1. Akouchekian M, Alizadeh R, Beiranvandi F, Dehghan Manshadi M, Taherizadeh F, Hakim Shooshtari M. Evaluation of DNA repair capacity in parents of pediatric patients diagnosed with autism spectrum disorder using the comet assay procedure. IBRO neuroscience reports. 2023; 15: 304-9.

BACKGROUND: Autism Spectrum Disorder (ASD) is characterized by impairments in social communication, limited repetitive behaviors, impaired language development, and interest or activity patterns, which include a group complex neurodevelopmental syndrome with diverse phenotypes that reveal considerable etiological and clinical heterogeneity and are also considered one of the most heritable disorders (over 90%). Genetic, epigenetic, and environmental factors play a role in the development of ASD. AIM: This study was designed to investigate the extent of DNA damage in parents of autistic children by treating peripheral blood mononuclear cells (PBMCs) with bleomycin and hydrogen peroxide (H2O2). METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated by the Ficoll method and treated with a specific concentration of bleomycin and H2O2 for 30 min and 5 min, respectively. Then, the degree of DNA damage was analyzed by the alkaline comet assay or single cell gel electrophoresis (SCGE), an effective way to measure DNA fragmentation in eukaryotic cells. RESULTS: Our findings revealed that there is a significant difference in the increase of DNA damage in parents with affected children compared to the control group, which can indicate the inability of the DNA molecule repair system. Furthermore, our study showed a significant association between fathers’ occupational difficulties (exposed to the influence of environmental factors), as well as family marriage, and suffering from ASD in offspring. CONCLUSION: Our results suggested that the influence of environmental factors on parents of autistic children may affect the development of autistic disorder in their offspring. Subsequently, based on our results, investigating the effect of environmental factors on the amount of DNA damage in parents with affected children requires more studies.

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2. Erdogan MA, Turk M, Doganay GD, Sever IH, Ozkul B, Sogut I, Eroglu E, Uyanikgil Y, Erbas O. Prenatal SARS-CoV-2 Spike Protein Exposure Induces Autism-Like Neurobehavioral Changes in Male Neonatal Rats. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology. 2023.

Recent research on placental, embryo, and brain organoids suggests that the COVID-19 virus may potentially affect embryonic organs, including the brain. Given the established link between SARS-CoV-2 spike protein and neuroinflammation, we sought to investigate the effects of exposure to this protein during pregnancy. We divided pregnant rats into three groups: Group 1 received a 1 ml/kg saline solution, Group 2 received 150 μg/kg adjuvant aluminum hydroxide (AAH), and Group 3 received 40 μg/kg spike protein + 150 μg/kg AAH at 10 and 14 days of gestation. On postnatal day 21 (P21), we randomly separated 60 littermates (10 male-female) into control, AAH-exposed, and spike protein-exposed groups. At P50, we conducted behavioral analyses on these mature animals and performed MR spectroscopy. Subsequently, all animals were sacrificed, and their brains were subject to biochemical and histological analysis. Our findings indicate that male rats exposed to the spike protein displayed a higher rate of impaired performance on behavioral studies, including the three-chamber social test, passive avoidance learning analysis, open field test, rotarod test, and novelty-induced cultivation behavior, indicative of autistic symptoms. Exposure to the spike protein (male) induced gliosis and neuronal cell death in the CA1-CA3 regions of the hippocampus and cerebellum. The spike protein-exposed male rats exhibited significantly greater levels of malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), nuclear factor kappa B (NF-κB), and lactate and lower levels of brain-derived neurotrophic factor (BDNF) than the control group. Our study suggests a potential association between prenatal exposure to COVID-19 spike protein and neurodevelopmental problems, such as ASD. These findings highlight the importance of further research into the potential effects of the COVID-19 virus on embryonic and fetal development and the potential long-term consequences for neurodevelopment.

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3. Ferina J, Kruger M, Kruger U, Ryan D, Anderson C, Foster J, Hamlin T, Hahn J. Predicting Problematic Behavior in Autism Spectrum Disorder Using Medical History and Environmental Data. Journal of personalized medicine. 2023; 13(10).

Autism spectrum disorder (ASD), characterized by social, communication, and behavioral abnormalities, affects 1 in 36 children according to the CDC. Several co-occurring conditions are often associated with ASD, including sleep and immune disorders and gastrointestinal (GI) problems. ASD is also associated with sensory sensitivities. Some individuals with ASD exhibit episodes of challenging behaviors that can endanger themselves or others, including aggression and self-injurious behavior (SIB). In this work, we explored the use of artificial intelligence models to predict behavior episodes based on past data of co-occurring conditions and environmental factors for 80 individuals in a residential setting. We found that our models predict occurrences of behavior and non-behavior with accuracies as high as 90% for some individuals, and that environmental, as well as gastrointestinal, factors are notable predictors across the population examined. While more work is needed to examine the underlying connections between the factors and the behaviors, having reasonably accurate predictions for behaviors has the potential to improve the quality of life of some individuals with ASD.

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4. Gilmore D, Hand BN. Diabetes mellitus in privately insured autistic adults in the United States. Autism : the international journal of research and practice. 2023: 13623613231206421.

Diabetes is a chronic health condition that is challenging to manage. Estimates of how common diabetes is among non-autistic adults are available, but improved estimates for autistic adults are needed. The purpose of this study was to obtain improved diabetes estimates for autistic adults. We analyzed a large private health insurance claims database to estimate how common diabetes was among autistic adults, and how likely autistic adults were to have diabetes compared to non-autistic adults at 5-year age intervals throughout adulthood (e.g. 18-22, 23-27). We found that diabetes was more common among autistic adults than non-autistic adults and that autistic adults were significantly more likely than non-autistic adults to have diabetes throughout most of adulthood. Our findings suggest that autistic adults may be more likely than non-autistic adults to experience diabetes in adulthood. The development of diabetes support services and programs that accommodate autistic adults’ individual needs are important for future study to promote positive diabetes outcomes for autistic adults.

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5. Guillén VM, Verdugo M, Jiménez P, Aguayo V, Amor AM. Support Needs of Children with Autism Spectrum Disorders: Implications for Their Assessment. Behavioral sciences (Basel, Switzerland). 2023; 13(10).

The construct of support needs has become a key aspect for the diagnostics, classification, and interventional management of autism spectrum disorders (ASDs). However, instruments specifically designed to assess support needs in this population are not available. Currently, the Supports Intensity Scale for Children (SIS-C), which could be administered to assess students with any type of intellectual disability (ID), is the only valid tool able to assess support needs in Spain. Our aim was to verify whether the SIS-C is useful for assessing the support needs of students with ASD, regardless of whether or not they present ID. The participants were subdivided into two groups. One group included students with ASD and ID (n = 248), and the other comprised participants with ASD without an ID (n = 44). The results of the two groups were compared with those reported in the original validation sample of the SIS-C, which involved participants with ID without ASD (n = 566). The results showed that this scale could be useful for assessing support needs in the three subgroups, but it appeared that different standardized norms based on the characteristics of each specific population would be appropriate.

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6. Kim SY, Song DY, Bottema-Beutel K, Gillespie-Lynch K. Time to level up: A systematic review of interventions aiming to reduce stigma toward autistic people. Autism : the international journal of research and practice. 2023: 13623613231205915.

How non-autistic people think about autistic people impacts autistic people negatively. Many studies developed trainings to reduce autism stigma. The existing trainings vary a lot in terms of study design, content, and reported effectiveness. This means that a review studying how the studies have been conducted is needed. We also looked at the quality of these studies. We collected and studied 26 studies that tried to reduce stigma toward autistic people. The studies often targeted White K-12 students and college students. Most trainings were implemented once. Trainings frequently used video or computer. Especially, recent studies tended to use online platforms. The study quality was poor for most studies. Some studies made inaccurate claims about the intervention effectiveness. Studies did not sufficiently address study limitations. Future trainings should aim to figure out why and how interventions work. How intervention changes people’s behavior and thoughts should be studied. Researchers should study whether the training can change the societal stigma. Also, researchers should use a better study design.

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7. Knott R, Mellahn OJ, Tiego J, Kallady K, Brown LE, Coghill D, Williams K, Bellgrove MA, Johnson BP. Age at diagnosis and diagnostic delay across attention-deficit hyperactivity and autism spectrums. The Australian and New Zealand journal of psychiatry. 2023: 48674231206997.

BACKGROUND: Despite the known benefits of accurate and timely diagnosis for children with attention-deficit hyperactivity disorder and autism spectrum disorders (autism), for some children this goal is not always achieved. Existing research has explored diagnostic delay for autism and attention-deficit hyperactivity disorder only, and when attention-deficit hyperactivity disorder and autism co-occur, autism has been the focus. No study has directly compared age at diagnosis and diagnostic delay for males and females across attention-deficit hyperactivity disorder, autism and specifically, attention-deficit hyperactivity disorder + autism. METHODS: Australian caregivers (N = 677) of children with attention-deficit hyperactivity disorder, autism or attention-deficit hyperactivity disorder + autism were recruited via social media (n = 594) and the Monash Autism and ADHD Genetics and Neurodevelopment Project (n = 83). Caregivers reported on their child’s diagnostic process. Diagnostic delay was the mean difference between general initial developmental concerns and the child’s attention-deficit hyperactivity disorder and autism diagnosis. RESULTS: Children with autism were significantly younger at autism diagnosis than the attention-deficit hyperactivity disorder + autism group (η(p)(2) = 0.06), whereas children with attention-deficit hyperactivity disorder were significantly older at attention-deficit hyperactivity disorder diagnosis than the attention-deficit hyperactivity disorder + autism group (η(p)(2) = 0.01). Delay to attention-deficit hyperactivity disorder and autism diagnosis was significantly longer in the attention-deficit hyperactivity disorder + autism group compared to attention-deficit hyperactivity disorder (η(p)(2) = 0.02) and autism (η(2) = 0.04) only. Delay to autism diagnosis for females with autism (η(2) = 0.06) and attention-deficit hyperactivity disorder + autism (η(2) = 0.04) was longer compared to males. CONCLUSIONS: Having attention-deficit hyperactivity disorder + autism and being female were associated with longer delays to diagnosis. The reasons for these delays and possible adverse effects on outcomes require further study.

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8. Kostanian D, Rebreikina A, Voinova V, Sysoeva O. Effect of presentation rate on auditory processing in Rett syndrome: event-related potential study. Molecular autism. 2023; 14(1): 40.

BACKGROUND: Rett syndrome (RS) is a rare neurodevelopmental disorder characterized by mutations in the MECP2 gene. Patients with RS have severe motor abnormalities and are often unable to walk, use hands and speak. The preservation of perceptual and cognitive functions is hard to assess, while clinicians and care-givers point out that these patients need more time to process information than typically developing peers. Neurophysiological correlates of auditory processing have been also found to be distorted in RS, but sound presentation rates were relatively quick in these studies (stimulus onset asynchrony, SOA < 1000 ms). As auditory event-related potential (ERP) is typically increased with prolongation of SOA we aim to study if SOA prolongation might compensate for observed abnormalities. METHODS: We presented a repetitive stimulus (1000 Hz) at three different SOAs of 900 ms, 1800 ms, and 3600 ms in children with RS (N = 24, Mean age = 9.0 ± 3.1) and their typical development (TD) peers (N = 27, Mean age = 9.7 ± 3.4) while recording 28-channels electroencephalogram, EEG. Some RS participants (n = 10) did not show clear ERP and were excluded from the analysis. RESULTS: Major ERP components (here assessed as N1P1 and P2N1 peak-to-peak values) were smaller at SOA 900 than at longer SOAs in both groups, pointing out that the basic mechanism of adaptation in the auditory system is preserved in at least in RS patients with evident ERPs. At the same time the latencies of these components were significantly delayed in the RS than in TD. Moreover, late components (P2N1 and N2P2) were drastically reduced in Rett syndrome irrespective of the SOA, suggesting a largely affected mechanism of integration of upcoming sensory input with memory. Moreover, developmental stagnation of auditory ERP characterized patients with RS: absence of typical P2N1 enlargement and P1 and N1 shortening with age at least for shortest SOA. LIMITATIONS: We could not figure out the cause for the high percentage of no-evident ERP RS participants and our final sample of the RS group was rather small. Also, our study did not include a control clinical group. CONCLUSIONS: Thus, auditory ERPs inform us about abnormalities within auditory processing that cannot be fully overcomed by slowing presentation rate.

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9. Lin X, Wang G, Shen S, Zhan J. Advances in the Diagnosis and Treatment of Autism Spectrum Disorders in Children. Alternative therapies in health and medicine. 2023.

OBJECTIVE: This study aims to review recent developments in the diagnosis and treatment of Autism Spectrum Disorder (ASD )and provide insights for its clinical management. METHODS: The literatures were researched fro the pubmed, Wanfang and CNKI. We searched for research on the etiology, pathogenesis, diagnosis (screening and evaluation), and treatment of Autism spectrum disorder. When selecting papers to be included, priority should be given to randomized clinical trials, systematic evaluations, meta-analyses, clinical practice guidelines, and articles related to general medical readers. RESULTS: ASD is a widely present neurodevelopmental disorder characterized by social and communication difficulties, narrow interests, and repetitive behavior, accompanied by symptoms such as irritability, self-harm, attention deficit hyperactivity disorder (ADHD), and sleep problems. Irritability, self-harm, ADHD, and sleep problems are common accompanying symptoms that contribute to the challenges faced by individuals with ASD. At present, there is no fully effective treatment method for ASD, and key factors affecting the prognosis of ASD include early diagnosis time, early language communication level, intelligence level, disease severity, comorbidities, family participation, appropriate intervention, and social support. Therefore, early individualized long-term comprehensive training and drug therapy, hyperbaric oxygen therapy, and combined family participation can improve the prognosis of pediatric patients. Before selecting treatment plans for children, collecting as much information as possible about various treatment methods and choosing personalized treatment plans based on the child’s developmental assessment level is necessary. In addition, the treatment of ASD is also influenced by factors such as family economic status, parental mentality, and social environment. During the training process, it is important to be family-centered, tolerant, and understand children’s behavior. CONCLUSION: It is significant to take effective treatment measures to improve the quality of life and prognosis of children with autism spectrum disorders.

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10. Ma W, Mao J, Xie Y, Li S, Wang M. Examining the Effects of Theory of Mind and Social Skills Training on Social Competence in Adolescents with Autism. Behavioral sciences (Basel, Switzerland). 2023; 13(10).

Individuals with autism spectrum disorders (ASD) have impairment in interpreting emotional communication and the mental states of others, which limits their social competence. Mounting evidence has suggested that theory of mind (ToM) is a vital strategy to enhance social communication and interaction skills of children with ASD. However, very little research has looked at how ToM and social skills training affect social competence in adolescents with autism. This study examined the effectiveness of an intervention program, ToM-SS, which integrated the ToM and social skills training to improve the social competence of three adolescents with autism. A multiple baseline across behaviors design was adopted to evaluate the participants’ learning outcomes and demonstrated a functional relationship between intervention and skill mastery. Results show that the intervention produced substantial improvements in students’ acquisition of ToM (e.g., seeing leads to knowing and identifying desire-based and context-based emotions) and targeted social skills (e.g., praising others, expressing emotion and seeking help). Feedback and comments from teachers and parents also indicate good social validity of the intervention program.

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11. Markfeld JE, Feldman JI, Daly C, Santapuram P, Bowman SM, Dunham-Carr K, Suzman E, Keçeli-Kaysılı B, Woynaroski TG. The Stability and Validity of Automated Indices of Vocal Development in Infants With Autistic and Non-Autistic Siblings. Journal of speech, language, and hearing research : JSLHR. 2023: 1-15.

PURPOSE: This study evaluates the extent to which automated indices of vocal development are stable and valid for predicting language in infants at increased familial likelihood for autism and/or language impairment and relatively lower likelihood infants. METHOD: A group of infants with autistic siblings (Sibs-autism; 20 infants) and a comparison group of infants with non-autistic siblings (Sibs-NA; 20 infants) wore Language ENvironment Analysis (LENA) recording devices for 16 hr on 2 days within a 1-week period. Extant software was used to derive several putative indices of vocal development from these recordings. Stability of these variables was examined across and within groups. Expressive and receptive language aggregates were calculated for each participant. Multiple regression analyses were used to (a) evaluate zero-order correlations for variables derived from LENA recordings with concurrent and future language and (b) test whether those associations were moderated by group status. RESULTS: Both stability and validity differed by variable and group status. All variables reached acceptable stability in the Sibs-autism group within two to three observations, whereas stability of most variables was attenuated in the Sibs-NA group. No variables were associated with concurrent language in the theoretically motivated direction across groups, but two variables were strongly associated with concurrent expressive language in only the Sibs-NA group. Additionally, two variables were associated with later expressive language, though these correlations were again stronger in the Sibs-NA versus Sibs-autism group. CONCLUSIONS: Although selected automated indices of vocal development were stable in Sibs-autism and/or valid for predicting expressive language within Sibs-NA, no scores showed strong, theoretically motivated associations with language within the Sibs-autism group. Automated indices of vocal development may, thus, have limited validity or clinical utility for predicting language development in infants at elevated familial likelihood for autism. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24415735.

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12. Matthews JS, Adams JB. Ratings of the Effectiveness of 13 Therapeutic Diets for Autism Spectrum Disorder: Results of a National Survey. Journal of personalized medicine. 2023; 13(10).

This study presents the results of the effectiveness of 13 therapeutic diets for autism spectrum disorder from 818 participants of a national survey, including benefits, adverse effects, and symptom improvements. The average Overall Benefit of diets was 2.36 (0 = no benefit, 4 = great benefit), which was substantially higher than for nutraceuticals (1.59/4.0) and psychiatric/seizure medications (1.39/4.0), p < 0.001. The average Overall Adverse Effects of diets was significantly lower than psychiatric/seizure medications (0.10 vs. 0.93, p < 0.001) and similar to nutraceuticals (0.16). Autism severity decreased slightly over time in participants who used diet vs. increasing slightly in those that did not (p < 0.001). Healthy and Feingold diets were the two top-rated diets by Overall Benefit; the ketogenic diet was the highest for nine symptoms (though had fewer respondents); and the gluten-free/casein-free diet was among the top for overall symptom improvements. Different diets were reported to affect different symptoms, suggesting that an individual's symptoms could be used to guide which diet(s) may be the most effective. The results suggest that therapeutic diets can be safe and effective interventions for improving some ASD-related symptoms with few adverse effects. We recommend therapeutic diets that include healthy foods and exclude problematic foods. Therapeutic diets are inexpensive treatments that we recommend for consideration by most people with ASD.

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13. Minagawa Y, Hata M, Yamamoto E, Tsuzuki D, Morimoto S. Inter-brain synchrony during mother-infant interactive parenting in 3-4-month-old infants with and without an elevated likelihood of autism spectrum disorder. Cerebral cortex (New York, NY : 1991). 2023.

Maternal bonding for mammalian infants is critical for their survival. Additionally, it is important for human infants’ development into social creatures. However, despite the ample neurobiological evidence of attachment for the mother’s brain, the interplay of this system in infants is poorly understood. We aimed to identify the neural substrates of synchrony in mothers and infants under three interactive conditions and compare the differences between groups with (n = 16) and without (n = 71) an elevated likelihood of autism spectrum disorder by examining the inter-brain synchrony between mothers and their 3-4-month-old infants. Mother-infant hyperscanning with functional near-infrared spectroscopy was performed during breastfeeding and while each of the mother and experimenter was holding the infants. The results showed almost no group differences, with both groups demonstrating the strongest inter-brain coupling for breastfeeding. The cerebral foci underlying these couplings differed between mothers and infants: the ventral prefrontal cortex, focusing on the right orbitofrontal cortex, in the mother and the left temporoparietal junction in the infant were chiefly involved in connecting the two brains. Furthermore, these synchronizations revealed many significant correlations with behavioral measures, including subsequent language development. The maternal reward-motivational system and the infant’s elementary mentalization system seem to underlie mother-infant coupling during breastfeeding.

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14. Mitchell L, Vellanki B, Tang L, Hunter K, Finnegan A, Swartz JJ, Huchko M. Contraceptive Provision to Women With Intellectual and Developmental Disabilities Enrolled in Medicaid. Obstetrics and gynecology. 2023.

OBJECTIVE: To compare contraceptive provision to women with and without intellectual and developmental disabilities enrolled in North Carolina Medicaid. METHODS: Our retrospective cohort study used 2019 North Carolina Medicaid claims to identify women aged 15-44 years with and without intellectual and developmental disabilities at risk for pregnancy who were continuously enrolled during 2019 or had Family Planning Medicaid with at least one claim. We calculated the proportion in each cohort who received 1) most or moderately effective contraception, 2) long-acting reversible contraception, 3) short-acting contraception, and 4) individual methods. We classified contraceptive receipt by procedure type and disaggregated across sociodemographic characteristics. Adjusting for age, race, ethnicity, and urban or rural setting, we constructed logistic regression models to estimate most or moderately effective contraceptive provision odds by intellectual and developmental disability status and by level or type of intellectual and developmental disability. We performed subanalyses to estimate co-occurrence of provision and menstrual disorders. RESULTS: Among 9,508 women with intellectual and developmental disabilities and 299,978 without, a significantly smaller proportion with intellectual and developmental disabilities received most or moderately effective contraception (30.1% vs 36.3%, P<.001). With the exception of injectable contraception, this trend was consistent across all measures and remained statistically significant after controlling for race, ethnicity, age, and urban or rural status (adjusted odds ratio 0.75, 95% CI 0.72-0.79; P<.001). Among those who received most or moderately effective contraception, a significantly greater proportion of women with intellectual and developmental disabilities had co-occurring menstrual disorders (31.3% vs 24.3%, P<.001). CONCLUSION: These findings suggest disparities in contraceptive provision and potential differences in clinical indication by intellectual and developmental disability status. Future studies should investigate reasons for and barriers to contraceptive use among women with intellectual and developmental disabilities.

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15. Musokhranova U, Grau C, Vergara C, Rodríguez-Pascau L, Xiol C, Castells AA, Alcántara S, Rodríguez-Pombo P, Pizcueta P, Martinell M, García-Cazorla A, Oyarzábal A. Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome. Journal of translational medicine. 2023; 21(1): 756.

BACKGROUND: Rett syndrome is a neuropediatric disease occurring due to mutations in MECP2 and characterized by a regression in the neuronal development following a normal postnatal growth, which results in the loss of acquired capabilities such as speech or purposeful usage of hands. While altered neurotransmission and brain development are the center of its pathophysiology, alterations in mitochondrial performance have been previously outlined, shaping it as an attractive target for the disease treatment. METHODS: We have thoroughly described mitochondrial performance in two Rett models, patients’ primary fibroblasts and female Mecp2(tm1.1Bird-/+) mice brain, discriminating between different brain areas. The characterization was made according to their bioenergetics function, oxidative stress, network dynamics or ultrastructure. Building on that, we have studied the effect of leriglitazone, a PPARγ agonist, in the modulation of mitochondrial performance. For that, we treated Rett female mice with 75 mg/kg/day leriglitazone from weaning until sacrifice at 7 months, studying both the mitochondrial performance changes and their consequences on the mice phenotype. Finally, we studied its effect on neuroinflammation based on the presence of reactive glia by immunohistochemistry and through a cytokine panel. RESULTS: We have described mitochondrial alterations in Rett fibroblasts regarding both shape and bioenergetic functions, as they displayed less interconnected and shorter mitochondria and reduced ATP production along with increased oxidative stress. The bioenergetic alterations were recalled in Rett mice models, being especially significant in cerebellum, already detectable in pre-symptomatic stages. Treatment with leriglitazone recovered the bioenergetic alterations both in Rett fibroblasts and female mice and exerted an anti-inflammatory effect in the latest, resulting in the amelioration of the mice phenotype both in general condition and exploratory activity. CONCLUSIONS: Our studies confirm the mitochondrial dysfunction in Rett syndrome, setting the differences through brain areas and disease stages. Its modulation through leriglitazone is a potential treatment for this disorder, along with other diseases with mitochondrial involvement. This work constitutes the preclinical necessary evidence to lead to a clinical trial.

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16. Nenadić I, Meller T, Evermann U, Pfarr JK, Federspiel A, Walther S, Grezellschak S, Abu-Akel A. Modelling the overlap and divergence of autistic and schizotypal traits on hippocampal subfield volumes and regional cerebral blood flow. Molecular psychiatry. 2023.

Psychiatric disorders show high co-morbidity, including co-morbid expressions of subclinical psychopathology across multiple disease spectra. Given the limitations of classical case-control designs in elucidating this overlap, new approaches are needed to identify biological underpinnings of spectra and their interaction. We assessed autistic-like traits (using the Autism Quotient, AQ) and schizotypy – as models of subclinical expressions of disease phenotypes and examined their association with volumes and regional cerebral blood flow (rCBF) of anterior, mid- and posterior hippocampus segments from structural MRI scans in 318 and arterial spin labelling (ASL) in 346 nonclinical subjects, which overlapped with the structural imaging sample (N = 298). We demonstrate significant interactive effects of positive schizotypy and AQ social skills as well as of positive schizotypy and AQ imagination on hippocampal subfield volume variation. Moreover, we show that AQ attention switching modulated hippocampal head rCBF, while positive schizotypy by AQ attention to detail interactions modulated hippocampal tail rCBF. In addition, we show significant correlation of hippocampal volume and rCBF in both region-of-interest and voxel-wise analyses, which were robust after removal of variance related to schizotypy and autistic traits. These findings provide empirical evidence for both the modulation of hippocampal subfield structure and function through subclinical traits, and in particular how only the interaction of phenotype facets leads to significant reductions or variations in these parameters. This makes a case for considering the synergistic impact of different (subclinical) disease spectra on transdiagnostic biological parameters in psychiatry.

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17. Nezamuldeen L, Jafri MS. Protein-Protein Interaction Network Extraction Using Text Mining Methods Adds Insight into Autism Spectrum Disorder. Biology. 2023; 12(10).

Text mining methods are being developed to assimilate the volume of biomedical textual materials that are continually expanding. Understanding protein-protein interaction (PPI) deficits would assist in explaining the genesis of diseases. In this study, we designed an automated system to extract PPIs from the biomedical literature that uses a deep learning sentence classification model, a pretrained word embedding, and a BiLSTM recurrent neural network with additional layers, a conditional random field (CRF) named entity recognition (NER) model, and shortest-dependency path (SDP) model using the SpaCy library in Python. The automated system ensures that it targets sentences that contain PPIs and not just these proteins mentioned in the framework of disease discovery or other context. Our first model achieved 13% greater precision on the Aimed/BioInfr benchmark corpus than the previous state-of-the-art BiLSTM neural network models. The NER model presented in this study achieved 98% precision on the Aimed/BioInfr corpus over previous models. In order to facilitate the production of an accurate representation of the PPI network, the processes were developed to systematically map the protein interactions in the texts. Overall, evaluating our system through the use of 6027 abstracts pertaining to seven proteins associated with Autism Spectrum Disorder completed the manually curated PPI network for these proteins. When it comes to complicated diseases, these networks would assist in understanding how PPI deficits contribute to disease development while also emphasizing the influence of interactions on protein function and biological processes.

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18. O’Nions E, McKechnie DG, Long C, Mandy W, Stott J. How can autistic adults be supported in primary care?. The British journal of general practice : the journal of the Royal College of General Practitioners. 2023; 73(736): 518-21.

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19. Ruiz M, Groessing A, Guran A, Koçan AU, Mikus N, Nater UM, Kouwer K, Posserud MB, Salomon-Gimmon M, Todorova B, Wagner IC, Gold C, Silani G, Specht K. Music for autism: a protocol for an international randomized crossover trial on music therapy for children with autism. Frontiers in psychiatry. 2023; 14: 1256771.

The notion of a connection between autism and music is as old as the first reported cases of autism, and music has been used as a therapeutic tool for many decades. Music therapy holds promise as an intervention for individuals with autism, harnessing their strengths in music processing to enhance communication and expression. While previous randomized controlled trials have demonstrated positive outcomes in terms of global improvement and quality of life, their reliance on psychological outcomes restricts our understanding of underlying mechanisms. This paper introduces the protocol for the Music for Autism study, a randomized crossover trial designed to investigate the effects of a 12-week music therapy intervention on a range of psychometric, neuroimaging, and biological outcomes in school-aged children with autism. The protocol builds upon previous research and aims to both replicate and expand upon findings that demonstrated improvements in social communication and functional brain connectivity following a music intervention. The primary objective of this trial is to determine whether music therapy leads to improvements in social communication and functional brain connectivity as compared to play-based therapy. In addition, secondary aims include exploring various relevant psychometric, neuroimaging, and biological outcomes. To achieve these objectives, we will enroll 80 participants aged 6-12 years in this international, assessor-blinded, crossover randomized controlled trial. Each participant will be randomly assigned to receive either music therapy or play-based therapy for a period of 12 weeks, followed by a 12-week washout period, after which they will receive the alternate intervention. Assessments will be conducted four times, before and after each intervention period. The protocol of the Music for Autism trial provides a comprehensive framework for studying the effects of music therapy on a range of multidimensional outcomes in children with autism. The findings from this trial have the potential to contribute to the development of evidence-based interventions that leverage strengths in music processing to address the complex challenges faced by individuals with autism. Clinical Trial Registration: Clinicaltrials.gov identifier NCT04936048.

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20. Sadeh H, Meiri G, Zigdon D, Ilan M, Faroy M, Michaelovski A, Sadaka Y, Dinstein I, Menashe I. Adherence to treatment and parents’ perspective about effectiveness of melatonin in children with autism spectrum disorder and sleep disturbances. Child and adolescent psychiatry and mental health. 2023; 17(1): 123.

OBJECTIVE: Melatonin is considered an effective pharmacological treatment for the sleep disturbances that are reported in > 50% of children with autism spectrum disorder (ASD). However, real-life data about the long-term course and effectiveness of melatonin treatment in children with ASD is lacking. METHODS: In this retrospective cohort study, we assessed the adherence to melatonin treatment and parents’ perspective of its effect on sleep quality and daytime behavior in children with ASD via a parental phone survey of children in the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) database. Cox regression analysis was used to assess the effect of key demographic and clinical characteristics on treatment adherence. RESULTS: Melatonin was recommended for ~ 8% of children in the ANCAN database. These children were characterized by more severe symptoms of autism. The median adherence time for melatonin treatment exceeded 88 months, with the most common reason for discontinuation being a lack of effectiveness (14%). Mild side-effects were reported in 14% of children, and 86%, 54%, and 45% experienced improvements in sleep onset, sleep duration and night awakenings, respectively. Notably, melatonin also improved the daytime behaviors of > 28% of the children. Adherence to treatment was independently associated with improvements in night awakenings and educational functioning (aHR = 0.142, 95%CI = 0.036-0.565; and aHR = 0.195, 95%CI = 0.047-0.806, respectively). CONCLUSIONS: Based on parents’ report, melatonin is a safe and effective treatment that improves both sleep difficulties and daily behavior of children with ASD.

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21. Sun B, Wang B, Wei Z, Feng Z, Wu ZL, Yassin W, Stone WS, Lin Y, Kong XJ. Identification of diagnostic markers for ASD: a restrictive interest analysis based on EEG combined with eye tracking. Frontiers in neuroscience. 2023; 17: 1236637.

Electroencephalography (EEG) functional connectivity (EFC) and eye tracking (ET) have been explored as objective screening methods for autism spectrum disorder (ASD), but no study has yet evaluated restricted and repetitive behavior (RRBs) simultaneously to infer early ASD diagnosis. Typically developing (TD) children (n = 27) and ASD (n = 32), age- and sex-matched, were evaluated with EFC and ET simultaneously, using the restricted interest stimulus paradigm. Network-based machine learning prediction (NBS-predict) was used to identify ASD. Correlations between EFC, ET, and Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) were performed. The Area Under the Curve (AUC) of receiver-operating characteristics (ROC) was measured to evaluate the predictive performance. Under high restrictive interest stimuli (HRIS), ASD children have significantly higher α band connectivity and significantly more total fixation time (TFT)/pupil enlargement of ET relative to TD children (p = 0.04299). These biomarkers were not only significantly positively correlated with each other (R = 0.716, p = 8.26e-4), but also with ADOS total scores (R = 0.749, p = 34e-4) and RRBs sub-score (R = 0.770, p = 1.87e-4) for EFC (R = 0.641, p = 0.0148) for TFT. The accuracy of NBS-predict in identifying ASD was 63.4%. ROC curve demonstrated TFT with 91 and 90% sensitivity, and 78.7% and 77.4% specificity for ADOS total and RRB sub-scores, respectively. Simultaneous EFC and ET evaluation in ASD is highly correlated with RRB symptoms measured by ADOS-2. NBS-predict of EFC offered a direct prediction of ASD. The use of both EFC and ET improve early ASD diagnosis.

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22. Wang X, Zhai F, Wang Y. Interplay between Tradition and Modernity: Stress and Coping Experiences among Parents of Children with Autism in Beijing, China. Behavioral sciences (Basel, Switzerland). 2023; 13(10).

In traditional Chinese culture, specific beliefs and values can influence parents’ experiences of stress and coping while raising children with autism. However, as China undergoes rapid social changes amid globalization, are these cultural influences still significant for today’s parents of young children with autism? This study delves into this question through 12 in-depth interviews with parents of children with autism in Beijing. Content analysis indicated that while influences from traditional culture remain, modern parents often diverge from them. They adopt Western views on autism to mitigate stigma, establish boundaries with grandparents to ensure effective early interventions, address imbalanced professional dynamics, adjust authoritarian parenting styles, and broaden their social networks. A mix of traditional and contemporary parenting characterizes their experiences. The discussion elaborates on the findings, emphasizing the importance of family support.

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23. Wilczyński KM, Auguściak-Duma A, Stasik A, Cichoń L, Kawalec A, Janas-Kozik M. Association of OXTR, AVPR1a, LNPEP, and CD38 Genes’ Expression with the Clinical Presentation of Autism Spectrum Disorder. Current issues in molecular biology. 2023; 45(10): 8359-71.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that affects social interactions, communication, and behavior. Although the predominant genetic predisposition to ASD seems beyond doubt, its exact nature remains unclear. In the context of social cognition disorders and the basis of ASD, the oxytocinergic and vasopresynergic systems arouse great interest among researchers. The aim of the present study was to analyze gene expression levels for oxytocin and vasopressin receptors, as well as CD38 protein and oxytocinase, in the context of the clinical picture of autism spectrum disorders. The study included 90 people, of whom 63 were diagnosed with ASD based on anamnesis, mental status testing, and the ADOS-2 protocol. The results obtained in the presented study indicate that the balance between the levels of expression of the CD38 gene and the oxytocinase gene plays a key role in the risk and clinical presentation of ASD. In a hypothetical scenario, an imbalance in the expression of CD38 and LNPEP could potentially lead to alterations in the concentrations of oxytocin and vasopressin. At the same time, the most frequently studied genes-AVPR1a and OXTR-seem to be at best of marginal importance for the risk of ASD.

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24. Yang Y, Yang R, Kang B, Qian S, He X, Zhang X. Single-cell long-read sequencing in human cerebral organoids uncovers cell-type-specific and autism-associated exons. Cell reports. 2023; 42(11): 113335.

Dysregulation of alternative splicing has been repeatedly associated with neurodevelopmental disorders, but the extent of cell-type-specific splicing in human neural development remains largely uncharted. Here, single-cell long-read sequencing in induced pluripotent stem cell (iPSC)-derived cerebral organoids identifies over 31,000 uncatalogued isoforms and 4,531 cell-type-specific splicing events. Long reads uncover coordinated splicing and cell-type-specific intron retention events, which are challenging to study with short reads. Retained neuronal introns are enriched in RNA splicing regulators, showing shorter lengths, higher GC contents, and weaker 5′ splice sites. We use this dataset to explore the biological processes underlying neurological disorders, focusing on autism. In comparison with prior transcriptomic data, we find that the splicing program in autistic brains is closer to the progenitor state than differentiated neurons. Furthermore, cell-type-specific exons harbor significantly more de novo mutations in autism probands than in siblings. Overall, these results highlight the importance of cell-type-specific splicing in autism and neuronal gene regulation.

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25. Yenkoyan K, Ounanian Z, Mirumyan M, Hayrapetyan L, Zakaryan N, Sahakyan R, Bjørklund G. Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies. Current medicinal chemistry. 2023.

Autism spectrum disorder (ASD) is an umbrella term for developmental disorders characterized by social and communication impairments, language difficulties, restricted interests, and repetitive behaviors. Current management approaches for ASD aim to resolve its clinical manifestations based on the type and severity of the disability. Although some medications like risperidone show potential in regulating ASD-associated symptoms, a comprehensive treatment strategy for ASD is yet to be discovered. To date, identifying appropriate therapeutic targets and treatment strategies remains challenging due to the complex pathogenesis associated with ASD. Therefore, a comprehensive approach must be tailored to target the numerous pathogenetic pathways of ASD. From currently viable and basic treatment strategies, this review explores the entire field of advancements in ASD management up to cutting-edge modern scientific research. A novel systematic and personalized treatment approach is suggested, combining the available medications and targeting each symptom accordingly. Herein, summarize and categorize the most appropriate ways of modern ASD management into three distinct categories: current, promising, and prospective strategies.

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26. Zhang D, Roberts E, Maddalozzo R, Li YF, Orsag M, Glass T. Post-Secondary Education Outcomes for Individuals with Intellectual and Developmental Disabilities: Self-Determination, Independent Living, Employment, and the Impact of COVID-19. Behavioral sciences (Basel, Switzerland). 2023; 13(10).

Post-secondary education (PSE) plays an important role in preparing individuals with an intellectual and developmental disability (IDD) to gain employment and independent living. Despite the recent increase in PSE programs, however, there is a lack of research examining outcomes of individuals with IDD who have attended a PSE program. This study examined three years of data from students who participated in one PSE program that focuses on the acquisition of skills regarding self-determination, employment, and independent living. We analyzed the outcome data of program graduates regarding their acquisition of skills in employment and self-determination, as well as follow-up data on employment. It was found that participation in the program increased self-determination and post-secondary readiness. Our findings also indicated that the COVID-19 pandemic impacted the self-determination scores of participants and their employment outcomes.

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