Abstract

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).

Highlights

  • 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 [1]

  • References were identified through electronic database searching in Medline (Ovid, 1946 to present) and EMBASE (Ovid), and they were adapted for Scopus (Elsevier), ERIC (Proquest), PubMed, and the Web of Science (ISI)

  • No significant associations were found for autism symptoms in glutamate and gamma aminobutyric acid (GABA) gene set which reinforces the need for further research on the genetics of excitatory/inhibitory imbalance in ASD [44]

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Summary

Introduction

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 [1]. There are several medical conditions comorbid to autism such as immunological disorders, gastrointestinal diseases, sleep-related breathing disorders, and there are several genetic syndromes commonly associated with autism (fragile X syndrome, Rett syndrome, Angelman syndrome, tuberous sclerosis complex, Phelan McDermid syndrome, Timothy syndrome, neurofibromatosis type 1, etc.) [6,7,8]. All these factors contribute to a phenotypic heterogeneity that necessarily reflects a complex multifactorial etiology of ASD. This review focuses on evidence that suggests a role for neurotransmission dysregulation in autism and how these alterations could be useful for pharmacologic intervention in autism or as precocious biomarkers

Aims and Methods
Gamma Aminobutyric Acid
Glutamate
Serotonin
Dopamine
Acetylcholine
N-acetyl Aspartate
Oxytocin and Arginine-Vasopressin
10. Melatonin
11. Vitamin D
12. Orexin System
13. Endogenous Opioids
Findings
14. Discussion
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