Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

Magnetic stimulation has made significant strides in the treatment of psychiatric disorders. Nonetheless, current magnetic stimulation techniques lack the precision to accurately modulate specific nuclei and cannot realize deep brain magnetic stimulation. To address this, we utilized superparamagnetic iron oxide nanoparticles as mediators to achieve precise targeting and penetration. We investigated the effects of magnetic fields with varying frequencies on neuronal activity and compared the activation effects on neurons using a 10-Hz precise magneto-stimulation system (pMSS) with repetitive transcranial magnetic stimulation in mice. Oxytocin levels, dendritic morphology and density, and mouse behavior were measured before and after pMSS intervention. Our findings suggest that pMSS can activate oxytocinergic neurons, leading to upregulation of oxytocin secretion and neurite outgrowth. As a result, sociability was rapidly improved after a one-week pMSS treatment regimen. These results demonstrate a promising magneto-stimulation method for regulating neuronal activity in deep brain nuclei and provide a promising therapeutic approach for autism spectrum disorder.
Animals ; Autism Spectrum Disorder/physiopathology* ; Paraventricular Hypothalamic Nucleus/physiology* ; Disease Models, Animal ; Transcranial Magnetic Stimulation/methods* ; Male ; Social Behavior ; Mice ; Oxytocin/metabolism* ; Mice, Inbred C57BL ; Neurons/physiology*

OBJECTIVES

This study aimed to describe the demographic profile, intervention sessions, goal attainment scaling (GAS), and health-related quality of life (HRQOL) of autistic children receiving speech and language therapy (SLT) in a higher educational institution in the Philippines.

Deidentified data from 18 autistic children aged 4–16 years (mean=8.2; SD=2.9) who received SLT for two months were analyzed. Their demographic profile, intervention sessions, GAS scores, and generic HRQOL scores were documented.

Most participants were school-age children (n=12; 66%) and were boys (n=14; 78%). After two months, the GAS scores of 11 participants (61%) increased by 1–2 points, whereas the scores of the remaining participants decreased (n=6; 33%) or did not change (n=1; 6%). Their mean generic HRQOL scores before and after SLT were 65.6 (SD=15.2) and 61.2 (SD=17.4), respectively.

While the GAS scores increased for most participants, their generic HRQOL scores did not show clinically significant changes after two months of SLT. This can be attributed to the few therapy sessions and short follow-up period. The findings highlight the need to provide long-term support to SLT services of autistic children in the Philippines to document more desirable quality of life outcomes.

: This study aimed to identify risk factors associated with problematic mealtime behaviors in Filipino children aged 3-11 years diagnosed with ASD and to validate the Filipino-translated Brief Autism Mealtime Behavior Inventory (BAMBI) for clinical use. The study examined demographics, socioeconomic status, and clinical characteristics of children with ASD in relation to feeding difficulties. MATERIALS AND METHODS: A cross-sectional study was conducted with 166 caregivers of Filipino children with ASD at the Philippine Children’s Medical Center. The BAMBI questionnaire, translated and validated into Filipino, was administered among patients evaluated under the Section of Neurodevelopmental Pediatrics. Content validity was established through neurodevelopmental pediatric experts, while face validity was achieved with feedback from 17 caregivers during the pilot test. Descriptive statistics and logistic regression were performed to identify the factors. RESULTS: The Filipino-translated BAMBI demonstrated good content and face va- lidity based on reviews and pilot testing. The tool showed acceptable internal consistency with a Cronbach’s alpha of 0.75, indicating good reliability. Seventy-seven percent (77%) of participants scored above the threshold for problematic mealtime behaviors, with multivariate analysis revealing a significant association between these behaviors and sensory sensitivities (OR = 3.0, 95% CI: 1.2 to 7.3, p = 0.0150). Additional factors, such as dietary habits and family structure, also showed trends toward significance but did not reach statistical significance. CONCLUSIONS AND RECOMMENDATIONS This study validates the Filipino BAMBI as a reliable tool for assessing mealtime behaviors in children with ASD, highlighting the high prevalence of feeding problems in this population. Sensory sensitivities emerged as a significant factor contributing to problematic mealtime behaviors, underscoring the importance of incorporating sensory processing strategies in interventions. Further research should explore other contributing factors, such as dietary habits and family dynamics, to develop more comprehensive, tailored interventions for children with ASD and their families.
Autism spectrum disorder ; mealtime behaviors ; feeding difficulties ; BAMBI ; parent questionnaire ; risk factors

OBJECTIVE: To explore the efficacy of acupuncture based on "gut-brain axis" combined with sensory integration training in children with autism spectrum disorder (autism) and its effect on gastrointestinal symptoms. METHODS: A total of 96 children with autism were randomized into an observation group and a control group, 48 cases in each group, with 3 cases dropped out. Children in the control group received sensory integration training. On the basis of the treatment in the control group, children in the observation group received acupuncture therapy based on "gut-brain axis", and the point selection of scalp acupuncture was forehead five needles, i.e. bilateral Touwei (ST8), Toulinqi (GB15), Shenting (GV24) and Sishencong (EX-HN1), the point selection of body acupuncture was Zhongshu (GV7) and bilateral Tianshu (ST25), Pishu (BL20), Xinshu (BL15), Zusanli (ST36), Hegu (LI4), Taichong (LR3). Acupuncture was delivered once every other day, 3 times a week. Both groups were treated for 12 weeks. Before and after treatment, the scores of autism behavior checklist (ABC), childhood autism rating scale (CARS), autism treatment evaluation checklist (ATEC) and gastrointestinal TCM symptoms, as well as the relative abundance of intestinal flora were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the ABC and CARS scores were decreased compared with those before treatment in the two groups (P<0.001, P<0.05), and the ABC and CARS scores in the observation group were lower than those in the control group (P<0.01). After treatment, the item scores of language, sensory perception, sociability, behavior, and the total score of ATEC in the observation group were decreased compared with those before treatment (P<0.001, P<0.01), the item scores of language, sociability, behavior, and the total score of ATEC in the control group were decreased compared with those before treatment (P<0.01, P<0.001, P<0.05); the each-item and total scores in the observation group were lower than those in the control group (P<0.05). After treatment, the scores of loose stool, stomach duct pain, stomach duct stuffiness, decreased appetite, and the total scores of gastrointestinal TCM symptoms were reduced compared with those before treatment in the two groups (P<0.001), and the above scores in the observation group were lower than those in the control group (P<0.001). After treatment, the relative abundance of Escherichia coli and Enterococcus was decreased compared with that before treatment in the two groups (P<0.001), and the above relative abundance in the observation group was lower than that in the control group (P<0.001); the relative abundance of Bifidobacterium and Lactobacillus was increased compared with that before treatment in the two groups (P<0.001), and the above relative abundance in the observation group was higher than that in the control group (P<0.001). The total effective rate was 88.9% (40/45) in the observation group, which was higher than 66.7% (30/45) in the control group (P<0.05). CONCLUSION On the basis of sensory integration training, acupuncture based on "gut-brain axis" can improve the behavioral status and gastrointestinal symptoms, and correct the imbalance of intestinal flora in children with autism.
Humans ; Acupuncture Therapy ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child, Preschool ; Child ; Acupuncture Points ; Treatment Outcome ; Brain-Gut Axis ; Gastrointestinal Diseases/physiopathology*

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

OBJECTIVE: To observe the clinical effect of Jin's three-needle therapy combined with game therapy on children with autism spectrum disorder (ASD). METHODS: Sixty children with ASD were randomly divided into an observation group and a control group, with 30 cases in each. The children in the observation group received Jin's three-needle therapy combined with game therapy. The acupoints used in Jin's three-needle therapy included Zhisanzhen, Niesanzhen, Sishenzhen and Naosanzhen, and matches acupoints with syndromes. The acupoints included Shenting (GV24), Naohu (GV17) and bilateral Benshen (GB13), Naokong (GB19), Xinshu (BL15), Zusanli (ST36), etc. The needles were retained for 1 h for scalp acupuncture and not retained for body acupuncture. Game therapy included social interaction, music and dance, language stimulation, etc. The children in the control group were treated with the same game therapy in the observation group. Treatments were administered once daily, five times a week, with a three-month course considered as one treatment cycle, and a total of two cycles were provided. The scores of childhood autism rating scale (CARS), autism behavior scale (ABC) and 0-6-year-old Children's neuropsychological development assessment scale (children's psychological scale) were compared between the two groups before treatment and after 3 and 6 months of treatment. RESULTS: After 3 and 6 months of treatment, the CARS and ABC scores of both groups were lower than those before treatment (P<0.01). After 6 months of treatment, the CARS and ABC scores of the observation group were lower than those of the control group (P<0.05). After 3 and 6 months of treatment, the scores of gross motor, fine motor, adaptive ability, language, and social behaviors in both groups were higher than those before treatment (P<0.01). After 3 months of treatment, the observation group showed a greater improvement in gross motor, fine motor, adaptive ability, and social behaviors compared to the control group (P<0.05). After 6 months of treatment, the observation group showed a greater improvement in gross motor, fine motor, adaptive ability, language, and social behaviors compared to the control group (P<0.01, P<0.05). CONCLUSION Jin's three-needle therapy combined with game therapy is an effective method for the treatment of ASD, which shows more obvious advantages than simple game therapy in promoting the improvement of children's ability and reducing related behavior.
Humans ; Autism Spectrum Disorder/psychology* ; Male ; Acupuncture Therapy/instrumentation* ; Female ; Child ; Child, Preschool ; Acupuncture Points ; Treatment Outcome ; Play Therapy ; Combined Modality Therapy

OBJECTIVE: To analyze the core acupoint selection rules and syndrome-based compatibility patterns of acupuncture for autism spectrum disorder (ASD) using data mining techniques. METHODS: Relevant literature of acupuncture for ASD was retrieved from CNKI, Wanfang, VIP, PubMed, and Web of Science. After applying inclusion and exclusion criteria, a prescription database was established based on the extracted effective data. Descriptive analysis was conducted on the frequency, meridian tropism, anatomical distribution, and specific point. High-frequency acupoints were visualized using Origin software. The Apriori algorithm in IBM SPSS Modeler 18.0 was used for association rule analysis of acupoint combinations. Cluster analysis of high-frequency acupoints was performed using IBM SPSS Statistics 26.0. The relationships between high-frequency syndromes and acupoints were visualized using Cytoscape 3.10.0. RESULTS: A total of 223 studies and 452 prescriptions were included, among which 223 were based on syndrome differentiation. A total of 205 acupoints were included with a cumulative frequency of 4 067. The top five most frequently used acupoints were Baihui (GV20), Sishenzhen, Zhisanzhen, Niesanzhen, and Neiguan (PC6). Acupoints were primarily from Jin's three-needle therapy, the governor vessel, scalp acupuncture, and the foot-taiyang bladder meridian, with a high proportion of acupoints located on the head and neck and the limbs. Among specific point, five-shu points, yuan-source points, and back-shu points were most frequently used. Association rule analysis revealed that the core acupoint group was Sishenzhen-Dingshenzhen-Zhisanzhen-Niesanzhen. Cluster analysis divided the top 20 high-frequency acupoints into four categories: governor vessel activation and brain awakening group, spleen strengthening and heart nourishing group, Jin's three-needle spirit-regulating group, and kidney-reinforcing and marrow-filling group. Clinically, the main syndrome patterns were kidney essence deficiency, hyperactivity of heart and liver fire, phlegm obstructing the heart orifices, dual deficiency of heart and spleen, and liver qi stagnation. CONCLUSION The core acupoint prescriptions of acupuncture for ASD are Sishenzhen, Dingshenzhen, Zhisanzhen, and Niesanzhen. The treatment emphasizes spirit regulation and mental tranquility, guided by the principles of harmonizing multiple zang-fu organs, regulating qi and blood, unblocking qi movement, and balancing yin and yang. Syndrome-based acupoint compatibility is recommended in clinical practice.
Humans ; Acupuncture Points ; Acupuncture Therapy ; Autism Spectrum Disorder/therapy* ; Data Mining ; Meridians

INTRODUCTION: This study aimed to examine patterns of diagnosis, cognitive and adaptive functioning, and school placement outcomes in autistic children in Singapore, and to assess earlier predictive factors of cognitive outcomes. METHOD: Retrospective data were extracted from medical records of a specialist developmental paediatrics service for children born in 2008-2011 and referred to the autism clinic or were given a diagnosis of autism. Data items included demographic data, diagnostic methods, psychological assessment results, early intervention attendance and school placement outcomes. RESULTS: A total of 2124 children (82.6% male; 66.4% Chinese, 13.4% Malay, 9.8% Indian and 10.5% Others) were diagnosed with autism from the 4 birth-year cohorts. The mean (SD) age of the first clinical diagnosis of autism was 3.56 (1.14) years, with 81.0% of children receiving a concordant initial clinical diagnosis. A total of 1811 (85.2%) had a formal diagnostic assessment using the Autism Diagnostic Observation Schedule (ADOS) at a mean (SD) age of 4.16 (1.11) years. Of 1326 with cognitive and adaptive assessment results, 16.6% had mild and 19.8% had moderate-severe cognitive impairment. Of 1483 with school placement outcomes, 45.9% went to mainstream schools, 21.8% entered SPED schools offering the national curriculum and 32.3% required customised curriculum SPED schools. Logistic regression showed that factors predicting intellectual impairment included higher ADOS scores (aOR 95% CI 1.13 [1.08-1.19] for Comm+SI total and 1.53 [1.33-1.75] for SBRI total), higher social communication level of support (based on the DSM-5 criteria) (aOR [95% CI] 2.14 [1.10-4.16] for level 2 and 14.94 [5.77-38.64] for level 3), and minority race (aOR [95% CI] 2.82 [1.52-5.20] for Malay, 5.19 [2.36-11.44] for Indian, and 4.54 [1.91-10.79] for Others). CONCLUSION These findings could guide policymakers and practitioners worldwide to strategically allocate diagnostic, intervention and educational resources, maximising developmental outcomes for autistic children across diverse settings.
Humans ; Singapore/epidemiology* ; Male ; Female ; Retrospective Studies ; Child, Preschool ; Autistic Disorder/complications* ; Child ; Early Intervention, Educational ; Cognitive Dysfunction/diagnosis* ; Cognition