Search Results (2,966)

Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota–gut–brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut–brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer’s disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer’s neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson–Konovalov disease (WD), multisystem atrophy (MSA), Huntington’s chorea (HC), Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut–brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases. Full article

Background/Objectives: Physical exercise (PE) has been shown to have positive effects on the symptoms associated with autism spectrum disorder (ASD). However, there is still no consensus on the most appropriate PE intervention model. With this in mind, we developed a program with the aim of determining the effects of PE on physical fitness, with a view to applying it as a potential treatment. Methods: Using an experimental methodology, this research work will recruit 18 institutionalized young people and adults who will be allocated to one of two groups, namely (i) the youth training group and (ii) the adult training group, using low-cost materials. Both intervention groups will perform 90 min of training per session, twice a week, for 12 weeks. Evaluations will be carried out at baseline and month 3. The impact of the exercise program will be assessed based on the variables of anthropometry, body composition, cardiovascular response, and cardiorespiratory fitness. Results: The results of this study will contribute to the development of more effective strategies, prescription recommendations, and interventions as a guarantee in future programs of better and greater adherence to PE by institutionalized individuals with ASD. Conclusions: In addition, we intend to make the PE program available if it promotes positive effects in the target population. Full article

Joint attention (JA), a core deficit in children with autism spectrum disorder (ASD), is crucial for social interaction, emotional understanding, and cognitive development. This study aims to compare and analyze the eye-tracking data of ASD and typically developing children (TDC) during virtual games, exploring how different cue types affect JA performance in ASD children. A total of 31 TDC and 40 ASD children participated in the study. Using eye-tracking devices, we recorded the children’s eye movements as they played virtual games, selecting the correct target based on cues provided by virtual characters. Our findings revealed that different cue types significantly impacted the game scores of ASD children but had no significant effect on TDC, highlighting a notable disparity between the two groups. ASD children showed a lower fixation frequency, irregular fixation paths, and increased attention to non-target objects compared to TDC. Interestingly, among the three cue types, ASD children exhibited a preference for the third type, leading to longer fixation on the region of interest and higher game scores. These results underscore the importance of cue selection in enhancing JA in ASD children. This study provides novel insights into the JA deficits in ASD children and offers a scientific basis for the development of targeted and individualized intervention programs. Full article

Background/Objectives: Autistic people employ various social strategies to form and maintain interpersonal relationships in their daily environments. These strategies can help autistic people with social interactions (leading to self-perceived efficacy of using social strategies), but can also lead to cognitive fatigue (self-perceived effort of using social strategies). However, previous studies have focused primarily on self-perceived effort, overlooking the self-perceived efficacy of using social strategies, and the balance between self-perceived effort and efficacy. To address this gap, this study examined the impact of autistic people’s use of social strategies on their well-being, focusing on self-perceived effort, self-perceived efficacy, and their interaction effect. Methods: An online survey was conducted among self-reported autistic people in Japan aged 18–65 years, using a modified Compensation Checklist. Data from 104 self-reported autistic participants were analyzed using linear regression. Results: High self-perceived effort in using social strategies was negatively associated with well-being, whereas high self-perceived efficacy was positively associated with well-being. The interaction effect between effort and efficacy was not significant. These results were supported even when loneliness was used as an index of social well-being. Additionally, the number of strategies used by an autistic person was positively associated with well-being. Conclusions: This study highlights the double-edged effect of autistic people using social strategies, and that using a broader repertoire of social strategies may improve the well-being of autistic people. These findings call for a nuanced approach by researchers and clinicians considering both the positive and negative aspects of using social strategies. Full article

Background/Objectives: Neurodevelopmental disorders (NDDs) include a wide range of conditions that develop during the formation of the central nervous system, such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Tourette syndrome (TS) is another neurodevelopmental disorder characterised by motor and vocal tics, which often co-occurs with ASD and ADHD. This study explores the feasibility of assessing joint hypermobility in children with specific neurodevelopmental conditions by measuring both ankles’ passive range of motion (pROM). Methods: This study involved children diagnosed with ASD, ADHD, and TS, aged 5 to 15 years, who were compared with a control group of healthy children. The Beighton and Brighton scores and the pROM of the left and right ankles were measured. Data were analysed using SPSS version 22.0 for Windows (IBM SPSS Statistics, Chicago, IL, USA). A total of 102 subjects participated in this study (72.52% male, with a mean age of 10.7 ± 2.2 years). The sample included 24 children with ASD, 27 with ADHD, 26 with TS, and 25 healthy controls. Results: The pROM of the right and left ankles showed a significant positive correlation with the Beighton and Brighton scores in children with NDDs (ASD, ADHD, and TS combined). A trend towards higher Beighton scores (≥6) was observed in the ADHD and TS groups, with significance found in the TS group (p = 0.013). The pROM of the right ankle was significantly higher in the ADHD (p = 0.021) and TS (p = 0.013) groups compared to the controls. Although the left ankle followed a similar trend in the TS group, the difference was not statistically significant (p = 0.066). Controlling for age, the diagnosis of ASD, ADHD, and TS does not appear to impact any of the variables examined. Conclusions: There is a trend towards a higher prevalence of individuals with elevated Beighton scores in the ADHD and TS groups, suggesting greater general flexibility or hypermobility in these patients. However, the pROM of the right ankle is significantly higher in the ADHD and TS groups, with solid evidence in the TS group. These findings were not observed in children with ASD. However, it is necessary to consider the measurements obtained in relation to the patients’ age. Finally, given that the pROM of the ankles correlates with the Beighton and Brighton scores, it could be utilised for the initial screening, monitoring, and follow-up of JH in some children with NDDs. Further investigations are required. Full article

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, and it has a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free and casein-free, and probiotic-rich diets, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact among children. This review aims to highlight the food preferences of the ASD population, analyze the effect of the physicochemical and nutritional properties of foods on the selectivity in its consumption, GI problems, and antioxidant deficiencies in individuals with ASD, and evaluate the effectiveness of therapeutic diets, including diets rich in antioxidants, gluten-free and casein-free, ketogenic and essential fatty acids, and probiotic-rich diets in managing these challenges. Full article

Background/Objectives The purpose of this study was to see whether there is a correlation between the behavior of autism spectrum disorder patients and brain abnormalities based on the velocity of blood flow in the MCA (middle cerebral artery). Methods: The use of HAP (High Altitude Protection) suits, which are used in aviation, to treat patients with ASD (autism spectrum disorder) causes significant changes in their functioning and physiological processes. These changes are not only noted in psychological tests but are observed in cerebral blood flow using transcranial Doppler ultrasound of the MCA. Results The results of this study made it possible to distinguish two groups with different flow velocities, which can be characterized as flows of less than 80 cm/s and flows of more than 80 cm/s. In addition, it was shown that in patients with elevated blood flow velocity, aggressive behaviors account for 86.96%, while self-aggressive behaviors account for 65.2%. On the other hand, in the case of patients with reduced flow velocity, i.e., less than 80 cm/s, the rate of aggressive behavior is 20% and that of self-aggressive behavior is 50%. The experiment showed that after therapy, there is a normalization of blood flow, which increased in the case of patients with a reduced flow rate below 80 cm/s and, in the case of elevated blood velocity after therapy, decreased towards normal levels. Conclusions The observed rate of normalization of flow velocities in the MCA translated into significant changes in the behavior and functioning of patients in the neurotypical direction, which was noticeable in the psychological tests conducted. Full article

Background: Autism spectrum disorder (ASD) has seen a rise in prevalence, and the immune system’s role in brain development is increasingly recognized. This study investigates the relationship between immune dysregulation and ASD by examining serum concentrations of interleukin 6 (IL-6), interleukin 8 (CXCL8), and tumor necrosis factor alpha (TNF-alpha) in children. Methods: Serum samples from 45 children with ASD and 30 controls, aged 2 to 12 years, were analyzed using electrochemiluminescence, chemiluminescent microparticle immunoassay, and chemiluminescent immunoassay. ASD symptoms were assessed using the Autism Spectrum Rating Scale (ASRS) and Social Communication Questionnaire (SCQ). Results: No significant correlation was observed between CXCL8 levels and ASD. IL-6 levels showed a trend toward elevation in boys with ASD. TNF-alpha levels were significantly higher in children with ASD under 5 years compared to older children and controls, though no correlation with symptom severity was found. Conclusions: TNF-alpha may be a potential biomarker for early ASD detection, especially in younger children. Further research on larger cohorts is needed to understand the role of immune dysregulation in ASD. Full article

Gut microbiota (GM), together with its metabolites (such as SCFA, tryptophan, dopamine, GABA, etc.), plays an important role in the functioning of the central nervous system. Various neurological and psychiatric disorders are associated with changes in the composition of GM and their metabolites, which puts them in the foreground as a potential adjuvant therapy. However, the molecular mechanisms behind this relationship are not clear enough. Therefore, before considering beneficial microbes and/or their metabolites as potential therapeutics for brain disorders, the mechanisms underlying microbiota–host interactions must be identified and characterized in detail. In this review, we summarize the current knowledge of GM alterations observed in prevalent neurological and psychiatric disorders, multiple sclerosis, major depressive disorder, Alzheimer’s disease, and autism spectrum disorders, together with experimental evidence of their potential to improve patients’ quality of life. We further discuss the main obstacles in the study of GM–host interactions and describe the state-of-the-art solution and trends in this field, namely “culturomics” which enables the culture and identification of novel bacteria that inhabit the human gut, and models of the gut and blood–brain barrier as well as the gut–brain axis based on induced pluripotent stem cells (iPSCs) and iPSC derivatives, thus pursuing a personalized medicine agenda for neuropsychiatric disorders. Full article

In rat models, it is well-documented that chronic administration of propionic acid (PPA) leads to autism-like behaviors. Although the intranasal (IN) insulin approach is predominantly recognized for its effects on food restriction, it has also been shown to enhance cognitive memory by influencing various proteins, modulating anti-inflammatory pathways in the brain, and reducing signaling molecules such as interleukins. This study seeks to explore the potential therapeutic benefits of IN insulin in a rat model of autism induced by PPA. Thirty male Wistar albino rats were categorized into three cohorts: the control group, the PPA-induced autism (250 mg/kg/day intraperitoneal PPA dosage for five days) group, treated with saline via IN, and the PPA-induced autism group, treated with 25 U/kg/day (250 µL/kg/day) insulin via IN. All treatments were administered for 15 days. After behavioral testing, all animals were euthanized, and brain tissue and blood samples were collected for histopathological and biochemical assessments. Following insulin administration, a substantial reduction in autism symptoms was observed in all three social behavior tests conducted on the rats. Moreover, insulin exhibited noteworthy capabilities in decreasing brain MDA, IL-2, IL-17, and TNF-α levels within autism models. Additionally, there is a notable elevation in the brain nerve growth factor level (p < 0.05) and GDF-15 (p < 0.05). The assessment of cell counts within the hippocampal region and cerebellum revealed that insulin displayed effects in decreasing glial cells and inducing a significant augmentation in cell types such as the Purkinje and Pyramidal cells. The administration of insulin via IN exhibits alleviating effects on autism-like behavioral, biochemical, and histopathological alterations induced by PPA in rats. Insulin-dependent protective effects show anti-inflammatory, anti-oxidative, and neuroprotective roles of insulin admitted nasally. Full article

The present study assessed the validity of one of the first autism-specific anxiety measures, the Anxiety Scale for Children with Autism Spectrum Disorder (ASC-ASD), and compared its ability to predict parent-reported clinical anxiety to a ‘traditional’ anxiety measure, the Spence Children’s Anxiety Scale (SCAS). Whether the inclusion of the child form for each measure improved the predictive ability of the parent forms was also examined. Eighty-seven parents of autistic children, aged 8–12 years, completed the ASC-ASD, the SCAS, and the Social Communication Questionnaire (SCQ), a screener for autism characteristics. Of these parents, 56 had their child complete the ASC-ASD and SCAS. The children with a reported anxiety diagnosis were rated significantly higher by their parents on both the SCAS and the ASC-ASD compared to the non-anxious children. Pearson’s correlation coefficients indicated that the ASC-ASD had good divergent and convergent validity, as demonstrated by a poor, non-significant correlation with the SCQ and a strong, significant correlation with the SCAS. Regression analyses indicated that while the ASC-ASD was a significant predictor of parent-reported clinical anxiety in autistic children, the SCAS was not. Neither model was improved with the inclusion of the respective child form. This study is the first to demonstrate the ability of the ASC-ASD to predict child clinical anxiety disorder status and adds to the growing body of evidence for the validity of this measure. The findings also suggest that parent reports of anxiety may be sufficient to identify autistic children warranting further clinical investigation of anxiety in this age group. Full article

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a highly variable expression of phenotypes (restricted interest or activity and repetitive behavior in communication and social interactions), genes (mutation), markers (alteration of transcription) and pathways. Loss of function of the CC2D1A gene appears to primarily affect the brain, leading to a range of behavioral problems in humans. In our study published in 2020, we found that the expressions of miR-19a-3p, miR-361-5p, miR-150-5p, miR-3613-3p, miR-126-3p and miR-499a-5p were downregulated in the serum samples of autistic patients, their families and mouse models (Cc2d1a +/− and valproic acid treated males). Here, acquired non-Mendelian hereditary character in a genetically defined mouse model of autism (Cc2d1a +/−) correlates with the transcriptional alteration of five miRNAs. We seek to test the hypothesis that miRNA levels vary by changes in RNA/DNA structure during development, thereby creating transcription alteration and cell memory. Behavioral tests were conducted on the offspring of Cc2d1a (+/−) mutant and control mice, such as novel object, social interaction, marble burying and tail suspension behavior. Two RNA fractions were isolated from mouse hippocampal tissues and sperm cells via standard TRIzol extraction: free RNA and the fraction of RNA bound to DNA in the form of a DNA/RNA hybrid (R-loop). The expression levels of miR-19a-3p, miR-361-5p, miR-150-5p, miR-126-3p and miR-499a-5p were investigated by quantitative real-time RT-PCR. We report differences in the distribution of five miRNAs in the hippocampus between male and female mice, particularly in colonies of Cc2d1a (+/−) mice. Furthermore, the number of miRNAs engaged in the DNA/RNA hybrid fraction is generally higher in the mutant pedigree than in the control group. On the other hand, in sperm, both fractions are at lower levels than in controls. R-loops contribute to the physiology and pathology of organisms including human disease. Here, we report a variation in five miRNA levels between gender and tissue. Our results suggest that the transcription levels of these five miRNAs are directly regulated by their RNA. Full article

The enteric nervous system (ENS) is a fundamental component of the gastrointestinal system, composed of a vast network of neurons and glial cells. It operates autonomously but is interconnected with the central nervous system (CNS) through the vagus nerve. This communication, known as the gut–brain axis, influences the bidirectional communication between the brain and the gut. Background/Objectives: This study aimed to review neurological pathologies related to the ENS. Methods: To this end, a comprehensive literature search was conducted in the “PubMed” database. Articles available in “free format” were selected, applying the filters “Humans” and limiting the search to publications from the last ten years. Results: The ENS has been linked to various neurological diseases, from autism spectrum disorder to Parkinson’s disease including neurological infection with the varicella zoster virus (VZV), even sharing pathologies with the CNS. This finding suggests that the ENS could serve as an early diagnostic marker or therapeutic target for neurological diseases. Gastrointestinal symptoms often precede CNS symptoms, and the ENS’s accessibility aids in diagnosis and treatment. Parkinson’s patients may show intestinal lesions up to twenty years before CNS symptoms, underscoring the potential for early diagnosis. However, challenges include developing standardized diagnostic protocols and the uneven distribution of dopaminergic neurons in the ENS. Continued research is needed to explore the ENS’s potential in improving disease prognosis. Conclusions: The ENS is a promising area for early diagnosis and therapeutic development. Nevertheless, it is essential to continue research in this area, especially to gain a deeper understanding of its organization, function, and regenerative capacity. Full article

Background: Developmental and epileptic encephalopathies (DEE) are a group of disorders often linked to de novo mutations, including those in the ATP6V1A gene. These mutations, particularly dominant gain-of-function (GOF) variants, have been associated with a spectrum of phenotypes, ranging from severe DEE and infantile spasms to milder conditions like autism spectrum disorder and language delays. Methods: We aim to expand ATP6V1A-related disease spectrum by describing a six-year-old boy who presented with a febrile seizure, mild intellectual disability (ID), language delay, acquired microcephaly, and dysmorphic features. Results: Genetic analysis revealed a novel de novo heterozygous pathogenic variant (c.82G>A, p.Val28Met) in the ATP6V1A gene. He did not develop epilepsy, and neuroimaging remained normal over five years of follow-up. Although ATP6V1A mutations have traditionally been linked to severe neurodevelopmental disorders, often with early-onset epilepsy, they may exhibit milder, non-progressive phenotypes, challenging previous assumptions about the severity of ATP6V1A-related conditions. Conclusions: This case expands the known clinical spectrum, illustrating that not all patients with ATP6V1A mutations exhibit severe neurological impairment or epilepsy and underscoring the importance of including this gene in differential diagnoses for developmental delays, especially when febrile seizures or dysmorphic features are present. Broader genotype–phenotype correlations are essential for improving predictive accuracy and guiding clinical management, especially as more cases with mild presentations are identified. Full article