2~3岁孤独症谱系障碍患儿脑白质体积的2年随访研究

Two-year follow-up study of white matter structures in 2-3 years old children with autism spectrum disorder

目的纵向对比分析孤独症谱系障碍(ASD)患儿脑白质体积的发育特征。方法对2011年5月至2014年9月在南京医科大学附属脑科医院儿童心理卫生研究中心就诊的37例ASD患儿(ASD组)及27例年龄、性别及发育商匹配的发育迟缓(DD)儿童(对照组)分别在2~3岁及4~5岁时进行结构磁共振成像(sMRI)扫描。使用基于感兴趣区(ROI)方法研究ASD患儿全脑及各脑叶白质体积随时间变化的特征,并进一步分析ASD患儿脑白质体积变化与临床症状严重程度变化之间的相关性。结果与对照组相比,2~3岁时ASD组患儿全脑白质体积[(383521.84±6427.57)mm^3比(364014.06±6856.97)mm^3]、左脑半球白质体积[(191609.35±3206.60)mm^3比(181695.89±3389.54)mm^3]、颞叶白质体积[(41860.49±816.38)mm^3比(39444.18±834.85)mm^3]、右侧颞叶白质体积[(21312.79±414.07)mm^3比(20084.22±412.13)mm^3]均显著增大,差异均有统计学意义(均P<0.05)。分别以年龄和全脑体积为协变量进行分析后,差异性均消失(均P>0.05)。2年后再进行比较,ASD组患儿全脑白质体积[(417651.42±6443.86)mm^3比(394317.27±6404.86)mm^3]、左脑半球白质体积[(208714.16±3214.61)mm^3比(197192.82±3262.02)mm^3]、右脑半球白质体积[(208937.26±3242.09)mm^3比(197124.45±3193.13)mm^3]、额叶白质体积[(107107.46±1681.99)mm^3比(100326.19±1883.24)mm^3]、左侧额叶白质体积[(54569.63±846.85)mm^3比(51177.25±979.09)mm^3]、右侧额叶白质体积[(52537.83±841.99)mm^3比(49148.94±928.31)mm^3]、颞叶白质体积[(45189.75±833.29)mm^3比(42487.73±786.27)mm^3]、左侧颞叶白质体积[(22204.21±411.77)mm^3比(20922.90±418.46)mm^3]、右侧颞叶白质体积[(22985.54±426.93)mm^3比(21564.83±378.78)mm^3]均大于对照组,差异均有统计学意义(均P<0.05)。以年龄为协变量进行协方差分析时,差异性仍存在(均P<0.05);以全脑体积为协变量分析时,上述差异均无统计学意义(均P>0.05)。2年随访期间,2组全脑、左脑半球、右脑半球、额叶、左侧额叶、右侧额叶、颞叶、左侧颞叶、右侧颞叶白质体积比较差异均有统计学意义(F=5.521、5.533、5.459、5.830、5.800、5.723、4.857、4.418、5.159,均P<0.05)。全脑体积及全脑、左脑半球、右脑半球、额叶、顶叶、右侧顶叶白质体积的变化与儿童孤独症评定量表(CARS)评分的变化呈正相关(r=0.367、0.343、0.321、0.349、0.296、0.308、0.351,均P<0.05)。结论2~3岁时ASD患儿就已出现脑白质体积增大,到4~5岁时脑白质体积增大的区域更为广泛及显著,主要集中在额叶和颞叶。全脑、双侧脑半球、额叶、顶叶及右侧顶叶白质体积的变化可能与ASD的疾病严重程度相关。

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) mm^3vs. (364 014.06±6 856.97) mm^3], the left cerebral hemisphere [(191 609.35±3 206.60) mm^3vs. (181 695.89±3 389.54) mm^3], temporal lobe [(41 860.49±816.38) mm^3vs. (39 444.18±834.85) mm^3] and the right temporal lobe [(21 312.79±414.07) mm^3vs. (20 084.22±412.13) mm^3] 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) mm^3vs. (394 317.27±6 404.86) mm^3], left cerebral hemisphere [(208 714.16±3 214.61) mm^3vs. (197 192.82±3 262.02) mm^3], right cerebral hemisphere [(208 937.26±3 242.09) mm^3vs. (7 124.45±3 193.13) mm^3], frontal lobe [(107 107.46±1 681.99) mm^3vs. (100 326.19±1 883.24) mm^3], left frontal lobe [(54 569.63±846.85) mm^3vs. (51 177.25±979.09) mm^3], right frontal lobe [(52 537.83±841.99) mm^3vs. (49 148.94±928.31) mm^3], temporal lobe [(45 189.75±833.29) mm^3vs.(42 487.73±786.27) mm^3], left temporal lobe [(22 204.21±411.77) mm^3vs. (20 922.90±418.46) mm^3], and right temporal lobe [(22 985.54±426.93) mm^3vs. (21 564.83±378.78) mm^3] were significantly larger in the ASD group, and the differences were statistically significant (all P<0.05). With the ana-lysis 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, right 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.