Plasma cytokine concentrations of children with autism spectrum disorder and neurotypical siblings.

Several studies of autism spectrum disorder (ASD) have shown cytokine dysregulation in children with ASD, leading to a consideration of the immune theory of the ASD etiopathogenesis and a debate about cytokines as potential biomarkers of ASD. However, the results of these studies are still inconsistent. Overall, studies comparing the cytokine levels of children with ASD and neurotypical siblings achieved relatively different results than studies with control groups of non-siblings. The studies suggest that the immune profile of siblings of individuals with ASD serving as control is more similar to children with ASD than the profile of non-siblings. However, there are still only a few studies with control groups including neurotypical siblings of children with ASD. The aim of our study was to determine whether the concentration of plasma cytokine levels may differentiate children with ASD from their neurotypical siblings. The sample consisted of 40 children with ASD (mean age 7.11 years, SD 2.9) and 21 neurotypical siblings (mean age 7.38, SD 3.3). Levels of 20 cytokines were included into the statistical analysis. A multiple logistic regression model using multiple corrections showed that an increase in log-transformed plasma G-CSF (granulocyte colony stimulating factor) concentration is associated with an increased risk of the child being diagnosed as an ASD case (OR = 4.35, 95% CI 1.77, 10.73). Although the significantly increased concentration of G-CSF suggests a slightly different activity of the immune system of children with ASD, the overall cytokine profile of their siblings appeared to be very similar.

Adaptive Behavior in Slovak Children with Intellectual Disability in Institutional Care.

This study aimed to analyze the adaptive skills of children with intellectual disabilities in institutional care. We focused on communication, socialization, daily living skills and their relationship with risk factors, and institutional care. Our sample included 197 children aged 5−18 years (M = 12.8, SD = 2.97), 50% boys, with IQ < 85 placed in different types and lengths of stay in institutional care. There were 17% that presented with borderline intellectual functioning (IQ 84−87) and 83% that had intellect disabilities. Adaptive behavior (AB) was assessed by Vineland Adaptive Behavior Scale (VABS-3). The BIF and Mild ID groups did not differ in Socialization. The profile of adaptive behavior for BIF and Mild ID was Daily Living Skills > Communication > Socialization, and for Moderate and Severe ID, Socialization > Daily Living Skills > Communication. Longer institutional care was associated with lower competencies in AB. Gender differences were found, females overperformed males in Socialization, Daily Living Skills, and ABC score. Levels of ID, gender, length of stay in institutional care, and neonatal difficulties were significant predictors in the model which explain the 63% variance of AB. The practical implications of the results are discussed related to the assessment of ID, prevention, and care for institutionalized children.

Comparing the impact of the first and second wave of COVID-19 lockdown on Slovak families with typically developing children and children with autism spectrum disorder.

LAY ABSTRACT: A global pandemic caused by a new coronavirus (severe acute respiratory syndrome coronavirus 2) affected everyday lives of all people, including individuals with special needs, such as autism spectrum disorder. The aim of this research was to compare the mental health of families with children with autism spectrum disorder to families with typically developing children, and between the first and the second wave of COVID-19 outbreak in Slovakia. This mainly included symptoms of depression, anxiety, and stress of parents and problem behavior or sleeping difficulties of their children. The research sample consisted of 332 parents (155 of which have children with autism spectrum disorder), 179 surveyed during the first wave and 153 during the second wave. Online parent questionnaire was created, including demographic and specific topic questions, Depression Anxiety and Stress Scale-42 questionnaire, and internalizing and externalizing maladaptive behavior subscales from Vineland Adaptive Behavior Scales. Our results show that during the first wave, parents of autism spectrum disorder children suffered high levels of anxiety. During the second wave, both groups of parents suffered increased anxiety, stress, and depression, but especially severe for parents of children with autism spectrum disorder. Internalizing maladaptive behavior of autistic children grew significantly between the waves. Parental depression, anxiety, and stress were interconnected with maladaptive behavior of both autism spectrum disorder and typically developing children, suggesting the importance of the therapy options for whole families.

The acute effect of psychosocial stress on the level of oxidative stress in children.

The effect of chronic stress on oxidative stress (OS) is commonly discussed while the effect of acute stress situation is not fully examined yet. The present study was aimed to analyse whether acute psychosocial strain causes changes in OS and antioxidant status. Unstimulated saliva was collected from 46 healthy prepubertal children during the control and stress day. On the stress day, collection was performed before and after a stress situation induced by the Trier social stress test. Saliva collection during the control day imitated the stress day without the stress strain. Samples were used for analysis of lipid peroxidation, thiobarbituric acid reactive substances (TBARS), advanced glycation end products (AGEs) and markers of antioxidant status, total antioxidant capacity (TAC) and ferric reducing antioxidant power (FRAP). On the stress day, increased level of FRAP was observed in the second saliva collection in comparison with the first collection. Within the same day, no significant changes in the levels of TBARS, AGEs and TAC were observed in samples taken before and after stress strain. Significantly higher levels of TBARS were observed on stress day in comparison to control day. In summary, acute psychosocial stress caused increase of FRAP during the stress day. TBARS did not increase during the stress day in the second sample but it was higher compared to the control day. None of the interactions with gender were statistically significant. It appears the short-term exposure to stress could potentially stimulate antioxidant activity.

A Novel UHPLC-MS Method Targeting Urinary Metabolomic Markers for Autism Spectrum Disorder.

Autism spectrum disorder is a heterogeneous neurodevelopmental disease. Currently, no biomarker of this disease is known. Diagnosis is performed through observation, standardized behavioral scales, and interviews with parents. In practice, diagnosis is often delayed to the average age of four years or even more which adversely affects a child's perspective. A laboratory method allowing to detect the disorder at earlier stages is of a great need, as this could help the patients to start with treatment at a younger age, even prior to the clinical diagnosis. Recent evidence indicates that metabolomic markers should be considered as diagnostic markers, also serving for further differentiation and characterization of different subgroups of the autism spectrum. In this study, we developed an ultra-high performance liquid chromatography-tandem triple quadrupole mass spectrometry method for the simultaneous determination of six metabolites in human urine. These metabolites, namely methylguanidine, N-acetyl arginine, inosine, indole-3-acetic acid, indoxyl sulfate and xanthurenic acid were selected as potential biomarkers according to prior metabolomic studies. The analysis was carried out by means of reversed-phase liquid chromatography with gradient elution. Separation of the metabolites was performed on a Phenomenex Luna® Omega Polar C18 (100 × 1.0 mm, 1.6 µm) column at a flow rate of 0.15 mL/min with acetonitrile/water 0.1% formic acid aqueous as the mobile phase. The analysis was performed on a group of children with autism spectrum disorder and age-matched controls. In school children, we have detected disturbances in the levels of oxidative stress markers connected to arginine and purine metabolism, namely methylguanidine and N-acetylargine. Also, products of gut bacteria metabolism, namely indoxyl sulfate and indole-3-acetic acid, were found to be elevated in the patients' group. We can conclude that this newly developed method is fast, sensitive, reliable, and well suited for the quantification of proposed markers.

Alteration of the steroidogenesis in boys with autism spectrum disorders.

The etiology of autism spectrum disorders (ASD) remains unknown, but associations between prenatal hormonal changes and ASD risk were found. The consequences of these changes on the steroidogenesis during a postnatal development are not yet well known. The aim of this study was to analyze the steroid metabolic pathway in prepubertal ASD and neurotypical boys. Plasma samples were collected from 62 prepubertal ASD boys and 24 age and sex-matched controls (CTRL). Eighty-two biomarkers of steroidogenesis were detected using gas-chromatography tandem-mass spectrometry. We observed changes across the whole alternative backdoor pathway of androgens synthesis toward lower level in ASD group. Our data indicate suppressed production of pregnenolone sulfate at augmented activities of CYP17A1 and SULT2A1 and reduced HSD3B2 activity in ASD group which is partly consistent with the results reported in older children, in whom the adrenal zona reticularis significantly influences the steroid levels. Furthermore, we detected the suppressed activity of CYP7B1 enzyme readily metabolizing the precursors of sex hormones on one hand but increased anti-glucocorticoid effect of 7α-hydroxy-DHEA via competition with cortisone for HSD11B1 on the other. The multivariate model found significant correlations between behavioral indices and circulating steroids. From dependent variables, the best correlation was found for the social interaction (28.5%). Observed changes give a space for their utilization as biomarkers while reveal the etiopathogenesis of ASD. The aforementioned data indicate a direction of the future research with a focus on the expression and functioning of genes associated with important steroidogenic enzymes in ASD patients from early childhood to adrenarche.

Gastrointestinal Symptoms and Feeding Problems and Their Associations with Dietary Interventions, Food Supplement Use, and Behavioral Characteristics in a Sample of Children and Adolescents with Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are characterized by impairments in social interaction, communication, and restricted, stereotyped behavior. Gastrointestinal (GI), nutritional, and feeding problems are often reported in ASD. We investigated the prevalence of GI symptoms, food selectivity, and mealtime difficulties, and their associations with dietary interventions, food supplement use, and behavioral characteristics in a sample involving 247 participants with ASD and 267 controls aged 2-18 years. Data were collected by a questionnaire. GI symptoms were observed in 88.9% of children and adolescents with ASD, more often in girls than in boys. High rates of food selectivity (69.1%) and mealtime problems (64.3%) were found. Food supplements were used by 66.7% of individuals, mainly vitamins/minerals, probiotics, and omega-3 fatty acids. In the ASD sample, 21.2% of subjects followed a diet, mostly based on gluten and milk restriction, including individuals exhibiting food selectivity. Frequency of GI symptoms, food selectivity, and mealtime problems correlated weakly, but significantly with behavioral characteristics in the ASD group, but not with food supplement use. The study demonstrated that higher frequency of GI symptoms, food selectivity, and mealtime problems are a common problem in pre-schoolers, schoolchildren, and adolescents with ASD, and together with dietary modification, they are significantly associated with ASD.