| Autism spectrum disorder(ASD)is a common neurodevelopmental disorder with highly heterogeneous clinical phenotypes.The genotype of most ASD children is still unclear;In addition,ASD and attention deficit hyperactivity disorder(ADHD)often co-occur. Endophenotype is a bridge between genotype and phenotype,which is of great significance for investigating the etiology,diagnosis and treatment.Cognitive function is one of the most potential endophenotypes.There was no study using Das-Naglieri Cognitive AssessmentSystem(DN-CAS)to evaluate the cognitive processes of children with ASD and ADHD.Neuro Image is also one of the most potential endophenotypes.Resting state functional magnetic resonance imaging is widely used in the studies investigating the etiology and neural mechanism of ASD.Researches had shown that functional connectivity(FC)of brain networks in ASD were affected by brain development and decreased with age.However,most of the subjects in the studies of resting state functional brain networks of patients with ASD and ADHD consisted of both children and adults.These studies had not furtherly analyzed the possible differences in FC of brain networks at different developmental stages,such as childhood and adolescence.There was no report comparing FC and topology attribute of brain networks of Chinese children with ASD and ADHD.PartⅠA Study on profiles of cognitive processes in children with autism and attention-deficit/hyperactivity disorderObjectives:In this study,we compared the cognitive processes of children with ASD and ADHD,children with pure ASD and children with typical development(TD)to explore the profiles of the cognitive endophenotype of children with ASD and ADHD.Methods:Children with ASD(n=75)were divided into two groups which consisted of children with ASD without(ASD~+ADHD~-,n=37)and with(ASD~+ADHD~+,n=38)ADHD,respectively.The TD group consisted of children with TD(TD,n=32).The TD group was set as a control group.Symptoms of ASD were evaluated by the Autism Diagnostic Observation Schedule 2nd Edition.Symptoms of ADHD were evaluated by the Vanderbilt ADHD Diagnostic Parent Rating Scale.Profiles of cognitive processes(planning,simultaneous processes,attention,and successive processes)were assessed by DN-CAS.First,analysis of variance was used to compare the scores of DN-CAS of three groups.Subsequently,the ROC curve was used to analyze the diagnostic efficacy of DN-CAS in the diagnosis of ASD without and with ADHD.Finally,linear regressions were conducted to determine the relationships between standardized scores of cognitive processes and scores of social impairment,stereotyped behavior,inattention and hyperactivity symptoms.Results:(1)The standardized scores of planning in ASD~+ADHD~-group were lower than those in TD group(P<0.05).(2)The standardized scores of planning,simultaneous processes and attention in ASD~+ADHD~+group were lower than those in TD group(P<0.05).The standardized scores of planning and attention in ASD~+ADHD~+group were lower than those in ASD~+ADHD~-group(P<0.05).(3)ROC curve analysis showed area under curve(AUC)of planning was 0.7(95%CI 0.581-0.818);The best cutoff value of standardized score of planning was 90.5,and the corresponding percentage of planning was 26.5%.The AUC of attention was 0.769(95%CI 0.658-0.880).The best cutoff value of standardized score of attention was 121,corresponding to the percentage of attention was 52.5%.Stereotyped behavior was an independent risk factor for impaired planning and attention in children with ASD(P<0.05).Impaired social affect was an independent risk factor for impaired overall cognitive processes in children with ASD(P<0.05).Conclusion:Children with pure ASD showed deficits in planning,normal in simultaneous processes,attention and successive processes.Children with ASD and ADHD showed a unique characteristic with deficits in planning,simultaneous processes,attention,and normal in successive processes.The cognitive function of children with ASD and ADHD more severely impaired than children with pure ASD.Planning and attention of DN-CAS may help diagnose ASD without and with ADHD.Stereotyped behavior and impaired social affect were independent risk factors for impaired planning,attention and overall cognitive processes in children with ASD,respectively.Our findings suggested that cognitive profiles may serve as an endophenotype to provide evidences for investigating the etiology,diagnosis,differential diagnosis,and treatment in children with ASD and ADHD.PartⅡA Study on the functional connectivity of brain networks in children with autism and attention-deficit/hyperactivity disorderObjectives:In this study,we tried to investigate the endophenotype of the resting state functional brain networks in children with ASD and ADHD at childhood and adolescence stages by studying the FC of the resting state functional brain networks.Methods:The resting state functional magnetic resonance data were collected from Autism Brain Imaging Data Exchange II(ABIDE-II).140 children with typical development were included as the TD group,74 children with ASD and ADHD were included as the ASD~+ADHD~+group,and 72 children with pure ASD were included as the ASD~+ADHD~-group.The three groups were furtherly divided into childhood group(<12 years old)and adolescent group(≥12 years old)respectively.The FC of resting state functional brain networks of the three groups at different developmental stages were compared.Results:(1)During the stage of childhood,compared with the TD group,the FC of whole brain networks in the ASD~+ADHD~-group were mainly enhanced,while the FC of whole brain networks in the ASD~+ADHD~+group were mainly weakened.The ASD~+ADHD~+group involved more dorsal attention network(DAN)and ventral attention network(VAN),while the ASD~+ADHD~+group involved more somatomotor network(SMN)and frontoparietal network(FPN).(2)During the stage of adolescence,compared with the TD group,the FC of whole brain networks in the ASD~+ADHD~-group were mainly weakened,while the FC of whole brain networks in the ASD~+ADHD~+group were mainly enhanced.The ASD~+ADHD~-group involves more DAN and FPN,while the ASD~+ADHD~+group involved more default mode network(DMN).(3)Compared with the TD group,the FC of whole brain networks in the ASD~+ADHD~-group mainly enhanced during childhood and weakened during adolescence.(4)Compared with the TD group,the FC of whole brain networks in the ASD~+ADHD~+group weakened mainly during childhood and enhanced mainly during adolescence.(5)Compared with the ASD~+ADHD~-group,the FC whole brain networks in the ASD~+ADHD~+group both enhanced and weakened during childhood,while only enhanced during adolescence.during both childhood and adolescence stages,the DMN was the network with the most significant differences.Conclusion:Compared with children with TD,the FC of whole brain networks of children with ASD and ADHD and children with pure ASD showed diametrically opposite characteristics during childhood and adolescence.Children with ASD and ADHD have unique brain networks characteristics that were different from children with pure ASD,and were age dependent.It may be a potential endophenotype used to help clinically identify whether ASD are coexisting with ADHD,and may also provide clues for the pathogenesis,diagnosis,and treatment of ASD and ADHD.Part III A study on the functional connectivity and topology attribute of brain networks in Chinese children with autism and attention-deficit/hyperactivity disorderObjectives:The goal of this study was to compare FC and topology attribute of brain networks in Chinese children with ASD with and without ADHD.Methods:Children with ASD with(n=34)and without(n=21)ADHD were compared on FC and topology attribute of brain networks.The correlation analysis was performed between behavioral phenotypes,cognitive endophenotypes and FC,graph theory analysis indicators which were significantly different between children with ASD and ADHD and pure ASD.Results:(1)Compared with children with ASD~+ADHD~-,the FC of brain networks of children with ASD~+ADHD~+were changed.The changed FC of brain networks involved central networks of cognitive control(FPN,VAN,DMN and DAN),processing networks of advanced cognitive processing(SMN).(2)Compared with children with ASD~+ADHD~-,children with ASD~+ADHD~+showed decreased degree in the DMN,increased degree in the SMN,increased nodal efficiency in the SMN and DAN,and increased betweenness in the VAN(P<0.05).(3)Compared with children with ASD~+ADHD~-,children with ASD~+ADHD~+showed a decreased trend of normalized clustering coefficient and small worldness,but the differences were not statistically significant(P=0.08,P=0.07).(4)Significant negative correlations were found between stereotyped behavior and FC from SMN to DAN,SMN to VAN in children with ASD(P<0.05).(5)Significant positive correlation was found between standardized score of attention process and FC from DMN to SMN in children with ASD(P<0.05).Conclusion:Compared with children with pure ASD,children with ASD and ADHD showed changed FC and topology attribute of brain networks.It was consistent with the results of first study that children with ASD and ADHD impaired more severely than pure ASD in cognitive processes.The aggravation of resting state functional brain networks dysfunction in children with ASD and ADHD may be the neural mechanism underlying the more severe impairment of cognitive processes in children with ASD and ADHD.The characteristics of cognitive processes and resting state functional brain networks of children with ASD and ADHD were different from those of pure ASD,suggesting that cognitive profiles and resting state functional brain networks may be serve as endophenotypes for investigating the pathogenesis,clinical diagnosis,differential diagnosis,treatment of ASD,and improving prognosis of ASD. |
PDF Full Text Request