Epigenetic Findings in Autism: New Perspectives for Therapy

Abstract

Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders characterized by dysfunctions in social interactions, communications, restricted interests, and repetitive stereotypic behaviors. Despite extensive genetic and biological research, significant controversy surrounds our understanding of the specific mechanisms of their pathogenesis. However, accumulating evidence points to the involvement of epigenetic modifications as foundational in creating ASD pathophysiology. Epigenetic modifications or the alteration of DNA transcription via variations in DNA methylation and histone modifications but without alterations in the DNA sequence, affect gene regulation. These alterations in gene expression, obtained through DNA methylation and/or histone modifications, result from transcriptional regulatory influences of environmental factors, such as nutritional deficiencies, various toxicants, immunological effects, and pharmaceuticals. As such these effects are epigenetic regulators which determine the final biochemistry and physiology of the individual. In contrast to psychopharmacological interventions, bettering our understanding of how these gene-environmental interactions create autistic symptoms should facilitate the development of therapeutic targeting of gene expression for ASD biomedical care.

Mitochondria, Microbiome and Their Potential Psychiatric Modulation

“…A recent study conducted on rodents administering propionic acid provides evidence that this SCFA can produce reversible behavioral changes, such as metabolic, neuroinflammatory, and epigenetic alterations, which are also identified in ASD [14]. Importantly, these alterations may be associated with mitochondrial dysfunction involving carnitine metabolism, as well as epigenetic modulation of the genes associated with ASD [8]. Taken together, the causes of ASDs are potentially influenced by environmental factors, which cause intestinal microbiota to become altered, suggesting novel prevention or treatment methods.…”

“…Epigenetic modifications, e.g., DNA methylation and histone modifications, certainly affect stereospecific regulatory processes of genetic outcomes. Siniscalco [8,9] and colleagues note that nutritional deficiencies and other chemical stressors appear to be epigenetic regulators, which affect individual health via affecting the gut microbiome. Preferential evidence favoring genetically driven etiological factors is compelling and is inherently complex, but perhaps underestimates the contribution of environmental determinants [2,28,29] such as the gut microbiome.…”

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

“…Hence, most cases still remain unknown, but potentially, including additional less penetrant rare variants or complex mechanisms, such as gene-gene interaction or gene-environment interaction. In this way, one might conclude that interactions between multiple genes cause "idiopathic" autism, but that "epigenetic dysregulation" and exposure to environmental modifiers might contribute to variable expression of autism-related traits [93] and to significant proportion of ASD cases [94][95][96].…”

Combined arsenic and di-(2-ethylhexyl) phthalate exposure elicits responses in brain ATPases different from hepatic and renal activities in rats

“…Environmental contaminants like arsenic and DEHP have been implicated in some neuropathological conditions (Testa et al, 2012;Siniscalco et al, 2013;Akyuzlu et al, 2014;Manivannan et al, 2015). There are also growing concerns about the adverse effects of toxicants on neurodevelopment (Kim et al, 2009;XiuJuan et al, 2013).…”