Transdiagnostic symptom subtypes across autism spectrum disorders and attention deficit hyperactivity disorder: validated by measures of neurocognition and structural connectivity.

BACKGROUNDS: Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders that exhibit within-disorder heterogeneity and cross-disorder phenotypic overlap, thus suggesting that the current disease categories may not fully represent the etiologic essence of the disorders, especially for highly comorbid neurodevelopmental disorders. In this study, we explored the subtypes of a combined sample of ASD and ADHD by integrating measurements of behavior, cognition and brain imaging. METHODS: A total of 164 participants, including 65 with ASD, 47 with ADHD, and 52 controls, were recruited. Unsupervised machine learning with an agglomerative hierarchical clustering algorithm was used to identify transdiagnostic symptom clusters. Neurocognition and brain structural connectivity measurements were used to assess symptom clusters. Mediation analysis was used to explore the relationship between transdiagnostic symptoms, neurocognition and brain structural connectivity. RESULTS: We identified three symptom clusters that did not fall within the diagnostic boundaries of DSM. External measurements from neurocognition and neuroimaging domains supported distinct profiles, including fine motor function, verbal fluency, and structural connectivity in the corpus callosum between these symptom clusters, highlighting possible biomarkers for ASD and ADHD. Additionally, fine motor function was shown to mediate the relationship between the corpus callosum and perseveration symptoms. CONCLUSIONS: In this transdiagnostic study on ASD and ADHD, we identified three subtypes showing meaningful associations between symptoms, neurocognition and brain white matter structural connectivity. The fine motor function and structural connectivity of corpus callosum might be used as biomarkers for neurodevelopmental disorders with social skill symptoms. The results of this study highlighted the importance of precise phenotyping and further supported the effects of fine motor intervention on ASD and ADHD.

Exploring the spatial working memory and visual perception in children with autism spectrum disorder and general population with high autism-like traits.

The aim of the study is to compare the spatial working memory and visual perception between children with autism spectrum disorder (ASD) and typically developing control (TDC). Furthermore, this study validated whether this impairment was a feature of autism in general population with different autism-like traits (ALTs). This study contains two parts: case-control study and community population study. The ASD group and the control group were enlisted voluntarily (ASD group, n = 52; control group, n = 32). In the population study, we recruited 2994 children. Based on the scores of Autism Spectrum Quotient (AQ), children were divided into two groups (higher ALTs n = 122, lower ALTs n = 122). The participants completed the cognition tasks focusing on spatial working memory, visual-motor integration, and Intelligence. Analysis of covariance (ANCOVA) was conducted, with potential confounders IQ, age, and gender were controlled. Pearson correlations were computed by controlling the IQ and age as covariate to better understand the relations between visual perception, spatial working memory, and autism-like traits. In the case-control study, the results of cognition tasks focusing on the spatial working memory and visual perception indicated underperformance in children with ASD. In the community population study, we found that individuals with higher ALTs performed worse than children with lower ALTs in spatial working memory. Pearson correlation analysis suggested that a correlation between SWM total errors and visual perception was identified both in the children with ASD and in community population (ASD group, r = -0.592, p<0.001; general population, r = -0.201, p = 0.003). It suggested that spatial working memory deficit was a characteristic of autism, and may be distributed across the general population. Furthermore, we speculated a correlation between spatial working memory and visual perception in children with ASD and in general population.

[Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders].

OBJECTIVE: To explore susceptibility genes for autism spectrum disorders (ASD). METHODS: Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates. RESULTS: A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2(0.8146)] and four medium-confidence genes [ERBB2(0.1322), LAMC3(0.1117), PPFIA4(0.1059), DISC1(0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes. CONCLUSION: Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high phenotypic and genetic heterogeneity. Whole-exome sequencing studies have shown that de novo single-nucleotide variations (SNVs) play an important role in sporadic ASD. The present study aimed to search for de novo SNVs using whole-exome sequencing in 59 unrelated Chinese ASD sporadic trios, and found 24 genes (including five reported ASD candidate genes CACNA1D, ACHE, YY1, TTN, and FBXO11) with de novo harmful SNVs. Five genes (CACNA1D, JAK2, ACHE, MAPK7, and PRKAG2) classified as "medium-confidence" genes were found to be related to ASD using the Phenolyzer gene analysis tool, which predicts the correlation between the candidate genes and the ASD phenotype. De novo SNVs in JAK2, MAPK7, and PRKAG2 were first found in ASD. Both JAK2 and MAPK7 were involved in the regulation of the MAPK signaling pathway. Gene co-expression and inter-gene interaction networks were constructed and gene expression data in different brain regions were further extracted, revealing that JAK2 and MAPK7 genes were associated with certain previously reported ASD genes and played an important role in early brain development. The findings of this study suggest that the aforementioned five reported ASD genes and JAK2 and MAPK7 may be related to ASD susceptibility. Further investigations of expression studies in cellular and animal models are needed to explore the mechanism underlying the involvement of JAK2 and MAPK7 in ASD.

Increased Left Inferior Temporal Gyrus Was Found in Both Low Function Autism and High Function Autism.

Previous neuroimaging studies of autism spectrum disorder (ASD) have focused on subjects with IQ > 70 or ASD without considering IQ levels. It remains unclear whether differences in brain anatomy in this population are associated with variations in clinical phenotype. In this study, 19 children with low functioning autism (LFA) and 19 children with high functioning autism (HFA) were compared with 27 healthy controls (HC). We found increased gray matter volume (GMV) in the left inferior temporal gyrus in subjects with both HFA and LFA and increased GMV of left middle temporal gyrus BA21 was found only in the LFA group. A significant negative correlation was found between the left inferior temporal gyrus (LITG) and the score of repetitive behavior in the HFA group.

[Reliability and Validity of the Abridged Chinese Version of Autism Spectrum Quotient-Child form in China].

OBJECTIVE: To determine the reliability and validity of the abridged Chinese version of the autism spectrum quotient (AQ) -child form. METHODS: A total of 86 children with autism spectrum disorder (ASD) were recruited from the West China Hospital from July 2014 to December 2016, along with 6 896 children recruited from three schools in Chengdu. The participants completed the AQ scale under instructions from a trained interviewer. Then 170 school children were selected and repeated the AQ scale within one month. RESULTS: All subscale scores were correlated with the scale score, but with weak inter-subscale correlations. The total AQ score of the control group was continuously distributed in the population, which was similar to the normal distribution. The skewness was -0.127 and the kurtosis was -0.124, indicating that the total AQ score was negatively skewed and slightly flat in the population.There were differences in AQ scores between different genders in community children (P<0.01), with male group (42.09±9.92) higher than female group (40.07±9.94).There was no gender difference in the ASD individuals. There was a correlation between age and AQ score (R=0.06).The autistic children had a higher AQ score (54.49±14.16) than the school children (41.12±9.98)(P<0.01). Similar results were found in the subscale scores, except for"attention to detail". The AQ scale had a Cronbach α coefficient of 0.71: ranging from 0.21 to 0.69 for the subscales. The test-retest reliability was good for the scale and the subscales (all P>0.05) . The sensitivity and specificity of AQ for screening ASD was both 0. 71. CONCLUSION: The abridged Chinese version of the AQ-child scale has good psychometrics properties and may be a valid and reliable instrument for ASD screening with a cut-off score of 48.

Parents' impaired emotion recognition abilities are related to children's autistic symptoms in autism spectrum disorder.

OBJECTIVE: We aimed to explore whether parents of children with autism spectrum disorder (ASD) had impaired emotion recognition abilities and whether this deficit was related to their children's autistic symptoms. METHODS: The autistic symptoms of 31 ASD children were assessed using the Autism Diagnostic Interview-Revised (ADI-R). Fifty parents of ASD children and 34 parents of typically developing (TD) children completed an emotion recognition task (ERT). RESULTS: The numbers of correct ERT responses were lower for parents of ASD children than for parents of TD children with respect to recognizing sadness, disgust, fear, and all emotions (P=0.01, 0.04, 0.02, and 0.00, respectively). Controlled for parental age, gender, and the intelligence quotients of both the parents and children, a negative correlation was found between the total number of correct ERT responses for parents of ASD children and these children's "restricted, repetitive, and stereotyped patterns of behavior" scores on the ADI-R (r=-0.32; P=0.03). CONCLUSION: Parents of ASD children showed impaired emotion recognition abilities compared with parents of TD children. This parental deficit in emotion recognition ability was related to the autistic symptoms of ASD children.

[Behavioral phenotypes of autism spectrum disorder patients and their parents].

OBJECTIVE: To explore the relationship between the behavior phenotypes of patients with autism spectrum disorder (ASD) and their parents through family study. METHODS: Forty-five core families with ASD and 30 control families from Chengdu area were examined using Autism Spectrum Quotient (AQ). Descriptive statistical analysis, correlation analysis, and Logistic regression analysis were used to investigate the effect of various factors, especially genetic factors that may affect the pathogenesis of ASD. RESULTS: The social skills factor and communication factor of the father's AQ scale, as well as the mother's age of childbearing and AQ social skills factor are related to whether children with ASD (R were 0.46, 0.39, 0.39 and 0.36, P<0.05). The communication factor of the parents' AQ and mother's attention to detail factor are related to whether children will show developmental anomaly before the age of 36 months (R were 0.55, 0.51 and 0.54, P<0.05). The social skill problems of parents and father's communication problems are risk factors for children with autism. CONCLUSION: ASD may be influenced by both genetic and environmental factors. The autistic behavior phenotype of parents is a risk factor for ASD and is associated with developmental anomalies of early childhood.