ABSTRACT
Objective To explore the developmental characteristics of white matter volume in autism spectrum disorder (ASD) children longitudinal.Methods From May 2011 to September 2014,37 ASD children (ASD group)and 27 developmental delays (DD) children (control group) were treated at the Child Mental Health Research Center,Nanjing Brian Hospital Affiliated of Nanjing Medical University,and the children whose age,gender and developmental quotient matched with the ASD children were scanned by structure magnetic resonance imaging (sMRI) at the age of 2-3 years old and 4-5 years old respectively.Region of interest (ROI) technology was adopted to investigate the change of the cerebrum white and the sub-lobes structure white matter volume with time.Then the correlation between clinical symptoms and brain white matter volume changes was analyzed.Results Among the 2-3 years old,compared with the control group,the white matter volume of the total brain[(383 521.84 ±6 427.57) mm3 vs.(364 014.06 ±6 856.97) mm3],the left cerebral hemisphere [(191 609.35 ± 3 206.60) mm3 vs.(181 695.89 ± 3 389.54)mm3],temporal lobe [(41 860.49 ±816.38) mm3 vs.(39 444.18 ± 834.85) mm3] and the right temporal lobe [(21 312.79 ± 414.07) mm3 vs.(20 084.22 ± 412.13) mm3] were significantly larger in the ASD group,and the differences were statistically significant (all P ＜ 0.05).With the analysis of covariance with age or the total brain volume as the covariate,the differences disappeared(all P ＞ 0.05).Among the 4-5 years old,compared with the control group,the white matter volumes of the total brain[(417 651.42 ± 6 443.86) mm3 vs.(394 317.27 ± 6 404.86)mm3],left cerebral hemisphere [(208 714.16 ±3 214.61) mm3 vs.(197 192.82 ±3 262.02) mm3],right cerebral hemisphere [(208937.26±3242.09) mm3 vs.(7 124.45 ±3 193.13) mm3],frontal lobe [(107 107.46±1 681.99) mm3 vs.(100 326.19 ± 1 883.24) mm3],left frontal lobe [(54 569.63 ± 846.85) mm3 vs.(51 177.25 ±979.09) mm3],right frontal lobe [(52 537.83 ± 841.99) mm3 vs.(49 148.94 ±928.31) mm3],temporal lobe [(45 189.75 ± 833.29) mm3 vs.(42 487.73 ± 786.27) mm3],left temporal lobe [(22 204.21 ±411.77) mm3 vs.(20 922.90 ± 418.46) mm3],and right temporal lobe [(22 985.54 ± 426.93) mm3 vs.(21 564.83 ± 378.78) mm3]were significantly larger in the ASD group,and the differences were statistically significant (all P ＜ 0.05).With the analysis of covariance with age as the covariate,the differences still existed (all P ＜ 0.05).With the analysis of covariance with the total brain volume as the covariate,the differences disappeared (all P ＞ 0.05).For longitudinal analysis,there was a significant difference in the white matter volume between the whole brain,left cerebral hemisphere,right cerebral hemisphere,frontal lobe,left frontal lobe,fight frontal lobe,temporal lobe,left temporal lobe,right temporal lobe and the differences were statistically significant (F =5.521,5.533,5.459,5.830,5.800,5.723,4.857,4.418,5.159,all P ＜0.05).There was a positive correlation between the changes of the volume of whole brain,the white matter volume in the whole brain,bilateral cerebral hemisphere,frontal lobe,parietal lobe,right parietal lobe and Childhood Autism Rating Scale (r =0.367,0.343,0.321,0.349,0.296,0.308,0.351,all P ＜ 0.05).Conclusions Among the 2-3 years old,the white matter volume of the brain regions have been increased significantly in ASD.Among the 4-5 years old,the increase of the white matter volume of the brain regions implicated more widely which mainly concentrated in the frontal and temporal lobe in ASD.The severity of the clinical symptoms of ASD may be associated with the white matter volume of the total brain,bilateral cerebral hemisphere,frontal lobe,parietal lobe and right parietal lobe.
ABSTRACT
Objective@#To conduct a follow-up investigation of structural changes of the corpus callosum fibers of toddlers (2 to 5 years of age) with autism spectrum disorder(ASD) and to explore the associations with clinical symptoms.@*Method@#In this prospective randomized controlled study, ASD children who were diagnosed in the Child Mental Health Research Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University from May 2011 to November 2012 were included in the ASD group, and developmentally delayed children were included in the control group (DD group). Diffusion tensor imaging (DTI) data from the two groups were obtained at two age levels: 2-3 years of age, and 4-5 years of age. Region of interest analysis was applied to assess characteristic values of total area and sub-regions of corpus callosum: the fraction anisotropy (FA), the mean diffusivity (MD), the radial diffusivity (RD) and the axial diffusivity (AD). All children were assessed using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Treatment Evaluation Checklist (ATEC). The characteristic values of total area and sub-regions of corpus callosum of ASD group at two age levels were analyzed by paired sample t test; the characteristic values of total area and sub-regions of corpus callosum of ASD group and DD group were analyzed by independent-sample t test; the correlations between FA values of the total area and sub-regions of corpus callosum and ADI-R or ATEC scores were analyzed by Pearson correlation analysis.@*Result@#Forty cases meeting inclusion criteria were enrolled in ASD group, and 31 eligible cases were enrolled in the control group. Four children in the ASD group were lost to follow-up, and 5 children in the control group were lost to follow-up. Longitudinal comparison between the two age subgroups of ASD patients showed that the FA values of the total corpus callosum increased (0.499 55±0.027 59 vs. 0.505 83±0.086 64, t=4.88, P<0.05), but MD values, RD values and AD values of the total corpus callosum area decreased (0.000 89±0.000 03 vs. 0.000 81±0.000 14, 0.000 61±0.000 04 vs. 0.000 55±0.000 09, 0.001 43±0.000 03 vs. 0.001 38±0.000 03, t=9.31, 7.90, 8.66, P<0.05 for all comparisons). In the area of corpus callosum genu, FA and AD values increased (t=5.59, 8.48, P<0.05 for both comparisons), but MD and RD values decreased (t=12.67, 11.28, P<0.05 for both comparisns). In the area of corpus callosum body, FA and RD values increased(t=5.46, 8.48, P<0.05 for both comparisons), but MD and AD values decreased (t=8.08, 6.22, P<0.05 for both comparisons). In the area of corpus callosum splenium, MD, RD and AD values decreased (t=6.81, 4.44, 5.51, P < 0.05 for all comparisons). Among the participants 2 to 3 years of age, there were no significantly differences in FA values of total area and sub-regions of corpus callosum between ASD group and the DD group (P > 0.05 for all comparisons); as compared with the DD group, ASD group had higher AD values of total area and splenium of corpus callosum (0.001 43±0.000 03 vs. 0.001 40±0.000 04, 0.001 34±0.000 03 vs. 0.001 32±0.000 04, t=1.56, 1.14, P < 0.05 for both comparisons); ASD group had lower AD values but higher RD and MD values of corpus callosum genu (t=0.07, 0.55, 0.07, P < 0.05 for all comparisons); ASD group had lower RD values of corpus callosum body (t=0.07, P < 0.05). Among the participants 4 to 5 years of age, as compared with the DD group, ASD group had higher FA value of total corpus callosum area(0.505 83±0.086 64 vs. 0.483 77±0.099 30, t=8.56, P < 0.05), lower RD value of total corpus callosum(0.000 55±0.000 09 vs. 0.000 56±0.000 12, t=14.44, P < 0.05), lower RD values of corpus callosum body (t=2.20, P < 0.05), higher FA values (t=3.35, P < 0.05) but lower AD values of corpus callosum splenium (t=2.20, P < 0.05). A correlation analysis between FA values of total area and sub-regions of corpus callosum and clinical variables showed that the FA values of total area and splenium of corpus callosum in ASD group at 2 to 3 years of age were negatively correlated with the scores of language skills in ATEC (r=-0.35,-0.36, P < 0.05 for both comparisons). And after two years, FA values of total corpus callosum were positively correlated with the scores of social communication in ATEC (r=0.34, P < 0.05). There was no significant correlation between FA values of sub-regions of corpus callosum and the scores of ATEC (P > 0.05 for all comparisons). There was no significant correlation between FA values of total area and sub-regions of corpus callosum and the scores of ADI-R (P > 0.05 for all comparisons).@*Conclusion@#The fiber structure of corpus callosum was still in the process of maturing during the age of 2 to 5 years; however, compared with DD group, ASD group had more extensive structural abnormalities of the corpus callosum fibers as age increased, and the structural abnormalities had correlation with the core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-OPC-17011995.