Construction Of A Special Cohort For High-risk Autism Spectrum Disorder And A Study On The Early Behavior And Brain Structure Characteristics Of Siblings

Study 1: Construction of special disease cohort of high risk autism spectrum disorderPurpose: The construction of the autism spectrum disorder(ASD)specific disease cohort,especially the high risk ASD prospective cohort,is an important method to study the pathophysiological mechanism,early identification,early intervention and prognosis of ASD.Therefore,in this study,a high-risk ASD special disease cohort and an electronic follow-up system for special disease cohorts will be constructed.Methods: We established the high risk ASD specific disease cohort including the early intervention follow-up cohort and the birth follow-up cohort of ASD siblings.The electronic follow-up system and biological sample database of ASD were established by collecting and inputting the baseline and follow-up clinical scale information,behavioral videos,biological samples and imaging data into the electronic information platform.Results: The high risk ASD special disease cohort and electronic follow-up system were completed and put into use in September 2019.Currently,all cohort work are carried out on the electronic platform.The cohort included a total of 257 members in the group,including 152 in the early intervention cohort and 105 in the siblings follow-up cohort.A total of more than 200 follow-up visits were carried out,and the follow-up dropout rate was 9.5%.Conclusion: The construction of the high risk ASD special disease cohort is a long-term process.The establishment of the entire cohort has laid a solid foundation for the development of a series of subsequent studies on ASD.Study 2: A study on the developmental level of ASD siblings within 12 months and parental reportsPurpose: Existing studies have shown that the early abnormal behaviors of autism spectrum disorder(ASD)usually appear in 12-24 months,but whether children with ASD have early suspicious signs within 1 year of age is still unknown.Therefore,this part of the study will explore the developmental levels of ASD siblings within one year of age and the differences in parental reports in different outcome groups.Methods: A total of 58 ASD siblings who completed the 12-month follow-up in the ASD siblings follow-up cohort were selected as the research objects.According to the12-month assessment of the autism diagnostic observation schedule(ADOS-2),they were divided into a development need warning group and a well developed group.The differences of development level and parental reports between the two groups at12 months and 6 months were compared.Results: The 12-month-old adaptability and personal social behavior development of the ASD siblings need warning group were lagging behind the well developed group,and the adaptability lag already existed at 6 months.There was significant difference between the two groups in the positive rate of the communication and symbolic behavior scales(ITC)at 12 months,but no significant difference was found at 6months.Conclusion: ASD siblings development need warning group may have signs of backward social adaptation and personal social skills as early as 6 months,and there are many areas of abnormalities that can cause parents to detect at the age of 1 year.These abnormal signs may be an important early indicator of the development of ASD and need to arouse the attention of parents and clinicians.Study 3: A study on brain volume and morphology of ASD siblings at 12-18 months of agePurpose: The current research reports on the early cortical morphological development of autism spectrum disorder(ASD)siblings still have great heterogeneity.Therefore,in this study,we will explore the differences of early brain volume and morphology development in different outcome groups of ASD siblings and their relationship with early behaviors.Methods: Forty-three subjects who completed magnetic resonance imaging scanning in ASD siblings cohort were selected as the research objects and divided into a development need warning group and a well developed group according to the evaluation of the Autism Diagnostic Observation Schedule(ADOS-2).The differences of gray matter structure between the two groups were compared by voxel based and surface based morphological analysis.Results: There was no significant difference in total brain volume,total gray/white matter volume and cerebrospinal fluid volume between the two groups,but the developmental need warning group had higher gray matter density in some areas of the frontal,occipital,temporal and cingulate than the well developed group.The cortical surface areas of the left paracentral lobule,posterior central gyrus,precuneus,superior parietal lobule,superior marginal gyrus,right posterior cingulate and precuneus cortex in the development warning group were smaller than those in the well developed group,and the cortical thickness of the left olfactory,posterior cingulate,precuneus,superior parietal gyrus,right precuneus and superior parietal cortex was thicker than that in the well developed group.And the volume of the anterior cingulate gyrus,amygdala and hippocampus was larger than that of the well developed group.The cortical thickness and surface area of some of the above differences were related to the clinical symptoms of ASD.Conclusion: Through the comparative study of brain morphology between different outcome groups of ASD siblings in the early stage,we found that ASD children had multiple brain structural abnormalities as early as 2 years old,which was related to the core symptoms of children.Study 4: A study on white matter network of ASD siblings at12-18 months of agePurpose: The abnormal brain network in ASD is closely related to its abnormal behavior,but the early development pattern of white matter network in ASD siblings is still unclear.Therefore,this study will explore the differences in the development of brain white matter network of ASD siblings with different outcomes in the early stage.Methods: Forty-three subjects who completed magnetic resonance imaging scanning in ASD siblings cohort were selected as the research objects and divided into a development need warning group and a well developed group according to the evaluation of the Autism Diagnostic Observation Schedule(ADOS-2).The differences between the topological attributes and core nodes of white matter network between the two groups were compared.Results: The modularity index of white matter network in the development need warning group was higher than that in the well developed group,but there was no significant difference in other global attributes between the two groups.The left central posterior gyrus is the unique core node of the development need warning group,and it is related to the severity of clinical symptoms.Conclusion: Although there is no significant difference in the overall properties of the early brain network between different outcome groups,there are abnormalities in the efficiency of the core nodes and local nodes in the development need warning group,which requires further attention.