Structural correlates of social impairment in adolescents with autism spectrum disorder: a voxel-based morphometry study Chen-Chia Lan, Ju-Wei Hsu, Pei-Chi Tu, Ying-Sheue Chen, Chia-Chien Liu, Tung-Ping Su Department of Psychiatry, Taipei Veterans General Hospital, Yuanshan Branch; Department of Psychiatry, Taipei Veterans General Hospital Department of Medical Research and Education, Taipei Veterans General Hospital; Department of Psychiatry, National Yang-Ming University Hospital Objectives: Autism spectrum disorder is a highly genetically determined neuropsychiatric disorder. A variety of data points to disturbances of brain growth and maturation as an important pathomechanism. Recent studies have used voxel-based morphometry (VBM) to detect subtle regional variations in brain anatomy. However, the results have been relatively inconsistent which might be due to the clinical and etiologic heterogeneity of the disorder. A quantitative measurement of autistic symptoms may provide more specific information and avoid the heterogeneity for the disease. The aim of the current study is to explore gray matter volume abnormalities and correlations with autism symptom measures in adolescents with autism spectrum disorder using voxel-based morphometry (VBM). Method: Included in the study were 24 individuals aged 12 to 18 years diagnosed with autism spectrum disorder (ASD) and 24 age-matched healthy comparison subjects (HC). Autistic symptoms were assessed by the Social Responsiveness Scale (SRS) [1], which is a 65-item questionnaire filled out by parents or teachers. The SRS is designed to give a quantitative assessment of autistic traits over five domains (social awareness, social cognition, social communication, social motivation, and autistic mannerism) in children aged 4-18 years. Whole brain, voxel-wise analyses of regional gray matter volume were conducted using VBM. Gray matter volume differences were compared between ASD and HC groups. And correlations of gray matter volume changes with the SRS measurements were performed. Results: The demographic data was shown in table 1. There were no significant difference among age, sex, or educational level between the ASD and HC groups. ASD patients’ full scale IQ was significantly lower than that of the HC group. In addition, the ASD group showed significantly higher scores among the five subscales and the total score of the SRS compared to the HC. Several areas of gray matter volume changes in the ASD group as compared to the HC group were noted, including volume decrement over left thalamus and bilateral putamen and volume increment over right superior parietal lobule and right superior frontal gyrus (Table 2 & Figure 1). Right superior parietal lobule and right superior frontal gyrus grey matter volume changes in ASD patients were correlated with the SRS measurements (Table 3). Subjects Characteristics ASD patients (n=24) Healthy controls t p Age (years) 14.8±2.3 14.8±1.6 0.73 .924 Sex 19M/5F 18M/6F .738 Education level 9.04±2.05 9.46±1.64 -.77 .441 Full Scale IQ 93.5±15.0 106.6±12.5 -3.2 0.002 SRS Awareness 12.21±3.45 4.96±2.9 7.83 .000 Cognition 20.33±6.32 6.38±4.5 8.80 Communication 38.00±10.85 8.29±7.7 10.89 Motivation 18.38±6.74 5.04±3.8 8.41 Mannerism 21.83±7.89 3.04±3.30 10.75 Total raw score 110.75±31.00 27.71±19.08 11.17 ASD SRS_awa SRS_cog SRS_com SRS_mot SRS_man SRS_T L. thalamus -0.091 -0.115 0.046 0.003 0.129 0.016 L. putamen 0.012 -0.047 0.110 0.000 0.024 0.036 R. putamen -0.134 -0.284 -0.171 -0.222 -0.141 -0.217 R, SPL -0.184 -0.439* -0.299 -0.278 -0.294 -0.350 R. SFG -0.351 -0.626** -0.631** -0.400 -0.471* -0.594** Table 3 Gray matter volume correlation with SRS measurements, age covariate. * p<0.05, ** p<0.001 ASD<HC Table 1 Demographic data. MNI Coordinate qFDR-corr kE x y z Structures ASD<HC <0.001 1765 -4 -18 1 Left thalamus 0.031 595 -21 8 4 Left putamen 0.001 1370 21 5 -2 Right putamen ASD>HC 1743 37 -40 57 Right superior parietal lobe 0.008 1058 30 44 Right superior frontal gyrus ASD>HC Table 2 Gray matter volume comparison between ASD and HC, p<0.05, corrected for FDR Figure 1 Gray matter volume comparison between ASD and HC Discussion & Conclusions: Gray matter changes noted between the ASD and HC groups strengthened the evidence that disturbances of brain growth and maturation are an important pathological process of autism spectrum disorder. By incorporating quantitative measurement of autistic symptoms, our study avoided the heterogeneity of the disorder and provided more specific information regarding gray matter volume changes. Gray matter volume of right superior parietal lobule and right superior frontal gyrus were larger among ASD groups compared with HC. However, within the ASD group, smaller gray matter volume over right superior parietal lobule and right superior frontal gyrus predicted greater SRS scores (meaning more severe autistic symptoms). Further studies are indicated to clarify the underlying pathomechanisms. Reference: 1. Constantino, J.N., et al., Validation of a brief quantitative measure of autistic traits: comparison of the social responsiveness scale with the autism diagnostic interview-revised. J Autism Dev Disord, 2003. 33(4): p. 427-33.