Gray matter abnormalities in pediatric autism spectrum disorder: a meta-analysis with signed differential mapping
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The gray matter abnormalities revealed by magnetic resonance imaging are inconsistent, especially in pediatric individuals with autism spectrum disorder (ASD) (age < 18 years old), a phenomenon possibly related to the core pathophysiology of ASD. The purpose of our meta-analysis was to identify and map the specific gray matter abnormalities in pediatric ASD individuals thereby exploring the potential effects of clinical and demographic characteristics of these gray matter changes. A systematic search was conducted to identify voxel-based morphometry studies in pediatric individuals with ASD. The effect-size signed differential mapping method was used to quantitatively estimate the regional gray matter abnormalities in pediatric ASD individuals. Meta-regression was used to examine the associations among age, gender, intelligence quotient, symptom severity and gray matter changes. Fifteen studies including 364 pediatric individuals with ASD (male = 282, age = 10.3 ± 4.4 years) and 377 healthy controls (male = 289, age = 10.5 ± 4.2 years) were included. Pediatric ASD individuals showed significant gray matter increases in the right angular gyrus, left superior and middle frontal gyrus, left precuneus, left inferior occipital gyrus and right inferior temporal gyrus, most of which involving the default mode network, and decreases in the left cerebellum and left postcentral gyrus. The meta-regression analysis showed that the repetitive behavior scores of the Autism Diagnostic Interview-Revised were positively associated with increased gray matter volumes in the right angular gyrus. Increased rather than decreased gray matter volume, especially involving the angular gyrus and prefrontal cortex may be the core pathophysiology in the early course of ASD.
KeywordsAutism spectrum disorder Pediatrics Structural MRI Gray matter Meta-analysis Signed differential mapping
This work was supported by National Natural Science Foundation of China (Grant Numbers 81371527, 81671664, 81621003), Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, Grant Number IRT16R52) of China. Dr. Lui would also like to acknowledge the support from Chang Jiang Scholars of China (Award Numbers Q2015154), National Program for Special Support of Eminent Professionals and National Program for Support of Top-notch Young Investigator (Award Numbers W02070140).
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Conflict of interest
None of the authors has potential conflicts of interest to report with regard to this manuscript.
- 1.Christensen DL, Baio J, Van Naarden Braun K, Bilder D, Charles J, Constantino JN, Daniels J, Durkin MS, Fitzgerald RT, Kurzius-Spencer M, Lee LC, Pettygrove S, Robinson C, Schulz E, Wells C, Wingate MS, Zahorodny W, Yeargin-Allsopp M (2016) Prevalence and characteristics of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network, 11 sites, United States, 2012. MMWR Surveill Summ 65:1–23CrossRefPubMedGoogle Scholar
- 15.Riva D, Annunziata S, Contarino V, Erbetta A, Aquino D, Bulgheroni S (2013) Gray matter reduction in the vermis and CRUS-II is associated with social and interaction deficits in low-functioning children with autistic spectrum disorders: a VBM-DARTEL Study. Cerebellum 12:676–685CrossRefPubMedGoogle Scholar
- 23.Radua J, Borgwardt S, Crescini A, Mataix-Cols D, Meyer-Lindenberg A, McGuire PK, Fusar-Poli P (2012) Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication. Neurosci Biobehav Rev 36:2325–2333CrossRefPubMedGoogle Scholar
- 30.Lord C, Risi S, Lambrecht L, Cook EH Jr, Leventhal BL, DiLavore PC, Pickles A, Rutter M (2000) The autism diagnostic observation schedule-generic: a standard measure of social and communication deficits associated with the spectrum of autism. J Autism Dev Disord 30:205–223CrossRefPubMedGoogle Scholar
- 41.Xiao Z, Qiu T, Ke X, Xiao X, Xiao T, Liang F, Zou B, Huang H, Fang H, Chu K, Zhang J, Liu Y (2014) Autism spectrum disorder as early neurodevelopmental disorder: evidence from the brain imaging abnormalities in 2–3 years old toddlers. J Autism Dev Disord 44:1633–1640CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Steinman K, Lotspeich L, Patnaik S, Hoefr F, Reiss A (2008) Structural brain differences between autistic children and their typically-developing siblings: a voxelbased morphometry analysis [ANA Annual Meeting abstract poster CD34]. Ann Neurol 64:S155Google Scholar
- 46.Boddaert N, Chabane N, Gervais H, Good CD, Bourgeois M, Plumet MH, Barthelemy C, Mouren MC, Artiges E, Samson Y, Brunelle F, Frackowiak RS, Zilbovicius M (2004) Superior temporal sulcus anatomical abnormalities in childhood autism: a voxel-based morphometry MRI study. Neuroimage 23:364–369CrossRefPubMedGoogle Scholar
- 48.Brieber S, Neufang S, Bruning N, Kamp-Becker I, Remschmidt H, Herpertz-Dahlmann B, Fink GR, Konrad K (2007) Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder. J Child Psychol Psychiatry 48:1251–1258CrossRefPubMedGoogle Scholar
- 54.Mengotti P, D’Agostini S, Terlevic R, De Colle C, Biasizzo E, Londero D, Ferro A, Rambaldelli G, Balestrieri M, Zanini S, Fabbro F, Molteni M, Brambilla P (2011) Altered white matter integrity and development in children with autism: a combined voxel-based morphometry and diffusion imaging study. Brain Res Bull 84:189–195CrossRefPubMedGoogle Scholar
- 64.Kosaka H, Omori M, Munesue T, Ishitobi M, Matsumura Y, Takahashi T, Narita K, Murata T, Saito DN, Uchiyama H, Morita T, Kikuchi M, Mizukami K, Okazawa H, Sadato N, Wada Y (2010) Smaller insula and inferior frontal volumes in young adults with pervasive developmental disorders. Neuroimage 50:1357–1363CrossRefPubMedGoogle Scholar
- 78.Mosconi M, Takarae Y, Sweeney J (2011) Motor impairments and dyspraxia in autism. Autism spectrum disorders. Oxford University Press Inc, New YorkGoogle Scholar