Genetic and environmental influences on structural brain measures in twins with autism spectrum disorder

Abstract Atypical growth patterns of the brain have been previously reported in autism spectrum disorder (ASD) but these alterations are heterogeneous across individuals, which may be associated with the variable effects of genetic and environmental influences on brain development. Monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD (aged 6–15 years) were recruited to participate in this study. T1-weighted MRIs (n = 164) were processed with FreeSurfer to evaluate structural brain measures. Intra-class correlations were examined within twin pairs and compared across diagnostic groups. ACE modeling was also completed. Structural brain measures, including cerebral and cerebellar gray matter (GM) and white matter (WM) volume, surface area, and cortical thickness, were primarily influenced by genetic factors in TD twins; however, mean curvature appeared to be primarily influenced by environmental factors. Similarly, genetic factors accounted for the majority of variation in brain size in twins with ASD, potentially to a larger extent regarding curvature and subcortical GM; however, there were also more environmental contributions in twins with ASD on some structural brain measures, such that cortical thickness and cerebellar WM volume were primarily influenced by environmental factors. These findings indicate potential neurobiological outcomes of the genetic and environmental risk factors that have been previously associated with ASD and, although preliminary, may help account for some of the previously outlined neurobiological heterogeneity across affected individuals. This is especially relevant regarding the role of genetic and environmental factors in the development of ASD, in which certain brain structures may be more sensitive to specific influences.

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Role of environmental and genetic factors in autism spectrum disorder

Bangabandhu Sheikh Mujib Medical University Journal ◽

10.3329/bsmmuj.v10i2.32385 ◽

2017 ◽

Vol 10 (2) ◽

pp. 76 ◽

Cited By ~ 1

Author(s):

Zakia Sultana ◽

Sarder Nasir Uddin ◽

Asif Ahmed

Keyword(s):

Risk Factors ◽

Autism Spectrum Disorder ◽

Environmental Factors ◽

Premature Birth ◽

Genetic Factors ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Multiple Factors ◽

Control Association

<p>The aim of this study was to find out the environmental as well as genetic factors responsible for increasing the number of autism spectrum disorder (ASD) patients in Bangladesh. A questionnaire was developed based on 12 environmental factors and genetic aspects. Sixty six patients of ASD and 66 non-ASD control were selected randomly. Among the environmental factors, the age of the mother, premature birth, air pollution, age of the father, hypoxia during childbirth and oral contraceptive came out as significant (p<0.05) factors for ASD incidence compared to the control. Association of multiple factors on an individual was found to be crucial to enhance the risk and exposure to five and six factors was statistically significant (p<0.05) for ASD development. Prospective parents should try to keep the number of risk factors as low as possible before 1-2 months of pregnancy, during pregnancy and 1-2 years after the child birth (for child only).</p>

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Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

Nature Communications ◽

10.1038/s41467-019-13005-8 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 23

Author(s):

Merel C. Postema ◽

Daan van Rooij ◽

Evdokia Anagnostou ◽

Celso Arango ◽

Guillaume Auzias ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Cortical Thickness ◽

Large Scale ◽

Brain Regions ◽

Autism Spectrum ◽

Brain Asymmetry ◽

Spectrum Disorder ◽

Data Sets ◽

Control Effect ◽

Structural Brain

Abstract Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen’s d = −0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

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Possibility that the Onset of Autism Spectrum Disorder is Induced by Failure of the Glutamine-Glutamate Cycle

Current Molecular Pharmacology ◽

10.2174/1874467213666200319125109 ◽

2020 ◽

Vol 14 (2) ◽

pp. 170-174

Author(s):

Koichi Kawada ◽

Nobuyuki Kuramoto ◽

Seisuke Mimori

Keyword(s):

Autism Spectrum Disorder ◽

Endoplasmic Reticulum ◽

Environmental Factors ◽

Endoplasmic Reticulum Stress ◽

Synapse Formation ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Neurodevelopmental Disease ◽

Number Of Patients ◽

The Brain

: Autism spectrum disorder (ASD) is a neurodevelopmental disease, and the number of patients has increased rapidly in recent years. The causes of ASD involve both genetic and environmental factors, but the details of causation have not yet been fully elucidated. Many reports have investigated genetic factors related to synapse formation, and alcohol and tobacco have been reported as environmental factors. This review focuses on endoplasmic reticulum stress and amino acid cycle abnormalities (particularly glutamine and glutamate) induced by many environmental factors. In the ASD model, since endoplasmic reticulum stress is high in the brain from before birth, it is clear that endoplasmic reticulum stress is involved in the development of ASD. On the other hand, one report states that excessive excitation of neurons is caused by the onset of ASD. The glutamine-glutamate cycle is performed between neurons and glial cells and controls the concentration of glutamate and GABA in the brain. These neurotransmitters are also known to control synapse formation and are important in constructing neural circuits. Theanine is a derivative of glutamine and a natural component of green tea. Theanine inhibits glutamine uptake in the glutamine-glutamate cycle via slc38a1 without affecting glutamate; therefore, we believe that theanine may prevent the onset of ASD by changing the balance of glutamine and glutamate in the brain.

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Exploring Growth in Expressive Communication of Infants and Toddlers With Autism Spectrum Disorder

Journal of Early Intervention ◽

10.1177/1053815121995578 ◽

2021 ◽

pp. 105381512199557

Author(s):

Jay Buzhardt ◽

Anna Wallisch ◽

Dwight Irvin ◽

Brian Boyd ◽

Brenda Salley ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Progress Monitoring ◽

Autism Spectrum ◽

Growth Patterns ◽

Spectrum Disorder ◽

Future Research ◽

Infants And Toddlers ◽

Early Communication ◽

Children With Asd ◽

Language Growth

One of the earliest indicators of autism spectrum disorder (ASD) is delay in language and social communication. Despite consensus on the benefits of earlier diagnosis and intervention, our understanding of the language growth of children with ASD during the first years of life remains limited. Therefore, this study compared communication growth patterns of infants and toddlers with ASD to growth benchmarks of a standardized language assessment. We conducted a retrospective analysis of growth on the Early Communication Indicator (ECI) of 23 infants and toddlers who received an ASD diagnosis in the future. At 42 months of age, children with ASD had significantly lower rates of gestures, single words, and multiple words, but significantly higher rates of nonword vocalizations. Children with ASD had significantly slower growth of single and multiple words, but their rate of vocalization growth was significantly greater than benchmark. Although more research is needed with larger samples, because the ECI was designed for practitioners to monitor children’s response to intervention over time, these findings show promise for the ECI’s use as a progress monitoring measure for young children with ASD. Limitations and the need for future research are discussed.

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Neural correlates of polygenic risk score for autism spectrum disorders in general population

Brain Communications ◽

10.1093/braincomms/fcaa092 ◽

2020 ◽

Vol 2 (2) ◽

Author(s):

Budhachandra Khundrakpam ◽

Uku Vainik ◽

Jinnan Gong ◽

Noor Al-Sharif ◽

Neha Bhutani ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

General Population ◽

Cortical Thickness ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Risk Scores ◽

Polygenic Risk ◽

Cortical Regions ◽

White Matter Connectivity

Abstract Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age2 on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (n = 391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study). We observed that children with higher polygenic risk for autism spectrum disorder exhibited greater cortical thickness for a large age span starting from 3 years up to ∼14 years in several cortical regions localized in bilateral precentral gyri and the left hemispheric postcentral gyrus and precuneus. In an independent case–control dataset from the Autism Brain Imaging Data Exchange (n = 560), we observed a similar pattern: children with autism spectrum disorder exhibited greater cortical thickness starting from 6 years onwards till ∼14 years in wide-spread cortical regions including (the ones identified using the general population). We also observed statistically significant regional overlap between the two maps, suggesting that some of the cortical abnormalities associated with autism spectrum disorder overlapped with brain changes associated with genetic vulnerability for autism spectrum disorder in healthy individuals. Lastly, we observed that white matter connectivity between the frontal and parietal regions showed significant association with polygenic risk for autism spectrum disorder, indicating that not only the brain structure, but the white matter connectivity might also show a predisposition for the risk of autism spectrum disorder. Our findings showed that the fronto-parietal thickness and connectivity are dimensionally related to genetic risk for autism spectrum disorder in general population and are also part of the cortical abnormalities associated with autism spectrum disorder. This highlights the necessity of considering continuum models in studying the aetiology of autism spectrum disorder using polygenic risk scores and multimodal neuroimaging.

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Autism spectrum disorder at the crossroad between genes and environment: contributions, convergences, and interactions in ASD developmental pathophysiology

Molecular Autism ◽

10.1186/s13229-020-00370-1 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Cristina Cheroni ◽

Nicolò Caporale ◽

Giuseppe Testa

Keyword(s):

Autism Spectrum Disorder ◽

Environmental Factors ◽

Neurodevelopmental Disorders ◽

Chemical Exposure ◽

Autism Spectrum ◽

Synaptic Function ◽

Spectrum Disorder ◽

Regulatory Pathways ◽

Genes And Environment ◽

Analytical Approaches

Abstract The complex pathophysiology of autism spectrum disorder encompasses interactions between genetic and environmental factors. On the one hand, hundreds of genes, converging at the functional level on selective biological domains such as epigenetic regulation and synaptic function, have been identified to be either causative or risk factors of autism. On the other hand, exposure to chemicals that are widespread in the environment, such as endocrine disruptors, has been associated with adverse effects on human health, including neurodevelopmental disorders. Interestingly, experimental results suggest an overlap in the regulatory pathways perturbed by genetic mutations and environmental factors, depicting convergences and complex interplays between genetic susceptibility and toxic insults. The pervasive nature of chemical exposure poses pivotal challenges for neurotoxicological studies, regulatory agencies, and policy makers. This highlights an emerging need of developing new integrative models, including biomonitoring, epidemiology, experimental, and computational tools, able to capture real-life scenarios encompassing the interaction between chronic exposure to mixture of substances and individuals’ genetic backgrounds. In this review, we address the intertwined roles of genetic lesions and environmental insults. Specifically, we outline the transformative potential of stem cell models, coupled with omics analytical approaches at increasingly single cell resolution, as converging tools to experimentally dissect the pathogenic mechanisms underlying neurodevelopmental disorders, as well as to improve developmental neurotoxicology risk assessment.

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Refractoriness of aggressive behaviour to pharmacological treatment: cortical thickness analysis in autism spectrum disorder

BJPsych Open ◽

10.1192/bjo.2020.71 ◽

2020 ◽

Vol 6 (5) ◽

Cited By ~ 1

Author(s):

Flavia Venetucci Gouveia ◽

Jürgen Germann ◽

Gabriel A. Devenyi ◽

Rosa M. C. B. Morais ◽

Ana Paula M. Santos ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Cortical Thickness ◽

Pharmacological Treatment ◽

Aggressive Behaviour ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Emotional Control ◽

Treatment Refractory ◽

Morphological Patterns

Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.

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