A brain structural connectivity biomarker for autism spectrum disorder diagnosis in early childhood

Background:Autism spectrum disorder(ASD)is associated with altered brain development,but it is unclear which specific structural changes may serve as potential diagnostic markers,particularly in young children at the age when symptoms become fully estab-lished.Furthermore,such brain markers need to meet the requirements of precision medicine and be accurate in aiding diagnosis at an individual rather than only a group level.Objective:This study aimed to identify and model brain-wide differences in structural connectivity using diffusion tensor imaging(DTI)in young ASD and typically developing(TD)children.Methods:A discovery cohort including 93 ASD and 26 TD children and two independent validation cohorts including 12 ASD and 9 TD children from three different cities in China were included.Brain-wide(294 regions)structural connectivity was measured using DTI(fractional anisotropy,FA)together with symptom severity and cognitive development.A connection matrix was constructed for each child for comparisons between ASD and TD groups.Pattern classification was performed on the discovery dataset and the resulting model was tested on the two independent validation datasets.Results:Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both autistic symptom severity and impaired general cognitive development.The majority(29/33)involved the frontal lobe and comprised five different networks with functional relevance to default mode,motor control,social recognition,language and reward.Overall,clas-sification achieved very high accuracy of 96.77%in the discovery dataset,and 91.67%and 88.89%in the two independent validation datasets.Conclusions:Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish novel individual ASD from TD children and may therefore represent a robust early brain biomarker which can address the requirements of precision medicine.

Development of an Autism Subtyping Questionnaire Based on Social Behaviors

Autism spectrum disorder can be differentiated into three subtypes （aloof, passive, and active-but-odd） based on social behaviors according to the Wing Subgroups Questionnaire （WSQ）. However, the correlations between the scores on some individual items and the total score are poor. In the present study, we translated the WSQ into Chinese, modified it, validated it in autistic and typically- developing Chinese children, and renamed it the Beijing Autism Subtyping Questionnaire （BASQ）. Our results demonstrated that the BASQ had improved validity and reliability, and differentiated autistic children into these three subtypes more precisely. We noted that the autistic symptoms tended to be severe in the aloof, moderate in the passive, and mild in the active-but-odd subtypes. The modified questionnaire may facilitate etiological studies and the selection of therapeutic regimes.

A Volumetric and Functional Connectivity MRI Study of Brain Arginine-Vasopressin Pathways in Autistic Children

Dysfunction of brain-derived arginine-vasopressin（AVP） systems may be involved in the etiology of autism spectrum disorder（ASD）. Certain regions such as the hypothalamus, amygdala, and hippocampus are known to contain either AVP neurons or terminals and may play an important role in regulating complex social behaviors.The present study was designed to investigate the concomitant changes in autistic behaviors, circulating AVP levels, and the structure and functional connectivity（FC） of speci？c brain regions in autistic children compared with typically developing children（TDC） aged from 3 to5 years. The results showed：（1） children with ASD had a signi？cantly increased volume in the left amygdala and left hippocampus, and a signi？cantly decreased volume in the bilateral hypothalamus compared to TDC, and these were positively correlated with plasma AVP level.（2） Autistic children had a negative FC between the left amygdala and the bilateral supramarginal gyri compared to TDC. The degree of the negative FC between amygdala and supramarginal gyrus was associated with a higher score on the clinical autism behavior checklist.（3） The degree of negative FC between left amygdala and left supramarginal gyrus was associated with a lowering of the circulating AVP concentration in boys with ASD.（4） Autistic children showed a higher FC between left hippocampus and right subcortical area compared to TDC.（5） The circulating AVP was negatively correlated with the visual and listening response score of the childhood autism rating scale.These results strongly suggest that changes in structure and FC in brain regions containing AVP may be involved in the etiology of autism.