1. Beversdorf DQ. Understanding the Heterogeneity of Neurodevelopmental Disorders and Its Implications: An Exploration of Repetitive Behaviors. Biol Psychiatry Cogn Neurosci Neuroimaging. 2024; 9(4): 370-1.

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2. Cai RY, Edwards C, Love AM, Brown L, Gibbs V. Self-compassion improves emotion regulation and mental health outcomes: A pilot study of an online self-compassion program for autistic adults. Autism. 2024: 13623613241235061.

Self-compassion is when we are aware of our feelings and thoughts, are friendly toward ourselves, and realize everyone feels pain and makes mistakes. Self-compassion is associated with having better mental health and well-being in autistic and non-autistic people. But we do not know if autistic people’s self-compassion can be improved through psychoeducation and self-compassion practices. We co-produced an online self-guided self-compassion program based on evidence-based self-compassion practices for autistic adults called the Self-compassion Program for Autistic Adults. This program included live-experiences videos of autistic adults reflecting on their self-compassion and self-critical experiences. This study piloted the program with 39 autistic adults. We wanted to see if these autistic adults’ self-compassion, emotion regulation, mental health, and psychological well-being improved after completing this program. We found that the autistic participants’ self-compassion, emotion regulation, mental health, and psychological well-being improved significantly after completing the program over 5 weeks. We also found that just over half of the participants reported experiencing negative reactions associated with self-compassion practices. We suggested some clinical implications, including a recommendation for emotion regulation interventions to incorporate self-compassion to help promote access to the affiliative system. In addition, autistic adults who are psychologically vulnerable may need to work with mental health professionals while developing self-compassion to help manage the possible negative reactions associated with some self-compassion practices.

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3. DuBois LA, Bradley V, Isvan N. An observational investigation of unemployment, underemployment, and competitive integrated employment of people with intellectual and developmental disabilities in 2021-2022. Disabil Health J. 2024: 101620.

BACKGROUND: Employment is an important component of community living, and a precursor to economic stability and independence. Despite this, research consistently demonstrates people with intellectual and developmental disabilities (IDD) have low rates of community-based employment. However, little research has been conducted to quantify competitive integrated employment, and which individuals have better employment outcomes as it relates to competitive integrated employment. OBJECTIVE: This study aims to explore the ways in which key service-related and demographic characteristics of individuals with IDD are associated with participation in competitive integrated employment. METHODS: We used the 2021-2022 National Core Indicators Intellectual and Developmental Disabilities In-Person Survey dataset. We conducted bivariate and multivariate analyses, using chi-square and generalized linear models, to examine the cross-sectional relationship between employment and demographic and service-related characteristics for 4629 individuals with IDD. RESULTS: Overall, 42% of the sample was unemployed but wanted a job, while 39% were underemployed and just 21% have competitive integrated employment. Several demographic and service-related characteristics were significantly associated with employment. After controlling for demographic and service-related correlates of employment, having an employment-related goal in one’s service plan was associated with 4.5 (95% CI: 3.6-5.5) times higher odds of competitive integrated employment relative to unemployment. CONCLUSIONS: This study underscores the value of person-centered planning for improved employment outcomes. Further research is needed to fully understand potential inequities in employment and system-level factors that are associated with competitive, integrated employment, as well as solutions to improve access to customized individual employment supports for all people with IDD.

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4. Garrido-Torres N, Marqués Rodríguez R, Alemany-Navarro M, Sánchez-García J, García-Cerro S, Ayuso MI, González-Meneses A, Martinez-Mir A, Ruiz-Veguilla M, Crespo-Facorro B. Exploring genetic testing requests, genetic alterations and clinical associations in a cohort of children with autism spectrum disorder. Eur Child Adolesc Psychiatry. 2024.

Several studies show great heterogeneity in the type of genetic test requested and in the clinicopathological characteristics of patients with ASD. The following study aims, firstly, to explore the factors that might influence professionals’ decisions about the appropriateness of requesting genetic testing for their patients with ASD and, secondly, to determine the prevalence of genetic alterations in a representative sample of children with a diagnosis of ASD. Methods: We studied the clinical factors associated with the request for genetic testing in a sample of 440 children with ASD and the clinical factors of present genetic alterations. Even though the main guidelines recommend genetic testing all children with an ASD diagnosis, only 56% of children with an ASD diagnosis were genetically tested. The prevalence of genetic alterations was 17.5%. These alterations were more often associated with intellectual disability and dysmorphic features. There are no objective data to explicitly justify the request for genetic testing, nor are there objective data to justify requesting one genetic study versus multiple studies. Remarkably, only 28% of males were genetically tested with the recommended tests (fragile X and CMA). Children with dysmorphic features and organic comorbidities were more likely to be genetic tested than those without. Previous diagnosis of ASD (family history of ASD) and attendance at specialist services were also associated with Genetically tested Autism Spectrum Disorder GTASD. Our findings emphasize the importance of establishing algorithms to facilitate targeted genetic consultation for individuals with ASD who are likely to benefit, considering clinical phenotypes, efficiency, ethics, and benefits.

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5. Girolamo T, Ghali S, Larson C. Sentence production and sentence repetition in autistic adolescents and young adults: Linguistic sensitivity to finiteness-marking. medRxiv. 2024.

PURPOSE: Despite the clinical utility of sentence production and sentence repetition to identify language impairment in autism, little is known about the extent to which these tasks are sensitive to potential dialectal variation. One promising method is strategic scoring (Oetting et al., 2016), which has good clinical utility for identifying language impairment in nonautistic school-age children across dialects of English. This report applies strategic scoring to analyze sentence repetition and sentence production in autistic adolescents and adults. METHOD: Thirty-one diverse autistic adolescents and adults with language impairment (ALI; n =15) and without language impairment (ASD; n =16) completed the Formulated Sentences and Recalling Sentences subtests of the Clinical Evaluation of Language Fundamentals-5 (th) Ed (Wiig et al., 2013). Descriptive analyses and regression evaluated effects of scoring condition, group, and scoring condition by group on outcomes, as well as group differences in finiteness-marking across utterances and morphosyntactic structures. RESULTS: Strategic and unmodified item-level scores were essentially constant on both subtests and significantly lower in the ALI than the ASD group. Only group predicted item-level scores. Group differences were limited to: percent grammatical utterances on Formulated Sentences and percent production of overt structures combined on Sentence Repetition (ALI < ASD). DISCUSSION: Findings support the feasibility of strategic scoring for sentence production and sentence repetition to identify language impairment and indicate that potential dialectal variation in finiteness-marking did not confound outcomes in this sample. To better understand the clinical utility of strategic scoring, replication with a larger sample varying in age and comparisons with dialect-sensitive measures are needed.

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6. Lavigne É, Abdulaziz KE, Murphy MS, Stanescu C, Dingwall-Harvey AL, Stieb DM, Walker MC, Wen SW, Shin HH. Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada. Environ Res. 2024: 118828.

BACKGROUND: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). METHODS: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). RESULTS: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. CONCLUSIONS: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

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7. Li Y, Huang Y, Yang S, Shychuk EM, Shenkman EA, Bian J, Angell AM, Guo Y. Machine Learning Prediction of Autism Spectrum Disorder Through Linking Mothers’ and Children’s Electronic Health Record Data. medRxiv. 2024.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder typically diagnosed in children. Early detection of ASD, particularly in girls who are often diagnosed late, can aid long-term development for children. We aimed to develop machine learning models for predicting ASD diagnosis in children, both boys and girls, using child-mother linked electronic health records (EHRs) data from a large clinical research network. Model features were children and mothers’ risk factors in EHRs, including maternal health factors. We tested XGBoost and logistic regression with Random Oversampling (ROS) and Random Undersampling (RUS) to address imbalanced data. Logistic regression with RUS considering a three-year observation window for children’s risk factors achieved the best performance for predicting ASD among the overall study population (AUROC = 0.798), boys (AUROC = 0.786), and girls (AUROC = 0.791). We calculated SHAP values to quantify the impacts of important clinical and sociodemographic risk factors.

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8. Manduca A, Buzzelli V, Rava A, Feo A, Carbone E, Schiavi S, Peruzzi B, D’Oria V, Pezzullo M, Pasquadibisceglie A, Polticelli F, Micale V, Kuchar M, Trezza V. Cannabidiol and positive effects on object recognition memory in an in vivo model of Fragile X Syndrome: Obligatory role of hippocampal GPR55 receptors. Pharmacol Res. 2024; 203: 107176.

Cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, has been recently approved for epileptic syndromes often associated with Autism spectrum disorder (ASD). However, the putative efficacy and mechanism of action of CBD in patients suffering from ASD and related comorbidities remain debated, especially because of the complex pharmacology of CBD. We used pharmacological, immunohistochemical and biochemical approaches to investigate the effects and mechanisms of action of CBD in the recently validated Fmr1-(Δ)exon 8 rat model of ASD, that is also a model of Fragile X Syndrome (FXS), the leading monogenic cause of autism. CBD rescued the cognitive deficits displayed by juvenile Fmr1-(Δ)exon 8 animals, without inducing tolerance after repeated administration. Blockade of CA1 hippocampal GPR55 receptors prevented the beneficial effect of both CBD and the fatty acid amide hydrolase (FAAH) inhibitor URB597 in the short-term recognition memory deficits displayed by Fmr1-(Δ)exon 8 rats. Thus, CBD may exert its beneficial effects through CA1 hippocampal GPR55 receptors. Docking analysis further confirmed that the mechanism of action of CBD might involve competition for brain fatty acid binding proteins (FABPs) that deliver anandamide and related bioactive lipids to their catabolic enzyme FAAH. These findings demonstrate that CBD reduced cognitive deficits in a rat model of FXS and provide initial mechanistic insights into its therapeutic potential in neurodevelopmental disorders.

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9. McQuaid GA, Ratto AB, Jack A, Khuu A, Smith JV, Duane SC, Clawson A, Lee NR, Verbalis A, Pelphrey KA, Kenworthy L, Wallace GL, Strang JF. Gender, assigned sex at birth, and gender diversity: Windows into diagnostic timing disparities in autism. Autism. 2024: 13623613241243117.

Later autism diagnosis is associated with risk for mental health problems. Understanding factors related to later autism diagnosis may help reduce mental health risks for autistic people. One characteristic associated with later autism diagnosis is female sex. However, studies often do not distinguish sex assigned at birth and gender identity. Gender diversity may be more common in autistic relative to neurotypical people, and autism is more common in gender-diverse populations. We studied age at autism diagnosis by sex assigned at birth, gender identity, and gender diversity (gender-diverse vs cisgender) status, separately. We studied three separate autistic samples, each of which differed in how they were diagnosed and how they were recruited. The samples included 193 persons (8.0-18.0 years) from a research-recruited academic medical center sample; 1,550 people (1.3-25.4 years) from a clinic-based sample; and 244 people (18.2-30.0 years) from a community-enriched sample. We found significant differences in the clinic-based and community-enriched samples. People assigned female sex at birth were diagnosed with autism significantly later than people assigned male at birth. People of female gender were diagnosed significantly later than people of male gender. Gender-diverse people were diagnosed significantly later than cisgender people. Sex assigned at birth, gender identity, and gender diversity may each show unique relationships with age of autism diagnosis. Differences in how autistic people are diagnosed and recruited are important to consider in studies that examine sex assigned at birth or gender identity. More research into autism diagnosis in adulthood is needed.

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10. Oates M, McCauley R, Bean A. Exploring Online Communication in Self-Identified Autistic Adolescents. J Speech Lang Hear Res. 2024; 67(4): 1165-72.

PURPOSE: Social media sites provide autistic youth a familiar space to interact that is devoid of many of the challenges that accompany face-to-face interactions. As such, it is important to determine whether the linguistic profiles observed during online interactions are consistent with face-to-face interactions. This preliminary study took a step in this direction by examining gender differences observed in autistic adolescents in an online forum to determine whether they are consistent with the emerging body of research investigating linguistic gender differences in autistic adolescents. METHOD: We analyzed the entries of self-identified autistic adolescents in an online forum to determine whether autistic girls (n = 99) and boys (n = 94) differ in their use of linguistic features as a proportion of total words produced. Transcriptions were coded across discourse, lexical, and semantic features and compared to previous research investigating linguistic gender differences in autistic people. Exploratory comparisons were also made to linguistic gender differences in neurotypical people. RESULTS: Of the linguistic features we examined, three out of four of the gendered usage patterns observed in the online forum language samples were consistent with previous research on face-to-face communication for autistic adolescents. Only one feature out of 12 occurred in the same gender distribution as previous research on neurotypical communication. CONCLUSIONS: Autistic girls and boys demonstrate largely consistent gender differences in their language use across in-person and online communication contexts. Interestingly, most of the significant gender differences previously reported in neurotypical communicators were not seen in this sample of autistic adolescents, suggesting that perhaps autistic individuals may linguistically express gender characteristics to a different extent or in a different manner than neurotypical individuals.

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11. Peterson T, Hosey T, Mosteller J, Sherwin R, Strale F, Jr. A Descriptive Study on the Impacts of Hyperbaric Oxygen Therapy on Autistic Individuals Using Parent Testimonies. Cureus. 2024; 16(3): e55648.

Introduction Hyperbaric oxygen therapy (HBOT) has been influential in treating many physical and psychological ailments, including the symptoms of autism. This current study aims to evaluate HBOT parents’ goals and exit interviews describing the positive, negative, or no impacts experienced from the HBOT dives, asking the question, « Are your child’s symptoms improving? » Methods Between January 2020 and July 2023, a Class B monoplace hyperbaric chamber (Sechrist 3300H, Sechrist Industries, Inc., Anaheim, California, United States) was used to administer HBOT sessions to patients with autism. Medical-grade oxygen was pressurized to 1.5-2.0 atmospheres absolute at a rate of 1-2 psi/min, with an average oxygen percentage of 100%, for up to five sessions per week. Retrospective descriptive data and patient information through parent testimonials were collected through a chart review of 30 children and one adult with autism who experienced HBOT sessions. Data were presented through exit interviews describing how parents felt about their child’s progress toward goals. Four raters rated parent testimonies on a 5-point Likert scale (1 = Much worse, 2 = Somewhat worse, 3 = Stayed the same, 4 = Somewhat improved, and 5 = Much improved), and an inter-rater reliability estimate using interclass correlation (2) (r = 0.831) was derived, indicating excellent agreement between raters. Results Parents/caregivers provided testimony in an exit interview with a registered nurse after the individual with autism received an entire course of HBOT dives. Descriptive statistics resulted in Rater #1 (M = 4.19, median = 4, SD = 0.654): 87.1% of Rater #1 ratings were Somewhat improved and Much improved; Rater #2 (M = 4.23, median = 4, SD = 0.717): 83.9% of Rater #2 ratings were Somewhat improved and Much improved; Rater #3 (M = 4.23, median = 4, SD = 0.560): 93.5% of Rater #3 ratings were Somewhat improved and Much improved; and Rater #4 (M = 4.26, median = 4, SD = 0.631): 90.3% of Rater #4 ratings were Somewhat improved and Much improved. One-way ANOVA resulted in F (3,123) = 0.052, p = 0.984, which indicated a nonstatistically significant mean difference between rater groups. Conclusions The current study assessed HBOT parents’/caregivers’ goals and exit interviews, describing the effects experienced from the complete course of HBOT dives on their children/individuals. A majority of parents/caregivers declared that their condition had « Much improved » or « Somewhat improved, » based on the 5-point Likert scale. Based on parents’/caregivers’ testimonies, HBOT was demonstrated as a safe and effective intervention, and side effects were primarily mild and did not lead to treatment discontinuation. As a result of this analysis, we recommend continued use of HBOT for treatment.

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12. Postma A, Ketelaar M, van Nispen Tot Sevenaer J, Downs Z, van Rappard D, Jongmans M, Zinkstok J. Exploring individual parent-to-parent support interventions for parents caring for children with brain-based developmental disabilities: A scoping review. Child Care Health Dev. 2024; 50(3): e13255.

BACKGROUND: Brain-based developmental disabilities (BBDDs) comprise a large and heterogeneous group of disorders including autism, intellectual disability, cerebral palsy or genetic and neurodevelopmental disorders. Parents caring for a child with BBDD face multiple challenges that cause increased stress and high risk of mental health problems. Peer-based support by fellow parents for a various range of patient groups has shown potential to provide emotional, psychological and practical support. Here, we aim to explore existing literature on individual peer-to-peer support (iP2PS) interventions for parents caring for children with BBDD with a view to (1) explore the impact of iP2PS interventions on parents and (2) identify challenges and facilitators of iP2PS. METHOD: An extensive literature search (January 2023) was performed, and a thematic analysis was conducted to synthesize findings. RESULTS: Fourteen relevant articles revealed three major themes regarding the impact of iP2PS on parents: (1) emotional and psychological well-being, (2) quality of life and (3) practical issues. Four themes were identified describing challenges and facilitators of iP2PS: (1) benefits and burden of giving support, (2) matching parent-pairs, (3) logistic challenges and solutions and (4) training and supervision of parents providing peer support. CONCLUSIONS: This review revealed that iP2PS has a positive impact on the emotional and psychological well-being of parents, as well as the overall quality of life for families caring for a child with a BBDD. Individual P2PS offers peer-parents an opportunity to support others who are facing challenges similar to those they have experienced themselves. However, many questions still need to be addressed regarding benefits of different iP2PS styles, methods of tailoring support to individual needs and necessity of training and supervision for peer support providers. Future research should focus on defining these components and evaluating benefits to establish effective iP2PS that can be provided as standard care practice for parents.

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13. Prince N, Peralta Marzal LN, Markidi A, Ahmed S, Adolfs Y, Pasterkamp RJ, Kumar H, Roeselers G, Garssen J, Kraneveld AD, Perez-Pardo P. Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder. Acta Pharmacol Sin. 2024.

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.

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14. Rowshan N, Anjomshoa M, Farahzad A, Bijad E, Amini-Khoei H. Gut-brain barrier dysfunction bridge autistic-like behavior in mouse model of maternal separation stress: A behavioral, histopathological, and molecular study. Int J Dev Neurosci. 2024.

Autism spectrum disorder (ASD) is a fast-growing neurodevelopmental disorder throughout the world. Experiencing early life stresses (ELS) like maternal separation (MS) is associated with autistic-like behaviors. It has been proposed that disturbance in the gut-brain axis-mediated psychiatric disorders following MS. The role of disruption in the integrity of gut-brain barrier in ASD remains unclear. Addressing this knowledge gap, in this study we aimed to investigate role of the gut-brain barrier integrity in mediating autistic-like behaviors in mouse models of MS stress. To do this, mice neonates are separated daily from their mothers from postnatal day (PND) 2 to PND 14 for 3 hours. During PND58-60, behavioral tests related to autistic-like behaviors including three-chamber sociability, shuttle box, and resident-intruder tests were performed. Then, prefrontal cortex (PFC), hippocampus, and colon samples were dissected out for histopathological and molecular evaluations. Results showed that MS is associated with impaired sociability and social preference indexes, aggressive behaviors, and impaired passive avoidance memory. The gene expression of CLDN1 decreased in the colon, and the gene expression of CLDN5, CLDN12, and MMP9 increased in the PFC of the MS mice. MS is associated with decrease in the diameter of CA1 and CA3 areas of the hippocampus. In addition, MS led to histopathological changes in the colon. We concluded that, probably, disturbance in the gut-brain barrier integrities mediated the autistic-like behavior in MS stress in mice.

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15. Sape RM, Shead DA, Maseko BC. Global pharmaceutical care approaches to autism spectrum disorder: a scoping review protocol. JBI Evid Synth. 2024.

OBJECTIVE: The aim of the review is to map the literary evidence on pharmaceutical care approaches and trends being seen globally in the treatment of the signs and symptoms of autism spectrum disorder (ASD). INTRODUCTION: ASD is a neurodevelopmental condition synonymous with sliding-scale behavioral, communication, and social problems. Causes include genetic and environmental factors. Pharmaceuticals are prescribed to treat the behavioral patterns of ASD. INCLUSION CRITERIA: This review will incorporate studies that report on the pharmaceutical care approaches used to treat the signs and symptoms of ASD as well as to identify the global trends related to their use. Studies not falling under the ASD umbrella will be excluded. All primary, secondary, and gray literature will be included. No language restrictions will be applied. Studies from January 1, 1984 will be included. METHODS: This review will be conducted in line with the JBI methodology for scoping reviews and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. A preliminary search of MEDLINE will be followed by searches of Emcare (Ovid), Nursing and Allied Health Premium (ProQuest), and Google Scholar. Two independent reviewers will screen titles and abstracts and extract data from selected sources. A third reviewer will adjudicate any conflicts until consensus is reached. The findings will be presented in a narrative summary with accompanying gap maps, figures, and tables. REVIEW REGISTRATION NUMBER: Open Science Framework https://doi.org/10.17605/OSF.IO/C234M.

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16. Smith SS, Benanni S, Jones Q, Kenney L, Evrard M. Manipulation of α4βδ GABA(A) receptors alters synaptic pruning in layer 3 prelimbic prefrontal cortex and impairs temporal order recognition: Implications for schizophrenia and autism. Brain Res. 2024: 148929.

Temporal order memory is impaired in autism spectrum disorder (ASD) and schizophrenia (SCZ). These disorders, more prevalent in males, result in abnormal dendritic spine pruning during adolescence in layer 3 (L3) medial prefrontal cortex (mPFC), yielding either too many (ASD) or too few (SCZ) spines. Here we tested whether altering spine density in neural circuits including the mPFC could be associated with impaired temporal order memory in male mice. We have shown that α4βδ GABA(A) receptors (GABARs) emerge at puberty on spines of L5 prelimbic mPFC (PL) where they trigger pruning. We show here that α4βδ receptors also increase at puberty in L3 PL (P < 0.0001) and used these receptors as a target to manipulate spine density here. Pubertal injection (14 d) of the GABA agonist gaboxadol, at a dose (3 mg/kg) selective for α4βδ, reduced L3 spine density by half (P < 0.0001), while α4 knock-out increased spine density ∼ 40 % (P < 0.0001), mimicking spine densities in SCZ and ASD, respectively. In both cases, performance on the mPFC-dependent temporal order recognition task was impaired, resulting in decreases in the discrimination ratio which assesses preference for the novel object: -0.39 ± 0.15, gaboxadol versus 0.52 ± 0.09, vehicle; P = 0.0002; -0.048 ± 0.10, α4 KO versus 0.49 ± 0.04, wild-type; P < 0.0001. In contrast, the number of approaches was unaltered, reflecting unchanged locomotion. These data suggest that altering α4βδ GABAR expression/activity alters spine density in L3 mPFC and impairs temporal order memory to mimic changes in ASD and SCZ. These findings may provide insight into these disorders.

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17. Thorsson M, Galazka MA, Åsberg Johnels J, Hadjikhani N. Influence of autistic traits and communication role on eye contact behavior during face-to-face interaction. Sci Rep. 2024; 14(1): 8162.

Eye contact is a central component in face-to-face interactions. It is important in structuring communicative exchanges and offers critical insights into others’ interests and intentions. To better understand eye contact in face-to-face interactions, we applied a novel, non-intrusive deep-learning-based dual-camera system and investigated associations between eye contact and autistic traits as well as self-reported eye contact discomfort during a referential communication task, where participants and the experimenter had to guess, in turn, a word known by the other individual. Corroborating previous research, we found that participants’ eye gaze and mutual eye contact were inversely related to autistic traits. In addition, our findings revealed different behaviors depending on the role in the dyad: listening and guessing were associated with increased eye contact compared with describing words. In the listening and guessing condition, only a subgroup who reported eye contact discomfort had a lower amount of eye gaze and eye contact. When describing words, higher autistic traits were associated with reduced eye gaze and eye contact. Our data indicate that eye contact is inversely associated with autistic traits when describing words, and that eye gaze is modulated by the communicative role in a conversation.

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18. Van Hirtum L, Van Damme T, Van Hove JLK, Steyaert JG. The behavioral phenotype of children and adolescents with attenuated non-ketotic hyperglycinemia, intermediate to good subtype. Orphanet J Rare Dis. 2024; 19(1): 150.

AIM: We aim to describe the behavioral phenotype of children and adolescents with the good to intermediate attenuated form of non-ketotic hyperglycinemia (NKH) and to explore associations between the behavioral phenotype and age, sex, plasma glycine levels and drug treatment. METHOD: Parents of children with attenuated NKH completed questionnaires assessing maladaptive behavior, adaptive behavior, social communication, speech/language development and motor development in addition to demographic and medical questions. RESULTS AND INTERPRETATION: Twelve children, age 6 to 21y, functioned at mild to severe intellectual disability levels. Their speech/language development was in line with their developmental quotient. Relative to their intellectual functioning, their motor development and communication were weaker in comparison to their general development. Their adaptive behavior, however, appeared a relative strength. There was no evidence for autism spectrum disorder occurring more frequently than expected, rather social skills, except for communication, were rated as a relative strength. Maladaptive behaviors with ADHD-like characteristics were present in more than two thirds of children. Maladaptive behaviors were significantly related to female sex and to taking dextromethorphan, but no significant relation between plasma glycine levels and behavior was found. Future studies will need to evaluate causality in the observed relation between dextromethorphan use and maladaptive behaviors. Clinicians should reconsider the benefit of dextromethorphan when presented with disruptive behaviors in children with attenuated NKH.

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19. Wan L, Yang G, Yan Z. Identification of a molecular network regulated by multiple ASD high risk genes. Hum Mol Genet. 2024.

Genetic sequencing has identified high-confidence ASD risk genes with loss-of-function mutations. How the haploinsufficiency of distinct ASD risk genes causes ASD remains to be elucidated. In this study, we examined the role of four top-ranking ASD risk genes, ADNP, KDM6B, CHD2, and MED13, in gene expression regulation. ChIP-seq analysis reveals that gene targets with the binding of these ASD risk genes at promoters are enriched in RNA processing and DNA repair. Many of these targets are found in ASD gene database (SFARI), and are involved in transcription regulation and chromatin remodeling. Common gene targets of these ASD risk genes include a network of high confidence ASD genes associated with gene expression regulation, such as CTNNB1 and SMARCA4. We further directly examined the transcriptional impact of the deficiency of these ASD risk genes. Our mRNA profiling with qPCR assays in cells with the knockdown of Adnp, Kdm6b, Chd2 or Med13 has revealed an intricate pattern of their cross-regulation, as well as their influence on the expression of other ASD genes. In addition, some synaptic genes, such as Snap25 and Nrxn1, are strongly regulated by deficiency of the four ASD risk genes, which could be through the direct binding at promoters or indirectly through the targets like Ctnnb1 or Smarca4. The identification of convergent and divergent gene targets that are regulated by multiple ASD risk genes will help to understand the molecular mechanisms underlying common and unique phenotypes associated with haploinsufficiency of ASD-associated genes.

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20. Wang YN, Lin QH, Meng D, Wang J, Xu HP, Wei WH, Zhang JY. Relationship between Mindfulness and Affiliate Stigma in Parents of Children with ASD in China:The Mediating Role of Coping Styles. Asian Nurs Res (Korean Soc Nurs Sci). 2024.

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the General Information Questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap method to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53(SD, 10.74). Parents’ age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = .33, P < .01) and negatively correlated with negative coping style, affiliate stigma(r = -.38, -.39, P < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -.34, P < .01) and positively correlated with negative coping style(r = .41, P < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSION: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

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21. Yim G, Roberts A, Lyall K, Ascherio A, Weisskopf MG. Multigenerational Association Between Smoking and Autism Spectrum Disorder: Findings from a Nation-Wide Prospective Cohort Study. Am J Epidemiol. 2024.

Animal studies have shown that exposure to cigarette smoke during pregnancy can induce neurobehavioral anomalies in multiple subsequent generations. However, little work has examined such effects in humans. We examined the risk of grandchild autism spectrum disorder (ASD) in association with grandmother smoking during pregnancy, using data from 53,562 mothers and grandmothers, and 120,267 grandchildren in the Nurses’ Health Study II using nurse reporting in 1999 of her mother’s smoking. Grandchildren’s ASD diagnoses were reported by the mothers in 2005 and 2009. Among grandmothers, 13,383 (25.0%) smoked during pregnancy, and 509 (0.4%) grandchildren were diagnosed with ASD. The adjusted odds ratio (aOR) of ASD for grandmother smoking during pregnancy was 1.52 (95% confidence limit [CI]: 1.06, 2.20). Results were similar with direct grandmother reporting in 2001 of her smoking during pregnancy from the Nurses’ Mothers Cohort Study subgroup (n=22,167 grandmothers, 49,917 grandchildren) and stronger among grandmothers who smoked ≥15 cigarettes per day during pregnancy (aOR=1.93; 95% CI: 1.10, 3.40; n=1,895 grandmothers, 4,212 grandchildren). Results were similar when adjusted for mother’s smoking during pregnancy. There was no association with grandfather’s smoking as reported by the grandmother. Our results suggest potential persistent impact of gestational exposure to environmental insults across three generations.

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22. Zeng X, Fan L, Li M, Qin Q, Pang X, Shi S, Zheng D, Jiang Y, Wang H, Wu L, Liang S. Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring. J Nutr Biochem. 2024: 109638.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a Traditional Chinese Medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

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