Stress In Autism Spectrum Disorders Research Articles

Concurrent Assessment of Oxidative Stress and MT-ATP6 Gene Profiling to Facilitate Diagnosis of Autism Spectrum Disorder (ASD) in Tamil Nadu Population.

Autism spectrum disorder (ASD) is a neurodevelopmental disability that causes social impairment, debilitated verbal or nonverbal conversation, and restricted/repeated behavior. Recent research reveals that mitochondrial dysfunction and oxidative stress might play a pivotal role in ASD condition. The goal of this case-control study was to investigate oxidative stress and related alterations in ASD patients. In addition, the impact of mitochondrial DNA (mtDNA) mutations, particularly MT-ATP6, and its link with oxidative stress in ASD was studied. We found that ASD patient's plasma had lower superoxide dismutase (SOD) and higher catalase (CAT) activity, resulting in lower SOD/CAT ratio. MT-ATP6 mutation analysis revealed that four variations, 8865 G>A, 8684 C>T, 8697 G>A, and 8836 A>G, have a frequency of more than 10% with missense and synonymous (silent) mutations. It was observed that abnormalities in mitochondrial complexes (I, III, V) are more common in ASD, and it may have resulted in MT-ATP6 changes or vice versa. In conclusion, our findings authenticate that oxidative stress and genetics both have an equal and potential role behind ASD and we recommend to conduct more such concurrent research to understand their unique mechanism for better diagnosis and therapeutic for ASD.

The Role of Oxidative Stress in Autism Spectrum Disorder: A Narrative Literature Review

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder that comprises a complex aetiology, where a genetic component has been suggested, together with multiple environmental risk factors. Because of its increasing incidence in the paediatric population and the lack of successful curative therapies, ASD is one of the most puzzling disorders for medicine. In the last two decades and more, the relationship between oxidative stress (OS) and ASD has been recurrently documented. For this reason, the former hypothesis, according to which reactive oxygen and nitrogen species (ROS and RNS) play an important role in ASD, is now a certainty. Thus, in this review, we will discuss many aspects of the role of OS in ASD. In addition, we will describe, in the context of the most recent literature, the possibility that free radicals promote lipid peroxidation, as well as an increase in other OS biomarkers. Finally, we will outline the possibility of novel nutritional interventions aimed at counteracting ROS production in people with ASD. In fact, new strategies have investigated the possibility that ASD symptoms, as well behavioral anomalies, may be improved after interventions using antioxidants as supplements or included in foods.

Phytochemicals And Nutraceuticals as A Promising Drug Candidate in Autism Spectrum Disorder

Autism is a diversified group of neurological disorders having unknown cause which are interpreted entirely based on behavioral examination. During the last two decades, the frequency and prevalence rate of autism spectrum disorder (ASD) have risen. The elevated level of oxidative stress and reduced antioxidant potential has been associated with this disorder. Further in autism, the genetic as well as environmental determinants may escalate susceptibility to oxidative stress. Elevated oxidative stress in ASD give rise to the development of this disorder regarding both clinical manifestations and pathological process. Autism manifests the characteristics like changes in complicated human behaviors which includes social interaction, communication and stereotypies. In addition, children suffering from autism may not be able to cope anxiety and behave unreasonably even to otherwise benign stimulators. It is proposed by growing evidence that epigenetic mechanisms play a role in the etiology of autism. To detect epigenetic biomarkers for ASD, numerous studies have endeavored until now. Children having autism spectrum disorder (ASD) usually show remarkable behavioral difficulties in combination with dysfunction in social relationship

Association between child behavioural problems and parenting stress in autism spectrum disorders: the role of parenting self-efficacy

Introduction: The present study build on previous research that found a bidirectional relation of parenting stress and negative behavioural outcomes in children with Autism Spectrum Disorders. Aim: To investigate the mediating role of parenting self-efficacy in the relationship of parenting stress and children’s behavioural and emotional problems. Materials and methods: The sample included 32 young children and their families. Sociodemographic and clinical data were collected. Hierarchical regression analysis revealed direct and indirect mediating effects. Results: Parenting self-efficacy mediated the relationship between parenting stress and children’s behavioural and emotional problems in fathers only. Conclusions: We discuss potential ways targeted parenting self-efficacy intervention can support fathers. Results contribute to gain father-informed knowledge in, a research branch generally focused on mothers.

Oxidative Stress in Autism Spectrum Disorder-Current Progress of Mechanisms and Biomarkers.

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. Existing data suggest that early diagnosis and intervention can improve ASD outcomes. However, the causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. More mechanisms and biomarkers of autism have been found with the development of advanced technology such as mass spectrometry. Many recent studies have found a link between ASD and elevated oxidative stress, which may play a role in its development. ASD is caused by oxidative stress in several ways, including protein post-translational changes (e.g., carbonylation), abnormal metabolism (e.g., lipid peroxidation), and toxic buildup [e.g., reactive oxygen species (ROS)]. To detect elevated oxidative stress in ASD, various biomarkers have been developed and employed. This article summarizes recent studies about the mechanisms and biomarkers of oxidative stress. Potential biomarkers identified in this study could be used for early diagnosis and evaluation of ASD intervention, as well as to inform and target ASD pharmacological or nutritional treatment interventions.

Learning Difficulties and Oxidative Stress in Autism Spectrum Disorder: A Review of the Role of Nutritional Interventions

Learning Difficulties and Oxidative Stress in Autism Spectrum Disorder: A Review of the Role of Nutritional Interventions

6.30 Biological and Psychosocial Correlates of Social Cognition in Adolescents with Autism Spectrum Disorder (ASD)

The dysfunctional immune responses in autism spectrum disorder (ASD) associated with increased impairments in social cognition and the impact of interpersonal and social stress in ASD on inflammatory pathways are well known. The connection between psychosocial stress, the immune system, and core deficits may provide greater insight into this debilitating disorder. Our major objectives include: 1) to examine the association of psychosocial stress with measures of social cognition; and 2) to assess the relationship between peripheral inflammatory and neurotrophic proteins, psychosocial stress, and social cognition. Preliminary analysis includes 30 adolescents ages 13 to 17 years old (N = 16 ASD; 12.5% female; N = 14 typically developed [TD; controls]; 21% female]. The Social Responsiveness Scale, Second Edition (SRS-2) was administered to measure social interaction and communication deficits. The Child and Adult versions of the Reading the Mind in the Eyes Tests (RMET-C and RMET-A, respectively) were administered as measures of theory of mind. Psychosocial stress measures included the Expressed Emotion (EE) assessed by the Five-Minute Speech Sample, NIH PROMIS scales. ProcartaPlex bead-based multiplex immunoassays were performed for simultaneous detection and quantitation of multiple protein targets in a subset of the plasma. Youth with ASD demonstrated higher familial EE than TD, although it was not statistically significant (p = 0.2). Parent-reported psychological stress in youth with ASD was significantly greater than TD (p = 0.001). Youth with ASD described greater impairments in peer relationships than TD youth (p = 0.004). Youth with ASD with greater psychological stress and impaired family and peer relationships demonstrated more errors on the RMET-A (p = 0.003, p = 0.03, and p = 0.009, respectively). Higher scores on the SRS-2 were seen in youth with ASD with greater psychosocial stress in EE and PROMIS measures, but this did not reach statistical significance. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) demonstrated significant associations with measures of psychological stress (p = 0.07 and p = 0.01, respectively), but no group differences were noted. The preliminary results are consistent with our hypotheses suggesting the presence of higher psychosocial stress in youth with ASD that contributes to greater impairments in social cognition and a dysregulated immune profile. Further analyses with the larger dataset could help identify risk factors that may affect the development and/or maintenance of these deficits and be prime targets for intervention.

The Gut Microbiota and Oxidative Stress in Autism Spectrum Disorders (ASD).

Autism spectrum disorders (ASDs) are a kind of neurodevelopmental disorder with rapidly increasing morbidity. In recent years, many studies have proposed a possible link between ASD and multiple environmental as well as genetic risk factors; nevertheless, recent studies have still failed to identify the specific pathogenesis. An analysis of the literature showed that oxidative stress and redox imbalance caused by high levels of reactive oxygen species (ROS) are thought to be integral parts of ASD pathophysiology. On the one hand, this review aims to elucidate the communications between oxidative stress, as a risk factor, and ASD. As such, there is also evidence to suggest that early assessment and treatment of antioxidant status are likely to result in improved long-term prognosis by disturbing oxidative stress in the brain to avoid additional irreversible brain damage. Accordingly, we will also discuss the possibility of novel therapies regarding oxidative stress as a target according to recent literature. On the other hand, this review suggests a definite relationship between ASD and an unbalanced gastrointestinal tract (GIT) microbiota (i.e., GIT dysbiosis). A variety of studies have concluded that the intestinal microbiota influences many aspects of human health, including metabolism, the immune and nervous systems, and the mucosal barrier. Additionally, the oxidative stress and GIT dysfunction in autistic children have both been reported to be related to mitochondrial dysfunction. What is the connection between them? Moreover, specific changes in the GIT microbiota are clearly observed in most autistic children, and the related mechanisms and the connection among ASD, the GIT microbiota, and oxidative stress are also discussed, providing a theory and molecular strategies for clinical practice as well as further studies.

How Robust is the Evidence for a Role of Oxidative Stress in Autism Spectrum Disorders and Intellectual Disabilities?

Growing interest in the pathogenesis of autism spectrum disorders (ASDs) and other intellectual and developmental disabilities (IDD) has led to emerging evidence implicating a role for oxidative stress. However, understanding the strength of this association is made challenging by the use of a variety of purported biomarkers of oxidative stress, many of which have either uncertain specificity or flawed methods of analysis. This review aims to address this issue, which is widespread in the ASD and IDD literature, by providing readers with information concerning the strengths and limitations of the choice and analysis of biomarkers of oxidative stress. We highlight that biomarkers and assays should be specific, sensitive, reproducible, precise, robust, and chosen with careful consideration. Future studies should be sufficiently powered and address sample collection, processing, and storage which are, additionally, poorly considered, sources of bad practice, and potential errors. Only with these issues considered, will the data lead to conclusions as to the precise role of oxidative stress in ASDs and IDD.

Assessment of oxidative stress in autism spectrum disorder using reactive oxygen metabolites and biological antioxidant potential.

There are several studies on oxidative stress of Autism Spectrum Disorder (ASD), but in these cases there is no study to measure oxidative stress and antioxidant capacity at the same time or studies considering childhood development. Therefore, this study comprehensively assessed the level of oxidative stress in ASD children by simultaneously measuring reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP). The subjects were Japanese, 77 typical development (TD) children, 98 ASD children, samples were plasma. The subjects were divided into age groups: toddlers/preschool age (2-6 years) and school age (7-15 years), to compare the relationships among the d-ROMs levels and BAP/d-ROMs ratios. Furthermore, the correlations between the Parent-interview ASD Rating Scales (PARS) scores and the measured values were analyzed. The levels of d-ROMs were significantly higher in the ASD (7-15 years) than in TD (7-15 years). The PARS scores were significantly higher in the ASD and were significantly correlated with d-ROMs levels. These results suggested that d-ROMs and BAP/d-ROMs ratios could be objective, measured indicators that could be used in clinical practice to assess stress in ASD children.

Modèle explicatif de la relation d’attachement parent-enfant chez la personne autiste : l’influence de la fratrie et du stress parental

The first bond formed between a child and his parent, generally his main attachment figure, remains essential for the development of the child’s autonomy. While around 1% of the world’s population is diagnosed with autism spectrum disorder (ASD; Fédération québécoise de l’autisme, 2019), some factors are said to negatively influence the development of the attachment between children with ASD and their parents, explaining why they seem more likely to develop an insecure attachment style (Oppenheim et al., 2012). An explanatory model has been proposed by Lapointe (2017), which suggests that certain factors, such as social communication deficits, associated disorders, and parental stress, could have a moderating effect on the relation between the quality of the attachment and the autistic symptoms. The following article proposes an enhancement of this theoretical model by considering a possible bidirectional link between siblings and parental stress. Keywords: parent-child attachment, insecure attachment style, autism spectrum disorder, parental stress in autism spectrum disorder, siblings of autistic children

Oxidative Stress in Autism Spectrum Disorder.

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

Plasma peroxiredoxin changes and inflammatory cytokines support the involvement of neuro-inflammation and oxidative stress in Autism Spectrum Disorder

BackgroundIt has been established that children with Autism Spectrum Disorders (ASD) are affected by oxidative stress, the origin of which is still under investigation. In the present work, we evaluated inflammatory and pro-oxidant soluble signature in non-syndromic ASD and age-matched typically developing (TD) control children.MethodsWe analyzed leukocyte gene expression of inflammatory cytokines and inflammation/oxidative-stress related molecules in 21 ASD and 20 TD children. Moreover, in another—comparable—group of non-syndromic ASD (N = 22) and TD (N = 21) children, we analyzed for the first time the protein expression of the four members of the antioxidant enzyme family of peroxiredoxins (Prx) in both erythrocyte membranes and in plasma.ResultsThe gene expression of IL6 and of HSP70i, a stress protein, was increased in ASD children. Moreover, gene expression of many inflammatory cytokines and inflammation/oxidative stress-related proteins correlated with clinical features, and appeared to be linked by a complex network of inter-correlations involving the Aryl Hydrocarbon Receptor signaling pathway. In addition, when the study of inter-correlations within the expression pattern of these molecules was extended to include the healthy subjects, the intrinsic physiological relationships of the inflammatory/oxidative stress network emerged. Plasma levels of Prx2 and Prx5 were remarkably increased in ASD compared to healthy controls, while no significant differences were found in red cell Prx levels.ConclusionsPrevious findings reported elevated inflammatory cytokines in the plasma of ASD children, without clearly pointing to the presence of neuro-inflammation. On the other hand, the finding of microglia activation in autoptic specimens was clearly suggesting the presence of neuro-inflammation in ASD. Given the role of peroxiredoxins in the protection of brain cells against oxidative stress, the whole of our results, using peripheral data collected in living patients, support the involvement of neuro-inflammation in ASD, and generate a rational for neuro-inflammation as a possible therapeutic target and for plasma Prx5 as a novel indicator of ASD severity.

Gender, Genetic, And Environmental Factors In The Neurodevelopmental Disorders

There is a clear sex effect of gestational stress exposition. Girls have more IUGR, but boys are less resilient than girls presenting higher birth mortality. Animal studies results provide insight into the temporal specificity of the effects of prenatal chronic variable stress (CVS) revealing a remarkable vulnerability during early development and a sexually dichotomous influence on cognitive abilities and stress-coping strategies. Males exposed to early gestational stress showed significantly impaired learning performance. Also it is clear that some neurodevelopmental disorders are more prevalent in boys than girls. Using a bioinformatics approach, we will present that SRY/SOX3 autosome target genes were enriched for autism spectrum disorder (ASD) and brain development gene modules expressed around the 8-10 gestational week or after the 20 gestational weeks, modules already associated to ASD. We suggest that the SRY/SOX3 mechanism can contribute to better understand the male vulnerability to early stress in autism spectrum disorder (ASD) as a model of neurodevelopmental disorder with a male bias.

Hesperetin and it nanocrystals ameliorate social behavior deficits and oxido-inflammatory stress in rat model of autism

Prenatal exposure to valproic acid (VPA) induces behavioral disorders and enhancement of oxido-inflammatory stress in Autism Spectrum Disorders (ASDs). The aim of this study was to investigate the comparative effects of hesperetin (Hst) and nano-hesperetin on social behavior deficits and oxido-inflammatory indexes in prenatally valproic acid-exposed rat offspring. Pregnant Wistar rats on embryonic day 0 (E0) were segregated into six groups; Group-1 served as vehicle, received distillated water orally (PO) from E1 until the end of lactation and saline intraperitoneally (i.p) on E12.5. Group-2 received sodium valproate (500 mg/kg in 0.9% saline, i.p) on E12.5 was considered as VPA-exposed group, Group-3 to 6 were VPA-exposed which received hesperetin and nano-hesperetin (10 and 20 mg/kg/day, PO) from E0 until the end of lactation respectively. Social interaction and open field tests were conducted on postnatal day 28 (PND 28) and PND 30, cerebral antioxidant enzymes activity and biochemical indexes, the level of inflammatory factors in plasma and histopathology of cerebellum were estimated on PND 28 and PND 30. Prenatal valproic acid-exposed rat exhibited poor sociability and high level of anxiety-like behaviors (P < 0.05). In addition, increased level of oxidative stress and inflammation were found by determining different oxido-inflammatory markers. Hesperetin and nano-hesperetin treatment improved the behavioral disorder and reduced the oxidative stress in brain and significantly (p < 0.05) plasma’s inflammation indexes. In conclusion, it can be state that nano-hesperetin exerts neuroprotective action in comparison with hesperetin and could be efficacious for treatment of VPA animal model of autism during pregnancy and lactation.

Implication of Endoplasmic Reticulum Stress in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder according to the Diagnostic and Statistical Manual of Disorders, Fifth Edition and is defined as a congenital impairment of the central nervous system. ASD may be caused by a chromosomal abnormality or gene mutation. However, these etiologies are insufficient to account for the pathogenesis of ASD. Therefore, we propose that the etiology and pathogenesis of ASD are related to the stress of the endoplasmic reticulum (ER). ER stress, induced by valproic acid, increased in ASD mouse model, characterized by an unfolded protein response that is activated by this stress. The inhibition of neurite outgrowth and expression of synaptic factors are observed in ASD. Similarly, ER stress suppresses the neurite outgrowth and expression of synaptic factors. Additionally, hyperplasia of the brain is observed in patients with ASD. ER stress also enhances neuronal differentiation. Synaptic factors, such as cell adhesion molecule and shank, play important roles in the formation of neural circuits. Thus, ER stress is associated with the abnormalities of neuronal differentiation, neurite outgrowth, and synaptic protein expression. ER stress elevates the expression of the ubiquitin-protein ligase HRD1 for the degradation of unfolded proteins. HRD1 expression significantly increased in the middle frontal cortex in the postmortem of patients with ASD. Moreover, HRD1 silencing improved the abnormalities induced by ER stress. Because other ubiquitin ligases are related with neurite outgrowth, ER stress may be related to the pathogenesis of neuronal developmental diseases via abnormalities of neuronal differentiation or maturation.

7.1 Clinical Perspective: Caregiver Stress in Autism Spectrum Disorder

7.1 Clinical Perspective: Caregiver Stress in Autism Spectrum Disorder

The Need for an Ecological Approach to Parental Stress in Autism Spectrum Disorders: The Combined Role of Individual and Environmental Factors.

This study aimed to identify parental stress predictors in ASD by considering individual and environmental factors in an ecological approach. Participants were 115 parents of children with ASD aged from 3 to 10years. Multiple regression analyses were conducted to determine the best predictors of parental stress among child-related, parent-related and environmental factors. Poor quality interactions within the extended family, high levels of expressed emotion and absence of children's schooling were associated with higher stress, regardless of the child's age and developmental quotient [F (3)=37.051; p<0.001; Adj. R(2)=0.457]. This study highlights the importance of considering environmental factors, specifically family variables, to understand parental stress. These key findings should be considered when designing support programs.

Behavioral and emotional profile and parental stress in preschool children with autism spectrum disorder

Parents of children with autism spectrum disorder (ASD) were shown to experience more stress than parents of typically developing peers, although little is known about risk factors predicting stress in this population. The aim of this study was to evaluate parental stress levels and behavioral and emotional problems in a sample of preschool children with ASD as compared to typically developing (TD) peers and to investigate the role of several factors, including the severity of autistic symptoms, adaptive skills, cognitive abilities and behavioral and emotional problems, on parental stress. Results confirmed that parents of children with ASD experience higher stress levels than parents of TD and that children with ASD show more behavioral and emotional problems than controls. Moreover, our results showed that behavioral and emotional problems are strong predictors of parental stress, while stress related to a parent–child dysfunctional relationship was associated with daily living and communication skills as well as cognitive abilities. Findings revealed different behavioral and emotional problems affecting parental stress in ASD and TD samples. No association between the severity of autism symptoms and parental stress was detected. These results suggest that dysfunctional behaviors in preschool children with ASD have a strong impact on parental stress, profoundly affecting the well-being of the entire family. Therefore, strategies aimed at the early detection and management of these behavioral and emotional problems are crucial in order to prevent parental stress and to develop the most appropriate treatment interventions.

Indian Hedgehog Protein Levels in Autistic Children: Preliminary Results

The etiology of autism spectrum disorders (ASD) is not well known but recently we reported that the serum levels of sonic hedgehog (SHH) protein and brain-derived neurotrophic factor (BDNF) might be linked to oxidative stress in ASD. We hypothesized that Indian hedgehog (IHH) protein which belongs to SHH family may play a pathological role in the ASD. We studied recently diagnosed patients in early stages of ASD (n=54) and age-matched, cognitively normal, individuals (n=25), using serum levels of IHH protein. We found statistically significantly higher-levels of serum IHH protein in ASD subjects (p=0.001) compared to control subjects. Our findings are the first to report a role of IHH in ASD children, suggesting a possible pathological role-played by IHH in early-stage in ASD. Such measures might constitute an early biomarker for ASD and ultimately offer a target for novel biomarker-based therapeutic interventions.