Exome functional risk score and brain connectivity can predict social adaptability outcome of children with autism spectrum disorder in 4 years' follow up.

Introduction: Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder emerging in early childhood, with heterogeneous clinical outcomes across individuals. This study aims to recognize neuroimaging genetic factors associated with outcomes of ASD after a 4-year follow-up. Methods: A total of 104 ASD children were included in this study; they underwent clinical assessments, MRI data acquisition, and the whole exome sequencing (WES). Exome functional risk score (EFRS) was calculated based on WES; and two modalities of brain connectivity were constructed based on MRI data, that is functional connectivity (FC) for functional MRI (fMRI), and individual differential structural covariance network (IDSCN) for structural MRI (sMRI), to explore the neuroimaging genetic biomarker of outcomes of ASD children. Results: Regression analysis found EFRS predicts social adaptability at the 4-year follow-up (Y = -0.013X + 9.29, p = 0.003). We identified 19 pairs of FC associated with autism symptoms severity at follow-up, 10 pairs of FC and 4 pairs of IDSCN associated with social adaptability at follow-up, and 10 pairs of FC associated with ASD EFRS by support vector regression (SVR). Related brain regions with prognostic predictive effects are mainly distributed in superior frontal gyrus, occipital cortex, temporal cortex, parietal cortex, paracentral lobule, pallidum, and amygdala for FC, and temporal cortex, thalamus, and hippocampus for IDSCN. Mediation model showed that ASD EFRS affects the social communication of ASD children through the mediation of FC between left middle occipital gyrus and left pallidum (RMSEA=0.126, CMIN=80.66, DF=42, p< 0.001, CFI=0.867, AIC=152). Discussion: Our findings underscore that both EFRS and brain connectivity can predict social adaptability, and that brain connectivity serving as mediator in the relationship of EFRS and behaviors of ASD, suggesting the intervention targets in the future clinical application.

Informational Analysis and Prediction of Obsessive-Compulsive Disorder Pathogenesis.

OBJECTIVE: We aimed to predict the possible mechanism of obsessive-compulsive disorder (OCD) by integrating and analyzing mRNA sequencing results from two datasets and to provide direction for future studies into the pathogenesis of OCD. METHODS: Two OCD datasets, GSE78104 and GSE60190, were obtained, and the intersection of the two gene sets with differential expression in OCD samples was selected. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment and Gene Ontology (GO) analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) online analysis website for the genes at the intersection, and the data were mapped using http://www.bioinformatics.com.cn. After genes with p≤0.05 had been screened out, protein-protein interaction (PPI) interaction analysis was conducted using Metascape to screen the key Molecular Complex Detection (MCODE) genes. MCODE genes were then enriched using the KEGG signaling pathway and GO classification. RESULTS: A total of 3,449 differentially expressed genes (DEGs) were obtained from the GSE78104 and GSE60190 datasets. KEGG, GO, and Gene Set Enrichment Analysis analyses of DEGs showed that the onset of OCD was related to oxidative phosphorylation and other metabolic processes, which may have a similar pathogenesis to other neurodegenerative diseases. Single-gene PPI analysis of SAPAP3 revealed that the mechanism by which SAPAP3 knockout induces OCD may also be caused by affecting oxidative phosphorylation. CONCLUSION: The mechanism of SAPAP3 knockout-induced OCD in mice may be due to the oxidative phosphorylation process in the body. Future studies on the neural circuit mechanism of OCD should be conducted.

Exploring the impact of PDGFD in osteosarcoma metastasis through single-cell sequencing analysis.

PURPOSE: The overall survival rate for metastatic osteosarcoma hovers around 20%. Responses to second-line chemotherapy, targeted therapies, and immunotherapies have demonstrated limited efficacy in metastatic osteosarcoma. Our objective is to validate differentially expressed genes and signaling pathways between non-metastatic and metastatic osteosarcoma, employing single-cell RNA sequencing (scRNA-seq) and additional functional investigations. We aim to enhance comprehension of metastatic mechanisms and potentially unveil a therapeutic target. METHODS: scRNA-seq was performed on two primary osteosarcoma lesions (1 non-metastatic and 1 metastatic). Seurat package facilitated dimensionality reduction and cluster identification. Copy number variation (CNV) was predicted using InferCNV. CellChat characterized ligand-receptor-based intercellular communication networks. Differentially expressed genes underwent GO function enrichment analysis and GSEA. Validation was achieved through the GSE152048 dataset, which identified PDGFD-PDGFRB as a common ligand-receptor pair with significant contribution. Immunohistochemistry assessed PDGFD and PDGFRB expression, while multicolor immunofluorescence and flow cytometry provided insight into spatial relationships and the tumor immune microenvironment. Kaplan-Meier survival analysis compared metastasis-free survival and overall survival between high and low levels of PDGFD and PDGFRB. Manipulation of PDGFD expression in primary osteosarcoma cells examined invasion abilities and related markers. RESULTS: Ten clusters encompassing osteoblasts, osteoclasts, osteocytes, fibroblasts, pericytes, endothelial cells, myeloid cells, T cells, B cells, and proliferating cells were identified. Osteoblasts, osteoclasts, and osteocytes exhibited heightened CNV levels. Ligand-receptor-based communication networks exposed significant fibroblast crosstalk with other cell types, and the PDGF signaling pathway was activated in non-metastatic osteosarcoma primary lesion. These results were corroborated by the GSE152048 dataset, confirming the prominence of PDGFD-PDGFRB as a common ligand-receptor pair. Immunohistochemistry demonstrated considerably greater PDGFD expression in non-metastatic osteosarcoma tissues and organoids, correlating with extended metastasis-free and overall survival. PDGFRB expression showed no significant variation between non-metastatic and metastatic osteosarcoma, nor strong correlations with survival times. Multicolor immunofluorescence suggested co-localization of PDGFD with PDGFRB. Flow cytometry unveiled a highly immunosuppressive microenvironment in metastatic osteosarcoma. Manipulating PDGFD expression demonstrated altered invasive abilities and marker expressions in primary osteosarcoma cells from both non-metastatic and metastatic lesions. CONCLUSIONS: scRNA-seq illuminated the activation of the PDGF signaling pathway in primary lesion of non-metastatic osteosarcoma. PDGFD displayed an inhibitory effect on osteosarcoma metastasis, likely through the suppression of the EMT signaling pathway.

Electron Delocalization of Au Nanoclusters Triggered by Fe Single Atoms Boosts Alkaline Overall Water Splitting.

The rational design and in-depth understanding of the structure-activity relationship (SAR) of hydrogen and oxygen evolution reaction (HER and OER) bifunctional electrocatalysts are vital to decreasing the energy consumption of hydrogen production by electrochemical water splitting. Herein, we report an inducing electron delocalization method where Fe single atoms as inducers are used to regulate the electron structure of Au nanoclusters by the M-Nx-C substrate to acquire satisfactory intrinsic HER activity. Meanwhile, Fe single atoms also serve as efficient OER active sites to construct bifunctional electrocatalysts. On account of the strong synergistic effect between Au nanoclusters and Fe single atoms, the hybrid catalyst Au-Fe1NC/NF performs an outstanding alkaline HER and OER activity. Only 35.6 mV, 246 mV, and 1.52 V are needed to reach 10 mA cm-2 for alkaline HER, OER, and two-electrode electrolytic cells, respectively. In addition, the bifunctional electrocatalysts also display excellent electrochemical stability. DFT calculations demonstrate that the strong synergistic effect can enhance the O-H bond activation ability of Au nanoclusters and upshift the d-band center of the Fe single atom to promote alkaline electrocatalytic water splitting. The strong synergistic effect is proven to arise from the electron delocalization of Au nanoclusters triggered by Fe single atoms.

Brain white matter microstructure abnormalities in children with optimal outcome from autism: a four-year follow-up study.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder, with only a small proportion of people obtaining optimal outcomes. We do not know if children with ASD exhibit abnormalities in the white matter (WM) microstructure or if this pattern would predict ASD prognosis in a longitudinal study. 182 children with ASD were recruited for MRI and clinical assessment; 111 completed a four-year follow-up visit (30 with optimal outcomes, ASD-; 81 with persistent diagnosis, ASD+). Additionally, 72 typically developing controls (TDC) were recruited. The microstructural integrity of WM fiber tracts was revealed using tract-based spatial statistics (TBSS) and probabilistic tractography analyses. We examined the neuroimaging abnormality associated with ASD and its relationship to ASD with optimal outcome. The ASD+ and TDC groups were propensity score matched to the ASD- group in terms of age, gender, and IQ. TBSS indicated that children with ASD exhibited abnormalities in the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF), and extending to the anterior thalamic radiation (ATR) and cingulum; whereas the ASD+ group showed more severe abnormalities than the ASD- group. Probabilistic tractography analysis revealed that ASD+ group exhibited lower Fractional Anisotropy (FA) of the left superior thalamic radiation (STR L) than ASD- group, and that FA value of the STR L was a significant predictor of optimal outcome (EX(B), 6.25; 95% CI 2.50-15.63; p < 0.001). Children with ASD showed significant variations in SLF_L and STR_L, and STR_L was a predictor of 'ASD with optimal outcome'. Our findings may aid in comprehension of the mechanisms of 'ASD with optimal outcome'.

Chronic Stress in Bipolar Disorders Across the Different Clinical States: Roles of HPA Axis and Personality.

Introduction: Chronic stress has been linked to the pathophysiology of bipolar disorder (BD); however, the underlying mechanism remains unclear. In BD patients, hypothalamic-pituitary-adrenal (HPA) axis activity is associated with stress. This study aimed to examine the relationship between HPA axis activity and BD symptoms in various clinical states, as well as how personality influences the process. Methods: This study investigated the differences in HPA axis activity among four BD states. We enrolled 813 BD patients in an 8-week longitudinal study to examine the relationship between HPA axis activity and symptom trajectories using dynamic temporal warping (DTW) analysis and an unsupervised machine learning technique. Furthermore, using mediation analyses, the relationship between the HPA axis, personality, and BD symptoms was investigated. Results: Analysis of variance (ANOVA) analysis showed that glucocorticoid cortisol (CORT) and adrenocorticotropin (ACTH) did not differ significantly among the four clinical states of BD. The DTW integrating clustering analysis revealed that the two clusters were optimal, with cluster 1 characterized by severe manic symptoms, which then improved, and cluster 2, characterized by milder manic severity, which also improved. The two clusters showed different ACTH levels (t = 2.289, p = 0.022), and logistic regression analysis revealed a slight positive association between ACTH levels and cluster 1. Furthermore, the mediation analysis indicated that ACTH influences curative efficacy via conscientiousness (ßc =0.103, p=0.001). Discussion: In conclusion, we found that a higher level of ACTH is associated with severe manic symptoms, indicating a chronic stress response in BD patients. Additionally, the ACTH levels affect short-term BD curative efficacy via the mediation of conscientiousness, providing a psychotherapeutic strategy direction for BD.

Influence of cyanobacterial bloom accumulation and dissipation on underwater light attenuation in a large and shallow lake.

Cyanobacterial bloom accumulation and dissipation frequently occur in Lake Taihu, a typically shallow, eutrophic lake due to wind wave disturbance. However, knowledge of the driving mechanisms of cyanobacterial blooms on underwater light attenuation is still limited. In this study, we collected a high-frequency in situ monitoring of the wind field, underwater light environment, and surface water quality to elucidate how cyanobacterial bloom accumulation and dissipation affect the variations in underwater light attenuation in the littoral zone of Lake Taihu. Results showed that cyanobacterial blooms significantly increased the diffuse attenuation coefficient of ultraviolet-B (Kd(313)), ultraviolet-A (Kd(340)), and photosynthetically active radiation (Kd(PAR)); the scattering of total suspended matter (bbp(λ)); and the absorption of phytoplankton (aph(λ)) and chromophoric dissolved organic matter (CDOM, ag(λ)) (p < 0.01). The Kd(PAR) decreased quickly during the processes of bloom dissipation, but the decrease of Kd(313) and Kd(340) lagged 0.5 day. Our results suggested that cyanobacterial blooms could increase particle matters and elevated the production of autochthonous CDOM, resulting in underwater light attenuation increase. Ultraviolet radiation (UVR) and PAR attenuation both have significant responses to cyanobacterial blooms, but the response processes were distinct due to the different changes of particle and dissolved organic matters. Our study unravels the driving mechanisms of cyanobacterial blooms on underwater light attenuation, improving lake ecosystem management and protection.

[Whole exome sequencing analysis of a patient with 45,X/46,XY mosaicism and autism spectrum disorder].

OBJECTIVE: To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter. RESULTS: The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance. CONCLUSION: Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.

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.

High-resolution temporal detection of cyanobacterial blooms in a deep and oligotrophic lake by high-frequency buoy data.

Cyanobacterial blooms are increasing in magnitude, frequency, and duration worldwide. However, our knowledge of cyanobacterial blooms dynamics and driving mechanisms is still limited due to their high spatiotemporal variability. To determine the potential driving mechanisms of cyanobacterial blooms in oligotrophic lakes, we collected a high-frequency depth profile of chlorophyll fluorescence (ChlF) and synchronous water quality, hydrometeorological data in early spring 2016 in oligotrophic Lake Qiandaohu. The vertical distribution of ChlF exhibited two patterns, "aggregated" and "discrete", using Morisita's index, and the aggregated ChlF presented subsurface chlorophyll maxima during the thermal stratification period. The ChlF concentration was positively correlated with water temperature and negatively correlated with turbidity. Significantly linear relationships were observed between ChlF vertical structure parameters (e.g., Morisita's index, subsurface chlorophyll maxima depth and thickness) and thermal stratification parameters (e.g., mixing layer depth and relative water column stability). After rainstorm floods, the ChlF pattern suddenly change from "aggregated" to "discrete" and a ChlF concentration <1 µg/L was observed for 7-11 days with a significant increase in the mixing depth layer and turbidity. The results suggest that cyanobacterial blooms are robustly associated with thermal stratification and rainstorm floods in the deep and oligotrophic lake. Thermal stratification boosts surface phytoplankton accumulation by increasing water temperature, enhancing light availability and restricting phytoplankton vertical distribution. Rainstorm floods interrupt the accumulation by disrupting thermal stratification and decreasing the available light. Furthermore, wind speed and air temperature both regulate the phytoplankton dynamics by affecting thermal stratification. Our research quantifies the cyanobacterial bloom dynamics and their relationship between environmental factors, improving our knowledge of the driving mechanisms of cyanobacterial bloom for the protection of drinking water safety and aquatic organism health in lakes.

Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis.

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, and methylphenidate (MPH) is considered one of the first-line medicine for ADHD. Unfortunately, this medication is only effective for some children with ADHD. This meta-analysis was conducted to evaluate whether noradrenergic gene polymorphisms impact the efficacy of MPH in children with ADHD. METHODS: Candidate gene studies published in English until March 1, 2020, were identified through literature searches on PubMed, Web of Science, and Embase. Data were pooled from individual clinical trials considering MPH pharmacogenomics. According to the heterogeneity, the odds ratio and mean differences were calculated by applying fixed-effects or random-effects models. RESULTS: This meta-analysis includes 15 studies and 1382 patients. Four polymorphisms of the NET gene (rs5569, rs28386840, rs2242446, rs3785143) and 2 polymorphisms of the α2A-adrenergic receptor gene (ADRA2A) gene (MspI and DraI) were selected for the analysis. In the pooled data from all studies, T allele carriers of the rs28386840 polymorphism were significantly more likely to respond to MPH (P < .001, ORTcarriers = 2.051, 95% confidence interval [CI]:1.316, 3.197) and showed a relationship with significantly greater hyperactive-impulsive symptoms improvement (P < .001, mean difference:1.70, 95% CI:0.24, 3.16). None of the ADRA2A polymorphisms correlated significantly with MPH response as a whole. However, G allele carriers of the MspI polymorphism showed a relationship with significantly inattention symptoms improvement (P < .001, mean difference:0.31, 95% CI: 0.15, 0.47). CONCLUSION: Our meta-analysis results indicate that the noradrenergic gene polymorphisms may impact MPH response. The NET rs28386840 is linked to improved MPH response in ADHD children. And the ADRA2A MspI is associated with inattention symptom improvements. Further investigations with larger samples will be needed to confirm these results.Registration: PROSPERO (no. CRD42021265830).

[A study on KIF1A gene missense variant analysis and its protein expression and structure profiles of an autism spectrum disorder family trio].

OBJECTIVE: To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene. METHODS: The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant. RESULTS: The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function. CONCLUSION: The KIF1A gene may be a risk gene for ASD.

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.

[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.

Comparisons between Psychiatric Symptoms of Patients with Anti-NMDAR Encephalitis and New-Onset Psychiatric Patients.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a potentially lethal autoimmune disease. Early diagnosis and immunotherapy can improve prognosis; however, early prominent psychiatric symptoms have led to misdiagnosis in numerous cases, delaying diagnosis and treatment. This study aimed to explore the clinical features and psychiatric symptoms of anti-NMDAR encephalitis and the association between antibody titers and psychiatric symptoms. METHODS: In this retrospective study, 43 patients with anti-NMDAR encephalitis and 70 new-onset psychiatric patients were enrolled. Psychiatric symptoms were assessed by trained psychiatrists using the Positive and Negative Syndrome Scale. RESULTS: There were significant differences in psychiatric symptoms between the antibody-positive and antibody-negative groups. The item scores for poor rapport (p < 0.01), difficulty in abstract thinking (p < 0.01), lack of spontaneity and flow of conversation (p < 0.01), unusual thought content (p < 0.01), and disorientation (p < 0.01) were significantly higher in the antibody-positive group, while the item scores for delusions (p < 0.01) were significantly higher in the antibody-negative group. These differences all remained significant after Holm-Bonferroni correction. In the antibody-positive group, scores for each item, subscale, and factor increased with increases in antibody titer, particularly for delusions (p < 0.05) and hallucinatory behavior (p < 0.01). Thereafter, only hallucinatory behavior remained significant. CONCLUSIONS: Patients with anti-NMDAR encephalitis with initial psychiatric symptoms may have the following characteristics: poor rapport, difficulty in abstract thinking, lack of spontaneity and flow of conversation, unusual thought content, and disorientation. Furthermore, antibody titer may be associated with psychiatric symptom severity, especially in hallucinatory behavior.