Autism Rating Research Articles

Tablet computer-based cognitive training for visuomotor integration in children with developmental delay: a pilot study

BackgroundImpaired visuomotor integration (VMI) is commonly observed in children with developmental delay (DD). This pilot study aimed to evaluate the effects of tablet computer-based cognitive training on the VMI in children with DD.MethodsThis study included children aged 4 to under 18 years diagnosed with DD. The children participated in a 12-week tablet computer-based visual-spatial and visuomotor training program. They were administered the Mind Rx Kids Program (Brain Academy, Seoul, South Korea). The participants underwent daily 30-min tablet computer-based training for 12 weeks. The primary visuomotor function was measured using the Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition (VMI-6). For secondary outcomes, measurements were taken before and after 12-week treatment using the Quality of Upper Extremity Skills Test (QUEST), Functional Independence Measure for Children (WeeFIM), Childhood Autism Rating Scale (CARS), Attention deficit hyperactivity disorder Rating Scale (ARS), and Child Smartphone Addiction Observer Scale. The Wilcoxon signed-rank test was used to compare the pre- and post-treatment outcomes.ResultsTen children with DD participated in this study. The results of the 12-week tablet computer-based cognitive training showed significant improvements in the raw score, standard score, percentile score, and equivalent age of the Beery VMI-6. Additionally, there were significant improvements in QUEST and WeeFIM scores. Although there were improvements in the CARS, ARS, and smartphone addiction observer scale, these were not statistically significant.ConclusionThis pilot study confirmed that applying tablet computer-based cognitive training to children with DD not only improves VMI, but also enhances fine motor skills and activities of daily living. Furthermore, the results of this study indicate that tablet computer-based cognitive training does not increase digital media addiction. Therefore, children with DD can engage in tablet computer-based cognitive training at home without concerns about digital media addiction.

Immune alterations in children with autism spectrum disorders

Autism spectrum disorders (ASD) are a heterogeneous group of mental and nervous system disorders. Patients with ASD are characterized by communication and cognitive impairments and obsessive behavior. The pathogenesis and etiology of ASD are still unclear. According to the literature, patients suffering from ASD have not only mental, but also somatic disorders, including changes in the immune system. The aim of this work was to study the concentration of cytokines in the blood plasma of children with ASD and the level of expression of proinflammatory genes in peripheral blood mononuclear cells. The clinical group included 71 children aged 4-12 years with a diagnosis of ASD (F84.02). Patients scored more than 36 on the Childhood Autism Rating Scale (CARS). The control sample included 27 apparently healthy children of the same age. The following methods were used in this study: isolation of mononuclear cells from heparinized peripheral blood, Ficoll-Verografin density gradient centrifugation, evaluation of cytokine blocks using commercially available enzyme immunoassay kits, isolation of random total RNA, reverse transcription using hexaprimers, and real-time polymerase chain reaction using intercalating dye SYBR Green. The concentration of proinflammatory cytokines IL-1β, IL-8, and IL-17A in the peripheral blood plasma of children with ASD was statistically significantly increased compared to the control sample. Moreover, the concentration of the anti-inflammatory cytokine IL-10 in patients with ASD was 3.6 times lower compared to the control sample (p 0.001). The level of expression of the NF-κB1, IL1β, IL8 and TNFα genes at the RNA level in peripheral blood mononuclear cells was increased by 2.8, 2.5, 4.8 and 4.2 times in patients with ASD compared to the control sample (all p 0.01). The results obtained indicate an increase in the concentration of proinflammatory cytokines (IL-1β, IL-8, IL-17A) in the blood plasma and a decrease in the concentration of anti-inflammatory cytokines (IL-10) in patients with ASD compared to the control sequence.

Expression of key molecules of the classical inflammation activation pathway in blood leukocytes of autistic children

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders, whose causes are currently not fully understood. Research suggests that inflammation and changes in immune functions may play an important role in the development of autism. Increased levels of proinflammatory cytokines in the brains of autistic children lead to negative regulation of synaptic plasticity, as well as impaired proliferation and differentiation of neurons through activation of the nuclear factor kappa B (NF-κB) signaling pathway. The purpose of the work is to analyze the levels of mRNA: TLR2, TLR4, MyD88, IκBα, NF-κB p50, NF-κB p65 in peripheral blood leukocytes of children in comparison with the severity of autism spectrum disorders. The study included 126 children aged from 3 to 13 years (the ratio of boys to girls was 4:1): 45 children with typical neurodevelopment, and 81 children with a clinically confirmed diagnosis of autism. According to the Childhood Autism Rating Scale, 51 children had mild to moderate ASD (CARS score: 29-36), and 30 children had severe autism (CARS score: 36-60). The expression of inflammatory signal transduction pathway molecules was determined in peripheral blood leukocytes using real-time polymerase chain reaction with SYBRGreen. To compare the samples, one-way ANOVA and Tukey’s test were used. It was found that in leukocytes of children with severe ASD, the expression of the adapter protein MyD88 and the p65 subunit of the nuclear transcription factor NF-κB was significantly reduced, and the expression of the NF-κB inhibitor, IκBα, was significantly increased, compared to the control group. In leukocytes of children with mild ASD, a decrease in NF-κB p65 expression was found at a trend level. When comparing groups of children with different severity of autism symptoms (mild/severe), no significant differences were found in the levels of mRNA of key signaling molecules of the classical inflammation activation pathway in blood leukocytes. Thus, in the blood leukocytes of children with severe ASD, suppression of the expression of key molecules of the classical inflammation activation pathway (NF-κB) is observed, which leads to a decrease in the expression of pro-inflammatory cytokines: IL-1β, IL-18 and IL-2, against the background of increased expression of key cytokine of Th1 cells – IFNγ.

Estimation of Plasma Concentration of L-Carnosine and its Correlation with Core Symptoms of Autism Spectrum Disorder Children: A Pilot Clinical Trial.

Literature indicates that L-carnosine may be deficient in autism spectrum disorder (ASD) children. The aim of the present study was to estimate the level of L-carnosine in plasma and correlate it with the Autism Treatment Evaluation Checklist (ATEC) and Childhood Autism Rating Scale 2nd Edition, Standard Version (CARS2-ST) scores. To measure L-carnosine level, a bio-analytical method was developed using reverse phase high- liquid chromatography and validated as per International Conference on Harmonization guidelines. Children were supplemented with L-carnosine (10-15 mg/kg) along with standard care therapies for 2 months. Before and after supplementation, scores on the ATEC, CARS2-ST, BEARS sleep screening tool, 6-item Gastrointestinal Severity Index, and Parental Stress Scale were evaluated, and L-carnosine was measured at the end of the trial. The calibration curve was linear in the range of 100-600 ng/mL (R2 = 0.998). The level of L-carnosine quantified was 33.7 ± 0.2 ng/mL. There was no significant difference found in any of the outcome measures (p > 0.05). Despite the fact that L-carnosine is detectable in the blood, it was found to be ineffective in the management of ASD in children. The study was registered in the Clinical Trial Registry-India, registration number: CTRI/2019/07/020102.

Characteristics of Individuals Losing Autism Diagnosis: A Comparative Study With Typically Developing and Autism Spectrum Disorder Individuals.

This study aims to reveal the characteristics of individuals who have lost an autism spectrum disorder (ASD) diagnosis and to evaluate their current psychiatric diagnoses. Additionally, the study aims to compare individuals who have lost ASD with typically developing (TD) individuals and those with ASD in terms of current psychopathology, functionality and sociodemographic and clinical variables. The study included a total of 85 participants aged between 5 and 18, comprising 30 individuals who no longer meet the criteria for ASD (loss of autism diagnosis or LAD), 32 individuals with ASD and 23 TD individuals. While the sociodemographic data form and Childhood Autism Rating Scale (CARS) were completed by the clinician, the Autism Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) were completed by the parents. It was found that the LAD group acquired speaking skills earlier, started special education sooner, received preschool education and physical exercise support for a longer duration and exhibited higher mental capacity and lower symptom severity compared to the ASD group. Moreover, 80% of the LAD group had at least one DSM-5 diagnosis. Scores on the ABC and SRS indicated a significant difference, with ASD > LAD > TD. Even if ASD regresses, individuals may still experience residual difficulties and remain at risk for other psychopathologies. Therefore, it is crucial to maintain monitoring and support processes.

Predicting language, cognition, and social skills in individuals with Autism spectrum disorder using the Arabic validation of Gilliam Autism Rating scale-Third Edition

The Gilliam Autism Rating Scale-Third Edition (GARS-3) has emerged as a pivotal instrument in the diagnostic assessment of Autism Spectrum Disorder (ASD), with its utility extending across linguistic and cultural boundaries. This study endeavors to adapt and validate the GARS-3 for the Arabic-speaking population, addressing the paucity of culturally congruent diagnostic tools in the Arab world. The primary objective is to validate the Arabic version of GARS-3 (A-GARS-3) to assess children with and without ASD, ensuring the scale’s reliability and validity within the target population. A methodical cross-sectional study design was employed, encompassing a sample of 178 participants from both educational and clinical settings in Saudi Arabia. The process involved direct translation, expert panel review, back-translation, and pilot testing to ensure semantic equivalence and cultural relevance. Data were collected using the A-GARS-3, and analyses included Exploratory and Confirmatory Factor Analysis (EFA and CFA), internal consistency reliability measures, and a One-Way Analysis of Variance (ANOVA) to establish concurrent validity. The A-GARS-3 demonstrated high internal consistency (Cronbach’s alpha = 0.971; McDonald’s omega = 0.972) and strong construct validity, with factor loadings and model fit indices substantiating the factor structure. Predictive validity was confirmed through significant correlations between the Autism Index and the subscales, particularly in the domains of social interaction and communication. The A-GARS-3 is a psychometrically sound instrument that offers reliable assessment for ASD within the Arab cultural context. The positive validation outcomes indicate that the scale is an effective, culturally adapted tool for the localized diagnosis of ASD. The validated scale has significant implications for enhancing ASD screening and diagnostic practices in Arabic-speaking regions, potentially improving early diagnosis and intervention strategies.

Creating a Short Form of the Gilliam Autism Rating Scale-3rd Edition (GARS-3) Parent Report

Creating a Short Form of the Gilliam Autism Rating Scale-3rd Edition (GARS-3) Parent Report

Unraveling the relative abundance of psychobiotic bacteria in children with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits. Accumulated evidence has shown a link between alterations in the composition of gut microbiota and both neurobehavioural and gastrointestinal symptoms in children with ASD which are related to the genera Lactobacillus and Bifidobacterium. These genera have been recently categorized as “psychobiotics”. Moreover, this study aimed to compare the relative abundance of psychobiotics (L. plantarum, L. reuteri, and B. longum) to the total gut microbiome in typically developing (TD) children and those with ASD in order to correlate the distribution of psychobiotic with the severity and sensory impairments in autism. The ASD children were assessed using the Childhood Autism Rating Scale (CARS), while sensory impairments were evaluated using the Short Sensory Profile (SSP). Furthermore, the gut microbiome was analyzed using the quantitative real-time PCR. The study revealed a statistically significant increase in the relative abundance of L. reuteri and L. plantarum in the TD group in comparison to ASD children. Regarding the SSP total score of ASD children, a statistically significant negative correlation was found between both Lactobacillus and L. plantarum with the under-responsive subscale. For the Autism Treatment Evaluation Checklist (ATEC) score, B. longum and Lactobacillus showed a significant positive correlation with Health/Physical/Behaviour.

Level of support/commitment and behavior during mealtime and dental care negatively impact the dental caries prevalence in autistic individuals: cross-sectional study.

To verify whether factors associated with Autism Spectrum Disorder (ASD) would have impact on the dental-caries prevalence. All ASD-individuals receiving care in a specialized center with minimum of 4y old were recruited. Demographic, socioeconomic and behavioral characteristics, level of support/commitment (Childhood Autism Rating Scale), mealtime behavior (Brief Autism Mealtime Behavior Inventory) and medication use were answered by ASD-individual's parents. Behavior during dental care was evaluated from Frankl scale. Dental-caries prevalence was the primary outcome. Three examiners calibrated/trained collected the data. Chi-square test was used to compare the variables impact on the dental-caries prevalence. 61 ASD-individuals were potentially eligible, and the all parents/guardians consent to participate. Dental-caries prevalence was 42.9%, which was statistically associated with lower toothbrushing frequency, higher level of support/commitment, and worse behavior at meals and during in dental care. Dental-caries prevalence was approximately higher twice in ASD-individuals: (i) uncooperative with dental care when compared those cooperative (62% versus 32%, respectively); (ii) with severe level of support when compared to those with mild/moderate level (58% versus 28%, respectively); and (iii) with worse mealtime behavior when compared to those with better behavior (59% versus 28%, respectively). A medium statistical correlation was observed between support level and mealtime behavior (rS=0.39). The BAMBI component statistically associated with dental-caries prevalence was the food refusal (capture problem when a child rejects a presented food, crying, spitting out food). higher required level of support, worse mealtime behavior and uncooperative profile in dental care negatively affect the dental-caries prevalence. our findings provide evidence of the need of specialized, preventive and individualized dental care among ASD-individuals.

Psychometric Properties of the Chinese Version of the Gilliam Autism Rating Scale-Third Edition (CV-GARS-3).

Gilliam Autism Rating Scale-Third Edition (GARS-3) serves as an effective screening tool for autism spectrum disorder (ASD) that is based on the latest and authoritative diagnostic criteria, however, there is a deficiency in adaptive research in China. We aimed to revise the Chinese version of GARS-3 (CV-GARS-3) and evaluate its psychometric characteristics, providing a theoretical basis for the improvement of ASD screening tools in China. This study developed CV-GARS-3 through translation and cultural adaptation of GARS-3. 362 ASD individuals, 126 typical development individuals, and 103 individuals with other disorders were recruited to analyze the psychometric characteristics of CV-GARS-3. The results showed that exploratory structural equation model demonstrated satisfactory goodness-of-fit. Within the non-verbal ASD samples, all items loaded on anticipated factors. Regarding verbal ASD samples, 3 items exhibited considerable cross-loadings and were categorized under unexpected factors. Meanwhile, acceptable criterion validity was reflected in the four subscales (r = 0.71) and the six subscales (r = 0.74). Satisfactory reliability was observed in the four subscales (Cronbach's α = 0.96, inter-rater consistency = 0.86, test-retest consistency = 0.87) and the six subscales (Cronbach's α = 0.94, inter-rater consistency = 0.81, test-retest consistency = 0.81). In addition, receiver operating characteristic analysis demonstrated that both the four subscales (sensitivity = 89%, specificity = 85%, accuracy = 88%) and the six subscales (sensitivity = 86%, specificity = 88%, accuracy = 86%) had outstanding screening effects. Therefore, the results suggested that the CV-GARS-3 is considered as a useful tool for the screening and auxiliary diagnosis of ASD. Notably, the expression of scale should be further improved to adapt the context of Chinese culture and achieve more precise diagnostic results.

Peripersonal Space Plasticity in Relation to Psychopathology and Anomalous Subjective Experiences in Individuals With Early-Onset and Adult-Onset Schizophrenia.

Individuals with schizophrenia present anomalies in the extension and plasticity of the peripersonal space (PPS), the section of space surrounding the body, shaped through motor experiences. A weak multisensory integration in PPS would contribute to an impairment of self-embodiment processing, a core feature of the disorder linked to specific subjective experiences. In this exploratory study, we aimed at: (1) testing an association between PPS features, psychopathology, and subjective experiences in schizophrenia; (2) describing the PPS profile in individuals with early-onset schizophrenia. Twenty-seven individuals with schizophrenia underwent a task measuring the PPS size and boundaries demarcation before and after a motor training with a tool. The Positive And Negative Syndrome Scale (PANSS), the Examination of Anomalous Self Experience scale (EASE) and the Autism Rating Scale (ARS) were used to assess psychopathology. Subsequently, participants were divided into two subgroups, early and adult-onset schizophrenia. The two groups were compared in regard to their PPS and psychopathological profiles. PPS patterns were associated with psychopathology, particularly positively with PANSS negative scale score, and negatively with subjective experiences of existential reorientation (EASE Domain 5 scores) and of social encounters (ARS scores). Only PPS parameters and ARS scores differentiated between early and adult-onset participants. Our results, although preliminary and exploratory, can suggest a link between PPS patterns, negative symptoms, and disturbances of the subjective experience, particularly in the intersubjective domain, in schizophrenia. Moreover, they seem to suggest that specific PPS profiles and schizophrenic autism traits could be markers of early-onset schizophrenia.

Effectiveness of the Good Behavior Game in Addressing the Maladaptive Behavior of Young Students

This action research project sought to review the relevant literature and determine what interventions an educational institution would find suitable to reshape a student's maladaptive behavior into behavior that is not detrimental to the classroom environment. Over the course of a year-long observation period, four students served as a target and control group for determining the effectiveness of The Good Behavior Game (GBG), a game in which students work as a group to complete a goal, scoring points for uncooperative behavior. The GBG was found beneficial for decreasing maladaptive behavior in preschool students, yet was determined ineffective at addressing maladaptive behavior in students who have a "Very Likely" Autism Spectrum Disorder (ASD) probability and are identified as requiring substantial support according to the Gilliam Autism Rating Scale, GARS-3.

Genetic Variations and Serum Levels of Leptin and Ghrelin in Autism Spectrum Disorder.

This study aims to examine leptin and ghrelin gene polymorphisms and serum levels in children with autism spectrum disorder (ASD). The study comprised a case group of 40 children aged 2-7 diagnosed with ASD and a control group of 40 healthy children. The severity of ASD symptoms was assessed using the Childhood Autism Rating Scale and the Autism Behavior Checklist. Leptin and ghrelin gene variants were genotyped using polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) methods. Serum ghrelin and leptin levels were measured using enzyme-linked immunosorbent assay kits. In this study, gene polymorphisms and allele frequencies were examined, and no significant difference was found (P > .05 for all). Our findings indicated no significant difference in leptin serum levels between the groups (P = .584). However, ghrelin serum levels were significantly lower in the ASD group (P = .027). Receiver operating curve analysis to determine the cutoff value of serum ghrelin level as a diagnostic indicator for ASD resulted in a cutoff value of 885.7 pg/mL with 42.50% sensitivity and 85% specificity (P = .021). No significant relationship was found between leptin and ghrelin serum levels and the severity of ASD (P > .05 for all). Our study is the first to evaluate leptin and ghrelin gene polymorphisms in ASD. Our findings indicate no association between leptin and ghrelin gene polymorphisms and ASD. However, our study suggests that ghrelin serum levels may potentially contribute to the etiology of ASD. More research is needed to understand the role of leptin and ghrelin in ASD.

Implicit learning in children and adolescents with and without autism spectrum disorders: Exploring the effects of individual differences.

Implicit learning plays an important role in the acquisition of various skills that are often deficient in individuals with autism spectrum disorder (ASD). The present study examines the implicit learning ability of children and adolescents with ASD, by comparing it to that of a typical group of peers, using the Artificial Grammar Learning (AGL) task. In addition, this study investigates whether the above ability is associated with individual characteristics, namely intelligence quotient (IQ), ASD symptoms severity, and individual perception style (global/holistic or local/focused). The sample consisted of 20 individuals with mild to relatively severe ASD symptoms and 20 age- and gender-matched typically developing (TD) individuals. The unconscious (implicit) nature of learning was assessed via a subjective measure, the "no-loss gambling" method, which allows an unbiased evaluation of the confidence accompanying each judgement. The results provided evidence of implicit learning, which was preserved in the ASD group, although reduced relative to the typical group. Multiple linear regressions with interaction terms between group and participants' scores on the Wechsler Abbreviated Scale of Intelligence (WASI), the Childhood Autism Rating Scale (CARS), and performance on a Navon-type task examined whether the possible relationships between each of the above scores and AGL and implicit learning differ in the two groups. Implicit learning was not significantly associated with IQ, ASD symptoms severity, or individual perception style (except for perception style in terms of reaction times [RTs] for the TD group). These results confirm and extend earlier findings supporting the resilience of implicit learning to individual differences.

Prompt Response, Cues-Pause-Point Therapies and Gender on Management of Echolalia among Children with Autism Spectrum Disorder

The repetitive and delayed nature of echolalia can hinder the development of adaptive behaviors and impact the ability to establish rapport with others. This study investigated the effects of prompt response and cues-pause-point therapies on the management of echolalia among children with autism spectrum disorder. A pre-test, post-test, and control group of a 3x2 factorial matrix of quasi-experimental research design was used to assess the effect of the therapies on children with autism spectrum disorder in Ibadan, Nigeria. 90children with autism spectrum disorder were purposively selected using Diagnostic Statistical Manual- V (DSM-V) for ASD (0.70), Gilliam Autism Rating Scale/Third Edition (GARS-3) (in terms of sensitivity= 0.97, ROU/AUC= 0.93). In contrast, the Autism Treatment Evaluation Checklist (ATEC) (0.90) was used for the pretest and posttest to ascertain the presence of echolalia. Participants were assigned to one of three groups: prompt response, cues-pause-point therapies, or control (N = 90, male = 44, female = 46, age range = 3 –5 years old). Twenty-four prompt response and cues-pause-point therapy were held for each experimental group. The findings showed that the main effect of treatment (prompt response and cues-pause-point therapies) (F (2; 72) = 45.519, p<.05, ƞ2 = .558) on the management of echolalia among children with autism was significant, premised on this, the null hypothesis was rejected. The post hoc estimated marginal mean indicates that prompt response treatment was higher than cues-pause-point therapy; however, this difference was statistically significant. The study findings indicated that the impact of gender on managing echolalia in individuals with ASD was not statistically significant. Based on the findings, it is recommended that speech therapists, caregivers, and parents of children with autism spectrum disorder should seek alternative therapy that will take into cognizance other underlying factors associated with the presence of echolalia.

Decreased levels of L‐selectin and platelet‐endothelial cell adhesion molecule‐1 in children with autism spectrum disorder

AbstractObjectiveThis study aimed to ascertain the serum levels of selectins (E, L, P) and platelet‐endothelial adhesion molecule‐1 (PECAM‐1) in preschool children with autism spectrum disorder (ASD) and to establish a comparison with the levels observed in healthy controls.MethodsThe study included 34 children aged 2–7 years diagnosed with ASD (ASD group) and 34 randomly selected healthy children matched for age and sex to the ASD group. The children were free of any genetic or physical disease, clinically active infection, or medication use. The sociodemographic data form was completed by all parents. The Childhood Autism Rating Scale (CARS) and the Autism Behavior Checklist (ABC) were administered to the patient group, and the Aberrant Behavior Checklist (AbBC) was completed by the families of all children. Serum selectin (E, L, P) and PECAM‐1 levels were measured using enzyme‐linked immunosorbent assay (ELISA) kits.ResultsThe results showed that the levels of both L‐selectin (p = 0.007) and PECAM‐1 (p = 0.019) were significantly lower in the ASD group than in the control group. No significant difference was observed between the groups concerning E‐selectin and P‐selectin levels (p > 0.05). It was observed that P‐selectin variables were statistically significant in predicting the presence of ASD (p = 0.019). A remarkable inverse correlation was found between the AbBC irritability subscale score and L‐selectin (r = −0.296, p = 0.014) and PECAM‐1 (r = −0.276, p = 0. 023); the AbBC Lethargy‐Social Withdrawal subscale score and E‐Selectin (r = −0.239, p = 0.049), L‐Selectin (r = −0.297, p = 0.014) and PECAM‐1 (r = −0.264, p = 0.029); L‐Selectin levels and the AbBC stereotypic behavior subscale (r = −0.248, p = 0.042). No statistically significant relationship was observed between selectins (E, L, P) and PECAM‐1 levels and CARS scale, ABC subscale or total scores and age variables (p > 0.05).ConclusionsThese study results suggest that L‐selectin, P‐selectin and PECAM‐1 may play a role in the pathophysiology of ASD.

Transmethylation and Oxidative Biomarkers in Children with Autism Spectrum Disorder: A Cross Sectional Study.

We aimed to investigate the potential role of biomarkers of transmethylation, oxidative stress, and mitochondrial dysfunction in children with Autism Spectrum Disorder (ASD) by comparing them with that of typically developing children (TDC) controls. We also tried to correlate them with severity of autism, sensory issues, behavioural comorbidities and developmental quotients 119 with ASD and 52 age and sex matched typically developing children (TDC) controls were enrolled excluding those with chronic-illness or on any antioxidant therapy/multivitamins/anti-epileptic drugs. Median levels of biomarkers- serum homocysteine, cysteine, methionine, urine uric acid-to-creatinine ratio, arterial lactate, serum vitamin E, vitamin B12, folate, Nε-carboxymethyllysine, Nω- carboxymethylarginine (CMA), dityrosine and MTHFR C677T polymorphism were calculated. Children with ASD were further characterised using Childhood Autism Rating Scale-2, Childhood behavioural checklist, child sensory profile 2 caregiver questionnaire, Developmental Profile 3 for any correlation with the various biomarker levels. The median level of serum homocysteine in ASD group was 9 μmol/L(Range, 7- 16μmol/L), which was significantly higher than controls 7 μmol/L(Range, 4- 11μmol/L)(p=0.01). The prevalence of hyper-homocystinemia(>15μmol/L) was 13.4% in ASD as compared to 3.8% in controls with a significant difference(p=0.04). Dityrosine level was higher among ASD children when compared to TDC (9.8 vs 2.2 counts per second(cps), p<0.001). No significant correlation was found between prevalence of hyperhomocysteinemia and severity of autism/DQ/behavioural issues. No significant difference was found between the median levels of other biomarkers. Results support possible role of transmethylation defects and oxidative stress in ASD pathogenesis. Further studies are warranted for a better understanding of ASD pathogenesis.

Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial.

The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD. We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16. Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms. BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.

Effect of Infra Low Frequency (ILF) neurofeedback training on EEG in children with autism spectrum disorders.

To investigate whether Infra-low frequency Neurofeedback (ILF-NFB) training can improve brain electrical activity in children with autism spectrum disorders ASD. This single arm pre and post intervention study was carried out at IBMS (Institute of Basic Medical Sciences), Khyber Medical University, Peshawar and Shaheed Zulfiqar Ali Bhutto Medical University (SZABMU), Islamabad from January 2021 to December 2022. A purposive sampling technique was used. Thirty-five ASD children (male=24; female=11; 7-17 years) were provided with 30 sessions of infra low frequency (ILF) neurofeedback training for 15-20 minutes, during 10 weeks. Childhood Autism Rating Scale (CARS) scoring was done and electroencephalogram (EEG) activity was compared before and after ILF-NF training sessions. Around 62.9% participants had mild-moderate autism and 37.1% had severe autism. Wilcoxon Signed rank test revealed a significant decline in delta (Pre-test=47.31±19.22, Post-test=22.07±6.83; p=<0.001), theta (Pre-test=24.75±16.62, Post-test=12.37±3.59; p=<0.001) and alpha (Pre-test=12.01±9.81, Post-test=4.03±1.61; p=< 0.001) waves. Mann Whitney U test exhibited no significant gender differences in EEG pattern before and after neurofeedback except in theta waves (p=0.03) before the intervention. Decline in delta, theta, beta and alpha waves propose that ILF-NF training can be effective in improving the EEG activity. ILF-NFB can be perceived as a valuable non-invasive, non-pharmacological intervention for improving EEG pattern via reintegration of brain activity resulting in increased the attention and focus, enhanced mental stability and cognitive engagement.

Toward an endophenotype for ADHD: Exploring the duration mismatch negativity in drug-free children with ADHD

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent disorders in children that is considered to affect early stages of information processes. Inefficient processing of temporal information, which is a vital auditory processing skill suggests itself as a potential candidate for investigating ADHD deficits. The Research Domain Criteria (RDoC), a neuroscience-based research framework, has been introduced to study mental illness without relying on pre-established diagnostic categories. In this regard, Mismatch Negativity (MMN) has been considered an ideal electrophysiological marker for investigating ADHD deficits. This study investigates alterations in the amplitude and latency of the MMN component in response to changes in the duration and Inter-Stimulus Interval (ISI) of basic sound stimuli within an oddball task. The MMN paradigm was employed to examine duration deviations in ADHD (n = 25, 84% male, mean age: 7.3 years, SD = 2.01) compared to Control group of typically developing (TD) children (n = 25, 72% male, mean age: 7.2 years, SD = 1.92). Participants with ADHD were introduced from an accredited psychiatrist. TD children were recruited from social media and online forms. Both groups were matched in terms of gender, age and IQ. The psychological tests conducted in this study included Conners’ Parent Rating Scale (CPRS), Gilliam Autism Rating Scale|Third Edition (Gars3), Sensory profile questionnaire and Edinburgh Handedness inventory. Our findings revealed reduced MMN amplitudes in response to two blocks of duration and ISI-based deviations in ADHD children. To elaborate in greater detail, at Fz, in Duration and ISI block, respectively, the ADHD group showed an amplitude of −1.2097 ± 0.2938 and −0.8553 ± 0.4423, while the normal group showed an amplitude of −1.8325 ± 0.3689 and −2.0855 ± 0.3802. Additionally, at Cz, the ADHD group exhibited a shorter amplitude (-1.2515 ± 0.3261 and −0.9367 ± 0.3432) compared to the normal group (−2.1319 ± 0.4445 and −2.7561 ± 0.4883), in the duration and ISI blocks, respectively. Furthermore, children with ADHD display longer MMN latencies in both experimental blocks, suggesting atypical responses. To provide more detail, at Fz, the ADHD group displayed MMN latencies of 239.68 ± 5.059 and 226.88 ± 4.885 in the Duration and ISI blocks, respectively, whereas the normal group showed MMN latencies of 228.56 ± 6.584 and 213.56 ± 4.153. Similarly, at Cz, the ADHD group exhibited longer MMN latencies (234.40 ± 5.741 and 231.44 ± 5.464) compared to the normal group (227.52 ± 6.710 and 218.00 ± 5.261) in the Duration and ISI blocks, respectively. Our findings were interpreted in the context of the internal clock model, which involves the pace of an internal pacemaker regulated by dopamine (DA) levels. The convergence of MMN and auditory timing abnormalities within the RDoC framework suggests their potential as endophenotypes for ADHD, highlighting the significance of sensory processing in understanding the disorder.