Autism spectrum disorder (ASD) refers to complex neurobehavioral and neurodevelopmental conditions characterized by impaired social interaction and communication, restricted and repetitive patterns of behavior or interests, and altered sensory processing. Environmental, immunological, genetic, and epigenetic factors are implicated in the pathophysiology of autism and provoke the occurrence of neuroanatomical and neurochemical events relatively early in the development of the central nervous system. Many neurochemical pathways are involved in determining ASD; however, how these complex networks interact and cause the onset of the core symptoms of autism remains unclear. Further studies on neurochemical alterations in autism are necessary to clarify the early neurodevelopmental variations behind the enormous heterogeneity of autism spectrum disorder, and therefore lead to new approaches for the treatment and prevention of autism. In this review, we aim to delineate the state-of-the-art main research findings about the neurochemical alterations in autism etiology, and focuses on gamma aminobutyric acid (GABA) and glutamate, serotonin, dopamine, N-acetyl aspartate, oxytocin and arginine-vasopressin, melatonin, vitamin D, orexin, endogenous opioids, and acetylcholine. We also aim to suggest a possible related therapeutic approach that could improve the quality of ASD interventions. Over one hundred references were collected through electronic database searching in Medline and EMBASE (Ovid), Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI).

Purpose. Immune system of some autistic patients could be abnormally triggered by gluten/casein assumption. The prevalence of antibodies to gliadin and milk proteins in autistic children with paired/impaired intestinal permeability and under dietary regimen either regular or restricted is reported.Methods. 162 ASDs and 44 healthy children were investigated for intestinal permeability, tissue-transglutaminase (tTG), anti-endomysium antibodies (EMA)-IgA, and total mucosal IgA to exclude celiac disease; HLA-DQ2/-DQ8 haplotypes; total systemic antibodies (IgA, IgG, and IgE); specific systemic antibodies:α-gliadin (AGA-IgA and IgG), deamidated–gliadin-peptide (DGP-IgA and IgG), total specific gliadin IgG (all fractions:α,β,γ, andω),β-lactoglobulin IgG,α-lactalbumin IgG, casein IgG; and milk IgE, casein IgE, gluten IgE, -lactoglobulin IgE, andα-lactalbumin IgE.Results. AGA-IgG and DPG-IgG titers resulted to be higher in ASDs compared to controls and are only partially influenced by diet regimen. Casein IgG titers resulted to be more frequently and significantly higher in ASDs than in controls. Intestinal permeability was increased in 25.6% of ASDs compared to 2.3% of healthy children. Systemic antibodies production was not influenced by paired/impaired intestinal permeability.Conclusions. Immune system of a subgroup of ASDs is triggered by gluten and casein; this could be related either to AGA, DPG, and Casein IgG elevated production or to impaired intestinal barrier function.

Introduction: The role of sleep in cognitive processes can be considered clear and well established. Different reports have disclosed the association between sleep and cognition in adults and in children, as well as the impact of disturbed sleep on various aspects of neuropsychological functioning and behavior in children and adolescents. Behavioral and cognitive dysfunctions can also be considered as related to alterations in the executive functions (EF) system. In particular, the EF concept refers to self-regulatory cognitive processes that are associated with monitoring and controlling both thought and goal directed behaviors. The aim of the present study is to assess the impact of the obstructive sleep apnea syndrome (OSAS) on EF in a large sample of school aged children. Materials and methods: The study population comprised 79 children (51 males and 28 females) aged 7–12 years (mean 9.14 ± 2.36 years) with OSAS and 92 healthy children (63 males and 29 females, mean age 9.08 ± 2.44 years). To identify the severity of OSAS, an overnight respiratory evaluation was performed. All subjects filled out the Italian version of the Modified Card Sorting Test to screen EFs. Moreover, to check the degree of subjective perceived daytime sleepiness, all subjects were administered the Pediatric Daytime Sleepiness Scale (PDSS). Results: No significant differences between the two study groups were found for age (P = 0.871), gender (P = 0.704), z-score of body mass index (P = 0.656), total intelligence quotient (P = 0.358), and PDSS scores (P = 0.232). The OSAS children showed a significantly higher rate of total errors (P < 0.001), perseverative errors (P < 0.001), nonperseverative errors (P < 0.001), percentage of total errors (P < 0.001), percentage of perseverative errors (P < 0.001), and percentage of nonperseverative errors (P< 0.001). On the other hand, OSAS children showed a significant reduction in the number of completed categories (P = 0.036), total correct sorts (P = 0.001), and categorizing efficiency (P < 0.001). The Pearson's correlation analysis revealed a significant positive relationship between all error parameters and apnea-hypopnea index, oxygen desaturation index, and percentage of mean desaturation of O₂ with a specular negative relationship between the error parameters and the mean oxygen saturation values, such as a significant negative relationship between apnea-hypopnea index, oxygen desaturation index, percent of mean desaturation of O₂, and the number of completed categories. Conclusion: Our study identified differences in the executive functioning of children affected by OSAS and is the first to identify a correlation between alteration in respiratory nocturnal parameters and EF that has not yet been reported in developmental age. These findings can be considered as the strength and novelty of the present report in a large pediatric population.

A large body of literature reports the higher prevalence of epilepsy in subjects with Autism Spectrum Disorder (ASD) compared to the general population. Similarly, several studies report an increased rate of Subclinical Electroencephalographic Abnormalities (SEAs) in seizure-free patients with ASD rather than healthy controls, although with varying percentages. SEAs include both several epileptiform discharges and different non-epileptiform electroencephalographic abnormalities. They are more frequently associated with lower intellectual functioning, more serious dysfunctional behaviors, and they are often sign of severer forms of autism. However, SEAs clinical implications remain controversial, and they could represent an epiphenomenon of the neurochemical alterations of autism etiology. This paper provides an overview of the major research findings with two main purposes: to better delineate the state-of-the-art about EEG abnormalities in ASD and to find evidence for or against appropriateness of SEAs pharmacological treatment in ASD.