Search

OBJECTIVE: Native American children disproportionally face many risk factors for poor developmental outcomes; these factors include poverty, environmental toxicant exposure, and limited medical, and intervention services. To understand these risks, comprehensive documentation of developmental and behavioral phenotypes are needed. In the current descriptive study, we assessed the neurodevelopment of young Diné (Navajo) children using standardized assessment instruments in combination with expert clinician judgment. METHODS: As part of an ongoing, population-based, prospective birth cohort study, we conducted comprehensive neurodevelopmental assessments of 138, 3-5-year-old, Diné children residing on or near the Navajo Nation. We report results from standardized parent reports, psychiatric examinations, and direct assessments of childrens language, cognitive, adaptive, and social-emotional development, as well as best estimate clinical diagnoses. RESULTS: Forty-nine percent of our sample met DSM-5 criteria for a neurodevelopmental disorder (NDD) diagnosis. Language and speech sound disorders were most common, although autism spectrum disorder (ASD) was also elevated compared to the general population. Though language performance was depressed amongst all groups of children with, and without, NDDs, those meeting criteria for certain NDDs performed significantly lower on all language measures, when compared to those without. Social-emotional, behavioral, and nonverbal cognitive ability were in the average range overall. CONCLUSIONS: Diné children in our study were found to have a high percentage of clinically significant developmental delays. Overall, children presented with a pervasive pattern of depressed language performance across measures, irrespective of diagnosis (or no diagnosis), while other domains of functioning were similar to normative samples. Findings support the need to identify appropriate intervention and educational efforts for affected youth, while also exploring the causes of the specific developmental delays. However, longitudinal studies are necessary to establish best practices for identifying delays and delineating resilience factors to optimize development of Diné children.

BackgroundHeterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services.MethodsUsing a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups.ResultsClustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup.LimitationsNotable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic.ConclusionsConcomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

ObjectivesHigher prevalence of suicidality has been reported in individuals with ASD. This study aimed to (1) Estimate the prevalence of suicidal ideation (SI) in epidemiologically-ascertained, population-based, samples of children with ASD or Autism Spectrum Screening Questionnaire (ASSQ) Screen Positivity (ASP); (2) Determine whether ASD/ASP is an independent risk factor for SI, controlling for known SI risk factors; and, (3) Develop an explanatory model for SI in children with ASD/ASP.MethodsParticipants came from three epidemiologically-ascertained samples of school-aged Korean children (n = 14,423; 3,702; 4,837). ASSQ ≥ 14 was the cutoff for ASP. A subsample (n = 86) was confirmed to have ASD. SI was based on parents' endorsement of items on the Behavioral Assessment System for Children-2-Parent Report Scale-Children. Logistic regressions were used to assess associations between SI and ASD/ASP, controlling for demographics, peer victimization, behavior problems, and depression. To develop an explanatory model for SI within ASD/ASP, the associations between SI and child characteristics (comorbid conditions, ASD symptoms, IQ, adaptive function) were tested.ResultsSI was higher in children with ASD (14%) and ASP (16.6-27.4%) than ASSQ Screen Negative (ASN) peers (3.4-6.9%). ASD/ASP was strongly predictive of SI (ORs: 2.87-5.67), after controlling for known SI risk factors compared to ASN. Within the ASD and ASP groups, anxiety was the strongest predictor of SI.ConclusionsSI prevalence was higher in non-clinical samples of children with ASD and ASP, relative to ASN peers. These results underscore the need for routine screening for SI in children with ASD and social difficulties, particularly those with high anxiety. HighlightsPopulation-based, epidemiologically-ascertained, school-aged childrenASD and ASP are independent risk factors for SI in school-aged childrenAnxiety is an independent risk factor for SI in children with ASD or ASP.

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

Lay abstractWhat is Already Known about This Subject: Genetics, (including de novo mutations), environmental factors (including toxic exposures), and their interactions impact autism spectrum disorder etiology. Paternal smoking is a candidate risk for autism spectrum disorder due to biological plausibility, high prevalence, and potential intervention.What This Study Adds: This original study and its replication confirms that paternal factors can substantially contribute to autism spectrum disorder risk for their offspring. It specifically indicates that paternal smoking both before and during pregnancy contributes significantly to autism spectrum disorder risk.Implications for practice, research, or policy: Smoking prevention, especially in pregnancy planning, may decrease autism spectrum disorder risk in offspring.

BackgroundConcerns have been raised that scores on standard measures of autism spectrum disorder (ASD) symptoms may differ as a function of sex. However, these findings are hindered by small female samples studied thus far. The current study evaluated if, after accounting for age, IQ, and language level, sex affects ASD severity estimates from diagnostic measures among children with ASD.MethodsData were obtained from eight sources comprising 27 sites. Linear mixed-effects models, including a random effect for site, were fit for 10 outcomes (Autism Diagnostic Observation Schedule [ADOS] domain-level calibrated severity scores, Autism Diagnostic Interview-Revised [ADI-R] raw scores by age-based algorithm, and raw scores from the two indices on the Social Responsiveness Scale [SRS]). Sex was added to the models after controlling for age, NVIQ, and an indicator for language level.ResultsSex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES]

BackgroundsWhether there is a true increase in autism spectrum disorder (ASD) frequency or not remains unclear. Additionally, the rates of co-existing neurodevelopmental disorders (NDD) in a total population sample has not been fully examined before. Therefore, using a total population sample in Japan, we aimed to estimate the prevalence and cumulative incidence of autism spectrum disorder (ASD) annually, to determine whether there is a true increase in ASD prevalence by estimating the cumulative incidence of ASD annually, and to examine the rates of co-existing neurodevelopmental disorders (NDD).MethodIn this cross-sectional sequential design study, all 5-year-old children in the catchment area underwent the screening annually from the year 2013-2016. Screen-positive children were invited to participate in a comprehensive assessment, including child and parent interview, behavioral observation, and cognitive and motor function testing. All cases were reviewed by a multidisciplinary research team.ResultsCaregivers of 3954 children returned the screening, among which 559 children underwent the assessment with 87 children receiving an ASD diagnosis. Adjusted ASD prevalence was 3.22% (95% confidence interval (CI) 2.66-3.76%). The male to female ratio of the crude prevalence was 2.2:1. The cumulative incidence of ASD up to 5 years of age for the total study years was 1.31% (95% CI 1.00-1.62%). A generalized linear model revealed no significant linear trends in 5-year cumulative incidence over the study years. Only 11.5% of children had ASD alone; the remaining 88.5% were found to have at least one co-existing NDD.LimitationsModest sample size for a total population study.ConclusionsOur findings demonstrate the stability of the 5-year cumulative incidence of ASD, implying no true rise in ASD incident cases over the 4-year study period in the study catchment area. High rates of co-existing NDDs reflect the importance of investigating broad developmental challenges in children with ASD.

Through this meta-analysis, we sought to examine the prevalence of, risks for, and factors associated with bullying involvement (victimization, perpetration, perpetration-victimization) among students with autism spectrum disorder (ASD). Additionally, we attempted to examine sources of variance in the prevalence and effect sizes of bullying in students with ASD across studies. Systematic database and literature review identified 34 relevant studies (31 for Western countries, three for Eastern countries). Pooled prevalence estimates for victimization, perpetration, and perpetration-victimization in general were 67%, 29%, and 14%, respectively. The risk of victimization in students with ASD was significantly higher than that in typically developing students and students with other disabilities. Further, deficits in social interaction and communication, externalizing symptoms, internalizing symptoms, and integrated inclusive school settings were related to higher victimization, and externalizing symptoms were related to higher perpetration. Finally, moderation analyses revealed significant variations in the pooled prevalences thereof depending on culture, age, school settings, and methodological quality and in the pooled effect sizes according to publication year and methodological quality. Our results highlight needs for bullying intervention for students with ASD, especially those who are younger, are in an inclusive school setting, and have higher social difficulties and externalizing/internalizing symptoms; for intensive research of bullying experiences among students with ASD in Eastern countries; and for efforts to improve the methodological quality of such research.

Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD. Casting noncoding variation in the context of a de novo risk score across multiple annotation categories, however, did demonstrate association with mutations localized to promoter regions. We found that the strongest driver of this promoter signal emanates from evolutionarily conserved transcription factor binding sites distal to the transcription start site. These data suggest that de novo mutations in promoter regions, characterized by evolutionary and functional signatures, contribute to ASD.

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

While a growing number of studies indicate associations between experiences of bullying and autism spectrum disorder (ASD), it is not clear what roles comorbid behavioral problems may play. We investigated the experiences of children with ASD as victims and/or perpetrators of bullying. Children with ASD epidemiologically ascertained participated in a cross-sectional study. Although children with ASD showed significantly increased risk for bullying involvement compared to community children, after controlling for comorbid psychopathology and other demographic factors, increased risks for being perpetrators or victim-perpetrators disappeared while risk for being bullied/teased continued to be significantly elevated. This finding will help guide medical, educational and community personnel to effectively identify children with ASD at risk for school bullying and develop interventions.

Discrepancy in perception of bullying experiences may lead to later internalizing or externalizing behavior in adolescents. A 1,663 South Korean 7th and 8th graders (mean age: 13.1 and 14.1 years old), were seen for a follow-up study to examine the relationships between the discrepancy in perception of their bullying experiences (defined as discrepancy between self- and peer-reports of bullying experiences) and internalizing or externalizing behavior at follow-up. Bullying was assessed by self- and peer-report. The discrepancy in perception of bullying experiences was defined by the concordance or discordance between self- and peer-reports. Internalizing and externalizing behavior was evaluated using the Youth Self Report and Child Behavior Checklist, at baseline and follow-up. Two by two ANCOVA was performed with a factorial design, categorizing discrepancy in perception of bullying experiences based on the agreement between self-report and peer-report. Internalizing/externalizing behavior-at-follow-up was used as an outcome, adjusting for other known risk factors for internalizing/externalizing behavior, including baseline internalizing/externalizing behavior, and bullying experiences. Adolescents with perceptions of bullying experiences discrepant from peer-reports showed increased internalizing/externalizing behavior at follow-up. Bullying also stands out as an independent risk factor for the development of future externalizing behavior even among adolescents with accurate perceptions of bullying experiences. These specific groups of youth warrant more focused assessment and intervention.

Our study aimed to examine psychometric properties and cross-cultural utility of the Behavior Assessment System for Children-2, Parent Rating Scale-Child (BASC-2 PRS-C) in Korean children.Two study populations were recruited: a general population sample (n

ObjectivesTo evaluate whether Asian (Korean children) populations can be validly diagnosed with autism spectrum disorder (ASD) using Western-based diagnostic instruments and criteria based on Diagnostic and Statistical Manual on Mental Disorders, 5th edition (DSM-5).MethodsParticipants included an epidemiologically ascertained 7-14-year-old (N = 292) South Korean cohort from a larger prevalence study (N = 55,266). Main outcomes were based on Western-based diagnostic methods for Korean children using gold standard instruments, Autism Diagnostic Interview-Revised, and Autism Diagnostic Observation Schedule. Factor analysis and ANOVAs were performed to examine factor structure of autism symptoms and identify phenotypic differences between Korean children with ASD and non-ASD diagnoses.ResultsUsing Western-based diagnostic methods, Korean children with ASD were successfully identified with moderate-to-high diagnostic validity (sensitivities/specificities ranging 64%-93%), strong internal consistency, and convergent/concurrent validity. The patterns of autism phenotypes in a Korean population were similar to those observed in a Western population with two symptom domains (social communication and restricted and repetitive behavior factors). Statistically significant differences in the use of socially acceptable communicative behaviors (e.g., direct gaze, range of facial expressions) emerged between ASD versus non-ASD cases (mostly p

Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.