ASD Severity Research Articles

Structure-function coupling in white matter uncovers the hypoconnectivity in autism spectrum disorder

BackgroundAutism Spectrum Disorder (ASD) is a neurodevelopmental disorder associated with alterations in structural and functional coupling in gray matter. However, despite the detectability and modulation of brain signals in white matter, the structure-function coupling in white matter in autism remains less explored.MethodsIn this study, we investigated structural-functional coupling in white matter (WM) regions, by integrating diffusion tensor data that contain fiber orientation information from WM tracts, with functional connectivity tensor data that reflect local functional anisotropy information. Using functional and diffusion magnetic resonance images, we analyzed a cohort of 89 ASD and 63 typically developing (TD) individuals from the Autism Brain Imaging Data Exchange II (ABIDE-II). Subsequently, the associations between structural-functional coupling in WM regions and ASD severity symptoms assessed by Autism Diagnostic Observation Schedule-2 were examined via supervised machine learning in an independent test cohort of 29 ASD individuals. Furthermore, we also compared the performance of multi-model features (i.e. structural-functional coupling) with single-model features (i.e. functional or structural models alone).ResultsIn the discovery cohort (ABIDE-II), individuals with ASD exhibited widespread reductions in structural-functional coupling in WM regions compared to TD individuals, particularly in commissural tracts (e.g. corpus callosum), association tracts (sagittal stratum), and projection tracts (e.g. internal capsule). Notably, supervised machine learning analysis in the independent test cohort revealed a significant correlation between these alterations in structural-functional coupling and ASD severity scores. Furthermore, compared to single-model features, the integration of multi-model features (i.e., structural-functional coupling) performed best in predicting ASD severity scores.ConclusionThis work provides novel evidence for atypical structural-functional coupling in ASD in white matter regions, further refining our understanding of the critical role of WM networks in the pathophysiology of ASD.

Widespread Associations between Behavioral Metrics and Brain Microstructure in ASD.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and repetitive behaviors. A diagnosis of ASD is provided by a clinician following cognitive and behavioral evaluations, but there is currently no biomarker associating these metrics with neurological changes. Our lab has previously found that g-ratio, the proportion of axon width to myelin diameter, and axonal conduction velocity, which is associated with the capacity of an axon to carry information, are both decreased in ASD individuals. By associating these differences with performance on cognitive and behavioral tests, we can evaluate which tests most reveal changes in the brain. Analyzing 273 participants (148 with ASD) ages 8-to-17 (49% female) through an NIH-sponsored Autism Centers of Excellence (ACE) network (Grant#: MH100028), we observe widespread associations between behavioral and cognitive evaluations of autism and between behavioral and microstructural metrics. Analyzing data from all participants, conduction velocity but not g-ratio was significantly associated with many behavioral metrics. However, this pattern was reversed when looking solely at ASD participants. This reversal may suggest that the mechanism underlying differences between autistic and non-autistic individuals may be distinct from the mechanism underlying ASD behavioral severity. Two additional machine learning cluster analyses applied to neuroimaging data reinforce the association between neuroimaging and behavioral metrics and suggest that age-related maturation of brain metrics may drive changes in ASD behavior. By associating neuroimaging metrics with ASD, it may be possible to measure and identify individuals at high risk of ASD before behavioral tests can detect them.

Implications of Childhood Autism Spectrum Disorder for Maternal Employment: United States vs. Norway

ObjectivesA country’s social welfare system may play an important role in maternal employment. This study compared the labor market participation of mothers of children within the United States (U.S.) and Norway to examine whether the child’s age and severity of the ASD affected mothers’ employment differently between the two countries.MethodsThe 2019 National Survey of Children’s Health was used for the U.S. analysis, and the 2019 administrative register data were used for the Norwegian analysis. A logit model was used to analyze the impact of a child’s age and ASD severity on maternal employment in the U.S. and Norway. We presented the results as average marginal effects obtained from the logistic regression analyses.ResultsAfter adjusting for mothers’ sociodemographic variables and the child’s age, U.S. mothers of children with mild ASD and moderate/severe ASD had respectively 12 and 25% points lower probability of being employed than U.S. mothers of children without special health care needs. In Norway, mothers of children with moderate/severe ASD had a 13% points lower probability of employment than mothers without special health care needs. The probability of being employed for mothers caring for a child with ASD was significantly greater as the child got older in both countries.Conclusions for PracticeThe employment gap was more substantial in the U.S. than in Norway. A general high employment participation rate among women and an elaborated welfare state and policy package seem to benefit employment among mothers of children with ASD in Norway.

Formation of cognitive processes in children with autism. Part II. Genetic mechanisms

Autism and autism spectrum disorders are neuropsychiatric diseases that begin to appear in children under 3 years. Over the past decade, the number of children with autism spectrum disorders has increased more than in 10-fold and continues to grow, accounting for 1–2% of the world’s population. Currently, the diagnosis of autism spectrum disorders is based only on clinical and behavioral tests, and there are no biological and genetic markers that could contribute to the early detection of this disorder. The review, based on the analysis of modern literature data about symptoms, genetic etiological factors that associated with autism, examines the possibility of using genes as diagnostic biomarkers in children with autism spectrum disorders. Analysis of literature data shows that disorders of attention, speed of information processing, working memory, learning are based on genetic (mutations, SNPs) and epigenetic (methylation) changes in the expression of many genes: BDNF, CAPS2, CNTNAP2, GABRB3, FMR1, FOXP1, GTF2I, HSD11B2, MECP2, NF2, NGF, NR3C1, OXTR, PAK2, RELN, SLC6A4, UBE3A, etc. Some of these genes (RELN) are associated with ASD severity.

National Survey on bladder and bowel dysfunctions in Autism Spectrum Disorder population.

To evaluate lower urinary tract symptoms (LUTS) and bowel disorders in a population of young subjects with autism spectrum disorder (ADS) by a national survey and to assess the relationship between the occurrence, frequency, and type of LUTS and the severity of behavioral and neuropsychiatric characteristics. A survey on LUTS and bowel disorders in the ASD population was sent by mail and social media through the main Italian Associations of ASD between February and September 2022. The correlation between LUTS and ASD severity was also assessed. The survey was completed by 502 subjects with a mean age of 16.6 years ± 10 years: male participants were 413 (mean age: 16.5 years ± 9.8 years), while female participants 89 (mean age: 17.2 years ± 10.9 years). ADS severity was found low in 29.9%, moderate in 27.1%, and severe in 43%. LUTS were reported by 77.1%, storage symptoms in 51.4%, and voiding symptoms in 60.6%. Urinary incontinence was reported by 12.5%. Enuresis was reported by 14.3% (72/502) of the respondents: primary enuresis in 70.8% (51/72), secondary in the remaining. Pads were used by 40 subjects with a median of 2.9 pads/day (range, 0-8). A toilet training program was performed by 61 of the respondents, with satisfactory results in 40/61 (65.6%). A significant correlation was found between greater ASD severity and higher LUTS rates. The mean VAS score on the impact of LUTS on family relationships was 2 ± 2.9. Regular bowel function was reported by 57.4% (288/502) of the respondents, while increased daily defecations were present in 11.2% (56/502), constipation in 31.5% (158/502), and fecal incontinence in 7.9% (40/502). This survey demonstrated that LUTS are very common in the young ASD population and that the prevalence of urinary symptoms is related to higher severity of the ASD condition. Bowel disorders are often associated with urinary symptoms and dysfunctions. Urologists should be aware of the frequent occurrence of urological disorders and symptoms in individuals with ASD and should be involved in their clinical management in a multidisciplinary team that cares for these people.

СРАВНИТЕЛЬНЫЙ АНАЛИЗ ПРЕДПОСЫЛОК СОЦИАЛЬНОЙ КОММУНИКАЦИИ ПОДРОСТКОВ С МЕНТАЛЬНЫМИ НАРУШЕНИЯМИ

Introduction. Currently, the issues of studying and developing communicative skills in children with disabilities are among the priority areas of modern correctional pedagogy and rehabilitation. The relevance of this issue is due to the need to expand the possibilities of their socialization, which is closely related to the formation of a system of life competencies based on knowledge of the basic patterns of social interaction, the ability to effectively use communication skills with other people in various situations of daily activity. The greatest risks of social and communicative maladjustment are observed among children with intellectual disabilities. The article presents the materials of theoretical analysis and the results of a comparative study of the social and communicative sphere of adolescents with different levels of intellectual underdevelopment. Materials and methods. The experiment involved 118 adolescents with varying degrees of intellectual development disorders (42 children with delay in mental development, 49 adolescents with mild delay in mental development and 27 children with moderate delay in mental development). Empirical data were obtained on the basis of the scientific and Practical Center for Mental Health of Children and Adolescents named after G. E. Sukhareva and the Center for Speech Pathology and Neurorehabilitation of the Moscow Department of Health. In the process of research and preparation of the article, methods of analyzing literary sources, experimental methods of studying the social and communicative sphere, methods of statistical processing of research results were used. The results. The specific difficulties of communicative behavior that arise in adolescents with ASD, mild and moderate severity of intellectual disabilities have been identified. The experimental data obtained can be taken into account to determine the content of speech therapy work aimed at developing social communication skills in children with varying degrees of intellectual underdevelopment. Conclusion. The problem requires further study, development and implementation of special differentiated technologies for the formation of competencies in the social and communicative sphere of adolescents with intellectual disabilities.

Cognitive-adaptive Functioning Gap and Mediating Factors that Impact Adaptive Functioning in Chinese Preschool-aged Children with Autism Spectrum Disorder.

This study aimed to investigate the gap between adaptive functioning and cognitive functioning, especially verbal and nonverbal intelligence quotient (IQ) in Chinese children with ASD. We systematically explored cognitive functioning, ASD severity, early signs of developmental abnormalities, and socioeconomic factors as mediating factors of adaptive functioning. We enrolled 151 children (age: 2.5?6 years) with ASD and categorized them into one group with IQ ≥70 and another with IQ <70. The two groups were calibrated for age, age at diagnosis, and IQ, and the relationship of adaptive skills with vocabulary acquisition index (VAI) and nonverbal index (NVI) were separately analyzed. Results show that the gap between IQ and adaptive functioning was significant in children with ASD having IQ ≥70, with both VAI and NVI showing statistically significant differences (all P <0.001). VAI correlated positively with scores for overall adaptive skills and specific domains, whereas NVI had no significant correlations with adaptive skill scores. Age of first walking unaided had an independent positive correlation (all P <0.05) with scores of adaptive skills and specific domains. IQ-adaptive functioning gap is significant in children with ASD having IQ ≥70, suggesting that defining "high-functioning autism" merely on the basis of IQ is not appropriate. Verbal IQ and early signs of motor development are specific and possible predictors of adaptive functioning in children with ASD, respectively.

Emotional problems in preschool and school-aged children with neurodevelopmental disorders in Spain: EPINED epidemiological project

BackgroundChildren with neurodevelopmental disorders (NDD) are often at risk of developing emotional problems. Aims and methodsThe co-occurrence of anxiety and depression with ASD and/or ADHD was determined by exploring the association with children’s clinical and neuropsychological functioning and their parent’s mental health. To this end, we assessed 295 preschoolers (PRE; 4–5 years old) and 486 school-aged children (SCH; 10–11 years old) in Tarragona, Spain. NDD diagnoses were based on DSM-5. Emotional problems were assessed using Achenbach’s scales. ResultsEmotional problems (PRE: 36%−78%; SCH: 32%−81%) were more common and more severe in participants with NDD than in controls and children in the ASD + ADHD school-aged group were the most affected. In ADHD, emotional problems were associated with more severe symptoms of attention deficit (PRE) and hyperactivity/impulsivity (SCH). In ASD + ADHD, emotional problems showed a trend of association with more severe ASD repetitive behaviours and impaired working memory, whereas in ASD were associated with greater overall ASD severity. Conclusions and implicationsChildren with NDD are vulnerable to emotional problems, which become more prevalent and interfering with age. Early detection and intervention aimed at tackling emotional problems can improve NDD prognosis.

Spatial Language and Cognition in Autistic Preschoolers.

ASD is associated with relative strengths in the visuospatial domain but varying abilities in the linguistic domain. Previous studies suggest parallels between spatial language and spatial cognition in older autistic individuals, but no research to date has examined this relationship in young autistic children. Therefore, the purpose of the present study was to investigate the connection between children's spatial language production and nonverbal spatial cognition over time. We also examined two potential predictors of spatial language observed in previous literature, ASD symptom severity and parent spatial language input. In past work investigating spatial language in NT children of the same age, parent-child interactions have been a primary context for study. Therefore, in the present study, we analyzed transcripts of dyadic naturalistic play interactions between autistic children and their parents over three visits from age 30 to 66 months and administered standardized cognitive and ASD diagnostic assessments at each visit. Spatial language production was related to nonverbal spatial cognition even when accounting for overall language production, though the strength of that relationship decreased over time. Parent spatial input (but not ASD severity) significantly predicted children's spatial language production over and above the effect of overall language production. Spatial language is associated with spatial cognition in young autistic children and appears to reflect the interaction of overall linguistic skills and nonverbal spatial cognitive ability regardless of autism severity. Parent-mediated interventions may be a promising context for increasing spatial language in autistic preschoolers.

Additive or Interactive Associations of Food Allergies with Glutathione S-Transferase Genes in Relation to ASD and ASD Severity in Jamaican Children.

To investigate additive and interactive associations of food allergies with three glutathione S-transferase (GST) genes in relation to ASD and ASD severity in Jamaican children. Using data from 344 1:1 age- and sex-matched ASD cases and typically developing controls, we assessed additive and interactive associations of food allergies with polymorphisms in GST genes (GSTM1, GSTP1 and GSTT1) in relation to ASD by applying conditional logistic regression models, and in relation to ASD severity in ASD cases as measured by the Autism Diagnostic Observation Schedule-2nd Edition (ADOS-2) total and domains specific comparison scores (CSs) by fitting general linear models. Although food allergies and GST genes were not associated with ASD, ASD cases allergic to non-dairy food had higher mean ADOS-2 Restricted and Repetitive Behaviors (RRB) CS (8.8 vs. 8.0, P = 0.04). In addition, allergy to dairy was associated with higher mean RRB CS only among ASD cases with GSTT1 DD genotype (9.9 vs. 7.8, P < 0.01, interaction P = 0.01), and GSTP1 Val/Val genotype under a recessive genetic model (9.8 vs. 7.8, P = 0.02, interaction P = 0.06). Our findings are consistent with the role for GST genes in ASD and food allergies, though require replication in other populations.

Distinct social attention profiles in preschoolers with autism contrasted to fragile X syndrome.

Social attention is a critical skill for learning and development. Social attention difficulties are present in both non-syndromic autism spectrum disorder (nsASD) and fragile X syndrome (FXS), and our understanding of these difficulties is complicated by heterogeneity in both disorders, including co-occurring diagnoses like intellectual disability and social anxiety. Existing research largely utilizes a single index of social attention and rarely includes children with intellectual impairment or uses a cross-syndrome approach. This study investigated whether multi-trait social attention profiles including naturalistic initial eye contact, facial attention, and social scene attention differ in preschool children with nsASD and FXS matched on developmental ability (DQ) and contrasted to neurotypical (NT) controls. The relationship between DQ, ASD severity, and social anxiety and social attention profiles was also examined. Initial eye contact related to social scene attention, implicating that naturalistic social attention is consistent with responses during experimental conditions. Reduced eye contact and lower social scene attention characterized nsASD and FXS. Children with nsASD displayed less facial attention than FXS and NT children, who did not differ. Lower DQ and elevated ASD severity associated with decreased eye contact in nsASD and FXS, and lower DQ was associated with lower social scene attention in FXS. Sex, social anxiety, and age were not associated with social attention. These findings suggest social attention profiles of children with nsASD are highly similar to, yet distinct from, children with FXS. Children with nsASD may present with a global social attention deficit whereas FXS profiles may reflect context-dependent social avoidance.

The Importance of Language Delays as an Early Indicator of Subsequent ASD Diagnosis in Public Healthcare Settings

Previous studies have reported that ASD children with more severe symptoms are diagnosed earlier. However, previous studies in community settings have mostly relied on retrospective parental reports without the use of quantitative standardized test scores. Here, we evaluated the association of language, cognitive, and ASD severity standardized scores with the age of diagnosis in 1-6-year-old children diagnosed in a public healthcare setting. The results revealed that language scores were the strongest variable associated with the age of diagnosis, explaining ~ 30% of the variability across children. Indeed, all children diagnosed before 30-months of age exhibited moderate-to-severe language delays. These results further substantiate the prominence of language delay as a highly visible symptom associated with earlier ASD diagnosis in community clinical settings.

3.34 Assessing the Clinical Utility of DSM-5 Severity Level Ratings for ASD

The DSM-5 features severity level ratings for the dyadic symptom groupings seen in ASD. Across social communication (SC) and restricted, repetitive behavior (RRB) groupings, clinicians use their judgment to distinguish between 3 severity classifications when using the rating tool. Based on symptom profile, the 3 classifications propose the amount of “support” (requiring support, substantial support, or very substantial support) a patient requires. This qualitative literature review seeks to explore the current operationalization of DSM-5 ASD severity levels by clinicians and factors associated in assigning them.

Novel clinical, molecular and bioinformatics insights into the genetic background of autism

BackgroundClinical classification of autistic patients based on current WHO criteria provides a valuable but simplified depiction of the true nature of the disorder. Our goal is to determine the biology of the disorder and the ASD-associated genes that lead to differences in the severity and variability of clinical features, which can enhance the ability to predict clinical outcomes.MethodNovel Whole Exome Sequencing data from children (n = 33) with ASD were collected along with extended cognitive and linguistic assessments. A machine learning methodology and a literature-based approach took into consideration known effects of genetic variation on the translated proteins, linking them with specific ASD clinical manifestations, namely non-verbal IQ, memory, attention and oral language deficits.ResultsLinear regression polygenic risk score results included the classification of severe and mild ASD samples with a 81.81% prediction accuracy. The literature-based approach revealed 14 genes present in all sub-phenotypes (independent of severity) and others which seem to impair individual ones, highlighting genetic profiles specific to mild and severe ASD, which concern non-verbal IQ, memory, attention and oral language skills.ConclusionsThese genes can potentially contribute toward a diagnostic gene-set for determining ASD severity. However, due to the limited number of patients in this study, our classification approach is mostly centered on the prediction and verification of these genes and does not hold a diagnostic nature per se. Substantial further experimentation is required to validate their role as diagnostic markers. The use of these genes as input for functional analysis highlights important biological processes and bridges the gap between genotype and phenotype in ASD.

Longitudinal developmental trajectories in young autistic children presenting with sleep problems, compared to those presenting without sleep problems, gathered via parent-report using a mobile application

The effect of sleep problems in 2- to 5-year-old autistic children was investigated in the largest and the longest observational study to-date. Parents assessed the development of 8540 children quarterly for three years on five orthogonal subscales: combinatorial receptive language, expressive language, sociability, sensory awareness, and health. 57% of caregivers reported no sleep problems, 31% reported mild sleep problems, 10% reported moderate sleep problems, and 2% reported severe sleep problems. In order to investigate the effect of sleep problems, children with moderate and severe sleep problems (N = 651) were matched to those with no sleep problems using a propensity score based on age, gender, expressive language, combinatorial receptive language, sociability, sensory awareness, and health at the 1st evaluation. There were 643 matched participants in each group. Children with no sleep problems developed faster compared to matched children with sleep problems in all subscales. The greatest difference in trajectories was detected in the health subscale. When controlling for the health score (in addition to each subscale score at baseline as well as gender and ASD severity), the effect of sleep problems decreased in all subscales except the combinatorial receptive language subscale (where the effect of sleep problems was increased), suggesting that sleep problems affect combinatorial language acquisition regardless of the overall health. This study confirms a high prevalence of sleep problems in autistic children and provides information on the effect of sleep problems on various aspects of children’s development.

A cross-cultural comparison of sleep patterns between typically developing children and children with ASD living in Saudi Arabia and the United Kingdom

BackgroundSleep is crucial for child development, especially for children with ASD. While it is known that children with ASD experience more severe sleep problems and that these problems tend to persist compared to their typically developing counterparts, these findings tend to come from only Western countries. A cross-cultural study is important to understand if the prevailing understanding of sleep in children with ASD can be extended to different cultural backgrounds. AimA cross-cultural study is conducted, involving typically developing children and children with ASD aged 5–12 across two countries: Saudi Arabia and the United Kingdom. Methods and proceduresUsing a combination of questionnaires measuring ASD severity (CARS-2), sleep quality (CSHQ), sociodemographic and lifestyle variables and sleep diaries, 244 children were sampled using a mixture of snowball and convenience sampling methods. Outcomes and resultsChildren with ASD experience more sleep problems compared to typically developing children in Saudi Arabia, and these problems similarly persist across time. Specifically, it was found that children with ASD in Saudi Arabia experience greater sleep onset latency and a greater number of night awakenings. Additionally, across the ASD groups, it was found that children from Saudi Arabia generally experienced poorer sleep than children in the United Kingdom in terms of shorter sleep duration, although children in the United Kingdom tended to report more instances of sleep anxiety and parasomnias. Conclusions and implicationsSeveral reasons such as parental education about sleep hygiene, cultural influences and social hours were put forward as potential explanations for cross-cultural differences. Findings served to emphasise the importance of culturally-appropriate interventions and public education regarding child sleep.

Qualitative analysis of verbal fluency in school-age children with high-functioning autism spectrum disorders. Associations with age and IQ

This study analyzes performance on both a Semantic and a Letter verbal fluency (VF) task in school-age children with high-functioning autism spectrum disorder (HF-ASD) (n = 20) and without ASD (n = 20) and investigates the relationship between VF indicators and age, verbal and non-verbal IQ, ASD severity, and attention deficit hyperactivity disorder (ADHD) symptomatology. Furthermore, the Poor Lexical-Semantic Structure Model and the Slow-Retrieval Model are tested if they could account for semantic retrieval difficulties in children with HF-ASD. The HF-ASD group generated significantly fewer correct responses in both VF tasks in comparison to the control group. The type of task significantly affected performance and both groups showed higher word generativity on the Semantic task. The groups did not differ in clustering, switching, and errors. Age significantly correlated with the VF indicators in the ASD group, but in the control group, there was a significant negative correlation with the number of errors. Non-verbal and verbal IQ did not correlate with any VF indicators in both groups, while ASD severity and ADHD symptomatology correlated positively and significantly with error responses in the ASD group. The Slow-Retrieval Model explains VF difficulties in the HF-ASD group indicating that poorer word generativity can be attributed to slower retrieval of words from the semantic network.

Antihuman Endogenous Retrovirus Immune Response and Adaptive Dysfunction in Autism.

ASD is a neurodevelopmental disorder of unknown aetiology but with a known contribution of pathogenic immune-mediated mechanisms. HERVs are associated with several neuropsychiatric diseases, including ASD. We studied anti-HERV-W, -K and -H-env immune profiles in ASD children to analyse differences between their respective mothers and child/mother control pairs and possible correlations to ASD severity and loss of adaptive abilities. Of the 84 studied individuals, 42 children (23 ASD and 19 neurotypical) and their paired mothers underwent clinical and neuropsychological evaluations. ASD severity was analysed with standardised tests. Adaptive functioning was studied with ABAS-II and GAC index. Plasma anti-env responses of HERV-K, -H and -W were tested with indirect ELISA. ASD and neurotypical children did not differ in age, gender, comorbidities and anti-HERV responses. In children with ASD, anti-HERV levels were not correlated to ASD severity, while a significant inverse correlation was found between anti-HERV-W-248-262 levels and adaptive/social abilities. Upregulation of anti-HERV-W response correlates to dysfunctional social and adaptive competences in ASD but not in controls, suggesting anti-HERV response plays a role in the appearance of peculiar ASD symptoms.

The Influence of ASD Severity on Parental Overload: The Moderating Role of Parental Well-Being and the ASD Pragmatic Level.

The aim of the present study is to analyze the relation between the severity of symptoms in people with ASD on their parents’ overload, moderated by parental well-being and the ASD pragmatic level. A sample consisted of 28 fathers and mothers whose children had ASD. The obtained results showed that the higher the ASD severity, the better the parental overload was perceived if parents had low well-being levels. However, this relation did not occur if the parental well-being level was high. Moreover, the relation between severity and parental overload moderated by parental well-being occurred regardless of the pragmatic language level. Therefore, the main results of this study are that the responsibility for parental overload depends more on parental well-being than on the symptom severity of the person with ASD. The relevance of carrying out interventions with not only people with ASD, but also with their parents or caregivers for their well-being is highlighted.

Self-esteem and family functioning mediates the association of symptom severity and parental affiliate stigma among families with children with ASD

PurposeTo investigate the level of affiliate stigma among parents of children with autism spectrum disorder and to explore the mediating role of self-esteem and family functioning. Design and methodsA cross-sectional study was conducted in a large regional hospital and two childhood rehabilitation centers in Guangdong, China. Data related to demographics, parental self-esteem, family functioning, and affiliate stigma were collected from 180 parents of children diagnosed with ASD. We used t-tests, analysis of variance, and correlation analysis to explore the related factors of parental affiliate stigma. Path analysis was used to determine the mediating roles of self-esteem and family functioning in the relationship between symptom severity and affiliate stigma. ResultsParents of children with autism spectrum disorder in China experienced low self-esteem, family functioning, and high affiliate stigma. Symptom severity was negatively correlated with self-esteem and family functioning. Self-esteem and family functioning were significantly negatively correlated with affiliate stigma. Symptom severity was positively correlated with affiliate stigma. Self-esteem and family functioning mediated the relationship between symptom severity and affiliate stigma. ConclusionsSymptom severity affects parental affiliate stigma among families with children with ASD. Self-esteem and family functioning are the two mediators in the relationship. We should take steps to improve self-esteem and family functioning in order to alleviate parental affiliate stigma. Practice implicationsThis study emphasizes the importance of the influence of ASD severity and family functioning on affiliate stigma. In clinical practice, psychological support should be provided for parents of children with ASD to improve their mental health.