, parent-reported cognitive impairment may be a good proxy for categorical IQ range for survey-based studies when specific IQ scores are not available, circumventing the logistical and financial obstacles of obtaining neuropsychological or neurodevelopmental testing.

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10. Nutor C, Dunlop A, Sadler O, Brennan PA. Prenatal Cannabis Use and Offspring Autism-Related Behaviors: Examining Maternal Stress as a Moderator in a Black American Cohort. Journal of autism and developmental disorders. 2023: 1-13.

Prenatal cannabis use and maternal stress have been proposed as risk factors for autism spectrum disorder (ASD). Black mothers and mothers of lower socioeconomic status (SES) may be especially likely to experience high levels of stress. This study examined the impact of prenatal cannabis use and maternal stress (i.e., prenatal distress, racial discrimination, and lower SES) on child ASD-related behaviors in a sample of 172 Black mother-child pairs. We found that prenatal stress was significantly associated with ASD-related behaviors. Prenatal cannabis use did not predict ASD-related behaviors and did not interact with maternal stress to predict ASD-related behaviors. These findings replicate previous work on prenatal stress-ASD associations and add to the limited literature on prenatal cannabis-ASD associations in Black samples.

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11. Patrick ME, Hughes MM, Ali A, Shaw KA, Maenner MJ. Social Vulnerability and Prevalence of Autism, Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP). Annals of epidemiology. 2023.

PURPOSE: The Metropolitan Atlanta Developmental Disabilities Surveillance Program (MADDSP) tracks autism spectrum disorder (ASD) in selected counties within Georgia as part of the Autism and Developmental Disabilities Monitoring Network. ADDM Network analyses have historically found higher prevalence of ASD in areas of higher socioeconomic status. METHODS: We linked 2018 data from CDC’s Social Vulnerability Index (SVI) to two MADDSP counties by census tract, grouped census tracts into tertiles representing low, medium, and high social vulnerability, and calculated ASD prevalence for each tertile, overall and by each of four SVI themes. RESULTS: We found that overall prevalence was higher in areas of low compared to high vulnerability for the socioeconomic status and transportation themes, and in areas of medium compared to high vulnerability for all themes. This pattern was consistent among males but varied for females and by race/ethnicity. CONCLUSION: Linking ASD prevalence to SVI metrics can improve understanding of inequities among children with ASD in racial and ethnic minority groups or those living in low resource settings. These methods can be applied to other ADDM Network surveillance sites and public health surveillance programs.

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12. Saggar M, Bruno JL, Hall SS. Brief intensive social gaze training reorganizes functional brain connectivity in boys with fragile X syndrome. Cerebral cortex (New York, NY : 1991). 2023; 33(9): 5218-27.

Boys with fragile X syndrome (FXS), the leading known genetic cause of autism spectrum disorder (ASD), demonstrate significant impairments in social gaze and associated weaknesses in communication, social interaction, and other areas of adaptive functioning. Little is known, however, concerning the impact of behavioral treatments for these behaviors on functional brain connectivity in this population. As part of a larger study, boys with FXS (mean age 13.23 ± 2.31 years) and comparison boys with ASD (mean age 12.15 ± 2.76 years) received resting-state functional magnetic resonance imaging scans prior to and following social gaze training administered by a trained behavior therapist in our laboratory. Network-agnostic connectome-based predictive modeling of pretreatment resting-state functional connectivity data revealed a set of positive (FXS > ASD) and negative (FXS < ASD) edges that differentiated the groups significantly and consistently across all folds of cross-validation. Following administration of the brief training, the FXS and ASD groups demonstrated reorganization of connectivity differences. The divergence in the spatial pattern of reorganization response, based on functional connectivity differences pretreatment, suggests a unique pattern of response to treatment in the FXS and ASD groups. These results provide further support for implementing targeted behavioral treatments to ameliorate syndrome-specific behavioral features in FXS.

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13. Simmons CA, Moretti AE, Lobo AF, Tremoulet PD. Direct Support Professionals’ Perspectives on Using Technology to Help Support Adults With Autism Spectrum Disorder: Mixed Methods Study. JMIR formative research. 2023; 7: e40722.

BACKGROUND: Documentation is a critical responsibility for direct support professionals (DSPs) who work with adults with autism spectrum disorder (ASD); however, it contributes significantly to their workload. Targeted efforts must be made to mitigate the burden of necessary data collection and documentation, which contributes to high DSP turnover rates and poor job satisfaction. OBJECTIVE: This mixed methods study aimed to explore how technology could assist DSPs who work with adults with ASD and prioritize aspects of technology that would be most useful for future development efforts. METHODS: In the first study, 15 DSPs who worked with adults with ASD participated in 1 of the 3 online focus groups. The topics included daily tasks, factors that would influence the adoption of technology, and how DSPs would like to interact with technologies to provide information about their clients. Responses were thematically analyzed across focus groups and ranked by salience. In the second study, 153 DSPs across the United States rated the usefulness of technology features and data entry methods and provided qualitative responses on their concerns regarding the use of technology for data collection and documentation. Quantitative responses were ranked based on their usefulness across participants, and rank-order correlations were calculated between different work settings and age groups. The qualitative responses were thematically analyzed. RESULTS: In study 1, participants described difficulties with paper-and-pencil data collection, noted benefits and concerns about using technology instead, identified benefits and concerns about particular technology features, and specified work-environment factors that impact data collection. In study 2, participants rated multiple features of technology as useful, with the highest usefulness percentages endorsed for task views (ie, by shift, client, and DSP), logging completed tasks, and setting reminders for specific tasks. Participants also rated most data entry methods (eg, typing on a phone or tablet, typing on a keyboard, and choosing from options on a touch screen) as useful. Rank-order correlations indicated that the usefulness of technology features and data entry methods differed across work settings and age groups. Across both studies, DSPs cited some concerns with technology, such as confidentiality, reliability and accuracy, complexity and efficiency, and data loss from technology failure. CONCLUSIONS: Understanding the challenges faced by DSPs who work with adults with ASD, and their thoughts about using technology to meet those challenges, represents an essential first step toward developing technology solutions that can increase DSPs’ effectiveness and job satisfaction. The survey results indicate that technology innovations should incorporate multiple features to account for different needs across DSPs, settings, and age groups. Future research should explore barriers to adopting data collection and documentation tools and elicit input from agency directors, families, and others interested in reviewing data about adults with ASD.

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14. Stania M, Emich-Widera E, Kazek B, Kamieniarz A, Swatowska-Wenglarczyk M, Juras G. Modulation of center-of-pressure signal in children on the autism spectrum: A case-control study. Gait & posture. 2023; 103: 67-72.

BACKGROUND: Proper postural and motor control plays a fundamental role in the child’s ontogenetic development. So far, the postural control in children on the autism spectrum has mainly been assessed with standard posturographic measurements of center of pressure (COP) displacements. RESEARCH QUESTION: What are the differences in postural control between autistic and typically developing children? METHODS: The study group comprised 16 autistic children aged 6-10 years, identified by a psychiatrist. The control group consisted of 16 typically developing children aged 6-10 years with no posture deformities, no pervasive developmental disorder and no history of postural control or movement deficits. The data were collected during quiet standing with eyes open using a force plate. To gain a better insight into the postural control processes, the rambling-trembling and sample entropy analyses were used in COP data processing. RESULTS: Compared to typically developing children, those with autism spectrum had significantly higher values of COP and rambling trajectory parameters in the antero-posterior direction during quiet standing. The variables of the trembling trajectory did not differ significantly between the groups. The autistic children had significantly lower values of sample entropy in the antero-posterior direction compared to typically developing children. SIGNIFICANCE: More advanced measures of COP displacements including the rambling-trembling method and sample entropy revealed differences in postural control between autistic and typically developing children. These methods may therefore contribute to functional assessment of postural control deficits in children on the autism spectrum.

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15. Tsai SJ, Hsu JW, Huang KL, Bai YM, Su TP, Chen TJ, Chen MH. Autism spectrum disorder and periodontitis risk: A cohort study of 38,203 adolescents. Journal of the American Dental Association (1939). 2023.

BACKGROUND: People with autism spectrum disorder (ASD) may have poor oral health status because they often experience challenges with daily oral hygiene and have inadequate access to oral health care services. This study explored periodontitis risk in adolescents with ASD compared with those who did not have a diagnosis of ASD. METHODS: Data from 2001 through December 31, 2011 from the Taiwan National Health Insurance Research Database on 3,473 adolescents with ASD and 34,730 age- and sex-matched people who did not have a diagnosis of ASD were obtained, and subsequent periodontitis was identified from enrollment through December 31, 2011. RESULTS: Adolescents with ASD (hazard ratio, 2.01; 95% CI, 1.84 to 2.20) were more likely to develop periodontitis at follow-up than those who did not have a diagnosis of ASD. Findings remained consistent in subanalyses stratified by sex and intellectual disability. People with ASD had periodontitis onset at an earlier mean (SD) age than those who did not have a diagnosis of ASD (17.97 [3.12] vs 21.86 [2.28] years; P < .001). CONCLUSIONS: ASD is an independent risk factor for subsequent periodontitis development. PRACTICAL IMPLICATIONS: Oral health should be closely monitored in adolescents with ASD. Future investigation of the common pathogenesis between periodontitis and ASD is warranted.

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16. van Trigt S, Colonnesi C, Brummelman E, Jorgensen TD, Nikolić M. Autistic traits and self-conscious emotions in early childhood. Child development. 2023.

Self-conscious emotions arise from evaluating the self through the eyes of others. Given that children with autistic traits may experience difficulties with understanding others’ minds, they might show less attuned self-conscious emotions. Two-to-five-year-old children’s (N = 98, M(age) = 48.54 months, 50% girls, 92% White) self-conscious emotions (guilt, embarrassment, and shame-like avoidance) were observed after children « broke » the experimenter’s favorite toy. Data were collected from March 2018 till June 2019. Children with more autistic traits showed less theory of mind (ToM), and more shame-like avoidance, but associations were not mediated by ToM. This provides initial evidence that children with more autistic traits may show disturbances in some but not all self-conscious emotions, which could hinder their social functioning.

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17. Yin H, Wang Z, Liu J, Li Y, Liu L, Huang P, Wang W, Shan Z, Sun R, Shen J, Duan L. Dysregulation of immune and metabolism pathways in maternal immune activation induces an increased risk of autism spectrum disorders. Life sciences. 2023; 324: 121734.

AIMS: Maternal immune activation (MIA) via infection during pregnancy is known to be an environmental risk factor for neurodevelopmental disorders and the development of autism spectrum disorders (ASD) in the offspring, but it still remains elusive that the molecular relevance between infection-induced abnormal neurodevelopmental events and an increased risk for ASD development. MAIN METHODS: Fully considering the extremely high genetic heterogeneity of ASD and the universality of risk-gene with minimal effect-sizes, the gene and pathway-based association analysis was performed with the transcriptomic and DNA methylation landscapes of temporal human embryonic brain development and ASD, and the time-course transcriptional profiling of MIA. We conducted the transcriptional profiling of mouse abnormal neurodevelopment two days following induced MIA via LPS injection at E10.5. KEY FINDINGS: A novel evidence was proved that illustrated altering four immune and metabolism-related risk pathways, including starch and sucrose metabolism, ribosome, protein processing in endoplasmic reticulum, and retrograde endocannabinoid signaling pathway, which were prominent involvement in the process of MIA regulating abnormal fetal brain development to induce an increased risk of ASD. Here, we have observed that almost all key genes within these risk pathways are significantly differentially expressed at embryonic days (E) 10.5-12.5, which is considered to be the optimal coincidence window of mouse embryonic brain development to study the intimate association between MIA and ASD using mouse animal models. SIGNIFICANCE: There search establishes that MIA causes dysregulation of immune and metabolic pathways, which leads to abnormal embryonic neurodevelopment, thus promoting development of ASD symptoms in offspring.

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