Abstract
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.
Highlights
Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders with multifactorial etiopathogenesis
Circulating unconjugated and conjugated steroids were detected in plasma of children diagnosed with autism categorized in module 1, ASD, and age-matched neurotypical controls, CTRL
The relationship between two independent variables i.e., group represented by CTRL or ASD and age and 83 individual potential predictors representing the hormones of steroid metabolic pathways were detected
Summary
Autism spectrum disorders (ASD) represent a group of neurodevelopmental disorders with multifactorial etiopathogenesis. One of them is the extreme male brain theory describing ASD cognitive traits in toward to a male behavioral pattern in a sense of dominance of systemizing as a male feature at the expense of empathizing as a female feature[1]. This theory together with the fetal androgen theory of autism[4] tries. TST plays an important role during early developmental stages of brain[5], these theories assume it might contribute to the development of autistic traits[1] This theory is supported by the fact that ASD is diagnosed in male individuals four times more likely than in females[6]. Studies performed on amniotic fluid found altered hormonal profile in a sense of higher level of androgens in children who turned to have ASD7,8
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