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.
- Publikační typ
- časopisecké články MeSH
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.
- MeSH
- biologické markery MeSH
- dítě MeSH
- lidé MeSH
- poruchy autistického spektra * MeSH
- předškolní dítě MeSH
- steroidy MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Biomechanical properties of erythrocytes play an important role in health and disease. Deformability represents intrinsic property of erythrocytes to undergo deformation that is crucial for their passage through the narrow capillaries. The erythrocyte damage can lead to compromised tissue perfusion and consequently play a role in the pathogenesis of various diseases including neurological ones. Data available in databases indicate that erythrocytes in autism spectrum disorder (ASD) are altered. This may affect the clinical symptoms of ASD. The aim of our study was to determine erythrocyte deformability in 54 children with ASD and correlate it with clinical symptoms. We found significant negative correlation between erythrocyte deformability and score in C domain of the Autism Diagnostic Interview-Revised (ADI-R) diagnostic tool describing the measure of restrictive, repetitive, and stereotyped behaviors and interests, mainly observable in C1 and C2, but not in C3 and C4 subdomains. This supports the findings of other authors and suggest that behavioral domain C comprises of more subcategories with different underlying etiology. Our results also indicate that abnormalities in erythrocyte deformability may be involved in ASD pathomechanisms and contribute to its clinical manifestation. Further research is necessary to bring more data and identify erythrocyte deformability as prognostic biomarker in ASD.
Adekvátny príjem kvalitatívne i kvantitatívne vyváženej potravy je u detí a adolescentov nevyhnutný pre zdravý psychosomatický vývin. V súčasnosti sa pozornosť odborníkov zameriava najmä na prevenciu nadmerného prísunu kalórii u detí, napriek tomu však podľa výskumov 3–4 % detí trpí závažným odmietaním jedla bez známej somatickej príčiny, označovaným ako psychogénna strata chuti do jedla. V liečbe tejto poruchy sa v súčasnosti najčastejšie uplatňuje „vyčkávacia“ metóda, preukázalo sa však, že najúčinnejšou intervenciou sú techniky založené na behaviorálnej terapii. Cieľom našej práce je popísať základné etiologické aspekty psychogénnej straty chuti do jedla a prezentovať techniky, ktoré sa vo svete najviac využívajú v psychoterapii tejto poruchy. Techniky vychádzajú najmä z princípov behaviorálnej terapie, pričom cieľom je primárne zmena správania. Poznanie a využívanie týchto stratégii má význam nielen pre vedeckú komunitu, ale aj klinických pracovníkov a rodičov.
Adequate intake of qualitatively and quantitatively balanced food is essential for healthy psychosomatic development of children and adolescents. At present time, the experts focus mostly on excessive calorie intake, due to high obesity prevalence in children. However, according to current knowledge 3-4% of children suffer from severe food refusal without a known somatic cause, referred to as avoidant/restrictive food intake disorder, or psychogenic loss of appetite. The “wait-and-see” method is currently the most commonly used in the management of this disorder, but the most effective intervention has been shown to be techniques based on behavioral therapy. The aim of our work is to describe the main etiological aspects of the avoidant/restrictive food intake disorder and to introduce methods that are most effective for its treatment. These methods are based primarily on behavioral therapy principles, where our goal is the behavioral change. Knowledge and application of these strategies is important for not only scientific community, but also for clinical professionals and parents.
Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impaired social interaction and communication, as well as repetitive behavior and restricted interests. There is convincing evidence that the intestinal inflammation is involved in etiology of ASD. Increased levels of inflammatory markers were shown to be associated with more aberrant behaviors and communication of subjects with ASD. Calprotectin in the feces is produced by activated neutrophils and epithelial cells of the gut mucosa, and its levels reflect local inflammation of the gastrointestinal tract. Concentration of fecal calprotectin was determined by ELISA method in 87 individuals with ASD and 51 controls, of that 29 siblings of children with ASD and 22 non-related controls. In non-relatives significantly lower values of fecal calprotectin were observed than in both subjects with ASD and their siblings. In the group with ASD significant correlations of fecal calprotectin with all domains of the ADI-R diagnostic tool were found: qualitative abnormalities in reciprocal social interaction and communication, restrictive and repetitive patterns of behavior. Results suggest that low grade intestinal inflammation may be one of factors implicated in the pathophysiology of ASD.
- MeSH
- dítě MeSH
- ELISA metody MeSH
- feces * chemie MeSH
- interpersonální vztahy * MeSH
- leukocytární L1-antigenní komplex analýza metabolismus MeSH
- lidé MeSH
- mladiství MeSH
- neuropsychologické testy * MeSH
- poruchy autistického spektra diagnóza epidemiologie metabolismus MeSH
- předškolní dítě MeSH
- průřezové studie MeSH
- zánět diagnóza epidemiologie metabolismus MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika epidemiologie MeSH
