Symptom severity and posttraumatic growth in parents of children with autism spectrum disorder: The moderating role of social support.

Parents of children with autism spectrum disorder (ASD) experience posttraumatic growth (PTG). No study has investigated the moderating effect of social support and family function between symptom severity and PTG. The study aims to examine whether social support and family function moderate the relationship between symptom severity and PTG among parents of children with ASD. Using a cross-sectional design, a total of 385 parents of children with ASD were recruited from September 2019 to November 2020 by convenience sampling. Participants completed the Posttraumatic Growth Inventory, Social Support Rating Scale, Autism Behavior Checklist, and Family Apgar Index. Both social support (r = 0.354, p < 0.01) and family function (r = 0.379, p < 0.05) were significantly related to PTG. Although symptom severity was not significantly related to PTG (p > 0.05), social support moderated the correlation between symptom severity and PTG [ß(SE) = -0.134 (0.719), p < 0.01, 95% CI = (-3.552, -0.723)]; the positive association was stronger for low social support [ß(SE) = 0.145 (0.054), t = 2.675, p < 0.01, 95% CI = (0.038, 0.252)], while the negative association was weaker for high social support [ß(SE) = -0.121 (0.051), t = -2.378, p < 0.05, 95% CI = (-0.221, -0.021)]. Family function did not moderate the relationship (p > 0.05). Higher social support appears to buffer the detrimental effect of symptom severity on PTG, and social support seems to be an important factor when delivering interventions aimed at decreasing symptom severity and improving positive growth. LAY SUMMARY: Both social support and family function were positively associated with PTG. Providing sufficient perceived social support and enhancing family function promoted parents' positive psychological experience. Higher social support seemed to buffer the detrimental effect of symptom severity on PTG, and it could be an important intervention target for improving the psychological growth of parents of children with ASD.

Parental self-efficacy and family quality of life in parents of children with autism spectrum disorder in China: The possible mediating role of social support.

OBJECTIVE: This study explored the related factors of FQOL in parents of children with ASD and examined whether social support mediates the relationship between parental self-efficacy and FQOL in parents of children with ASD. DESIGN AND METHODS: Using a cross-sectional design, a total of 260 parents of children with ASD were recruited from September 2019 to November 2020. They completed the Beach Center Family Quality of Life Scale, the Parenting Sense of Competence Scale, and the Social Support Rating Scale. RESULTS: Parental self-efficacy and social support explained approximately 49.5% of the variance in FQOL. After controlling for the confounding influence of parents' education level, parental self-efficacy had a direct effect on FQOL (ß = 0.292, SE = 0.108, P < 0.01) and an indirect effect on FQOL (ß = 0.165, SE = 0.069, P < 0.01). Effects were mediated through social support, with partial mediating effects accounting for 36.11% of the total effect. CONCLUSIONS: Both parental self-efficacy and social support are critical to promoting FQOL, and a partial mediating effect of social support was established. PRACTICAL IMPLICATIONS: Interventions for families with children with ASD should focus on enhancing parental self-efficacy, followed by a perceived social support and FQOL prompt.

Application of Clustering Method to Explore the Correlation Between Dominant Flora and the Autism Spectrum Disorder Clinical Phenotype in Chinese Children.

Autism spectrum disorder (ASD) is characterized by deficits in social interactions and repetitive, stereotypic behaviors. Evidence shows that bidirectional communication of the gut-brain axis plays an important role. Here, we recruited 62 patients with ASD in southern China, and performed a cross-sectional study to test the relationship between repeated behavior, gut microbiome composition, and alpha diversity. We divided all participants into two groups based on the clustering results of their microbial compositions and found Veillonella and Ruminococcus as the seed genera in each group. Repetitive behavior differed between clusters, and cluster 2 had milder repetitive symptoms than Cluster 1. Alpha diversity between clusters was significantly different, indicating that cluster 1 had lower alpha diversity and more severe repetitive, stereotypic behaviors. Repetitive behavior had a negative correlation with alpha diversity. We demonstrated that the difference in intestinal microbiome composition and altered alpha diversity can be associated with repetitive, stereotypic behavior in autism. The role of Ruminococcus and Veillonella in ASD is not yet understood.

Comparison of beta diversity measures in clustering the high-dimensional microbial data.

The heterogeneity of disease is a major concern in medical research and is commonly characterized as subtypes with different pathogeneses exhibiting distinct prognoses and treatment effects. The classification of a population into homogeneous subgroups is challenging, especially for complex diseases. Recent studies show that gut microbiome compositions play a vital role in disease development, and it is of great interest to cluster patients according to their microbial profiles. There are a variety of beta diversity measures to quantify the dissimilarity between the compositions of different samples for clustering. However, using different beta diversity measures results in different clusters, and it is difficult to make a choice among them. Considering microbial compositions from 16S rRNA sequencing, which are presented as a high-dimensional vector with a large proportion of extremely small or even zero-valued elements, we set up three simulation experiments to mimic the microbial compositional data and evaluate the performance of different beta diversity measures in clustering. It is shown that the Kullback-Leibler divergence-based beta diversity, including the Jensen-Shannon divergence and its square root, and the hypersphere-based beta diversity, including the Bhattacharyya and Hellinger, can capture compositional changes in low-abundance elements more efficiently and can work stably. Their performance on two real datasets demonstrates the validity of the simulation experiments.

Posttraumatic Growth Among Parents of Children with Autism Spectrum Disorder in China and Its Relationship to Family Function and Mental Resilience: A Cross-Sectional Study.

OBJECTIVE: This study was conducted to examine the posttraumatic growth (PTG) of parents of children with autism spectrum disorder (ASD) and the association among family function, mental resilience and PTG. DESIGN AND METHODS: This descriptive cross-sectional study was conducted with 205 parents of children with ASD in the clinical department of a university-affiliated hospital in Guangzhou from January to October 2019. The Posttraumatic Growth Inventory, Family Assessment Device, and Connor-Davidson Resilience Scale were employed for data collection. RESULTS: The mean PTG score of parents was 59.56±18.46; and 24.63%, 43.84%, and 32.51% of parents exhibited a high level, moderate level and low level, respectively, of PTG. The problem-solving dimension of family function (p = 0.005) and the strength dimension of mental resilience (p ≤0.001) were positively related to PTG. CONCLUSIONS: Parents of children with ASD experienced moderate PTG overall. The problem-solving dimension of family function and the strength dimension of mental resilience were significant predictors of PTG. PRACTICAL IMPLICATIONS: Interventions to improve family function and the mental resilience of parents with ASD children could contribute to improving the PTG of parents.

Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.

The genotype-first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype-specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype-to-genotype approach, we performed whole-exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head-size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3) implicated in ASD and related neurodevelopmental disorders. We identify genotype-phenotype correlations for head-size-associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype-to-genotype strategy would accelerate the elucidation of genotype-phenotype relationships for ASD by using phenotype-restricted cohorts.

Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.

Background: We previously performed targeted sequencing of autism risk genes in probands from the Autism Clinical and Genetic Resources in China (ACGC) (phase I). Here, we expand this analysis to a larger cohort of patients (ACGC phase II) to better understand the prevalence, inheritance, and genotype-phenotype correlations of likely gene-disrupting (LGD) mutations for autism candidate genes originally identified in cohorts of European descent. Methods: We sequenced 187 autism candidate genes in an additional 784 probands and 85 genes in 599 probands using single-molecule molecular inversion probes. We tested the inheritance of potentially pathogenic mutations, performed a meta-analysis of phase I and phase II data and combined our results with existing exome sequence data to investigate the phenotypes of carrier parents and patients with multiple hits in different autism risk genes. Results: We validated recurrent, LGD, de novo mutations (DNMs) in 13 genes. We identified a potential novel risk gene (ZNF292), one novel gene with recurrent LGD DNMs (RALGAPB), as well as genes associated with macrocephaly (GIGYF2 and WDFY3). We identified the transmission of private LGD mutations in genes predominantly associated with DNMs and showed that parental carriers tended to share milder autism-related phenotypes. Patients that carried DNMs in two or more candidate genes show more severe phenotypes. Conclusions: We identify new risk genes and transmission of deleterious mutations in genes primarily associated with DNMs. The fact that parental carriers show milder phenotypes and patients with multiple hits are more severe supports a multifactorial model of risk.

Investigating the validation of the Chinese Mandarin version of the Social Responsiveness Scale in a Mainland China child population.

BACKGROUND: Researchers from several different countries have found the Social Responsiveness Scale (SRS) to have good psychometric properties. However, to our knowledge, no studies on this subject have been reported in Mainland China. In this study, we investigated the psychometric properties of the Chinese Mandarin version of the SRS when used in Mainland China. METHODS: The reliability and validity of the parent-report SRS in a sample of 749 children of 4- to 14-year-olds: 411 typically developing and 338 clinical participants (202 with autism spectrum disorder (ASD)) were examined. RESULTS: Internal consistency for total scale (0.871-0.922), test-retest reliability (0.81-0.94), and convergent validity with the Autism Behavior Checklist (ABC) (0.302-0.647) were satisfactory. The SRS total score discriminated between the ASD and other developmental disorders. Receiver operating characteristic (ROC) analyses revealed that the SRS was predicted to accurately classify 69.2-97.2% of youth ASD. Exploratory factor analysis (EFA) supported a single-factor solution for the ASD subsample. Confirmatory factor analysis (CFA) did not confirm the theoretical construct of five factors model with inadequate fit in the ASD subsample. CONCLUSIONS: Overall, our findings supported the reliability and validity of the parent-report SRS as one ASD screening instrument. In addition, we also suggest that the use of separate cut-offs for screening purposes (optimizing sensitivity) vs. clinical confirmation (optimizing specificity) should be considered.

De novo genic mutations among a Chinese autism spectrum disorder cohort.

Recurrent de novo (DN) and likely gene-disruptive (LGD) mutations contribute significantly to autism spectrum disorders (ASDs) but have been primarily investigated in European cohorts. Here, we sequence 189 risk genes in 1,543 Chinese ASD probands (1,045 from trios). We report an 11-fold increase in the odds of DN LGD mutations compared with expectation under an exome-wide neutral model of mutation. In aggregate, ∼4% of ASD patients carry a DN mutation in one of just 29 autism risk genes. The most prevalent gene for recurrent DN mutations is SCN2A (1.1% of patients) followed by CHD8, DSCAM, MECP2, POGZ, WDFY3 and ASH1L. We identify novel DN LGD recurrences (GIGYF2, MYT1L, CUL3, DOCK8 and ZNF292) and DN mutations in previous ASD candidates (ARHGAP32, NCOR1, PHIP, STXBP1, CDKL5 and SHANK1). Phenotypic follow-up confirms potential subtypes and highlights how large global cohorts might be leveraged to prove the pathogenic significance of individually rare mutations.

[Copy-number variations of SHANK3 and related clinical phenotypes in children with autism].

OBJECTIVE: To explore possible relationship between copy-number variations (CNVs) in 15q11-13, 16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification (MLPA) and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism. METHODS: The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-IV, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains. RESULTS: Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANK3 microdeletion, accounting for approximately 2% (2/109) of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation. CONCLUSIONS: SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANK3 microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism.