Epigenetic Understanding of Gene-Environment Interaction in Autism Spectrum Disorder

2017 ◽  
Vol 15 (03) ◽  
pp. 099-104
Author(s):  
Takeo Kubota

AbstractThe number of children with autism spectrum disorder (ASD) has increased in many countries over the past 10 years. Genetic studies have revealed that ASD is caused by mutations in the genes coding proteins related to neuronal function. However, such genetic abnormalities cannot underlie the increase in this disorder since mutations do not accumulate among children in the short-term. Epigenetics is a mechanism that is involved in gene regulation not by changing DNA sequence (mutations) but by changing the chemical modifications of DNA and histone proteins. Current studies suggest that mental stress and other forms of environmental stress in early life alter the epigenetic status of genes and change the neuronal gene function, resulting in persistent behavioral abnormalities. Therefore, it can be speculated that the current increase in the prevalence of ASD is partially caused by epigenetic changes in the brains of children induced by some recent socio-environmental conditions. However, epigenetic changes are reversible. Indeed, it has been demonstrated that some drugs for mental disorders reverse the altered epigenetic state and recover the expression of neuronal genes. It has also been demonstrated that offering an appropriate nurturing environment in early life reverses the altered epigenetic state and recovers the neurological gene function in mouse models of ASD. Therefore, from the epigenetic point of view, early medical and educational interventions may be important for children with ASD.

2019 ◽  
Author(s):  
◽  
Kwame De Jongge-Moore

Problem Statistics indicate that Autism Spectrum Disorder (ASD) is on the increase in America and worldwide (Xu, Strathearn, Liu, & Bao, 2018; Baio et al., 2018). Autism spectrum disorder can impair an individual’s ability to engage in neurotypical behavior, which has the potential to increase their vulnerability to being shunned and bullied. This makes autism a major societal concern with significant costs to the individual, their family, private/public health insurance, state financial aid programs, and to the nation. This present study was undertaken to determine, in the opinions of those connected to the case, whether the interventions engaged in this case were effective and to what extent the educational and social interventions practiced in this specific case were responsible for enabling Carter to reach the place where the diagnosticians felt that he no longer met the criteria for receiving services for autism spectrum disorder. Purpose The purpose of this study was to identify social and educational interventions used in Carter's journey with Autism Spectrum Disorder and to document the social and educational interventions employed by several individuals who worked with him. Further, the study sought to describe the impact of these interventions on Carter, from the perspectives of the key individuals involved in the early education of the child. Additionally, the study set out to determine whether these interventions actually enabled Carter to no longer meet the criteria for receiving services for autism spectrum disorder. -- Method The study employed a qualitative case study approach which gathered data mainly through semi-structured interviews and focus groups. Other data sources included Carter’s mother's (Meghan's) account of her experience, key documents, and examples of learning activities found to be of benefit to the child. The nine individuals who were interviewed were invited to participate because they had been directly involved with the case. The data was analyzed using NVivo data analysis. Results The results from the analysis of the data study indicate that there was a positive relationship between the interventions reported and Carter's no longer meeting the criteria for services for ASD. The activities reported proved to be too numerous to be mentioned individually and were therefore grouped thematically. The two large groups were the social interventions and the educational interventions. The social interventions group was comprised of activities, such as Gymfants (gymnastics for young children), Children’s Choir, Adventurers Club, and attending regular school which promoted social interactions. These groups facilitated Carter’s working with others, taking directions from others, imitating others, leading, following, and taking turns. Language was key to these interactions. Educational interventions included; reading, attending homeschool, regular school, strategic games such as Connect Four, Uno, and geographical puzzles, floor puzzles; foreign language videos and science videos among other activities. These interventions incorporated language and encouraged Carter in individual work, seated work, pattern identification, and viewing for a purpose among other things. These interventions were planned by Meghan outside of the Individualized Educational Plan (IEP) and in addition to Speech Therapy. Conclusions As a result of this study, the reader can see that the curriculum developed for Carter by Meghan was directly related to his progress. The study concluded that Carter's family working together to provide the program of interventions contributed greatly to his no longer meeting the criteria to remain in the autism therapy program designed for him by the Individualized Educational Plan (IEP) team. It appeared that the intentionality of Carter’s support team had a significant relationship with his progress. It was also concluded that there was a strong relationship between Music as a theme and Carter's progress. The study concluded that the combination of educational and social interventions employed with Carter helped to eliminate the need for him to receive services for autism spectrum disorder. The study showed that intervention in autism requires parental involvement as the delivery of a variety of social and educational interventions through the medium of the home allowed for a natural, meaningful and permanent transfer of knowledge and growth in a number of areas. It is therefore obligatory that the parent/therapist/school partnership be supported and empowered.


2020 ◽  
Vol 174 (7) ◽  
pp. 690 ◽  
Author(s):  
Karen Frankel Heffler ◽  
Danielle M. Sienko ◽  
Keshab Subedi ◽  
Kathleen A. McCann ◽  
David S. Bennett

Autism ◽  
2017 ◽  
Vol 23 (1) ◽  
pp. 60-70 ◽  
Author(s):  
Katie Maras ◽  
Tim Gamble ◽  
Mark Brosnan

Previous research suggests impaired metacognitive monitoring and mathematics under-achievement in autism spectrum disorder. Within educational settings, metacognitive monitoring is supported through the provision of feedback (e.g. with goal reminders and by explicitly correcting errors). Given the strength of the relationship between metacognition, learning and educational attainment, this research tested new computer-based metacognitive support (the ‘Maths Challenge’) for mathematics learners with autism spectrum disorder within the context of their classroom. The Maths Challenge required learners to engage in metacognitive monitoring before and after answering each question (e.g. intentions and judgements of accuracy) and negotiate with the system the level of difficulty. Forty secondary school children with autism spectrum disorder and 95 typically developing learners completed the Maths Challenge in either a Feedback condition, with metacognitive monitoring support regarding the accuracy of their answers, goal reminders and strategy support, or with No Feedback. Contrary to previous findings, learners with autism showed an undiminished ability to detect errors. They did, however, demonstrate reduced cohesion between their pre- and post-test intentions. Crucially, support from the Feedback condition significantly improved task performance for both groups. Findings highlight important implications for educational interventions regarding the provision of metacognitive support for learners with autism to ameliorate under-performance in mathematics within the classroom.


Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 28
Author(s):  
Iris W. Riemersma ◽  
Robbert Havekes ◽  
Martien J. H. Kas

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is characterized by differences in social interaction, repetitive behaviors, restricted interests, and sensory differences beginning early in life. Especially sensory symptoms are highly correlated with the severity of other behavioral differences. ASD is a highly heterogeneous condition on multiple levels, including clinical presentation, genetics, and developmental trajectories. Over a thousand genes have been implicated in ASD. This has facilitated the generation of more than two hundred genetic mouse models that are contributing to understanding the biological underpinnings of ASD. Since the first symptoms already arise during early life, it is especially important to identify both spatial and temporal gene functions in relation to the ASD phenotype. To further decompose the heterogeneity, ASD-related genes can be divided into different subgroups based on common functions, such as genes involved in synaptic function. Furthermore, finding common biological processes that are modulated by this subgroup of genes is essential for possible patient stratification and the development of personalized early treatments. Here, we review the current knowledge on behavioral rodent models of synaptic dysfunction by focusing on behavioral phenotypes, spatial and temporal gene function, and molecular targets that could lead to new targeted gene-based therapy.


2021 ◽  
Author(s):  
◽  
Caren L. August

<p>Autism Spectrum Disorder is a complex neurodevelopmental disorder which is often associated with increased anxiety and deficits in cognitive ability. The present research investigated a potential gene*environment interaction between two factors previously implicated in ASD in a rat model; prenatal exposure to valproate (VPA) and genetic reduction of the serotonin transporter (SERT). Wildtype and heterozygous SERT knockout rats prenatally exposed to VPA or saline on gestational day12.5 (G12.5) were assessed on measures of anxiety: elevated plus-maze and novelty suppressed-feeding and cognitive ability: prepulse inhibition and latent inhibition. A significant main effect was found for VPA exposure in all paradigms, showing increased anxiety-typical behaviour and abnormal cognitive ability. However, no significant effect of genotype or interaction was observed. Results from the present study do not confirm gene*environment interaction between prenatal VPA and heterozygous SERT knockout but this may be due to several factors that are discussed within the thesis. In any case, this study represents a starting point for further studies investigating other combinations of genetic and environmental factors as models of ASD pathogenesis.</p>


Author(s):  
Alessandro Miani ◽  
Giovanni Imbriani ◽  
Giovanni De Filippis ◽  
Donato De Giorgi ◽  
Luigi Peccarisi ◽  
...  

Background: Autism spectrum disorder (ASD) diagnoses have rapidly increased globally. Both environmental and genetic factors appear to contribute to the development of ASD. Several studies have shown a potential association between prenatal or postnatal pesticide exposure and the risk of developing ASD. Methods: We reviewed the available literature concerning the relationship between early life exposure to pesticides used in agriculture, such as organochlorines, organophosphates and pyrethroids, and ASD onset in childhood. We searched on Medline and Scopus for cohort or case–control studies published in English from 1977 to 2020. Results: A total of seven articles were selected for the review. We found a remarkable association between the maternal exposure to pyrethroid, as well as the exposure to organophosphate during pregnancy or in the first years of childhood, and the risk of ASD onset. This association was found to be less evident with organochlorine pesticides. Pregnancy seems to be the time when pesticide exposure appears to have the greatest impact on the onset of ASD in children. Conclusions: Among the different environmental pollutants, pesticides should be considered as emerging risk factors for ASD. The potential association identified between the exposure to pesticides and ASD needs to be implemented and confirmed by further epidemiological studies based on individual assessment both in outdoor and indoor conditions, including multiple confounding factors, and using statistical models that take into account single and multiple pesticide residues.


Autism ◽  
2022 ◽  
pp. 136236132110682
Author(s):  
Cindy Pham ◽  
Christos Symeonides ◽  
Martin O’Hely ◽  
Peter D Sly ◽  
Luke D Knibbs ◽  
...  

Mounting evidence finds that early life environmental factors increased the probability of autism spectrum disorder. We estimated prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93; 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status; maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress; prenatal alcohol; environmental air pollutant exposures, including particulate matter < 2.5 µm at birth, child secondhand tobacco smoke exposure at 12 months, dampness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression, and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways. Lay abstract Mounting evidence indicates the contribution of early life environmental factors in autism spectrum disorder. We aim to report the prospective associations between early life environmental factors and autism spectrum disorder symptoms in children at the age of 2 years in a population-derived birth cohort, the Barwon Infant Study. Autism spectrum disorder symptoms at the age of 2 years strongly predicted autism spectrum disorder diagnosis by the age of 4 years (area under curve = 0.93; 95% CI (0.82, 1.00)). After adjusting for child’s sex and age at the time of behavioural assessment, markers of socioeconomic disadvantage, such as lower household income and lone parental status; maternal health factors, including younger maternal age, maternal pre-pregnancy body mass index, higher gestational weight gain and prenatal maternal stress; maternal lifestyle factors, such as prenatal alcohol and environmental air pollutant exposures, including particulate matter < 2.5 μm at birth, child secondhand tobacco smoke at 12 months, dampness/mould and home heating with oil, kerosene or diesel heaters at 2 years postnatal. Lower socioeconomic indexes for area, later birth order, higher maternal prenatal depression and maternal smoking frequency had a dose-response relationship with autism spectrum disorder symptoms. Future studies on environmental factors and autism spectrum disorder should consider the reasons for the socioeconomic disparity and the combined impact of multiple environmental factors through common mechanistic pathways.


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