scholarly journals Altered structural brain asymmetry in autism spectrum disorder: large-scale analysis via the ENIGMA Consortium

2019 ◽  
Author(s):  
Merel C. Postema ◽  
Daan van Rooij ◽  
Evdokia Anagnostou ◽  
Celso Arango ◽  
Guillaume Auzias ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Surface Area ◽  
Cortical Thickness ◽  
Large Scale ◽  
Autism Spectrum ◽  
Brain Asymmetry ◽  
Scale Analysis ◽  
Large Scale Analysis ◽  
Cortical Regions ◽  
Structural Brain

AbstractBackgroundLeft-right asymmetry is an important organizing feature of the healthy brain. Various studies have reported altered structural brain asymmetry in autism spectrum disorder (ASD). However, findings have been inconsistent, likely due to limited sample sizes and low statistical power.MethodsWe investigated 1,774 subjects with ASD and 1,809 controls, from 54 datasets, for differences in the asymmetry of thickness and surface area of 34 cerebral cortical regions. We also examined global hemispheric measures of cortical thickness and area asymmetry, and volumetric asymmetries of subcortical structures. Data were obtained via the ASD Working Group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. T1-weighted MRI data were processed with a single protocol using FreeSurfer and the Desikan-Killiany atlas.ResultsASD was significantly associated with reduced leftward asymmetry of total hemispheric average cortical thickness, compared to controls. Eight regional thickness asymmetries, distributed over the cortex, also showed significant associations with diagnosis after correction for multiple comparisons, for which asymmetry was again generally lower in ASD versus controls. In addition, the medial orbitofrontal surface area was less rightward asymmetric in ASD than controls, and the putamen volume was more leftward asymmetric in ASD than controls. The largest effect size had Cohen’sd= 0.15. Most effects did not depend on age, sex, IQ, or disorder severity.ConclusionAltered lateralized neurodevelopment is suggested in ASD, affecting widespread cortical regions with diverse functions. Large-scale analysis was necessary to reliably detect, and accurately describe, subtle alterations of structural brain asymmetry in this disorder.

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

2019 ◽  
Vol 10 (1) ◽  
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.

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

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.

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

2019 ◽  
Vol 25 (10) ◽  
pp. 2556-2566 ◽  
Author(s):  
John P. Hegarty ◽  
Luiz F. L. Pegoraro ◽  
Laura C. Lazzeroni ◽  
Mira M. Raman ◽  
Joachim F. Hallmayer ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Environmental Factors ◽  
Cortical Thickness ◽  
Genetic Factors ◽  
Brain Size ◽  
Environmental Influences ◽  
Autism Spectrum ◽  
Growth Patterns ◽  
Spectrum Disorder ◽  
Structural Brain

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.

scholarly journals Author Correction: Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Merel C. Postema ◽  
Daan van Rooij ◽  
Evdokia Anagnostou ◽  
Celso Arango ◽  
Guillaume Auzias ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Brain Asymmetry ◽  
Spectrum Disorder ◽  
Structural Brain

scholarly journals Increased Surface Area, but not Cortical Thickness, in a Subset of Young Boys With Autism Spectrum Disorder

2015 ◽  
Vol 9 (2) ◽  
pp. 232-248 ◽  
Author(s):  
Haruhisa Ohta ◽  
Christine Wu Nordahl ◽  
Ana-Maria Iosif ◽  
Aaron Lee ◽  
Sally Rogers ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Surface Area ◽  
Cortical Thickness ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Subcortical brain volume, regional cortical thickness and cortical surface area across attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD)

2019 ◽  
Author(s):  
Premika S.W. Boedhoe ◽  
Daan van Rooij ◽  
Martine Hoogman ◽  
Jos W.R. Twisk ◽  
Lianne Schmaal ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Attention Deficit Hyperactivity Disorder ◽  
Surface Area ◽  
Cortical Thickness ◽  
Attention Deficit ◽  
Age Groups ◽  
Autism Spectrum ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Hyperactivity Disorder

ABSTRACTObjectiveAttention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders.MethodsStructural T1-weighted whole-brain MRI of controls (n=5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures).ResultsWe found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed.ConclusionOur findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippocampal alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.

scholarly journals Development of cortical thickness and surface area in autism spectrum disorder

2017 ◽  
Vol 13 ◽  
pp. 215-222 ◽  
Author(s):  
Vincent T. Mensen ◽  
Lara M. Wierenga ◽  
Sarai van Dijk ◽  
Yvonne Rijks ◽  
Bob Oranje ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Surface Area ◽  
Cortical Thickness ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Analysis of structural brain asymmetries in Attention-Deficit/Hyperactivity Disorder in 39 datasets

2020 ◽  
Author(s):  
Merel C. Postema ◽  
Martine Hoogman ◽  
David C. Glahn ◽  
Neda Jahanshad ◽  
Sarah E. Medland ◽  
...  
Keyword(s):  
Attention Deficit Hyperactivity Disorder ◽  
Surface Area ◽  
Attention Deficit ◽  
Multiple Testing ◽  
Age Groups ◽  
Autism Spectrum ◽  
Brain Asymmetry ◽  
Small Samples ◽  
Hyperactivity Disorder ◽  
Structural Brain

ABSTRACTObjectiveSome studies have suggested alterations of structural brain asymmetry in attention-deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small samples. Here we performed the largest-ever analysis of brain left-right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium.MethodsWe analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,978 people with ADHD and unaffected 1,917 controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modelling was applied separately in children, adolescents, adults, and the total sample, to test exhaustively for potential associations of ADHD with structural brain asymmetries.ResultsThere was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls (t=2.4, P=0.019). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD (t=2.4, P=0.007) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study-wide correction for multiple testing.ConclusionPrior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.

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