Pubmed du 06/08/25

Pubmed du jour

1. Uncovering my hidden autism. Bmj. 2025; 390: r1359.

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2. Aiona K, Crume T, Reyes N, Schmiege SJ, Young J, Holst B, M SD, DiGuiseppi C. Associations of Characteristics of Parental Country of Birth with Autism Spectrum Disorder and Early Learning Delay Among Immigrant Populations in the US: Findings from the Study to Explore Early Development. J Autism Dev Disord. 2025.

Our objective was to explore associations between human development and gender inequality indices in the birth country of immigrant parents and child risk for autism spectrum disorder (ASD) alone, ASD with early learning delay (ELD), and ELD alone. We used data from a multi-site case-control study that recruited US-born children aged 2-5 years with ASD and developmental delays through clinical and educational sources and a population control group through vital records. We defined ELD as Mullen Scales of Early Learning composite score ≤ 70. Parental birth country and socio-demographics were collected via interview. Associations between United Nations Development Programme human development (low-medium/high-very high), inequality-adjusted human development (< 50th /≥50th percentile) and gender inequality (≥ 50th /<50th percentile) indices with ASD/ELD categories were assessed with multinomial logistic regression. Effect modification by having a non-US born mother vs. non-US-born father only, and age at parental immigration was assessed. Odds for ASD + ELD were higher if parents immigrated from a country with lower human development, both overall and adjusted for inequality, and more gender inequalities. None of the indices were significantly associated with ASD alone nor ELD alone. Having a non-US-born mother vs. non-US-born father only and parental age at immigration did not modify these relationships. This study supports evidence that health, well-being and equality conditions in the birth country of immigrant parents may influence ASD + ELD risk but not ASD alone or ELD alone. Results can be used to support families immigrating from countries with low human development and high gender inequality indices and their US-born children.

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3. Aldekhail NM, Khojah H, Alsaadoun NH, Al-Sanea MM, Alshammari SB, Alhazeemi AH, Aldekhail AM, Aldekhail KM, Alazmi BH, Alrayes RA, Aljaber AM, Alanazi L, Agili AAA, Gamal M. Herbal Medicines in Autism Spectrum Disorder: Therapeutic Potential, Plant Components, and Dosage Guidelines. Altern Ther Health Med. 2025.

BACKGROUND: Background • Autism spectrum disorder (ASD), marked by social communication deficits and repetitive behaviors, significantly impacts the quality of life for kids and caregivers. Herbal medicines help manage symptoms, yet no comprehensive review has collectively summarized recent evidence (2018-mid-2025). Methods • This narrative review utilized searches across PubMed, Scopus, Web of Science, and Google Scholar to identify studies published on herbal medicines for ASD. Inclusion criteria prioritized clinical trials and preclinical studies detailing plant bioactive compounds, dosing, and mechanisms. Key Findings • Prominent herbs include Bacopa monnieri, which can enhance cognitive flexibility via bacosides; Curcuma longa (curcumin), which can reduce oxidative stress and repetitive behaviors; and Green Tea Extract (luteolin), which can modulate neuroinflammation. Cannabinoids show modest improvements in sleep and social engagement, while Ginkgo biloba improves cerebral blood flow. Passionflower and Valerian Root alleviate anxiety and hyperactivity through GABAergic pathways, and probiotic-fermented herbal combinations target gut-brain axis dysfunction. Ashwagandha demonstrates neuroprotective effects in preclinical trials. Clinical Implications • Herbal therapies may address core ASD symptoms (anxiety and hyperactivity) and comorbidities (sleep disturbances and gastrointestinal issues). However, standardization of herbal formulations and rigorous dosing protocols are needed. Integrative approaches combining herbs with behavioral therapies show accepted synergistic potential but require further validation. While herbal medicine may offer supportive benefits, it should never be intended to replace other evidence-based therapies (e.g., applied behavior analysis and speech therapy). Future Directions • Large-scale randomized clinical trials are crucial to confirming efficacy, safety, and optimal dosing. Research must address herb-drug interactions, long-term effects, and biomarkers for personalized treatment. KEYWORDS: autism spectrum disorder, herbal medicines, narrative review, doses recommendation, therapeutic effects, side effects.

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4. Antonyan L, Shaheen SM, Burton C, Gehring W, Soreni N, Falzarano Szura P, Bellamy J, Rajan U, Rosenberg D, Hanna G, Arnold P. Polygenic Risk Scores for Pediatric Obsessive-Compulsive Symptoms and their Mediating Effect in Clinically Diagnosed Samples of Obsessive-Compulsive Disorder, Attention-Deficit/Hyperactivity Disorder, Anxiety, Depression, Autism and Tourette syndrome. Res Sq. 2025.

Here, we present the first genome-wide association study of obsessive-compulsive symptoms in a sample of clinically diagnosed pediatric participants and healthy controls. Using a psychiatric questionnaire score as a quantitative trait we conducted a large-scale genetic analysis and ran multiple post-association analyses to investigate the mediating role of obsessive-compulsive symptoms in six comorbid neuropsychiatric disorders. Although no SNPs reached genome-wide significance, we identified suggestive associations on chromosomes 4, 5, 6, 7, 9, 17, 19, and 22. Notable genes mapped to these regions were highlighted, though none met the threshold for multiple testing correction. Further, polygenic risk scoring and Mendelian randomization analyses explored the potential mediating role and genetic disposition of obsessive-compulsive symptoms in obsessive-compulsive disorder, anxiety, attention-deficit/hyperactivity disorder, depression, autism spectrum disorders and/or Tourette syndrome. We found that genetic predisposition for OCS accounts for approximately 2% in individuals with one or more of these six disorders, with a particularly strong mediation effect observed for anxiety disorders. This study underscores the value of examining genetic risk across the symptom spectrum of mental illnesses, rather than relying solely on binary diagnostic categories.

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5. Barnard-Brak L, Hutchison A, Renda C. Heightened sensory sensitivity and subsequent engagement among individuals with ASD. J Psychiatr Res. 2025; 190: 69-75.

The literature on sensory sensitivity with respect to individuals with Autism Spectrum Disorder continues to evolve with mixed results. The current study examines the influence of reported sensory sensitivities with engagement across time of students with ASD while participating in physical computing, or robotics activities, and computer programming. The results of the current study indicate that among those individuals with a heightened sensory sensitivity, an increase in the number of sessions was associated with increased engagement. This statistically significant result was able to be recovered via 1000 replications as simulated, further supporting the results of the current study. However, results according to specific modality of sensory sensitivity were statistically non-significant or not replicable when statistically significant. The current study demonstrates the power of simulation techniques when results are from small but meaningful samples. This brief report suggests the use of simulation techniques to provide greater generalizability.

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6. Beckwith R, Stephens-Lewis D. « There’s no one-size-fits-all kind of solution »: An interpretative phenomenological analysis of the experiences of autistic individuals living with Ehlers-Danlos syndrome. Res Dev Disabil. 2025; 164: 105084.

OBJECTIVE: Approximately a third of individuals live with multiple health conditions and this number is rising. Research suggests that living with a chronic condition can profoundly impact upon one’s life and identity, however little attention has been paid to the experiences of those with multiple conditions. Ehlers-Danlos syndrome (EDS) is a rarely-diagnosed connective tissue disorder causing extensive debilitating symptoms and while these symptoms are primarily physical, EDS often co-occurs with autism. This study sought to gain insight into the experience of autistic individuals living with EDS and thus investigate how illness identity occurs with multiple conditions. DESIGN: Interpretative Phenomenological Analysis (IPA) was used. METHODS: Semi-structured interviews were conducted with four autistic women living with EDS. RESULTS: Analysis resulted in three superordinate themes, consisting of ‘Transformation,’ ‘Making sense,’ and ‘The negatives.’ While interrelated, these themes capture the ways in which the conditions have changed the participants’ lives, both positively and negatively. Furthermore, they capture how the participants make sense and create meaning in their new identities. CONCLUSION: Individuals living with co-occurring conditions have multiple illness identities which affect their overall sense of self. Within this study, participants incorporated both conditions into their new identities, although the extent to which they rejected or accepted these conditions varied individually based on numerous biopsychosocial factors, which shifted continually, including healthcare professionals’ attitudes and awareness of conditions, stigma, finding community and symptom severity. Thus, illness identity is in a constant state of flux. These findings highlight the need for more individualised, supportive care for autistic individuals living with EDS.

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7. Chen Z, Wang X, Hu Y, Zhang S, Han F. Effect of maternal diet on gut bacteria and autism spectrum disorder in offspring. Front Cell Neurosci. 2025; 19: 1623576.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that manifests in early childhood, with its specific causes and pathogenesis remaining incompletely understood. The gut bacteria plays a pivotal role in host health and neurodevelopment. Maternal eating disorders may disrupt maternal gut bacteria and subsequently influence fetal and neonatal gut bacteria through the gut-placental axis and breastfeeding. This disruption can ultimately impact the microbial-gut-brain axis, the immune system, neurotransmitter dysregulation, and metabolite abnormalities, thereby increasing the risk of ASD in offspring. This paper reviews the adverse effects of bad maternal dietary habits, including high-sugar, high-salt, high-fat diets, alcohol consumption, dietary fiber deficiency, and the intake of ultra-processed foods, on the gut bacteria. It also explores the mechanisms by which gut microbiota disorder may induce ASD through the immune system, neurotransmitters, and metabolites. Additionally, the article proposes potential strategies to prevent ASD by adjusting dietary structures and enhancing gut bacteria health.

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8. Cheng S, Xu X, Yan CS, Mao MC, Luo KX, Zhang XF, Liang QH, Long XJ, Ao LJ, Chen MX. Case Report: Low-intensity transcranial focused ultrasound stimulation improves social interaction and stereotyped behavior in a boy with autism spectrum disorder. Front Psychiatry. 2025; 16: 1606300.

OBJECTIVES: Presently, no biomedical therapies are available that specifically address the core symptoms of autism spectrum disorders. Given the evidence of cortical malfunction in ASD, low-intensity transcranial focused ultrasound stimulation has been discussed as a prospective therapeutic technique. METHODS: We describe the application of transcranial focused ultrasound to the left dorsolateral prefrontal cortex in a boy with ASD, which was applied for 30 minutes each consecutive weekday for four weeks (20 sessions in total). Social interaction, stereotyped behavior and language were assessed by scales before the first transcranial focused ultrasound session, immediately after 2 and 4 weeks of treatment. Besides, functional near-infrared spectroscopy was used to detect functional connections between regions of interest and the whole brain in individuals with ASD. RESULTS: Scale assessments revealed several improvements in social and stereotypical behavior after low-intensity transcranial focused ultrasound. The results of functional near-infrared spectroscopy indicated increasing functional connections between the SM1 and other cortical regions as well as the whole brain, which accounted for the outcomes evaluated by the scale. CONCLUSIONS: Low-intensity transcranial focused ultrasound in ASD potentially rectified cortical dysfunction, thereby presenting a novel pathway for the advancement of biomedical interventions targeting the impaired social and stereotypical behaviors in ASD.

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9. Ciobanu M, Barnes G, Castell NJ, Adelson RP, Garikipati A, Singh NP, Mao Q, Das R. Quality of life in a family-centric applied behavior analysis model: A case series study. PLoS One. 2025; 20(8): e0329939.

Autism spectrum disorder (ASD) is a condition with growing prevalence that results in significant healthcare spending, reduced parent income, high levels of family stress, and decreased quality of life (QoL). QoL is a measure for assessing overall wellness, and in the context of ASD is related to parent self-efficacy. Validated treatments, of which applied behavior analysis (ABA) is the gold standard, can mitigate some of the consequences that may be detrimental to parental QoL. We examined changes in parental QoL across multiple domains within three parent-child dyads in the context of a parent-led ABA model where the treatment was delivered by the parent. We hypothesized that parental QoL would be increased concurrently with ABA treatment lowering the frequency of interfering behaviors, which contribute to parental stress and limited self-efficacy. QoL components improved between the first and follow-up evaluations, though not all QoL component score changes achieved clinical significance. This study demonstrates a correlation between parental QoL and clinical treatment progress; with further validation, QoL assessment may serve as a tool to guide individualized treatment approaches that improve family outcomes.

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10. Eid LT, El-Habeby MM, Issa NM, Nooreldien NM. The possible role of lycopene on the cerebellum of albino rat prenatally exposed to valproic acid: Animal model of autism spectrum disorder. Tissue Cell. 2025; 97: 103062.

Autism is a serious neurodevelopmental disorder with a rising global prevalence. Prenatal exposure to valproic acid (VPA), a common antiepileptic drug, is associated with autism in offspring. Lycopene, a potent antioxidant and anti-inflammatory compound, may counteract VPA-induced neurotoxicity. To the best of our knowledge, this research is the first attempt to assess the beneficial role of lycopene supplementation in a VPA model of autism. In total, 30 pregnant female albino rats were grouped into five groups: control, lycopene-treated (5 mg/kg/day orally), VPA-treated (50 mg/kg/day orally), VPA-protected with lycopene, and VPA-treated with lycopene. After the scarification of rats, biochemical, histological, immunohistochemical, and ultrastructural analyses were performed on the cerebellum. VPA produced degenerative changes in the cerebellum with increased glial fibrillary acidic protein (GFAP) and Bax while decreasing myelin basic protein (MBP) and Tau1 expressions. Moreover, it increased the brain levels of malondialdehyde (MDA), acetylcholinesterase enzyme (AChE), tumor necrosis factor-alpha (TNF-α), and glutamate. It also reduced brain-derived neurotrophic factor (BDNF) and superoxide dismutase (SOD) levels. Lycopene reversed these effects by reducing oxidative stress and inflammatory markers, and restoring antioxidant levels. In conclusion, lycopene mitigated VPA-induced cerebellar damage through its antioxidant and anti-inflammatory effects and its ability to modulate neurotransmission, suggesting a potential therapeutic role in autism.

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11. Fan XR, He Y, Wang YS, Li L, Duan X, Zuo XN. Profiling brain morphology for autism spectrum disorder with two cross-culture large-scale consortia. Commun Biol. 2025; 8(1): 1157.

We explore neurodevelopmental heterogeneity in Autism Spectrum Disorder (ASD) through normative modeling of cross-cultural cohorts. By leveraging large-scale datasets from Autism Brain Imaging Data Exchange (ABIDE) and China Autism Brain Imaging Consortium (CABIC), our model identifies two ASD subgroups with distinct brain morphological abnormalities: subgroup « L » is characterized by generally smaller brain region volumes and higher rates of abnormality, while subgroup « H » exhibits larger volumes with less pronounced deviations in specific areas. Key areas, such as the isthmus cingulate and transverse temporal gyrus, were identified as critical for subgroup differentiation and ASD trait correlations. In subgroup H, the regional volume of the isthmus cingulate cortex showed a direct correlation with individuals’ autistic mannerisms, potentially corresponding to its slower post-peak volumetric declines during development. These findings offer insights into the biological mechanisms underlying ASD and support the advancement of subgroup-driven precision clinical practices.

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12. Ferreira HA, Pacheco PM, Santos THF, Molini-Avejonas DR. Early speech therapy intervention in children with Autism Spectrum Disorder. Codas. 2025; 37(4): e20240245.

PURPOSE: To analyze the results of speech therapy intervention based on the principles of the DIR/Floortime model in early childhood in children with Autism Spectrum Disorder. METHODS: A longitudinal, quantitative, and prospective manner with direct and indirect intervention, whose target population was children up to three years and eleven months of age, with atypical language development associated with Autism Spectrum Disorder. It led twenty-four speech therapy early intervention sessions based on the DIR Floortime model, in addition to two initial assessment sessions, and two sessions for final assessment. RESULTS: Twenty children completed the research, with an average age of 29 months at the initial assessment and 36 months in the final assessment. Among the children, 90% already had a diagnosis of Infantile Autism (F84.0). Comparing the results of the Pragmatic Profile, There was an average increase of 0.8 communicative acts and 6.66% in the occupation of the communicative space with statistical significance, as well as a decrease in the use of gestures. There was also a positive glow with moderate significance between « Intentional two-way communication » and the number of acts expressed per minute (the greater the capacity for intentional two-way communication, the greater the number of acts per minute). CONCLUSION: When analyzing the pre- and post-intervention results, a consistent and statistically significant evolution is observed. In social communication, skills are interconnected and need to be worked on in a correlational manner, observing the individual needs of each child.

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13. Gholizadeh MA, Behjati F, Garshasbi M. Genetic Investigation of Inherited Variants in a Multiplex Autism Spectrum Disorder (ASD) Family Using Whole-Genome Sequencing (WGS). Iran J Public Health. 2025; 54(5): 1087-97.

BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by early-onset challenges in social communication, repetitive behaviors, and clinical diversity. ASD is a highly heritable disorder, however, the exact mechanism by which inherited variants contribute to ASD in multiplex families, where more than one affected individual within a family is presented, remains unclear. We aimed to identify inherited genes in patients with ASD in a family with two affected siblings using Whole Genome Sequencing (WGS). METHODS: We performed WGS on two patients from a single family diagnosed with ASD. All of the patients were diagnosed with ASD using the gold-standard Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We used various bioinformatics approaches to identify a list of prioritized candidate genes that may be associated with ASD or other neurodevelopmental disorders in this family. RESULTS: Our WGS analysis identified three potential candidate genes (EVI5:c.-82+866C>T, RAPGEF1:c.668C>T;p. Thr223Ile and PDZD4:c. -457G>A)) associated with ASD shared by the two patients. Additionally, utilizing various in-silico prediction tools and analysis of bioinformatics databases revealed that these rare variants are predicted to be deleterious and may contribute to ASDs. The identified variants are the first variants reported in ASD patients in the Iranian population that could be subjected to further validation studies. CONCLUSION: These findings shed light on the genetic diversity of ASD within multiplex families and emphasize the complexity of genetic basis of ASD. Understanding the underlying genetic architecture of ASD is pivotal for advancing precise diagnostics and tailored therapeutic strategies.

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14. Hu C, Li W, Ruan M, Yu X, Deshpande S, Paul LK, Wang S, Li X. Exploiting Large Language Models for Diagnosing Autism Associated Language Disorders and Identifying Distinct Features. Res Sq. 2025.

Diagnosing language disorders associated with autism is a complex challenge, often hampered by the subjective nature and variability of traditional assessment methods. In this study, we explored Large Language Models (LLMs) to overcome the speed and precision obstacles by enhancing sensitivity and profiling linguistic features for autism diagnosis. This research utilizes natural language understanding capabilities of LLMs to simplify and improve the diagnostic process, focusing on identifying autism-related language patterns. We showed that the proposed method demonstrated improvements over the baseline models, with over a 10% increase in both sensitivity and positive predictive value in a zero-shot learning configuration. Combining accuracy and applicability, the framework could serve as a valuable supplementary tool within the diagnostic process for ASD-related language patterns. We identified ten key features of autism-associated language disorders across scenarios. Features such as echolalia, pronoun reversal, and atypical language usage play a critical role in diagnosing ASD and informing tailored treatment plans.

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15. Imamatdinova A, Samambayeva A, Akhtaeva N, Kozhageldiyeva L, Sabyrdilda Z, Kapanova G, Kosherbayeva L. Autism spectrum disorders: experience of parents in Kazakhstan. BMC Public Health. 2025; 25(1): 2676.

BACKGROUND: Autism spectrum disorders (ASD) is a neurodevelopmental disorder manifested by a violation of the lack or deficiency of communication, socialization and repetitive behavior. The prevalence of ASD is rising globally. Early identification of children and comprehensive assistance are critical to reduce the burden. The purpose of our work is to study the current practice and experience of parents of children with ASD in obtaining care for their children and identify future directions for improving systemic care in Kazakhstan. METHODS: The multidisciplinary team of specialists, including parents of children with ASD were involved in developing the questionnaire that aimed to identify the gaps in complex care for children with ASD. A cross-sectional study was conducted for 390 parents of children with ASD from all regions, including urban and rural areas of Kazakhstan. Statistical analysis was performed using the chi-square test. RESULTS: Parents of children with ASD living in cities have higher income and education level compared to those living in rural areas. About 16.3% of the participants belonged to single-parent families, and a third of the families did not own their home. In most cases, only one parent (63.3%) was employed. Additionally, 25.4% of parents, especially mothers, had to quit their jobs, while 18.8% opted to change employment areas or shifts. Insufficient state financial support was reported by 73.3% of respondents, particularly with regard to the costs of education in correctional centers and child treatment, which were statistically significant. Respondents also highlighted the needs for legal advice. CONCLUSION: This study offers valuable insights into the current state of care and support for children with ASD in Kazakhstan. The findings emphasize the challenges faced by families in securing appropriate care for their children, particularly in relation to financial burden, limited access to specialists, and the need for comprehensive support systems.

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16. Karaçam Doğan M, Fusar-Poli L, Arias-Magnasco A, Pries LK, Lin BD, Klingenberg B, Bortoletto R, Colizzi M, Menne-Lothmann C, Decoster J, van Winkel R, Collip D, Delespaul P, De Hert M, Derom C, Thiery E, Jacobs N, van Os J, Rutten B, Luykx J, Prachason T, Guloksuz S. Examining psychological protective mechanisms as moderators of the association between autistic traits and psychosis expression in a general population twin sample. Schizophr Res. 2025; 284: 133-40.

BACKGROUND: Psychological protective factors, such as coping styles, extraversion, and optimal parenting, may reduce the risk of psychosis. However, their role in moderating the association between autistic traits (ATs) and psychosis expression (PE) remains understudied. METHODS: This study analyzed the first-wave data from the TwinssCan Project (n = 792 twins and siblings, 60.2 % female, mean age = 17.4 ± 3.6). ATs and PE were assessed using the Autism-Spectrum Quotient and the Community Assessment of Psychic Experiences (CAPE), respectively. Multilevel linear regression models were used to evaluate the moderating effects of seven coping styles (active coping, avoidance, reassuring thoughts, expressing emotions, seeking social support, palliative-reacting, and passive-reacting coping), extraversion, and optimal parenting. RESULTS: Seeking social support (B[95 %CI]:-0.005[-0.009,-0.001]), reassuring thoughts (B[95 %CI]:-0.005[-0.009,-0.001]), extraversion (B[95 %CI]: -0.03[-0.04,-0.01]) and optimal parenting (B[95 %CI]: -0.02[-0.03,0]) weakened the associations between ATs and CAPE total frequency scores, suggestive of protective mechanisms, whereas passive-reacting coping (B[95 %CI]:0.007[0.004,0.010]) strengthened this, suggestive of a risk factor. Additionally, avoidance(B[95 %CI]:0.09[0.02,0.16]) emerged as a risk factor in confirmatory analyses by significantly interacting with ATs in predicting CAPE total severity scores. CONCLUSIONS: Engagement coping, extraversion, and optimal parenting may mitigate psychosis vulnerability in individuals with higher ATs, while passive-reactive coping and avoidance may heighten psychosis vulnerability. Although further research is needed, our findings provide a rationale for developing and testing targeted preventive strategies aimed at enhancing resilience in individuals with ATs.

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17. Lampinen LA, Ederer JE, Bal VH. Associations Between the SRS-2 and the ASEBA Adult Self Report: Implications for Interpretation of the SRS-2 in Autistic Adults. J Autism Dev Disord. 2025.

PURPOSE: The Social Responsiveness Scale, 2nd Edition (SRS-2) is widely used to characterize autistic features and screen for autism in clinical and research settings. Previous research indicates that scores on the parent-report SRS-2 School-age form are associated with internalizing and externalizing symptoms in both autistic and non-autistic children, yet less is known about the self-report SRS-2-Adult (SRS-2-A). Considering the widespread use of the SRS-2-A for a variety of different research and clinical purposes, examining how non-autism-specific factors affect SRS-2-A scores is warranted. METHODS: This study aimed to examine the relationship between scores on the SRS-2-A and the ASEBA Adult Self Report in a sample of 203 autistic independent adults. RESULTS: Findings indicate that the SRS-2-A was significantly associated with scales designed to screen for internalizing, externalizing, and personality disorders. The Avoidant Personality scale has direct overlap with SRS-2 items, which may partially explain associations with this scale. The Depressive and Anxiety scales are somewhat less easily explained. CONCLUSION: Taken together, results suggest that SRS-2-A scores may reflect a combination of diagnostic and autism-related features, as well as symptoms associated with non-autism co-occurring conditions. Caution is warranted when using SRS-2-A scores to characterize autistic adults. Information from multiple sources is needed to help distinguish autistic features from those related to commonly co-occurring conditions, such as depression and anxiety, and ultimately inform understanding of how these features interact with other individual and contextual factors to improve measurement of autism diagnostic features.

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18. Li B, Qiao Y, Li Y. Porphyromonas gingivalis deteriorates autism spectrum disorders by disturbing the gut and oral microbiota. Front Microbiol. 2025; 16: 1579128.

Autism spectrum disorder (ASD) significantly impairs socialization and communication, posing a major societal challenge due to limited understanding of its pathogenesis and lack of effective treatments. Recent studies have shown an imbalance in the oral and intestinal microbiota of individuals with ASD, which may exacerbate ASD symptoms. In this study, we successfully established an ASD mouse model induced by Porphyromonas gingivalis (Pg) solution. Bio-behavioral experiments, including the elevated plus maze test, demonstrated that Pg. induced anxiety-like behaviors in mice. Analysis of oral and intestinal microbiota revealed significant alterations in microbial richness, diversity, and evenness in Pg-treated mice, indicating that Pg. disrupted the normal bacterial community structure and function. Subsequent 16S rRNA sequencing showed increased abundance of amino acid metabolism pathways in Pg-intervened mice, highlighting the close link between bacterial community function and carbohydrate, amino acid, and nucleotide metabolic pathways. These findings provide promising clinical targets for ASD treatment and offer insights into developing new therapeutic strategies.

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19. Li G, Ji Y, Zhang A, Yang M, Fang X. [Chitayat syndrome due to variant of ERF gene: A case report and literature review]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2025; 42(6): 729-35.

OBJECTIVE: To explore the clinical features and management of a child with Chitayat syndrome. METHODS: A child presented at the Fengqing People’s Hospital on August 8 2019 was selected as the study subject. Clinical data of the child were retrospectively analyzed. Peripheral blood samples were collected from the child and his father and sister. Whole-exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing. Genome Browser, AlphaFold, and PolyPhen-2 were employed for protein structure simulation and amino acid sequence conservation analysis. Pathogenicity of the variant was rated based on guidelines from the American College of Medical Genetics and Genomics (ACMG). Literature was retrieved from databases including CNKI, Wanfang, and PubMed using the keyword « Chitayat syndrome ». The clinical characteristics and prognosis of patients with Chitayat syndrome were reviewed and analyzed. This study was approved by the Ethics Committee the Seventh Affiliated Hospital of Sun Yat-sen University (Ethics No.: KY-2024-086-01). RESULTS: The child was born at full term and had special facial features, skeletal abnormalities, recurrent respiratory tract infections and global developmental delay. WES and Sanger sequencing revealed that he has harbored a heterozygous c.266A>G p.(Tyr89Cys) variant of the ERF gene. Protein structure modeling suggested that the mutant protein has increased spatial distance between the side chain group and DNA, which may reduce its binding affinity to DNA. Amino acid sequence analysis indicated that the p.Tyr89 residue is highly conserved across multiple species. The variant was therefore classified as pathogenic (PM1+PM2_Supporting+PM6+PS1+PP3). The patient was diagnosed with « Chitayat syndrome ». Nutritional support and rehabilitation training were recommended, though the child had died of severe pneumonia at 13 months old. Literature retrieval has collected 7 relevant articles, which involved 14 cases of Chitayat syndrome confirmed by genetic testing. Together with our case, all patients had facial dysmorphisms and skeletal deformities. Fourteen patients (93.3%) had respiratory distress. Seven of them (46.7%) had recurrent respiratory infections and 7 (46.7%) were confirmed with respiratory tract malacia. Eight (53.3%) patients had neuropsychological retardation, while 8 (53.3%) had growth delay. The main interventions for Chitayat syndrome include respiratory and nutritional support, and rehabilitation training for developmental delays. CONCLUSION: Chitayat syndrome is rarely seen and its clinical manifestations may vary. Airway management and early intervention of developmental delay are important for improving the prognosis.

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20. Massaguer-Bardají B, Grau-Touriño A, Gómez-Hinojosa AM. Behavioral Alterations in Adolescents and Young Adults With Autism Spectrum Disorder in a Hospitalization Unit: An Analysis of Self-Injury. Rev Neurol. 2025; 80(6): 45344.

BACKGROUND: Individuals with Autism Spectrum Disorder (ASD), may present with behavioral disturbances, difficulties dealing with change, restricted interests and/or sensory disturbances. Among their characteristic behaviors are self-injurious behaviors that tend to be compulsive, unplanned, rhythmic and repetitive. The aim of this study was to investigate the relationship between self-injurious behaviors in hospitalized adolescents with ASD, depression and anxiety. METHODS: The sample included 50 patients with ASD, aged between 14 and 27 years. These patients were assessed using the Autism Diagnostic Observation Scale (ADOS-2), the Autism Diagnostic Interview-Revised (ADI-R), the Trait-State Anxiety Questionnaire, the Beck Depression Inventory (BDI), the Adolescent/Adult Sensory Profile (AASP) and the Inventory of Statements About Self-injury (ISAS). RESULTS: The results revealed significant and positive correlations between the level of self-injury and its dimensions: self-regulation (ρ = 0.861), sensation seeking and strength (ρ = 0.767), suicide avoidance (ρ = 0.732), revenge (ρ = 0.643), self-control (ρ = 0.700), manifestation of distress (ρ = 0.828) and blunting (ρ = 0.702). CONCLUSIONS: There is evidence of a positive relationship between levels of self-harm and sensory defensiveness, specifically in the emotion avoidance profile. eng.

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21. Meng Y, Jia J, Ding Y, Wang P, Wang Z, Zhang R, He Z, Wang Z, Zhang H, Feng L, Li Y, Shi X, Shan L, Liao M, Li Y. Characterizing immune and metabolic profiles in autism spectrum disorder through combined transcriptomics-metabonomics analysis. J Psychiatr Res. 2025; 190: 92-101.

BACKGROUND: Autism Spectrum Disorders (ASD) encompass a range of complex neurodevelopmental conditions marked by difficulties in social communication, restricted interests, and repetitive behavior. In this study, we explore the potential interplay between metabolic and transcriptional alterations in ASD, aiming to uncover common biological disturbances that may contribute to the phenotype across cohorts. METHODS: Transcriptional and metabolomic data for ASD and typically developing (TD) samples were sourced from the GEO database. After rigorous quality control and alignment of transcriptomic data using DESeq2 identified differentially expressed genes (DEGs). For metabolomic data, MetaboAnalyst was used to find differentially expressed metabolites (DMs). Functional annotation was done using KEGG and GO, while Cytoscape facilitated network analysis. RESULTS: The analysis revealed significant upregulation of immune-related genes, including IL-1β and IFN-γ, indicating an activated immune response in ASD. Conversely, downregulation of synaptic genes suggests potential synaptic function impairments. These findings highlight the influence of immune responses on neurodevelopment. Furthermore, notable metabolic changes were observed, with increases in metabolites like phenylalanine and citrulline, alongside alterations in lipid metabolism, aligning with dysregulated immune pathways and synaptic signaling. Key transcription factors, such as RARA and NFKB2, were also identified, emphasizing their critical roles in modulating these interconnected biological processes. CONCLUSION: The parallel findings of dysregulation of metabolic and transcriptomic pathways in ASD from distinct cohorts point towards intricate commonalities that contribute to its phenotype. This multi-omics approach provides valuable insights and supports the development of precision medicine strategies. Future research should focus on longitudinal studies to explore these changes across developmental stages and environmental influences, offering a more comprehensive perspective on ASD management.

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22. Messaoud M, Joya HU, Alansari AN, Jouini A, Ksiaa A, Zrig A, Sahnoun L. A Rare Case of Ileal Intussusception Caused by Primary Small Bowel Trichobezoar and Meckel’s Diverticulum in an Autistic Child. Clin Case Rep. 2025; 13(8): e70745.

Intussusception is a condition in which one part of the intestine slides into an adjacent part of the intestine. Intussusception is an important cause of an acute abdomen and the second most common cause of bowel obstruction in children. Trichobezoars, which are rare in children and often linked to psychiatric disorders, seldom cause intestinal intussusception. While Rapunzel syndrome-a form of gastric trichobezoar extending into the small bowel-is a recognized cause, primary small-bowel trichobezoars are exceptionally rare. We report a unique pediatric case of ileo-ileal intussusception triggered by a 30-cm primary small-bowel trichobezoar coexisting with Meckel’s diverticulum, an association not previously documented. A 6-year-old autistic boy presented with symptoms suggestive of bowel obstruction. Imaging suggested small-bowel intussusception related to Meckel’s diverticulum. Surgery revealed an ileo-ileal intussusception secondary to a 30-cm obstructive trichobezoar located proximal to the invagination and an inflamed Meckel’s diverticulum. The diverticulum was resected, the trichobezoar was removed, and ileo-ileal anastomosis was performed, with no postoperative complications. The combination of a primary small-bowel trichobezoar and Meckel’s diverticulum leading to intussusception is exceedingly rare and poses unique diagnostic and therapeutic challenges, particularly in special pediatric populations. Early recognition and surgical intervention are essential to prevent bowel ischemia, perforation, and sepsis.

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23. Michels S, Mali A, Jäntti H, Rezaie M, Malm T. Microglial involvement in autism spectrum disorder: insights from human data and iPSC models. Brain Behav Immun. 2025; 130: 106071.

Autism spectrum disorder (ASD) presents a range of lifelong challenges in social communication, repetitive behaviors, and restricted interests, affecting over 2% of the preschool population. Early neurodevelopmental disruptions, particularly those affecting microglia, appear to be central to the pathophysiology of ASD, with microglia influencing synaptic development and stability in the brain. However, the neurobiological mechanisms underlying ASD are still not fully understood. Traditional ASD studies, which rely on animal models and postmortem tissues, have limitations in capturing human-specific neurodevelopmental dynamics. Recent advances in human model systems, including induced pluripotent stem cell (iPSC)-derived neural cultures and brain organoids, offer promising insights into microglia-neuron interactions relevant to ASD. This review evaluates current research using human-based models to explore ASD pathophysiology, focusing on the role of microglia in neurodevelopment, and discusses the strengths and future potential of these innovative approaches.

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24. Mokhwelepa LW, Sumbane GO, Ngwenya MW. The dynamic trajectory of autistic life and its changing challenges: a scoping review. BMC Psychiatry. 2025; 25(1): 769.

BACKGROUND: There is a noticeable knowledge vacuum on the ways in which autism interacts with the difficulties associated with aging, even though in recent decades there has been a growing recognition of the different needs and experiences of those on the autistic spectrum. Importantly, experiences across earlier life stages such as youth and young adulthood also influence later outcomes and warrant consideration within this dynamic trajectory, meaning the ongoing and evolving developmental path individuals follow throughout life. OBJECTIVES: This study aimed to review the existing literature on the unique needs, challenges, and experiences of autistic adults as they progress into later stages of life. METHODOLOGY: The scoping review was carried out by following a structure that included defining the research topic, finding pertinent studies, choosing studies, charting data, and ultimately compiling, summarizing, and synthesizing the findings, the scoping review was carried out. PubMed, PsycINFO, Google Scholar, and ScienceDirect are the databases that were used to perform an exhaustive search of the literature from 2010 to 2023. Studies were screened for inclusion based on predefined criteria. RESULTS: Despite an initially large dataset, only a limited number of studies directly addressed the intersection of autism and aging in sufficient depth. This review yielded only two themes: (1) Challenges experienced by adults with autism when aging; (2) interventions and support strategies. CONCLUSION: The important need for greater comprehension of the relationship between autism and aging was highlighted by this study. It exposed a wide range of difficulties that autistic adults encounter as they age, such as inequalities in healthcare and problems integrating into society. This review will contribute to a deeper understanding by highlighting the evolving challenges, unmet needs, and support mechanisms required by autistic adults as they age, offering insights for research, policy, and practice.

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25. Murakami T, Oshima F, Morimoto T, Annaka H. Schema Therapy for Individuals With Subthreshold Autistic Traits and Recurrent Depressive Disorder: A Case Study. Cureus. 2025; 17(7): e87357.

Schema therapy (ST) is a therapeutic approach to address chronic and complex psychological difficulties. ST is also used to treat mental health problems that individuals on the autism spectrum have. However, no practical reports exist on its application to cases involving subthreshold autistic traits with associated psychological difficulties. This report describes schema therapy for a woman with subthreshold autistic traits and raised in an abusive environment. The intervention was based on schema therapy for individuals on the autism spectrum and consisted of a total of 42 sessions. The effects of schema therapy remained effective at an eight-month follow-up. This practice suggests that the promotion of understanding of autistic traits and experiential techniques are helpful in schema therapy for cases with subthreshold autistic traits.

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26. Osorio S, Tan J, Levine G, Ahlfors SP, Graham S, Mamashli F, Khan S, Joseph RM, Nayal Z, Losh A, Pawlyszyn S, McGuiggan NM, Hämäläinen MS, Bharadwaj H, Kenet T. Lower cortical activation and altered functional connectivity characterize passive auditory spatial attention in ASD. bioRxiv. 2025.

Autism Spectrum Disorder (ASD) is a developmental condition characterized by difficulties in social interaction, communication and sensory processing. The ability to orient towards sounds is a key component of social interactions, yet auditory spatial attention remains relatively understudied in ASD, despite prior research indicating differences in this domain. Here, we investigate the neural signatures associated with passive auditory spatial attention in children with ASD (n = 21, ages 6-17) relative to age- and IQ-matched typically developing (TD) children (n = 31), using source-localized magnetoencephalography (MEG). Participants listened passively, while watching a silenced movie, to non-social auditory stimuli designed to either remain lateralized to one hemifield (stay trials), or to change in location from one side to the contralateral hemifield (jump trials). Linear mixed effects modeling showed lower cortical activation in the auditory cortex in the ASD group in response to jump trials, relative to the TD group. Additionally, functional connectivity analyses showed higher alpha-band functional connectivity in the ASD group between left auditory cortex seeds and right prefrontal and left parietal regions known to be recruited during auditory spatial attention. Right prefrontal alpha-band connectivity estimates were associated with behaviorally assessed auditory processing scores, whereas left parietal connectivity estimates were associated with ASD symptomatology. Our results align with the hypothesis that auditory spatial attention generally, and specifically orientation to sounds even when experienced passively, differs in ASD individuals.

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27. Pecukonis M, Gerson J, Gustafson-Alm H, Wood M, Yücel M, Boas DA, Tager-Flusberg H. The neural bases of language processing during social and non-social contexts: a fNIRS study of autistic and neurotypical preschool-aged children. Mol Autism. 2025; 16(1): 40.

BACKGROUND: Little is known about how autistic children’s brains process language during real-world « social contexts, » despite the fact that challenges with language, communication, and social interaction are core features of Autism Spectrum Disorder (ASD). METHODS: We investigated the neural bases of language processing during social and non-social contexts in a sample of autistic and neurotypical (NT) preschool-aged children, 3-6 years old, living in the United States. Functional near-infrared spectroscopy was used to measure children’s brain response to « live language » spoken by a live experimenter during an in-person social context (i.e., book reading) and « recorded language » played via an audio recording during a non-social context (i.e., screen time). We examined within-group and between-group differences in the strength and localization of brain response to live language and recorded language, as well as correlations between children’s brain response to live language versus recorded language and their language skills, as measured by the Preschool Language Scales. RESULTS: In the NT group, brain response to live language was greater than brain response to recorded language in the right temporal parietal junction (TPJ). In the ASD group, the strength of brain response did not differ between conditions in any brain regions of interest after correction for multiple comparisons. Children who showed a greater difference in right TPJ brain response to live language versus recorded language had higher language skills; this significant correlation was driven by the ASD group. LIMITATIONS: Findings should be considered preliminary until they are replicated in a larger sample. CONCLUSIONS: Group level findings indicate that for NT children, but not autistic children, the right TPJ responds more strongly to live language presented during a social context compared to recorded language presented during a non-social context. However, individual differences in how the right TPJ responds to language during social versus non-social contexts may help to explain why language skills are so variable across children on the autism spectrum.

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28. Sharma G, Russell AL, Dixon KG, Fusha R, Triplett JW. Extracellular spike waveform analysis reveals cell type-specific changes in the superior colliculus of fragile X mice. bioRxiv. 2025.

A long-standing goal of neuroscience has been to elucidate the diverse complement of neurons in the brain, which can be defined by several criteria. Analysis of action potential shape in extracellular recordings has revealed subpopulations in several regions of the brain, allowing for insights into neuronal subtype-specific function in the intact brain. The superior colliculus (SC) is a critical sensorimotor region, integrating visual, somatosensory, auditory, and nociceptive inputs to direct complex behaviors. Recent work suggests that the SC may be adversely impacted in neurodevelopmental disorders (NDDs), underscoring its importance. However, our understanding of cellular diversity in the SC lags in comparison to other regions, limiting our ability to parse circuit changes in NDDs. Here, we utilized semi-automated clustering methods to classify neurons in the mouse SC based on multiple features of extracellularly recorded waveforms to identify five putative cell types. Secondary analysis of firing statistics and visual tuning properties supported the cluster segregation. Interestingly, the proportions of units assigned to each cluster differed in the SC of a mouse model of fragile X syndrome (FXS, Fmr1 (-/y) ), with only four of five types identified. Furthermore, we observed changes in waveform properties and firing statistics, but not visual tuning properties, between genotypes in a subtype-specific manner. Taken together, these data add to our understanding of neuronal diversity in the SC and alterations of visual circuit organization and function in NDDs.

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29. Siedler A, Zasępa E, Idczak-Paceś E, Saad D, Zębrowska I. Coping strategies as mediators of internalizing symptoms on quality of life in school-aged children with autism spectrum disorder and typical development. Res Dev Disabil. 2025; 164: 105083.

BACKGROUND: Children with autism spectrum disorder (ASD) often report lower quality of life (QoL) than their typically developing peers, yet the coping processes that underlie these differences remain unclear. AIMS: This study investigated which coping styles mediate the impact of internalizing symptoms (depression, anxiety, anger control difficulties) on children’s self-reported QoL and whether these pathways differ between ASD and typically developing groups. METHODS: A total of 172 school-aged children (80 ASD and 92 typically developing) completed standardized measures of QoL, internalizing symptoms, and four coping styles. Moderated mediation analyses tested coping as parallel mediators and diagnostic group as a moderator. RESULTS: Across both groups, higher internalizing symptoms were linked to poorer QoL. Problem-solving coping emerged as a protective mediator in typically developing children only, while other coping styles did not mediate symptom-QoL links in either group. CONCLUSIONS: Problem-focused coping supports QoL in typically developing youth but appears less effective in ASD. Children with ASD derived immediate relief from palliative strategies (e.g., structured calming techniques), yet these strategies did not attenuate the negative impact of internal distress on their broader day-to-day well-being. Interventions that adapt problem-solving strategies to the needs of children with ASD may enhance their well-being.

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30. Sohn JS, Lee E, Kim JJ, Oh HK, Kim E. Implementation of generative AI for the assessment and treatment of autism spectrum disorders: a scoping review. Front Psychiatry. 2025; 16: 1628216.

INTRODUCTION: Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and restrictive, repetitive behaviors. Current diagnostic and intervention pathways rely heavily on clinician expertise, leading to delays and limited scalability. Generative artificial intelligence (GenAI) offers emerging opportunities for automatically assisting and personalizing ASD care, though technical and ethical concerns persist. METHODS: We conducted systematic searches in Embase, PsycINFO, PubMed, Scopus, and Web of Science (January 2014 to February 2025). Two reviewers independently screened and extracted eligible studies reporting empirical applications of GenAI in ASD screening, diagnosis, or intervention. Data were charted across GenAI architectures, application domains, evaluation metrics, and validation strategies. Comparative performance against baseline methods was synthesized where available. RESULTS: From 553 records, 10 studies met the inclusion criteria across three domains: (1) screening and diagnosis (e.g., transformer-based classifiers and GAN-based data augmentation), (2) assessment and intervention, (e.g., multimodal emotion recognition and feedback systems), and (3) caregiver education and support (e.g., LLM-based chatbots). While most studies reported potential performance improvements, they also highlighted limitations such as small sample sizes, data biases, limited validation, and model hallucinations. Comparative analyses were sparse and lacked standardized metrics. DISCUSSION: This review (i) maps GenAI applications in ASD care, (ii) compares GenAI and traditional approaches, (iii) highlights methodological and ethical challenges, and (iv) proposes future research directions. Our findings underscore GenAI’s emerging potential in autism care and the prerequisites for its ethical, transparent, and clinically validated implementation. SYSTEMATIC REVIEW REGISTRATION: https://osf.io/4gsyj/, identifier DOI: 10.17605/OSF.IO/4GSYJ.

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31. Tang L, Shen C. Multimodal AI-driven object detection with uncertainty quantification for cardiovascular risk assessment in autistic patients. Front Cardiovasc Med. 2025; 12: 1606159.

INTRODUCTION: Artificial Intelligence (AI) has transformed medical diagnostics, offering enhanced precision and efficiency in detecting cardiovascular risks. However, traditional diagnostic approaches for cardiovascular risk assessment in autistic patients remain limited due to the complexity of medical data, inter-individual variability, and the challenges of integrating multi-modal clinical information. Conventional methods, relying heavily on manually extracted features and rule-based analysis, often fail to capture subtle cardiovascular abnormalities, leading to suboptimal clinical outcomes. METHODS: To address these limitations, we propose an AI-driven object detection framework that leverages advanced deep learning techniques for automated, accurate cardiovascular risk assessment in autistic patients. Our approach integrates multi-modal medical data, including imaging and electronic health records, through a novel feature fusion mechanism, enhancing diagnostic precision. Furthermore, an uncertainty quantification module is embedded to improve model interpretability and reliability, addressing concerns regarding AI-based medical decision-making. RESULTS: Experimental evaluations demonstrate that our method significantly outperforms traditional diagnostic techniques in sensitivity and specificity, making it a robust tool for clinical applications. DISCUSSION: The proposed framework represents a significant step towards personalized and data-driven cardiovascular care for autistic patients, aligning with the need for tailored diagnostic solutions in this specialized medical domain.

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32. Wagatsuma N, Nobukawa S, Kurikawa T. Excitatory/inhibitory ratio disruption modulates neural synchrony and flow directions in a cortical microcircuit. PLoS Comput Biol. 2025; 21(8): e1013306.

Autism spectrum disorder (ASD) and schizophrenia are complex and heterogeneous mental disorders involving the dysfunction of multiple neural systems. The atypical and heterogenous temporal coordinations of neuronal activity, which are widely observed in these two disorders, are hypothesized to stem from an excitatory/inhibitory (E/I) imbalance in the brain. To investigate the association between the E/I imbalance and atypical neural activities, and to assess the influence of specific subtypes of inhibitory interneurons on network activity regulation, we developed a computational microcircuit model with biologically plausible layer 2/3 of visual cortex that combined excitatory pyramidal neurons with three subtypes of inhibitory interneurons (parvalbumin [PV], somatostatin [SOM], and vasoactive intestinal polypeptide [VIP]). We numerically explored the role of distinct types of E/I imbalance by changing the population size of different subtype neurons. We find that when the E/I balance is disrupted by decreasing the PV population size, activity of the PV population precedes that of the pyramidal population, which enhances beta and gamma oscillations. Conversely, pyramidal neuronal population activity was the precursor of PV interneuron activity when the E/I imbalance was induced by decreasing the SOM population size; this preferentially impaired gamma-frequency activity. The disruption of E/I balance altered the information flow between pyramidal and PV populations, modulating neuronal dynamics. Our results suggest that E/I imbalance due to different subtype interneurons would induce the distinct types of the atypical neural behaviors associated with neural system dysfunction.

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33. Walker H, Kwak D, Devaraju P, Curd BC, Chikuni AM, Frost NA. Impaired Spatiotemporal Encoding of Social Behavior and Anxiety in the Prefrontal Cortex of Mice Lacking ASD-Risk Gene Shank3. bioRxiv. 2025.

The prefrontal cortex is a central regulator of complex behaviors, including social interaction and anxiety-related behaviors. The prefrontal cortex encodes these behaviors using heterogeneous groups of neurons, or ensembles, which collectively process inputs and communicate with distributed brain regions. We examined whether loss of the Autism-risk gene Shank3 alters the recruitment of neurons encoding socioemotional behavior collectively, or if abnormal activity during specific behaviors might affect functionally or anatomically defined populations of neurons. To do this, we combined spatially-resolved microendoscopic calcium imaging across the prefrontal microcircuit with functionally defined labeling of neurons as control and mutant mice engaged in social interaction or anxiety-provoking behaviors. We then utilized a non-biased transcriptomic method to identify neurons activated by social interactions. We show that the recruitment of heterogeneous neuronal populations are altered in a cell type and spatially dependent manner by loss of Shank3, with impaired recruitment of behavior-specific activity patterns within superficial, but not deeper aspects of the prefrontal cortex.

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34. Wang X, Pei C, He J, Xu J. A deep learning model for diagnosing autism using brain time series. Neuroscience. 2025; 583: 120-35.

The early identification of autism is especially critical as it can significantly enhance the effectiveness of intervention strategies. However, the recognition task remains challenging due to the subtle differences between ASD patients and neurotypical individuals. The presented approach leverages a hybrid model that combines Long Short-Term Memory (LSTM) networks with an Attention mechanism, enabling the extraction of both long-term and short-term features for more accurate autism diagnosis. Additionally, we integrate a residual block with channel Attention to enhance feature fusion and mitigate the risk of network degradation. Innovatively, we introduce a sliding window-based data preprocessing method alongside a voting strategy and validate the framework using subject-level 5-fold cross-validation to ensure generalizability across data splits. Our model was evaluated on the Region of Interest (ROI) time series dataset from the Autism Brain Imaging Data Exchange (ABIDE), achieving 73.1 % accuracy on the DOS brain atlas and 81.1 % on the HO brain atlas-outperforming baseline models. Moreover, we constructed brain functional connectivity topological structures for both ASD patients and healthy individuals, providing valuable resources for future autism research.

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35. Yang H, Lu F, Zhao X. Factors influencing the effect of melatonin on sleep quality in children with autism spectrum disorder: a systematic review and meta-analysis. Sleep Breath. 2025; 29(4): 262.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interaction and communication. The prevalence of ASD has risen globally. Sleep disturbances exacerbates the core symptoms of children with ASD, and numerous studies demonstrated that melatonin is efficacious in treating autism-related insomnia in children. This study intended to comprehensively analyze the therapeutic effects of melatonin on sleep disturbances in children with autism, focusing on effect sizes across different treatment parameters, including medication dosage, type, treatment course, and the age of the children. Additionally, the analysis examines the effects of melatonin on various sleep indicators. Through systematic review and meta-analyses, data from existing studies were collected and categorizing them based on medication parameters and the age of the participants. The influence of melatonin on multiple sleep indicators was evaluated, revealing that melatonin significantly improves sleep quality and total sleep time in children with autism. The Hedges’ g values for these two indicators were 0.75 and 0.58, with both P-values less than 0.05. The overall effect of melatonin displayed a parabolic relationship with dosage, achieving its optimal effectiveness at approximately 5.7 mg. Subject age also influenced the therapeutic effect with optimal results observed in children aged 10 years and older, where the Hedges’ g effect size reached 0.09. Melatonin shows substantial effectiveness in improving the sleep in children with ASD, with minimal and mild adverse reactions. These findings support the development of individualized treatment approaches for melatonin administration in this population.

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36. Zhang QM, Chen YF, Xing YY, Yang M, Li N, Jiang X, Gao H, Lu SY, Yao J. Anterior insular cortex regulates depression-like and ASD-like behaviors via the differential contribution of two subsets of microglia. Mol Psychiatry. 2025.

The anterior insular cortex (aIC) is involved in multiple neuropsychiatric disorders. Here, using the Cntnap2-deficient autism spectrum disorder (ASD) mouse model and the chronic social defect stress (CSDS)-induced depression mouse model, we show that two subpopulations of microglia in the mouse aIC played differential roles in ASD-like and depression-like behavioral phenotypes differentially. The Cx3cr1(+) microglia had morphological deficits in the Cntnap2-deficient mice and were involved in social deficits and restricted repetitive behaviors, while the Tmem119(+) microglia had morphological deficits in the CSDS-induced mice and contributed to impairments in sucrose preference and forced swim performance. Further, we showed that the two subsets of microglia had differential features in morphology, transcriptional profiles, electrophysiological properties, and impacts on synaptic functions. Using proteomic and metabonomic analyses, we identified two secretory factors, Fbl and Hp1bp3, that were crucial for the dysfunctions of the Cx3cr1(+) and Tmem119(+) microglia, respectively. Finally, we verified that Fbl and Hp1bp3 played essential roles in the behavioral deficits of the Cntnap2-deficient and the CSDS-induced mice, respectively. Our study can help understand the contribution of microglia and the aIC to neuropsychiatric-like behaviors.

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37. Zhang Y, Shen L, Li Y, Guo H, Xie F, Li S, Li Y, Chen J, Chen J. Lead-driven synergistic interactions in environmental metal (loid) mixtures: Systemic inflammation mediating autism spectrum disorder risk in Chinese children. Int J Hyg Environ Health. 2025; 269: 114645.

Environmental metal (loid) exposure, particularly to lead (Pb), constitutes a growing concern for potential associations with autism spectrum disorder (ASD). Current risk assessments may underestimate neurodevelopmental impacts due to co-exposure interactions, while systemic inflammation’s mediating role in Pb-ASD relationships remains poorly characterized. This case-control study quantified serum concentrations of eight metal (loid)s via inductively coupled plasma mass spectrometry (ICP-MS) in 81 ASD cases and 402 typically developing (TD) Chinese children. Logistic regression demonstrated significantly elevated ASD risk with increasing Pb exposure quartiles (Q3 vs. Q1: OR = 2.64, 95 % CI 1.42-4.89; Q4 vs. Q1: OR = 6.85, 95 % CI 3.24-14.48; P(trend) < 0.001). Restricted cubic spline analysis confirmed a positive nonlinear dose-response relationship between log-transformed Pb levels and ASD risk (P(non-linear) = 0.004, P(overall) < 0.001). Multi-pollutant mixture analyses identified Pb as the predominant contributor to ASD risk in both quantile g-computation (weight = 0.5099) and Bayesian kernel machine regression (PIP = 1.00) models, with evidence of significant cobalt (Co)-Pb interaction. Mediation analyses indicated systemic inflammation indices (SIRI, SII) partially mediated the Pb-ASD association (15.8 % and 8.6 %, respectively). These findings identify Pb as a principal determinant of metal (loid)-associated ASD risk, with inflammatory pathways contributing to its neurotoxicity. The observed Co-Pb interaction warrants investigation into co-exposure neurotoxicity mechanisms.

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38. Zhao S, Chen X, Sun Q, Zhu H, Yang S, Song X, Chen J, Zhang C, Wu L. Dihydroquercetin Nanomicelles Mitigate Hippocampal Apoptosis and Alleviate Autism-Like Behaviors in ASD Rats via the IKK/IKB/NF-κB Signaling Pathway. Mol Pharm. 2025.

Dihydroquercetin (DHQ), a compound with neuroprotective effects, has shown its potential in a variety of nervous system diseases. However, its mechanism of action in autism spectrum disorder (ASD) remains to be further explored. Due to its poor solubility, the clinical application of DHQ is restricted. In this study, we aimed to improve the solubility of DHQ by constructing a novel nanodrug delivery system. We utilized the amphiphilic block copolymer MANNOSE-PEG2000-DSPE to encapsulate DHQ, and the resulting formulation was abbreviated as MAN@DHQ. The ASD rats were treated with MAN@DHQ for 7 days. The results of in vivo experiments confirmed that MAN@DHQ could effectively alleviate autism-like behaviors of ASD rats. Western blot results demonstrated that MAN@DHQ mitigate hippocampal apoptosis and ameliorated neuronal damage in the hippocampus of ASD rats via the IKK/IKB/NF-κB signaling pathway. The therapeutic potential of MAN@DHQ in ASD treatment represents a paradigm-shifting advancement in autism pharmacotherapy and offers promise for clinical interventions for ASD patients.

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39. Zheng Q, Zhao Y, Cheng Q, Wang H, Liu F, Lai J, Liu Y, Zhang X, Kang Y, Li Z, Cao B, Wei C, Qian Z, Fan J, Ren W, Tian Y. Potentiation of nigra-striatal dopaminergic projection underpins core autism-like behaviors in valproate-exposed mice. J Neurosci. 2025.

Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. However, the underlying neural circuit dysfunction that accounts for these coexisting symptoms in autism remains poorly understood. Here we revealed that prenatal valproate exposure induced functional alterations of dopaminergic projections from substantia nigra pars compacta (SNc) to dorsomedial striatum (DMS). Specifically, we observed enhanced excitatory input and increased excitability in SNc-DMS dopamine (DA) neurons, resulting in a basal state of potentiation. This potentiated baseline activity blunted the phasic responses of SNc-DMS projections, as evidenced by reduction of transient Ca(2+) and DA signaling during social interaction and expression of repetitive behaviors in valproate-exposed male mice. We then utilized chronic chemogenetic and optogenetic approaches to selectively manipulate the abnormal basal activity of SNc-DMS dopaminergic signaling. This targeted intervention successfully rectified the dysfunction in D1R expressed medium spiny neurons (D1-MSNs) associated with social deficits, while simultaneously restoring the functionality of D2-MSNs linked to repetitive behaviors. Collectively, our findings support the hypothesis that prenatal valproate exposure disrupts SNc-DMS dopaminergic signaling, which mediates the coexistence of two core autism-like behaviors by reshaping the dynamics of direct and indirect pathway MSNs. Moreover, these results highlight potential therapeutic targets for developing interventions for both core symptoms of autism.Significance statement Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although the two core symptoms are apparently different and seemingly unrelated, they are actually associated each other, social behaviors need to be processed by a series of actions. Repetitive behaviors, especially the high-order restrictive interests, have their scopes to cognitive and emotional domains. This study, for the first time, revealed that prenatal valproate exposure disrupts nigrostriatal dopaminergic signaling, which mediated the coexistence of two core autism-like behaviors by reshaping the dynamics of direct and indirect pathway MSNs. These results offer insights regarding dopaminergic signaling as a hub underpinning the two coexisting behavioral abnormalities, and highlighting potential therapeutic targets for autism.

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