PURPOSE:Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by persistent deficits in social communication and the presence of restrictive, repetitive patterns of behaviour. Although its exact aetiology remains multifaceted and partially understood, recent clinical interest has shifted towards neurobiological substrates, specifically neuroaxonal and astroglial integrity. This study aims to compare serum levels of Neurofilament Light Chain (NfL), Glial Fibrillary Acidic Protein (GFAP), Tau and S100B between children with ASD and healthy controls, while investigating the influence of these biochemical variables on autism severity and behavioural manifestations. METHODS:The study cohort consisted of 44 children (aged 24-72 months) diagnosed with ASD according to DSM-5-TR criteria and 40 age-matched healthy controls. Clinical assessments were conducted using the Childhood Autism Rating Scale (CARS), the Aberrant Behaviour Checklist (ABC) and the Autism Behaviour Checklist. Serum concentrations of the targeted biomarkers were measured using the ELISA method from venous blood samples. RESULTS:Serum NfL, Tau, GFAP and S100B concentrations did not differ significantly between children with ASD and healthy controls. Exploratory analyses suggested possible associations between selected biomarkers and clinical characteristics; however, these associations did not remain statistically significant after age adjustment and correction for multiple comparisons. Further studies using larger cohorts and ultrasensitive analytical platforms are needed to validate these preliminary findings. CONCLUSION:These findings indicate that serum NfL, Tau, GFAP and S100B did not differentiate children with ASD from healthy controls. Exploratory biomarker-clinical associations did not remain statistically significant after age adjustment and correction for multiple comparisons. Larger longitudinal studies using ultrasensitive analytical platforms are warranted.
Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by inattention, hyperactivity and impulsive behaviour, which impair patient functioning. There is a growing trend among parents to use complementary and alternative medicines alongside conventional treatments to manage their children's ADHD symptoms. The aim of this review is to elucidate the therapeutic methods of Traditional Chinese Medicine (TCM) by discussing their scientifically established mechanisms of action, effectiveness and side effects, thereby creating a comparative understanding relative to current pharmaceutical treatments for ADHD. Psychostimulants are the first-choice pharmacological treatment; they are effective in alleviating symptoms but are often associated with side effects. These issues have prompted interest in complementary and alternative medicine (CAM) approaches. TCM offers various methods for managing ADHD. This review synthesizes current evidence on the TCM perspective regarding ADHD aetiology and its main therapeutic options, including herbal treatments, acupuncture, Tai Chi and paediatric tuina, along with their proposed neurobiological mechanisms. The clinical safety and efficacy of these treatments were evaluated based on randomized controlled trials (RCTs) and meta-analyses. These findings demonstrate that TCM interventions significantly reduce core ADHD symptoms, often with acceptable safety profiles. This review concludes that TCM represents a valuable complementary approach; however, more high-quality research is needed to standardize treatments and facilitate their evidence-based integration into conventional psychiatric management and therapy.
Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with a broad spectrum of symptoms, which makes timely and accurate diagnosis challenging. The development of machine learning (ML) and deep learning (DL) has created opportunities for automated ASD screening and detection. This systematic review focuses on the analyses of 59 peer-reviewed studies on unimodal and multimodal approaches to ASD detection that were published between 2019 and 2025. The results demonstrated that classical ML algorithms (such as logistic regression [LR], support vector machines [SVM] and random forests [RF]) and DL models (convolutional neural networks [CNN], recurrent neural networks (RNN) and transformers) were used to assess the accuracy of the diagnosis for a variety of data modalities ranging from behavioural measures to neuroimaging, electroencephalography (EEG), eye tracking and speech, with accuracy from 68% to 99%. A careful examination of these studies, however, shows that they share certain common flaws, including small sample size, demographic bias, overfitting and absence of external validation. Hybrid multimodal frameworks have been shown to yield consistent performance improvements over unimodal frameworks, with accuracies of 95%-99% achieved through attention, graph-based learning and hybrid fusion approaches. This review highlights four major points: (1) a critical review of dataset ethics and validity, even for non-clinical facial image datasets; (2) an architectural comparison of multimodal fusion strategies (early fusion, late fusion and hybrid fusion) focusing on computational complexity and clinical applicability; (3) a quantitative summarization of the performance trends by modalities and sample size; and (4) a structured review of indicators of reproducibility and regulatory hurdles for clinical translation. This review suggests the need to develop large, well-balanced datasets, the application of explainable AI (XAI) techniques, standardization (e.g., brain imaging data structure [BIDS]) and regulatory guidelines for facilitating the clinical translation of ASD detection systems.
SLC13A3 pathogenic variants are associated with acute reversible leukoencephalopathy and α-ketoglutarate accumulation (ARLIAK), a rare neurological disorder characterized by recurrent episodes of encephalopathy and transient white matter abnormalities. Pathogenic variants reported so far include missense, nonsense and small deletion variants, highlighting substantial allelic heterogeneity. We describe a patient presenting with multiple episodes of acute encephalopathy, elevated urinary α-ketoglutarate and reversible white matter lesions on MRI, consistent with SLC13A3-related ARLIAK. Genetic analysis identified novel compound heterozygous variants: a missense variant (p.Leu46Pro) in a highly conserved region and a larger deletion encompassing exons 2-3. Our findings indicate that conventional sequencing alone may miss larger deletions, suggesting the need for copy number analysis as part of the diagnostic protocol for suspected ARLIAK cases. The elevated urinary α-ketoglutarate in our patient supports its potential as a noninvasive biomarker. MRI findings demonstrated typical transient and reversible white matter abnormalities, aligning with previously reported cases. This study expands the molecular and phenotypic spectrum of SLC13A3-related ARLIAK and underscores the importance of combining sequencing with copy number analysis for accurate diagnosis. The identification of novel variants contributes to a better understanding of the disease mechanism and suggests a broader allelic heterogeneity than previously recognized.
BACKGROUND:This study compared peripheral haematological inflammation indices obtained from complete blood count (CBC) parameters between preschoolers with developmental language disorder (DLD) and typically developing peers (TD) and examined the role of peripheral inflammatory processes in preschoolers with DLD. METHODS:One hundred twenty-seven children (61 with DLD and 66 TD) aged 36-60 months were included in this hospital-based, retrospective, case-controlled study. Complete blood count parameters and the resulting indices were compared: Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). Statistical analyses included group comparisons, multivariable logistic regression, and Receiver Operating Characteristic (ROC) analysis. RESULTS:The DLD registered significantly lower lymphocyte, higher monocyte, and NLR, SII and SIRI values compared to the TD (p = 0.015, p < 0.001, p < 0.001, p = 0.007, p < 0.001, respectively). Analysis of covariance revealed that the groups had a significant main effect on monocytes, NLR, SII and SIRI levels and that this effect was independent of age and gender. At multivariable logistic regression, SIRI emerged as a significant independent predictor of DLD, alongside male gender and a lower paternal education level ((p = 0.002, p = 0.007, p = 0.009, respectively). ROC analysis showed that SIRI had discriminative ability for DLD (AUC = 0.765, p < 0.001). CONCLUSION:The findings suggest that peripheral inflammatory processes, reflected by NLR, SII and particularly SIRI, may be associated with DLD in preschoolers. Although SIRI showed high specificity but low sensitivity, the present results provide preliminary evidence that it may represent a potential peripheral inflammation index associated with DLD.
The current comprehensive literature review delves into the executive functioning and the significant social and emotional challenges of a specific group: children diagnosed with 22q11.2 Deletion Syndrome (22q11DS). In 22q11DS, deficits in executive functions are, at least in part, a result of the deletion on chromosome 22. Nonetheless, the manifestation of the EF phenotype in 22q11DS is diverse and may be affected by specific risk factors that are more prevalent in this group. Consequently, 22q11DS provides an opportunity to examine how these factors influence executive function within the framework of a singular genetic basis. This review also indicates that children with 22q11DS exhibit impairments in inhibition and shifting, whereas updating may remain intact during childhood. It is also important to highlight that deficits in executive functions are observed in this group even when accounting for cognitive abilities, reinforcing the idea that executive function and intelligence are distinct constructs. Recent findings indicate that risk factors commonly recognized in the general population, like congenital heart defects or low socioeconomic status, might not influence executive functioning in the same manner in 22q11DS. While illustrating how research on the 22q11DS population can enhance our comprehension of executive function development, we underscore the relevant practical implications, pinpoint the existing gaps in the literature and emphasize the potential avenues for future inquiry.
PURPOSE:To examine whether obsessive-compulsive disorder (OCD) diagnosis was associated with greater infection-preventive behaviour and altered inhibitory-control performance in adolescents during the early COVID-19 lockdown in Türkiye while considering the roles of age and anxiety. METHODS:Seventy-two adolescents aged 12-18 years, including 22 with OCD and 50 without OCD, completed a COVID-19 preventive behaviour questionnaire and the child and parent versions of the Revised Child Anxiety and Depression Scale. Participants also completed an online go/no-go task. Ordinary least squares models were used to test whether age, anxiety, OCD diagnosis and their interactions were associated with behavioural change and mean Go-trial reaction time. RESULTS:The model predicting infection-preventive behavioural change was significant, F(7,64) = 2.54, p = 0.023, R2 = 0.218. OCD diagnosis did not predict behavioural change. In contrast, younger age and higher anxiety were associated with greater increases in infection-preventive behaviour, and the age-by-anxiety interaction indicated that anxiety-related increases were more pronounced among younger adolescents. The model predicting mean Go-trial reaction time was also significant, F(7,58) = 3.07, p = 0.008, R2 = 0.27. Adolescents with OCD showed slower Go-trial reaction times than comparison participants, and the diagnosis-by-age interaction suggested weaker age-related differences in response speed in the clinical group. CONCLUSIONS:During the early lockdown phase of COVID-19, developmental and affective factors were more closely associated with adolescents' infection-preventive behaviour than OCD diagnosis. In contrast, OCD diagnosis was more strongly associated with reduced response efficiency on the inhibitory-control task. These findings support the importance of considering developmental stage and anxiety, alongside diagnosis, in understanding adolescents' behavioural adaptation during public-health crises.
Alzheimer's disease (AD) represents the most prevalent neurodegenerative disorder worldwide, affecting millions of individuals and imposing substantial socioeconomic burdens. While traditional research has focused on amyloid-β (Aβ) plaques and neurofibrillary tangles as primary pathological hallmarks, mounting evidence implicates neuroinflammation as a critical third pillar in AD pathogenesis. This review critically evaluates current understanding of neuroinflammatory mechanisms in AD, examining the complex interplay between cellular mediators, molecular pathways and environmental triggers across a temporal disease-stage framework. We explore the dual and stage-dependent roles of microglia and astrocytes, expand discussion of blood-brain barrier (BBB) dysfunction and peripheral immune infiltration as underappreciated pathogenic contributors, and integrate emerging evidence linking neuroinflammation specifically to tau pathology and its stereotyped propagation through the brain. Diagnostic biomarkers, including translocator protein-positron emission tomography (TSPO-PET) and plasma glial fibrillary acidic protein (GFAP), are evaluated with explicit attention to clinical utility, technical limitations, and their relationship to established AD biomarkers. Therapeutic strategies are critically assessed with careful distinction between preclinical proof-of-concept data and available clinical evidence, and key translational challenges are highlighted throughout. The review emphasizes the need for stage-appropriate intervention windows, patient stratification by neuroinflammatory endotype, and biologically rational combination strategies. Understanding neuroinflammation's temporal and spatial dynamics offers promising but as yet insufficiently realized avenues for early intervention and disease modification in AD.
Neurodevelopmental disorder with spasticity, epilepsy and brain atrophy (NEDESBA) is a rare autosomal recessive condition, first described in 2020. It has been associated with biallelic pathogenic variants in the Trafficking Protein Particle Complex Subunit 4 (TRAPPC4) gene. This disorder belongs to the expanding group of TRAPPopathies, caused by mutations in genes encoding components of the transport protein particle (TRAPP) complex, which are essential for intracellular trafficking, autophagy and dendritic spine morphogenesis. Variants in these genes typically result in overlapping clinical features, including microcephaly, early-onset epilepsy, intellectual disability, neurodevelopmental regression, spasticity and abnormal brain MRI findings. Here, we report a 13-month-old affected male born to consanguineous parents, presenting with epileptic spasms and progressive neurodevelopmental delay. Importantly, proband also exhibits hair loss and skin rashes in early infancy. Initial metabolic screening suggested biotinidase deficiency, based on low biotin levels (0.6 nmol/min/mL; normal > 5) and overlapping clinical symptoms. However, confirmatory biochemical and enzymatic studies ruled out classic biotinidase deficiency. Whole exome sequencing revealed a homozygous splice-site variant (c.454+3A>G) in the TRAPPC4 gene, confirming the diagnosis of NEDESBA. This variant has been reported in multiple previous reports, mainly born out of consanguineous marriages. The phenotypic overlap between metabolic and genetic neurodevelopmental disorders in these cases emphasizes the critical role of early molecular testing in achieving a precise diagnosis.
Autism spectrum disorder (ASD) consists of a spectrum of neurodevelopmental conditions characterized by complex behavioural traits and subtle, atypical facial morphologies. Analysing these facial biomarkers provides a promising, non-invasive avenue for objective clinical screening, addressing the subjectivity of traditional diagnostic processes. Therefore, the present study aims to introduce DHCA-Net, a deep learning framework designed for automated ASD detection through the analysis of facial images. The proposed architecture uses different levels of attention and different adaptive tuning to advance discriminative learning. Specifically, DHCA-Net introduces three novel attention mechanisms to advance discriminative learning: a hierarchical channel module for spatial-semantic processing, a temporal-depth convolutional module for local contextual control and an inverted residual multi-core module for dynamic feature learning. An adaptive refinement step is also introduced to denoise clinical features. To bolster and diversify the classifier, the model exploits deep spatial and contextual resources via a multi-head feature fusion (MHFF) mechanism. We conducted extensive testing on a benchmark dataset comprising 2936 diverse, preprocessed facial images (86.4% train, 10.2% test, 3.4% validation splits). A comparative analysis evaluated DHCA-Net against architectures such as DenseNet, Xception, EfficientNet and Swin-Transformer. The proposed model achieved 93.7% classification accuracy, a 0.9365 F1 score and a 0.9887 AUC, demonstrating superior performance. Furthermore, the model maintains an efficient average inference latency of 70.14 ms despite its mid-to-high computational complexity. This explainable framework offers significant clinical applicability for scalable screening, though future work must address generalization across broader demographic populations.
WDR83OS-related neurodevelopmental disorder is a rare autosomal recessive condition characterized by developmental delay, dysmorphic features and variable hepatic involvement, particularly hypercholanaemia. Here, we report a female patient presenting with global developmental delay, syndromic facial features and scaphocephaly due to sagittal craniosynostosis, representing a previously unreported phenotypic feature. The patient was born to consanguineous parents and exhibited delayed motor and language milestones. Physical examination revealed characteristic dysmorphic features, whereas routine laboratory findings, including liver function tests, were within normal limits. Serum bile acid levels were not assessed. Cranial imaging confirmed sagittal craniosynostosis. Whole exome sequencing identified a novel homozygous nonsense variant in WDR83OS, classified as likely pathogenic according to ACMG criteria. No additional candidate variants, including those associated with craniosynostosis, were detected. This case possibly expands the phenotypic spectrum of WDR83OS-related disorder by identifying scaphocephaly as a novel feature. Our findings highlight the importance of comprehensive genomic evaluation in syndromic neurodevelopmental disorders and suggest that WDR83OS should be considered in the differential diagnosis of patients with craniosynostosis and developmental delay, even in the absence of overt hepatic involvement.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and repetitive behaviours. Diagnosing ASD early is difficult for healthcare professionals due to its diverse and intricate presentation. However, early detection is vital for enhancing outcomes and enabling the children to access targeted therapies that support the development of social and communication skills. Moreover, Classical models were time-consuming and resource-intensive, and they required lengthy assessments and specialized training. To bridge these complications, this research proposes a Sales Training-Based Optimization enabled Deep High-Order Principal Component Network (STBO_DHPCNet) for ASD classification using resting-state fMRI (rs-fMRI) brain images from 1114 subjects in the ABIDE dataset. First, gamma correction is applied to enhance the quality of the autism brain image. Next, the Region of Interest (ROI) extraction is performed. Afterwards, the nub region extraction is performed based on Sales Training Based Optimization (STBO). On the other hand, feature extraction is done based on an enhanced brain image. Finally, the classification of ASD is done by using DHPCNet, and it is trained using STBO. Here, DHPCNet is developed by incorporating the Deep High-Order Attention Neural Network (DHA-Net) and Principal Component Analysis Network (PCA-Net). Moreover, the evaluation results show that the DHPCNet gained an increased range of accuracy, sensitivity and specificity as 95.62%, 94.79%, and 95.86%.
OBJECTIVE:This study examined the psychometric properties of the Turkish versions of the Executive Functioning Scale (EFS) and the Daily Living Skills Scale (DLSS) in children and adolescents. METHODS:The sample included 197 participants (11-18 years), comprising 107 with neurodevelopmental disorders and 90 healthy controls. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was evaluated over 2 weeks in a subsample of 37 parents. Construct validity was examined with confirmatory factor analysis. Convergent validity of the EFS was assessed using correlations with the Teenage Executive Functioning Inventory (TEXI) and Trail Making Test (TMT); DLSS convergent validity was examined via correlations with the TEXI and EFS. Discriminant validity was determined by comparing clinical and control groups. RESULTS:The EFS showed high internal consistency (α = 0.969; subscales: 0.704-0.922) and strong test-retest reliability (r = 0.869). EFS total scores correlated strongly and negatively with TEXI (r = -0.78, p < 0.001), and TMT-B scores were significantly related to several EFS subscales. The DLSS had high internal consistency (α = 0.959) and good test-retest reliability (r = 0.823). DLSS total scores correlated negatively with TEXI (r = -0.495) and positively with EFS (r = 0.572). Both scales distinguished between clinical and control groups (p < 0.001). However, CFA findings indicated inadequate model fit for both scales (EFS: CFI = 0.636, RMSEA = 0.117; DLSS: CFI = 0.411, RMSEA = 0.191), suggesting that the original factor structures were not adequately replicated in the current sample. CONCLUSION:The Turkish versions of the EFS and DLSS demonstrated strong internal consistency, acceptable test-retest reliability and supportive evidence of convergent and known-groups validity. However, confirmatory factor analyses did not adequately support the original factor structures of either scale. Therefore, further studies are needed to clarify the structural validity and latent dimensional structure of these instruments in Turkish populations.
Sodium channelopathies represent a leading monogenic cause of epilepsy, epileptic encephalopathy and autism spectrum disorder. Pathogenic variants in voltage-gated sodium channels can lead to either gain-of-function or loss-of-function, resulting in highly diverse clinical phenotypes associated with the same gene. In this case report, we aimed to discuss a patient who presented with afebrile seizures at 6 months of age and was diagnosed with 'self-limited infantile epilepsy (SeLIE)' following the identification of a gain-of-function pathogenic variant in the SCN8A gene, in light of current guidelines and consensus recommendations. Furthermore, considering recent advancements, we aimed to emphasize that bioinformatic software tools for assessing the functional impact of pathogenic variants in ion channels can serve as a crucial guide for clinicians in treatment selection.
BACKGROUND:Celiac disease is an important gastrointestinal disorder affecting many children and adolescents worldwide. Although psychiatric conditions associated with celiac disease have been previously investigated, studies examining its relationship with newly identified psychiatric diagnoses are limited. The aim of this study was to examine the relationship between attention-deficit/hyperactivity disorder (ADHD) and a newer diagnostic construct, cognitive disengagement syndrome (CDS). METHOD:The study included children and adolescents aged 7-18 years with a confirmed diagnosis of celiac disease who were followed at a university hospital, as well as a control group of nonceliac patients attending the same hospital. The two groups were compared in terms of CDS scores, ADHD scores as well as depression and anxiety levels. RESULTS:A total of 128 participants were included, comprising 64 children with celiac disease and 64 controls. Statistically significant differences were observed between the groups in total ADHD and total CDS scores (p < 0.05). In addition, depression and anxiety scores differed significantly between the groups (p < 0.01). Specific CDS items, such as SCT-1 and SCT-10, also showed significant differences (total Hedge's g = 0.799, p < 0.05). CONCLUSION:These findings suggest that celiac disease is associated with both ADHD and CDS. Therefore, in the clinical management of children with celiac disease, it is important to consider not only gastrointestinal symptoms but also potential neuropsychiatric manifestations, including attention and cognitive disengagement difficulties, in order to provide comprehensive care.
AIM:Attention-deficit/hyperactivity disorder (ADHD) is associated with heterogeneous cognitive profiles, yet the extent to which comorbid Specific Learning Disorder (SLD) contributes to domain-specific cognitive variability remains unclear. This study aimed to examine Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) index-level cognitive profiles in children with ADHD and to evaluate the independent impact of comorbid SLD using regression-based and discriminative analyses. MATERIALS AND METHODS:This retrospective study included 105 children aged 6-16 years diagnosed with ADHD in a clinical setting. Cognitive functioning was assessed using WISC-IV index scores (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed). Group comparisons were conducted based on the presence of comorbid SLD. Pearson correlation and multiple linear regression analyses were performed to identify independent predictors of cognitive performance. In addition, receiver operating characteristic (ROC) analysis was used to assess the discriminative utility of cognitive indices. RESULTS:Working Memory Index (WMI) scores were the lowest among all WISC-IV domains. Children with ADHD and comorbid SLD demonstrated significantly lower scores in Verbal Comprehension, Perceptual Reasoning, and Working Memory compared with those with ADHD alone (p < 0.05), whereas the between-group difference in Processing Speed did not reach statistical significance. Regression analyses confirmed that SLD was independently associated with lower Perceptual Reasoning and Working Memory scores. Despite statistically significant group differences, effect sizes were modest and ROC analysis indicated limited discriminative performance (AUC = 0.58). These differences, however, were modest in magnitude. CONCLUSIONS:These findings suggest that comorbid SLD in children with ADHD is associated with a domain-specific pattern of cognitive vulnerability, with working memory emerging as the most prominently affected cognitive domain, rather than reflecting a generalized cognitive impairment. However, the modest effect sizes and limited discriminative utility indicate that these differences should be interpreted as clinically informative rather than diagnostically definitive. This study highlights the importance of domain-specific cognitive assessment in clinically referred ADHD populations.
OBJECTIVE:To observe the content characteristics and variation rules of partial biochemical substances in peripheral blood of autism model rats at different weeks of age. METHODS:This was an experimental study. Time-mated female Sprague-Dawley (SD) rats were given a single intraperitoneal injection of 600 mg/kg valproic acid (VPA) and 20 mg/kg polyinosinic:polycytidylic acid (poly I:C) on gestational day 12.5. Offspring rats were screened as autism model rats through behavioural tests including stereotypic behaviour assessment, marble burying test and three-chamber social interaction test. A total of 12 autism model rats (six males and six females) were selected as the experimental group, and 12 normal rats (six males and six females) were selected as the control group. Periorbital venous blood samples were collected at 2, 4, 6 and 8 weeks of age, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of brain-derived neurotrophic factor (BDNF), glutathione (GSH), neurotrophin-3 (NT3), neurotrophin-4 (NT4), interleukin-6 (IL-6) and serotonin (5-HT) in peripheral blood. The content characteristics of the aforementioned biochemical substances between the experimental group and the control group, as well as the dynamic changes in blood test results of rats at different weeks of age, were compared. RESULTS:At 2 and 4 weeks of age, the levels of BDNF, NT3, NT4, IL-6 and 5-HT in peripheral blood of autism model rats were significantly higher, whereas the level of GSH was significantly lower than those of normal rats (p < 0.05). At 6 weeks of age, the level of IL-6 was significantly higher and the level of GSH was significantly lower in the experimental group than in the control group (p < 0.05), whereas there were no significant differences in BDNF, NT3, NT4 and 5-HT levels between the two groups (p > 0.05). At 8 weeks of age, the levels of BDNF, NT3, NT4, GSH and 5-HT in the experimental group were significantly lower, whereas the level of IL-6 was significantly higher than those in the control group (p < 0.05). No significant differences were found in the levels of the aforementioned substances between male and female rats within both groups (p > 0.05). CONCLUSION:With the increase of age, the levels of BDNF, NT3, NT4 and 5-HT in peripheral blood of autism model rats gradually decrease to the level of normal rats and eventually become lower than those of normal rats. The level of IL-6 remains high and the level of GSH remains low throughout the whole life cycle of autism model rats. The dynamic changes and status of these factors in peripheral blood may provide certain references for the blood research of children with autism spectrum disorder.
BACKGROUND:Neurodevelopmental disorders were a wide range of cognitive and behavioural disorders. Its pathogenic genes, transduction beta like 1 X-linked receptor 1 (TBL1XR1), had been a hot research topic recently. However, reports involving treatment and long-term follow-up were still limited. METHODS:Exome sequencing of the family was performed. The clinical data and genetic variants, treatment and long-term follow-up were summarized. Moreover, treatment of published cases was also summarized to systematically understand its treatment strategies. RESULTS:Genetic screening revealed a de novo variant of TBL1XR1 [NM_024665.7: c.1372_1387dup, p.Asp463Glyfs*6]. The variant was a 16-bp nucleotide duplication in exon 14, caused a conversion of the aspartic amino acids to glycine amino acids at the 463rd and finally generated a stop codon 6 amino acids after the 462nd amino acids. It was classified as a variant of pathogenic (P) according to the ACMG (American College of Medical Genetics and Genomics) guidelines. Valproic acid was administered up to 20 mg/kg/day, which resulted in satisfactory seizure control. Long-term follow-up confirmed the complete disappearance of seizures at 5 and 6 months of age, although hyperactivity, attention deficit and global developmental delay persisted. CONCLUSION:Our results expanded the pathogenic variant spectrum and treatment of TBL1XR1-related neurodevelopmental disorders.
Autism spectrum disorders (ASD) are frequently associated with sensory abnormalities, particularly altered pain sensitivity, which may manifest as either hypo- or hypersensitivity to painful stimuli. Despite the higher prevalence of ASD in males, few studies have investigated sex differences in pain sensitivity within animal models of autism. This study evaluated thermal and mechanical pain sensitivity in male and female rats at juvenile, pubertal and adult stages, using a model of autism induced by prenatal exposure to lipopolysaccharide (LPS). Reduced social behaviour, a critical behaviour impairment in autism, was assessed, and molecular analyses of Oprm1 gene expression and mu-opioid receptor (MOR-1) protein levels in the periaqueductal grey (PAG) were performed in adulthood. At weaning, both male and female offspring prenatally exposed to LPS exhibited reduced social behaviour, consistent with behavioural phenotypes observed in ASD models. In mechanical nociceptive tests, males and females showed similar pain sensitivity at weaning, whereas only males displayed decreased sensitivity at puberty and adulthood. In thermal tests, males showed reduced nociceptive responses across all ages, whereas females exhibited this pattern only during the juvenile and pubertal stages. Both sexes in the LPS group showed increased Oprm1 gene expression in the PAG; however, MOR-1 protein content was decreased in males and increased in females in adulthood. Thus, our model of autism-induced hypoalgesia via enabling the opioid system, mainly in male rats. Sexual dimorphism was observed in both pain tests and MOR-1 protein levels in adult rats, with female rats being less sensitive to pain.
OBJECTIVE:Little is known about how the effects of pregestational stress on seizure susceptibility in male and female offspring might be attenuated. The current study was undertaken to determine whether Dracocephalum moldavica (DM) administration during gametogenesis could affect stress-precipitated pentylenetetrazol (PTZ)-induced seizure in the offspring of rats. METHODS:Male and female Wistar rats were subjected to restraint stress and administered 100 mg/kg of DM extract orally for 50 days (males) or 15 days (females). The rats were then mated to generate eight coupling combinations, comprising four groups without DM extract and four groups with extract: McFc, McFs, MsFc, MsFs, McFc + EX, McFs + EX, MsFc + EX and MsFs + EX (M: male; F: female; C: control; S: stress; EX: extract). Pregnant dams were left undisturbed throughout gestation. Following parturition, each dam and her litter were housed in a separate cage under standard laboratory conditions until weaning. Offspring body weight was recorded at multiple time points. On the postnatal day (PND) 26, two pups per dam, one male and one female, were administered pentylenetetrazol (PTZ) intraperitoneally and evaluated for PTZ-induced seizures. RESULTS:The DM extract significantly enhanced weight gain in offspring across all experimental groups compared with control pups. In addition, DM extract treatment reduced both the frequency and duration of tonic-clonic seizures. Notably, the latency to the first epileptic manifestation was significantly prolonged in the MsFc+EX group compared with its corresponding control. CONCLUSION:The results indicated that DM extract attenuates pregestational stress precipitating epileptic behaviours probably by suppressing oxidative stress.
