Role In Autism Research Articles

Characterization of Yeast Isolated from the Gut Microbiota of Tunisian Children with Autism Spectrum Disorder

Research on the microbiota–gut–brain axis in autism has primarily focused on bacteria, with limited attention to fungi. There is a growing interest in understanding the involvement of fungi, particularly Candida, in patients with autism spectrum disorder. The aim of this study was to assess the prevalence, antifungal susceptibility profiles and virulence factors of Candida isolates from the guts of Tunisian children with autism. Twenty-eight children with autism and forty-six controls were enrolled. Candida isolates from the faecal samples were identified using biochemical and molecular methods; antifungal susceptibility testing was determined by the EUCAST broth microdilution method and virulence factors, including biofilm formation, cell surface hydrophobicity and phospholipase and proteinase activities, were assessed in vitro. As a result, Candida was detected in 13 children with autism (46.4%) and 14 control children (30.4%). Candida albicans was found to be the most common species isolate in the faeces of both groups of children. Antifungal susceptibility profiles showed that one Candida isolate was resistant to amphotericin B and anidulafungin (3.7%), six were resistant to micafungin (22.2%) and five were resistant to fluconazole (18.5%). All Candida isolates were biofilm producers. Of the twenty-seven isolates, only four showed phospholipase activity (14.8%), eight showed aspartyl-proteinase activity (29.6%) and nine were hydrophobic (33.3%). These results highlight the presence of Candida in the guts of children with autism, as well as the ability to express multiple virulence factors and the antifungal resistance, and they emphasize the need for further studies to confirm intestinal Candida colonization and its potential role in autism.

NEAT1 Promotes Valproic Acid-Induced Autism Spectrum Disorder by Recruiting YY1 to Regulate UBE3A Transcription.

Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.

Pre-attentive and Attentive Auditory Event-related Potentials in Children With Attention-Deficit Hyperactivity Disorder and Autism.

Abnormalities in auditory processing are believed to play a major role in autism and attention-deficit hyperactivity disorder (ADHD). Both conditions often co-occur in children, causing difficulties in deciding the most promising intervention. Event-related potentials (ERPs) have been investigated and are showing promise to act as potential biomarkers for both conditions. This study investigated mismatch negativity (MMN) using a passive listening task and P3b in an active auditory go/no-go discrimination task. Recordings were available from 103 children (24 females): 35 with ADHD, 27 autistic, 15 autistic children with co-occurring ADHD, and 26 neurotypical (NT) children. The age range considered was between 4 and 17 years, but varied between groups. The results revealed increases in the MMN and P3b amplitudes with age. Older children with ADHD exhibited smaller P3b amplitudes, while younger autistic children showed reduced MMN amplitudes in response to phoneme changes compared to their NT counterparts. Notably, children diagnosed with autism and ADHD did not follow this pattern; instead, they exhibited more similarities to NT children. The reduced amplitudes of phonetically elicited MMN in children with autism and reduced P3b in children with ADHD suggest that the two respective ERPs can act as potential biomarkers for each condition. However, optimisation and standardisation of the testing protocol, as well as longitudinal studies are required in order to translate these findings into clinical practice.

Rare predicted deleterious FEZF2 variants are associated with a neurodevelopmental phenotype.

FEZF2 encodes a transcription factor critical to neurodevelopment that regulates other neurodevelopment genes. Rare variants in FEZF2 have previously been suggested to play a role in autism, and cases of 3p14 microdeletions that include FEZF2 share a neurodevelopmental phenotype including mild dysmorphic features and intellectual disability. We identified seven heterozygous predicted deleterious variants in FEZF2 (three frameshifts, one recurrent missense in two independent cases, one nonsense, and one complete gene deletion) in unrelated individuals with neurodevelopmental disorders including developmental delay/intellectual disability, autism, and/or attention-deficit/hyperactivity. Variants were confirmed to be de novo in five of seven cases and paternally inherited from an affected father in one. Predicted deleterious variants in FEZF2 may affect the expression of genes that are involved in fate choice pathways in developing neurons, and thus contribute to the neurodevelopmental phenotype. Future studies are needed to clarify the mechanism by which FEZF2 leads to this neurodevelopmental disorder.

The role of autism and alexithymia traits in behavioral and neural indicators of self-concept and self-esteem in adolescence.

Developing a positive view of the self is important for maintaining a good mental health, as feeling negative about the self increases the risk of developing internalizing symptoms such as feelings of depression and anxiety. Even though autistic individuals regularly struggle with these internalizing feelings, and both self-concept and internalizing feelings are known to develop during adolescence, there is a lack of studies investigating the development of positive self-concept and self-esteem in autistic adolescents. Here, we studied academic, physical, and prosocial self-concept as well as self-esteem in adolescent males with and without autism on both the behavioral and neural level. We additionally focused on similarities in one's own and peers' perspectives on the self, and we assessed a potential role of alexithymia (i.e. having trouble identifying and describing one's feelings) in developing a more negative view of the self. Results showed that there were no group differences in self-esteem, self-concept, or underlying neural activation. This shows that autistic adolescent males use the same neural processes when they evaluate their traits. However, regardless of clinical diagnosis, a higher number of autism traits was related to a less positive physical and prosocial self-concept, whereas more difficulty identifying one's feelings was related to lowered self-esteem and less activation in medial prefrontal cortex during self-evaluations. Therefore, in treatment of autistic adolescents with low self-esteem, it is important to take into account and possibly aim to improve alexithymic traits as well.

Effects of paternal and chronological age on BEGAIN methylation and its possible role in autism.

Children from old fathers carry an increased risk for autism spectrum (ASD) and other neurodevelopmental disorders, which may at least partially be mediated by paternal age effects on the sperm epigenome. The brain enriched guanylate kinase associated (BEGAIN) protein is involved in protein-protein interactions at and transmission across synapses. Since several epigenome-wide methylation screens reported a paternal age effect on sperm BEGAIN methylation, here we confirmed a significant negative correlation between BEGAIN promoter methylation and paternal age, using more sensitive bisulfite pyrosequencing and a larger number of sperm samples. Paternal age-associated BEGAIN hypomethylation was also observed in fetal cord blood (FCB) of male but not of female offspring. There was no comparable maternal age effect on FCB methylation. In addition, we found a significant negative correlation between BEGAIN methylation and chronological age (ranging from 1 to 70 years) in peripheral blood samples of male but not of female donors. BEGAIN hypomethylation was more pronounced in male children, adolescents and adults suffering from ASD compared to controls. Both genetic variation (CC genotype of SNP rs7141087) and epigenetic factors may contribute to BEGAIN promoter hypomethylation. The age- and sex-specific BEGAIN methylation trajectories in the male germ line and somatic tissues, in particular the brain, support a role of this gene in ASD development.

Family - an important role in autism

Autism is a widespread developmental disorder that has plagued human beings for a long time. It is complex and special, and mostly occurs in children. Regardless of the etiology, diagnosis and treatment intervention of autism, it is closely related to the family of autistic patients. Therefore, this article will focus on the perspective of the family. What’s more, it will analyze the close relationship between the family and autism from the etiology and other aspects. This article tries to maximize the positive role of the family in the process of autism from onset to treatment, and reduce the negative impact of the family in the whole process. The aim is to popularize autism related knowledge. More families can understand what autism is. And measures can be taken as soon as possible. The direction of cooperation treatment will be pointed out for the families of autistic patients. At the same time, it can provide a certain basis for the future research of autism, and promote the development of autism related theory and practice.

Sialic acid and anti-ganglioside M1 antibodies are invaluable biomarkers correlated with the severity of autism spectrum disorder

BackgroundAutism spectrum disorders (ASD) are devastating neurodevelopmental disorders that showed global increased prevalence. They are characterized by impairment of social communication and stereotyped patterns. ObjectiveThis study aimed at measuring the levels of total sialic acid (SA) and anti-ganglioside M1 (anti- GM1) IgG antibodies as essential biomarkers in a cohort of children with ASD to identify their diagnostic yield as well as their correlation with the severity of autistic behaviors. MethodsThe demographic characteristics, anthropometric measurements, and clinical data were recorded. The levels of total plasma SA and serum anti-GM1 IgG antibodies levels were measured in 100 children with ASD and 100 healthy controls. The severity of ASD-related symptoms was assessed by using the Childhood Autism Rating Scale (CARS). ResultsChildren with ASD had significantly higher levels of both SA and anti-GM1 antibodies than healthy controls (p < 0.001). SA showed a statistically significant moderate diagnostic performance while anti-GM1 antibody showed a statistically significant high diagnostic in differentiating severe from mild to moderate autism. Moreover, both SA and anti-GM1 antibodies levels were significantly correlated to the severity of ASD symptoms (p < 0.001). ConclusionThe significantly increased levels of SA and anti-GM1 antibodies in children with ASD and their correlation with autism-related symptoms suggest their possible etiopathogenic role in autism as one of the pediatric autoimmune neuropsychiatric disorders. However, further large-scale studies are still needed to explore their possible bidirectional relationship as biomarkers for autism.

Detecting dodgy behaviour: The role of autism, autistic traits and theory of mind.

Difficulties in reading others' minds make it difficult to anticipate their future behaviour. It has often been argued that such difficulties contribute to autistic individuals becoming enmeshed in criminal activity. However, supportive scientific evidence is virtually non-existent. We compared the ability of groups of autistic and non-autistic adults of similar intellectual ability to detect dodgy or suspicious behaviour across a wide range of scenarios. Although the autistic group performed more poorly than the non-autistic group on an established measure of mindreading, there were no group differences in the ability to detect dodginess. Nor did we find any evidence that detecting dodgy behaviour was associated with the degree of autistic traits reported by individual participants. However, when we combined the two groups, difficulty reading the minds of others was indeed associated with poorer detection of dodginess, thus highlighting a characteristic of individuals that may well increase the likelihood of becoming involved in crime or exploited for autistic and non-autistic individuals alike.

Fentanyl induces autism-like behaviours in mice by hypermethylation of the glutamate receptor gene Grin2b

BackgroundEnvironmental factors contribute to autism spectrum disorder. Fentanyl, one of the most widely used opioid analgesics in anaesthesia, can induce neurotoxicity, but its role in autism remains unknown. We determined whether fentanyl induced autism-like behaviours in young mice and the underlying mechanisms. MethodsYoung male and female mice received fentanyl at postnatal days 6, 8, and 10, and performed behavioural tests, including three-chamber social preference, elevated plus maze, grooming behaviour, and open-field test, from postnatal days 30–32. Expression of Grin2b, the gene encoding the GluN2B subunit of the N-methyl-d-aspartate receptor, was assessed in the anterior cingulate cortex of male mice using fluorescence in situ hybridisation histochemistry. We used bisulfite target sequencing to determine Grin2b hypermethylation sites after fentanyl treatment. In the specific activation and rescue experiments, we injected the mu opioid receptor agonist [D-Ala,2 N-MePhe,4 Gly-ol]-enkephalin (DAMGO) or Grin2b overexpression lentivirus into the anterior cingulate cortex of male mice. ResultsFentanyl induced autism-like behaviours in both young male and female mice, and downregulated Grin2b expression (0.49-fold [0.08] vs 1.00-fold [0.09]; P<0.01) and GluN2B protein amounts (0.38-fold [0.07] vs 1.00-fold [0.12]; P<0.01) in the anterior cingulate cortex through hypermethylation of Grin2b. The mu-opioid receptor antagonist naloxone and overexpression of Grin2b in anterior cingulate cortex attenuated the fentanyl-induced effects, whereas DAMGO injection into the anterior cingulate cortex induced autism-like behaviours. ConclusionsThese data suggest that fentanyl induces autism-like behaviours in young mice via an epigenetic mechanism. Further research is required to determine possible clinical relevance to autism risk.

Electroacupuncture at Zusanli ameliorates the autistic-like behaviors of rats through activating the Nrf2-mediated antioxidant responses

ObjectiveEmerging evidence suggests that acupuncture plays a neuroprotective role in autism. This study aimed to explore the effect of electroacupuncture at Zusanli (ST36) on autistic-like behaviors and the underlying mechanism. MethodPregnant rats were administered with valproic acid (VPA) on gestational day 12.5 to induce an autism spectrum disorder (ASD) model. The pups were given electroacupuncture at ST36 daily from postnatal day (PND) 28–48. On PND28, the adenoviral vector containing small interfering RNA Nrf2 (Ad-siRNA-Nrf2) was injected into the prefrontal cortex of rats. The behavioral analysis was performed on PND 44–48. On PND48, the animals were euthanized and the brains were collected for further detection. Nissl staining was performed to detect neuronal viability. The biochemical markers of oxidative stress were subsequently measured. ResultElectroacupuncture at ST36 ameliorated the locomotor activity, social behavior, spatial learning and memory and repetitive behavior compared with ASD rats. It was notable that the electroacupuncture decreased oxidative stress markers in the tissues of prefrontal cortex, enhanced translocation of nuclear factor erythroid2-related factor2 (Nrf2) from cytoplasm to nucleus, and up-regulated the levels of NADP(H) quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). However, these effects induced by electroacupuncture at ST36 were abolished after injection of Ad-siRNA-Nrf2. ConclusionThese data suggested that electroacupuncture at ST36 protected nerve function in ASD rats through Nrf2 activation and the antioxidant response.

The Oxidative status in Children with Autism receiving Melatonin

Objectives: To determine the changes in the levels of Malondialdehyde (MDA) and antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) in autistic children receiving melatonin supplementation to evaluate its antioxidant role in autism. Methods: A follow-up study was carried out in the Department of therapeutics and clinical pharmacy, Baghdad College of Medical Sciences, Baghdad - Iraq. The study was performed on 55 autistic children who had recruited from several private institutions specialized in autistic children care, Baghdad, Iraq between June 2018 and November 2018. The levels of melatonin, MDA, SOD and CAT were measured in the serum of 55 patients before and after receiving melatonin supplementation for three months. Results: The results revealed statistically significant differences in the levels of melatonin, MDA, SOD and CAT between patients before and after receiving melatonin supplement. Furthermore, melatonin levels showed significant positive correlations with both SOD and CAT in addition to a significant positive correlation between SOD and CAT while MDA levels showed significant negative correlations with melatonin, SOD and CAT in autistic patients before and after receiving the supplement. Conclusions: Melatonin levels, CAT and SOD activity showed to be improved significantly by melatonin supplementation with a concomitant reduction in the levels of MDA as an indicator of a decrease in an oxidative stress in autistic children.

Postnatal expression profiles of atypical cadherin FAT1 suggest its role in autism.

ABSTRACTGenetic studies have linked FAT1 (FAT atypical cadherin 1) with autism spectrum disorder (ASD); however, the role that FAT1 plays in ASD remains unknown. In mice, the function of Fat1 has been primarily implicated in embryonic nervous system development with less known about its role in postnatal development. We show for the first time that FAT1 protein is expressed in mouse postnatal brains and is enriched in the cerebellum, where it localizes to granule neurons and Golgi cells in the granule layer, as well as inhibitory neurons in the molecular layer. Furthermore, subcellular characterization revealed FAT1 localization in neurites and soma of granule neurons, as well as being present in the synaptic plasma membrane and postsynaptic densities. Interestingly, FAT1 expression was decreased in induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPCs) from individuals with ASD. These findings suggest a novel role for FAT1 in postnatal development and may be particularly important for cerebellum function. As the cerebellum is one of the vulnerable brain regions in ASD, our study warrants further investigation of FAT1 in the disease etiology.

Patterns of de novo tandem repeat mutations and their role in autism.

Autism Spectrum Disorder (ASD) is an early onset developmental disorder characterized by deficits in communication and social interaction and restrictive or repetitive behaviors1,2. Family studies demonstrate that ASD has a significant genetic basis with contributions both from inherited and de novo variants3,4. It has been estimated that de novo mutations may contribute to 30% of all simplex cases, in which only a single child is affected per family5. Tandem repeats (TRs), defined here as 1-20bp sequences repeated consecutively, comprise one of the largest sources of de novo mutations in humans6. TR expansions are implicated in dozens of neurological and psychiatric disorders7. Yet, de novo TR mutations have not been characterized on a genome-wide scale, and their contribution to ASD remains unexplored. We develop novel bioinformatics methods for identifying and prioritizing de novo TR mutations from sequencing data and then perform a genome-wide characterization of de novo TR mutations in ASD-affected probands and unaffected siblings. Compared to recent work on TRs in ASD8, we explicitly infer mutation events and their precise changes in repeat number, and primarily focus on more prevalent stepwise copy number changes rather than large expansions. Our results demonstrate a significant genome-wide excess of TR mutations in ASD probands. Mutations in probands tend to be larger, enriched in fetal brain regulatory regions, and predicted to be more evolutionarily deleterious. Overall, our results highlight the importance of considering repeat variants in future studies of de novo mutations.

Despite flurry of findings, doubts dog gut microbes’ role in autism

Despite flurry of findings, doubts dog gut microbes’ role in autism

Analysis ups estimate of spontaneous mutations’ role in autism

Analysis ups estimate of spontaneous mutations’ role in autism

Autism spectrum disorders and terrorism: how different features of autism can contextualise vulnerability and resilience

ABSTRACT There is no empirical evidence to link autism and terrorism, in the general population. However, when terrorist acts are planned or executed by individuals with autism, it is important to develop an understanding of the individual’s autistic functioning and how it may contextualise factors that push them towards terrorism and aspects of terrorism that may pull them in, in order to manage and reduce risk. The role of autism in resilience also needs to be considered in order to capitalise on natural and individually meaningful sources of motivation and protection. This paper explores how different features of autism may contextualise risk and resilience and the implications for support and diversion approaches. Caution is encouraged against drawing conclusions of causality and over-simplification of autism-terrorism links, especially in individuals with co-existing mental health problems and psychosocial adversities. The need for highly individualised formulations that take into account the heterogeneity of autism and how it is functionally expressed, as well as the complexity of terrorism, is strongly advocated. Finally, the limitations in the empirical evidence and research in the field of autism and terrorism are highlighted.

Carers' views on autism and eating disorders comorbidity: qualitative study.

Patients with co-occurring anorexia nervosa and autism respond differently to eating disorder treatments. Previous interviews with patients with both conditions and clinicians working in eating disorder services has highlighted service and treatment adaptations might be beneficial and could improve outcomes for these individuals. The aim of this study was to explore carers' experiences of current treatment approaches for people with autism who have anorexia nervosa, and their views on how these can be improved. Ten carers of a loved one diagnosed with autism and anorexia nervosa were interviewed using a semi-structured interview schedule and the transcripts were analysed with thematic analysis. Four key themes emerged from the interviews: the role of autism in anorexia nervosa, carers' problems with clinical services, the impact on carers and suggestions for future improvements. Carers agreed that autism played a significant role in the development and maintenance of their daughters' anorexia nervosa. However, this comorbidity does not appear to be appropriately addressed in current treatment provisions. They described several difficulties, including problems getting an autism diagnosis and the perception that eating disorder services did not accept or adapt around the condition. This resulted in feelings of frustration and isolation for families, a scenario exacerbated by a perceived lack of support or specific resources for carers of individuals on the autism spectrum. Clinical recommendations on the basis of the current and previous studies are outlined.

Beliefs in vaccine as causes of autism among SPARK cohort caregivers

BackgroundFear of autism has led to a decline in childhood-immunization uptake and to a resurgence of preventable infectious diseases. Identifying characteristics of parents who believe in a causal role of vaccines for autism spectrum disorder (ASD) in their child may help targeting educational activities and improve adherence to the immunization schedule. ObjectivesTo compare caregivers of children with ASD who agree or disagree that vaccines play an etiological role in autism for 1) socio-demographics characteristics and 2) developmental and clinical profiles of their children. MethodsData from 16,525 participants with ASD under age 18 were obtained from SPARK, a national research cohort started in 2016. Caregivers completed questionnaires at registration that included questions on beliefs about the etiologic role of childhood immunizations and other factors in ASD. Data were available about family socio-demographic characteristics, first symptoms of autism, developmental regression, co-occurring psychiatric disorders, seizures, and current levels of functioning. ResultsParticipants with ASD were 80.4% male with a mean age of 8.1 years (SD = 4.1). Overall, 16.5% of caregivers endorsed immunizations as perceived causes of autism. Compared to caregivers who disagreed with vaccines as a cause for ASD, those who believed in vaccine causation came disproportionately from ethnic minority, less educated, and less wealthy backgrounds. More often their children had experienced developmental regression involving language and other skills, were diagnosed earlier, had lost skills during the second year of life, and had worse language, adaptive, and cognitive outcomes. ConclusionOne in six caregivers who participate in a national research cohort believe that child immunizations could be a cause of autism in their child. Parent social background (non-White, less educated) and child developmental features (regression in second year, poorer language skills, and worse adaptive outcomes) index caregivers who are more likely to harbor these beliefs and could benefit from targeted educational activities.

The effect of melatonin administration on the oxidative status in children with autism

To determine the changes in Malondialdehyde (MDA) levels in addition to measuring the changes in the activity of superoxide dismutase (SOD) and catalase (CAT) which considered as antioxidant enzymes in autistic children receiving melatonin supplementation to evaluate its antioxidant role in autism. A follow-up study was performed in therapeutics and clinical pharmacy Department, Baghdad College of Medical Sciences, Baghdad - Iraq. The study was performed on 55 autistic children who had recruited from several private institutions specialized in autistic children care, Baghdad, Iraq between June 2018 and November 2018. The levels of melatonin, MDA, SOD and CAT were measured in the serum of 55 patients before and after receiving melatonin supplementation for three months. The results revealed statistically significant differences in the levels of melatonin, MDA, SOD and CAT between patients before and after receiving melatonin supplement. Furthermore, melatonin levels showed significant positive correlations with both SOD and CAT in addition to a significant positive correlation between SOD and CAT while MDA levels showed significant negative correlations with melatonin, SOD and CAT in autistic patients before and after receiving the supplement. Melatonin levels, CAT and SOD activity, showed to be improved significantly by melatonin supplementation with a concomitant reduction in the levels of MDA as an indicator of a decrease in oxidative stress in autistic children.