Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

Abstract

Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multi‐omics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. The non‐targeted omics and targeting studies of diagnostic markers for ASD were also reviewed. Moreover, we summarized the progress and methods of behavioral and educational interventions, intervention methods related to technological devices, and research on medical interventions and potential drug targets. This review highlighted the application of high‐throughput omics methods in ASD research and emphasized the importance of seeking homogeneity from heterogeneity and exploring the convergence of disease mechanisms, biomarkers, and intervention approaches, and proposes that taking into account individuality and commonality may be the key to achieve accurate diagnosis and treatment of ASD.

Roles of Epigenetics and Glial Cells in Drug-Induced Autism Spectrum Disorder

“…Interestingly, high levels of p-cresol, which is produced by bacterial fermentation of protein in the human large intestine, and correlates with ASD severity, have been detected in blood, urine, and stool of children with ASD. These children also express other gut microbial metabolites, including SCFAs, free amino acids, indoles, and lipopolysaccharides, in their blood and urine [181]. Thus, it has been proposed that the analysis of gut microbes and the detection of microbial-derived metabolites in stool, blood, and urine may provide an alternative method for the early diagnosis of ASD [181].…”

“…These children also express other gut microbial metabolites, including SCFAs, free amino acids, indoles, and lipopolysaccharides, in their blood and urine [181]. Thus, it has been proposed that the analysis of gut microbes and the detection of microbial-derived metabolites in stool, blood, and urine may provide an alternative method for the early diagnosis of ASD [181]. The outcome is a disturbance in the homeostasis, which can also involve glial dysregulation.…”

“…Although neither specific biomarkers nor cures for ASD are available, there are several ways to minimize symptoms and maximize abilities. In this regard, behavioral management therapy, cognitive behavioral therapy, speech language therapy, social skills training, and physical and nutritional therapies, as well treatments with medications for the alleviation of some symptoms, are common interventions [181]. The latter include the use of SSRI and tricyclic antidepressants, psychoactive or antipsychotic medications, stimulants, anxiolytics, and anticonvulsants [181,192].…”

“…In this regard, behavioral management therapy, cognitive behavioral therapy, speech language therapy, social skills training, and physical and nutritional therapies, as well treatments with medications for the alleviation of some symptoms, are common interventions [181]. The latter include the use of SSRI and tricyclic antidepressants, psychoactive or antipsychotic medications, stimulants, anxiolytics, and anticonvulsants [181,192]. Moreover, because oxidative stress, inflammation, and mitochondrial dysfunction are common pathophysiological mechanisms of ASD, drugs targeting these factors are being advocated [181].…”

“…The latter include the use of SSRI and tricyclic antidepressants, psychoactive or antipsychotic medications, stimulants, anxiolytics, and anticonvulsants [181,192]. Moreover, because oxidative stress, inflammation, and mitochondrial dysfunction are common pathophysiological mechanisms of ASD, drugs targeting these factors are being advocated [181]. In addition, probiotics, prebiotics, fecal microbiota transplantation, microbiota transfer therapy, antibiotics, and dietary adjustment methods may provide additional reliefs [181,[192][193][194].…”