Abstract
Background: The occurrence of neurodevelopmental disorders (NDDs) is determined by complex and multiple causal factors. In other words, NDDs arise as a result of a combination of genetic, biological, psychosocial, and environmental risk factors. Prospective studies indicate that exposure to organochlorine pesticides (OCPs) during fetal life, infancy, and early childhood may be associated with features of NDDs in children. However, few studies have investigated the concentrations of serum OCPs in children with categorically diagnosed NDDs. Moreover, there is evidence that children with NDDs may exhibit atypical responses to stress and alterations in concentrations and diurnal secretion of stress hormones. Also, immune system perturbations have been reported in several NDDs. For example, high mobility group box 1 protein (HMGB1), which is a protein from the alarmin family, has been suggested to be involved in the immune dysfunction and inflammation reported in Autism Spectrum Disorder (A ...
Background: The occurrence of neurodevelopmental disorders (NDDs) is determined by complex and multiple causal factors. In other words, NDDs arise as a result of a combination of genetic, biological, psychosocial, and environmental risk factors. Prospective studies indicate that exposure to organochlorine pesticides (OCPs) during fetal life, infancy, and early childhood may be associated with features of NDDs in children. However, few studies have investigated the concentrations of serum OCPs in children with categorically diagnosed NDDs. Moreover, there is evidence that children with NDDs may exhibit atypical responses to stress and alterations in concentrations and diurnal secretion of stress hormones. Also, immune system perturbations have been reported in several NDDs. For example, high mobility group box 1 protein (HMGB1), which is a protein from the alarmin family, has been suggested to be involved in the immune dysfunction and inflammation reported in Autism Spectrum Disorder (ASD). Methods: In the current thesis three independent cross-sectional studies are presented. The aim of the first study was to assess the serum concentrations (SCs) and detection rates (DRs) of Dichlorodiphenyltrichloroethane (DDT) metabolites, Hexachlorocyclohexane (HCH) isomers, cyclodienes, and methoxychlor in children with ASD, Attention-Deficit Hyperactivity Disorder (ADHD), and Specific Learning Disorder (SLD), all of normal intelligence, compared to Typically Developing controls (TD). In total 114 schoolchildren, of both sexes, aged 6-13 years old, were distributed into four groups: ASD (n=39), ADHD (n=21), SLD (n=32) and TD (n=18). Each clinical group was compared to the TD group. SCs were determined by gas chromatography and are presented as nanograms/gram lipid. In the second study, we assessed diurnal profiles and stress responses of salivary cortisol and α-amylase (sAA) in children with ASD, ADHD, and SLD compared to TD children. A total of 157 children of both sexes, aged 6-12 years old, distributed into four groups: ADHD (N=34), ASD (N=56), SLD (N=43), TD (N=24). Salivary samples were collected at three time points during the day, as well as before and 5 min after an academic performance test and a moral cognition task. Finally, the third study aimed to assess HMGB1 SCs in high-functioning ASD children compared to TD controls and to explore their associations with the Autism Spectrum Quotient (AQ), the Empathy Quotient (EQ), and the Systemizing Quotient (SQ). The study involved 42 ASD children and 38 TD children, all-male, aged 6-13 years old. HMGB1 SCs were measured by enzyme-linked immunosorbent assay. Groups were comparable regarding age, general IQ, birth weight, and maternal age at birth.Results: Regarding the first study, SCs of β-HCH, the sum of HCH isomers, and o,p΄-DDD were significantly higher in ASD children. The DRs of p,p΄-DDT, at least one substance from DDTs detected, and heptachlor epoxide were significantly lower in the ASD group. No significant differences were observed between the ADHD or SLD groups and the TD group. As for the second study, ADHD children had a lower evening and diurnal sAA levels and ASD children showed lower diurnal sAA secretion, adjusted for age. The mean percentage change for salivary cortisol and sAA after both tests did not differ between the groups. Concerning the third study, ASD group showed significantly higher HMGB1 SCs vs. TD children. Also, Spearman’s rho revealed that HMGB1 SCs were positively correlated with the AQ attention to detail subscale and with the SQ total score in the ASD group.Conclusion: Firstly, we demonstrated higher SCs and DRs of selected OCPs in ASD than TD children. These results add to potential neurodevelopmental concerns surrounding OCPs and provide evidence of specificity in the relations between HCHs and ASD. Regarding the stress system functioning, the present study contributes to the existing data on the alterations observed in the stress system activity in children with NDDs. We demonstrated alterations in diurnal autonomic functioning in children with ADHD and ASD, while HPA axis functioning did not differ between the clinical and the comparison groups. Also, the responses of the stress system to the cognitive tests administered did not differ between the study groups. In general, our findings are placed in the wider literature that shows ANS dysfunction in both children with ADHD and children with ASD. Finally, the results of the study on HMGB1 serum levels in ASD children provide data on the possible role of inflammatory processes in the pathophysiology of ASD. In addition, the present study provides data on the association between inflammatory processes, particularly elevated serum HMGB1 levels, and AQ and SQ variables, suggesting that inflammatory processes mediated by HMGB1 may be associated with specific cognitive features characterizing ASD.
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