Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder

Yui, Kunio; Tanuma, Nasoyuki; Yamada, Hiroshi; Kawasaki, Yohei

doi:10.1016/j.ijdevneu.2016.08.003

Cited by 12 publications

(4 citation statements)

References 80 publications

(101 reference statements)

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“…The superior performance of the SVM using a radial kernel function indicates that individuals with ASD might have levels of 8-OH-dG below or above an optimal range [46,47], rather than simply levels that are higher than neurotypical individuals. This could explain some the disparate findings of previous studies, among which some have found increased levels of 8-OH-dG in individuals with ASD [12,48,49], while others have not [35,36,50]. In individuals with ASD, such deviations from an optimal level of 8-OH-dG could be a reflection of a departure from an appropriate range of ROS expression, which has been shown to be important in regulating neuronal differentiation, migration [51,52], and synaptic pruning [53,54], which are all processes thought to be involved in the etiology of ASD [55,56].…”

Section: Discussionmentioning

confidence: 83%

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Urinary Markers of Oxidative Stress in Children with Autism Spectrum Disorder (ASD)

et al. 2019

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Background: Autism spectrum disorder (ASD) is a developmental disorder characterized by deficits in social interaction, restricted interest and repetitive behavior. Oxidative stress in response to environmental exposure plays a role in virtually every human disease and represents a significant avenue of research into the etiology of ASD. The aim of this study was to explore the diagnostic utility of four urinary biomarkers of oxidative stress. Methods: One hundred and thirty-nine (139) children and adolescents with ASD (89% male, average age = 10.0 years, age range = 2.1 to 18.1 years) and 47 healthy children and adolescents (49% male, average age 9.2, age range = 2.5 to 20.8 years) were recruited for this study. Their urinary 8-OH-dG, 8-isoprostane, dityrosine and hexanoil-lisine were determined by using the ELISA method. Urinary creatinine was determined with the kinetic Jaffee reaction and was used to normalize all biochemical measurements. Non-parametric tests and support vector machines (SVM) with three different kernel functions (linear, radial, polynomial) were used to explore and optimize the multivariate prediction of an ASD diagnosis based on the collected biochemical measurements. The SVM models were first trained using data from a random subset of children and adolescents from the ASD group (n = 70, 90% male, average age = 9.7 years, age range = 2.1 to 17.8 years) and the control group (n = 24, 45.8% male, average age = 9.4 years, age range = 2.5 to 20.8 years) using bootstrapping, with additional synthetic minority over-sampling (SMOTE), which was utilized because of unbalanced data. The computed SVM models were then validated using the remaining data from children and adolescents from the ASD (n = 69, 88% male, average age = 10.2 years, age range = 4.3 to 18.1 years) and the control group (n = 23, 52.2% male, average age = 8.9 years, age range = 2.6 to 16.7 years). Results: Using a non-parametric test, we found a trend showing that the urinary 8-OH-dG concentration was lower in children with ASD compared to the control group (unadjusted p = 0.085). When all four biochemical measurements were combined using SVMs with a radial kernel function, we could predict an ASD diagnosis with a balanced accuracy of 73.4%, thereby accounting for an estimated 20.8% of variance (p < 0.001). The predictive accuracy expressed as the area under the curve (AUC) was solid (95% CI = 0.691–0.908). Using the validation data, we achieved significantly lower rates of classification accuracy as expressed by the balanced accuracy (60.1%), the AUC (95% CI = 0.502–0.781) and the percentage of explained variance (R2 = 3.8%). Although the radial SVMs showed less predictive power using the validation data, they do, together with ratings of standardized SVM variable importance, provide some indication that urinary levels of 8-OH-dG and 8-isoprostane are predictive of an ASD diagnosis. Conclusions: Our results indicate that the examined urinary biomarkers in combination may differentiate children with ASD from healthy peers to a significant extent. However, the etiological importance of these findings is difficult to assesses, due to the high-dimensional nature of SVMs and a radial kernel function. Nonetheless, our results show that machine learning methods may provide significant insight into ASD and other disorders that could be related to oxidative stress.

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Section: Discussionmentioning

confidence: 83%

“…HEL can be a useful biomarker for initial stages of lipid peroxidation [34]. Urinary levels of HEL were also found to be elevated in children with ASD [35], with a recent study by Yui et al showing that increased HEL is associated with decreased antioxidant capacity in children with ASD [36].…”

Section: Introductionmentioning

confidence: 99%

Urinary Markers of Oxidative Stress in Children with Autism Spectrum Disorder (ASD)

et al. 2019

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“… 12 , 20 The excreted antioxidants are lower in autistic patients compared with healthy age-matching subjects and upon correlation with severity of the disease, such as superoxide dismutase. 21 , 22 Also, ceruloplasmin and transferrin antioxidants show suboptimal levels in serum of autistic children, leading to abnormal metabolism of toxic and oxidative stress–mediating metal ions. 23 Recent genetic studies have identified variants of some antioxidant enzyme-coding genes that increase the susceptibility to autism.…”

Section: Introductionmentioning

confidence: 99%

Expression of Reactive Oxygen Species–Related Transcripts in Egyptian Children With Autism

et al. 2017

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The molecular basis of the pathophysiological role of oxidative stress in autism is understudied. Herein, we used polymerase chain reaction (PCR) array to analyze transcriptional pattern of 84 oxidative stress genes in peripheral blood mononuclear cell pools isolated from 32 autistic patients (16 mild/moderate and 16 severe) and 16 healthy subjects (each sample is a pool from 4 autistic patients or 4 controls). The PCR array data were further validated by quantitative real-time PCR in 80 autistic children (55 mild/moderate and 25 severe) and 60 healthy subjects. Our data revealed downregulation in GCLM, SOD2, NCF2, PRNP, and PTGS2 transcripts (1.5, 3.8, 1.2, 1.7, and 2.2, respectively;P < .05 for all) in autistic group compared with controls. In addition, TXN and FTH1 exhibited 1.4- and 1.7-fold downregulation, respectively, in severe autistic patients when compared with mild/moderate group (P = .005 and .0008, respectively). This study helps in a better understanding of the underlying biology and related genetic factors of autism, and most importantly, it presents suggested candidate biomarkers for diagnosis and prognosis purposes as well as targets for therapeutic intervention.

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“…In a study in which 68 children diagnosed with ASD were compared with 54 healthy controls, 8-OHdG levels in peripheral lymphocyte DNA were found to be significantly higher in the ASD group [20]. However, in other studies no significant difference was found between autism and healthy control groups in terms of urinary 8-OHdG levels [38,39]. In the present study, when 8-OHdG values were compared between the ASD and control groups, the 8-OHdG value was found to be significantly higher in ASD patients.…”

Section: Discussionmentioning

confidence: 96%

Antineuronal antibodies and 8-OHdG an indicator of cerebellar dysfunction in autism spectrum disorder: a case–control study

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et al. 2019

Psychiatry and Clinical Psychopharmacology

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Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental disorder, that starts in early childhood and presents with deficiencies in social-communicational domains along with restricted and repetitive behaviours/interests. While genetic factors are dominant in its pathogenesis, many factors, including neurological, environmental and immunological have been identified. Furtheremore, although cerebellar dysfunction in the etiology of autism has been shown in different studies, the possible causes of the dysfunction and the role of neuroinflammation among these causes have not been clarified yet. Anti-Yo, anti-Hu, anti-Ri and anti-Amphiphysin antibodies have been found to be associated with cerebellar degeneration. The aim of the present study was to compare anti-Yo, anti-Hu, anti-Ri and anti-Amphiphysin antibodies and 8-OHdG values in blood using the ELISA method between ASD patients and healthy children to demonstrate the role of neuroinflammation as a potential cause of cerebellar dysfunction and DNA damage and evaluate the relationship between Childhood Autism Rating Scale (CARS) scores in children diagnosed with ASD and these parameters. Methods: Thirty-five consecutive children between the ages of 3 and 12 referred to the Child and Adolescent Psychiatry Outpatient Clinic of Harran University Hospital and diagnosed with ASD according to the DSM-5 diagnostic criteria were included in the study. The children did not have any chronic physical disorders and were treatment naive. Thirty-three healthy children between the ages of 3 and 12 without any physical or psychiatric disorders were included as the healthy control group. For psychiatric evaluation, a sociodemographic form and to measure the severity of autism, CARS was used. In the study, anti-Yo, anti-Hu, anti-Ri and anti-Amphiphysin antibodies and 8-OHdG values in blood were investigated using the ELISA method. Results: Thirty-five cases with autism (62.9% males) and thirty-three healthy controls (72.7% males) were included in the present study (p = 0.385). The median age was 6.0 in the ASD group and 7.0 in the control group (p = 0.146). Among ASD patients, anti-Ri antibody positivity was detected, while no anti-Ri antibody positivity was found in the control group (p = 0.002). In the ASD group, the anti-Hu and 8-OHdG values were found to be significantly higher than those of the controls (p < 0.001, p = 0.001); no significant difference was found between the ASD and control groups with regard to the anti-Yo and anti-Amphiphysin values (p = 0.113, p = 0.275). Conclusions:The results of the present study suggest that antibodies against cerebellum may be present among children with ASD and DNA damage may occur due to oxidative stress.

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Reduced endogenous urinary total antioxidant power and its relation of plasma antioxidant activity of superoxide dismutase in individuals with autism spectrum disorder

Cited by 12 publications

References 80 publications

Urinary Markers of Oxidative Stress in Children with Autism Spectrum Disorder (ASD)

Urinary Markers of Oxidative Stress in Children with Autism Spectrum Disorder (ASD)

Expression of Reactive Oxygen Species–Related Transcripts in Egyptian Children With Autism

Antineuronal antibodies and 8-OHdG an indicator of cerebellar dysfunction in autism spectrum disorder: a case–control study

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