Caitlin C. Clements

Researchers frequently rely on the Infant Behavior Questionnaire–Revised Short Form (IBQ-R SF) to assess caregiver-reported infant temperament. However, understanding infant temperament depends on the validity of the measures used to assess it. This study examined the validity of the IBQ-R SF factor structure, which underlies its scoring system that uses 14 dimension scores to generate three factor scores (Surgency/Extraversion, Negative Affectivity, and Orienting/Regulation). In a sample of 979 infants aged 3, 5, 7, 10 or 12 months, results suggested that the original and several subsequently published factor structures showed inadequate fit. After testing in discovery and replication datasets, we propose an alternative factor model with four factors that adds a Sustained Engagement factor consisting of the Duration of Orienting and Low Intensity Pleasure scales. The corresponding alternative scoring system is provided. Additional measurement invariance analyses assessed whether the IBQ-R SF measures temperament similarly at each age. Configural and metric invariance were achieved, indicating comparable relationships between IBQ-R SF dimension and factor scores across ages and rank-order stability. Failed scalar invariance may reflect age-related changes in the expression of temperament; we recommend using age as a covariate in IBQ-R SF analyses, as scores are not directly comparable across ages.

Importance. Autistic females are consistently underidentified relative to males. Whether item-level sex bias in the Autism Diagnostic Observation Schedule (ADOS), the gold standard observational assessment of autism spectrum disorder, contributes to this disparity across the full developmental and language range remains unknown. Objectives. To examine differential item functioning (DIF) by sex in ADOS algorithm items across all modules. Design. Cross-sectional study. Setting. Item-level ADOS data were drawn from the NIMH Data Archive, Simons Simplex Collection, Simons Foundation Powering Autism Research for Knowledge, and Autism Inpatient Collection. Participants. Individuals with item-level ADOS or ADOS-2 data who were administered the age-appropriate module. Exposure. Sex (female vs. male) Main Outcome and Measures. Sex-based DIF was examined separately within each of 8 module and language-level combinations, covering 112 algorithm items total. For each combination, a graded response item response theory model was fit to the item set, and DIF was evaluated using likelihood ratio test approach. Results. A total of 19,569 individuals (14,807 male [75.7%]; 4,760 female [24.3%]) aged 12 months to 75 years were included. Of 112 items analyzed, eleven unique items showed significant sex DIF after correcting for type I error. No significant DIF was detected in the Toddler Module, Module 1 Low Language, or Module 2 after correction. Significant DIF was detected in Module 1 High Language (3 items) and Module 3 (1 item), with Module 4 showing the greatest number of significant items (7 of 14). Overall, adult females tended to be underscored on social communication items and overscored on items concerning restricted and repetitive behaviors and interests. All effect sizes were small except one (stereotyped language, Module 1 High Language). Conclusions and Relevance. These findings suggest that the ADOS is largely robust to sex-based measurement bias for younger individuals and those with less language, but significant bias exists for verbally fluent adolescents and adults. The domain-specific pattern of bias is consistent with female camouflaging of social difficulties and sex differences in the presentation of restricted, repetitive behaviors and interests. Clinician training and future instrument development should account for these differences to improve diagnostic equity across sex.

Purpose: Emerging research highlights sex differences in autism presentation, raising questions about the validity of clinician-administered diagnostic tools like the gold-standard Autism Diagnostic Observation Schedule (ADOS). This study examines whether clinicians’ perceptions, potentially biased toward male-typical presentations, contribute to sex bias in ADOS items and the under-identification of autism in females. Methods: In a sample of 813 children, multidimensional item response theory graded response models were employed to analyze differential item functioning (DIF) of items in ADOS Module 3 (the version commonly administered to school-aged children with fluent spoken language). Results: Six items showed significant sex bias. On four social communication items, females tended to be underscored, meaning rated as showing fewer autistic features (e.g., more emotion talk) than males with equivalent levels of autism latent traits. In contrast, females tended to be overscored on two items related to restricted or repetitive behaviors and interests (i.e., more finger mannerisms, specific interests, or repetitive behaviors). The impact of sex bias on overall scores was small, ranging from 0.10 to 0.28 points per item, and approximately 0.41 points on the overall test score. Conclusion: This analysis joins three previous reports of specific ADOS items that function differently in females than males, with converging evidence identifying two problematic items (D2 and D4). Overall, DIF was small and unlikely to affect ADOS classification. We speculate that the direction and consistency of DIF in social communication items might reflect underlying phenomena (viz., masking, clinician bias) that may relate to female underdiagnosis more generally.

Purpose: Emerging research highlights sex differences in autism presentation, which raises questions about the validity of clinician-administered diagnostic tools like the gold-standard Autism Diagnostic Observation Schedule (ADOS) for females. This study examines whether clinicians’ perceptions, potentially biased toward male-typical presentations, contribute to sex bias in ADOS item and the under-identification of autism in females.Methods: In a sample of 813 children, multidimensional item response theory graded response models were employed to analyze differential item functioning (DIF) of items in ADOS Module 3 (the version commonly administered to school-aged children with fluent spoken language).Results: Six items showed significant sex bias. On four social communication items, females tended to be underscored, meaning rated as showing fewer autistic features (e.g., more emotion talk) than males with equivalent levels of autism latent traits. In contrast, females tended to be overscored on two items related to restricted or repetitive behaviors and interests (i.e., more finger mannerisms, specific interests, or repetitive behaviors). The impact of sex bias on overall scores was small, ranging from 0.10 to 0.28 points on an item, and approximately 0.41 points on the overall test score.Conclusion: This analysis joins three previous reports of specific ADOS items that function differently in females than males, with converging evidence identifying two problematic items (D2 and D4). Overall, DIF was small and unlikely to affect ADOS classification; however, we speculate that the underlying phenomena (viz., masking and clinician bias) may obscure certain social communication symptoms and partially explain the underdiagnosis of autism in females. Abbreviations: Autism Diagnostic Observation Schedule (ADOS); differential item functioning (DIF)

Given the rising prevalence of autism among racial minority children in the United States, but persistent service use disparities, this study examines potential bias in specific items from the autism diagnostic observation schedule (ADOS), a highly regarded autism evaluation. We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to be rated as showing autistic behaviors than White children with similar autism levels. The impact of racial bias on the item score was small, and the impact on the overall test score was even smaller: on a scale of 0–48 points, the effect of racial bias was estimated at 0.23 total points for Black/African American children and 0.16 points for Asian children. Furthermore, none of the items showing significant bias contribute to the autism classification algorithm. This analysis suggests a small but detectable amount of bias in several specific ADOS items, but not in items central to informing an autism diagnosis. Thus, bias appears statistically, but not clinically, significant. This contributes to examinations of racial bias in the ADOS as the first analysis of Asian children and the first in‐depth look at all items in the most commonly used version among school‐aged children.

Given the rising prevalence of autism among racial minority children in the U.S., but persistent service use disparities, this study examines potential bias in specific items from the Autism Diagnostic Observation Schedule (ADOS), a highly regarded autism evaluation. We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to be rated as showing autistic behaviors than White children with similar autism levels. The impact of racial bias on the item score was small, and impact on the overall test score was even smaller: on a scale of 0-48 points, the effect of racial bias was estimated at 0.23 total points for Black/African American children, and 0.16 points for Asian children. Furthermore, none of the items showing significant bias contribute to the autism classification algorithm. This analysis suggests a small but detectable amount of bias in several specific ADOS items, but not in items central to informing an autism diagnosis. Thus, bias appears statistically, but not clinically, significant. This contributes to examinations of racial bias in the ADOS as the first analysis of Asian children, and the first in-depth look at all items in the most commonly used version among school-aged children.

Background: The Autism Diagnostic Observation Schedule (ADOS) is one of the most highly regarded autismevaluations. Unfortunately, multiple studies have demonstrated significant differential itemfunctioning (DIF) for individuals from different racial groups, and the mechanism for racial bias inthe ADOS remains unknown because DIF effects are inconsistently replicated across items.Although the ADOS consists of 5 modules and 2 historical versions (ADOS and ADOS-2), studiessearching for bias using item response theory-based DIF analyses often compromise statisticalpower to account for these differences by subdividing their samples. A moderated nonlinear factoranalysis (MNLFA) is more appropriate because it allows for the presence of multiple moderators,where there may be multiple sources of bias, and it allows the specification of bias receptors (e.g.,item-level, factor-level). To date, six studies have used MNLFA to assess differential itemfunctioning in the ADOS for age or sex. No study has used MNLFA to examine racial bias, nor hasit been used to examine differences across the different modules and versions of the ADOS.Objectives: To test for differential functioning in the ADOS items across race (African-American, Asian,White), module (1-4), and version (ADOS and ADOS-2).Methods:The current study is the largest examination of DIF in the ADOS to date (N = 4354+), utilizing datafrom the Simons Simplex Collection (n = 2851) and the NIMH Data Archive (n = 1503). Datacollection is complete for Module 3 and forthcoming for Modules 1, 2, and 4 (due to a recentshutdown of the NIMH Data Archive). First, item response theory-based DIF was conducted on the14 algorithm items using the lordif package in R. A graded response model was selected given theordinal response data. Chi-square significance tests were used to detect significant uniform andnon-uniform DIF, with an alpha cutoff value of 0.05. DIF analysis will be further conducted withdata from all modules and versions aggregated. Second, measurement invariance will be tested viaMNLFA, using the OpenMx package in R. A confirmatory one-factor model, specified with the 14algorithm ADOS items as manifest variables and with race, version, and module as moderatingeffects for the factor loadings and item intercepts in Figure 1, will be used.Preliminary Results:Within Module 3 aggregated across versions 1 and 2, four algorithm items showed significant DIF:B1 “Eye Contact” (Pr(χ212)=0.117, Pr(χ223)=0.001), B4 “Shared Enjoyment’ (Pr(χ212)=0.709,Pr(χ223)=0.004), B11 “Quality Rapport” (Pr(χ212)=0.001, Pr(χ223)=0.267), and D2 “ComplexMannerisms” (Pr(χ212)=0.021, Pr(χ223)=0.675). The item characteristic curves of B11 and D2suggest uniform DIF, whereas DIF in B1 and B4 is non-uniform (Figure 2).Conclusion:In the largest sample to date, we have identified bias in four ADOS Module 3 algorithm items. Wewill conduct a larger analysis with MNLFA to determine whether the source of racial bias is due tospecific modules or versions of the ADOS. This analysis will allow us to pinpoint specific moduleitems and offer solutions to improve the measure and thereby diagnostic accuracy and equity fordiverse individuals.

Introduction: Given the rising prevalence of autism among racial minority children in the U.S., but persistent service use disparities, this study examines potential bias in specific items from the Autism Diagnostic Observation Schedule (ADOS), a highly regarded autism evaluation. Method: We leveraged unidimensional item response theory graded response models and a sample of 735 children to analyze the differential item functioning (DIF) of items within ADOS Module 3. Results: Three items showed significant signs of racial bias: A1 (overall language level), A5 (offers information), and D5 (compulsions and rituals). On these items, Black/African American and Asian children were usually more likely to be rated as showing autistic behaviors than White children with similar autism levels. The impact of racial bias on the item score was small, and impact on the overall test score was even smaller: on a scale of 0-48 points, the effect of racial bias was estimated at 0.23 total points for Black/African American children, and 0.16 points for Asian children. Furthermore, none of the items showing significant bias contribute to the autism classification algorithm. Discussion: This analysis suggests a small but detectable amount of bias in several specific ADOS items, but not in items central to informing an autism diagnosis. Thus, bias appears statistically, but not clinically, significant. This study provides the third racial bias analysis of the ADOS, the first analysis of Asian children, and the first in-depth look at all items in the most commonly used version among school-aged children.Abbreviations: Autism Diagnostic Observation Schedule (ADOS); differential item functioning (DIF)Keywords: autism, racial bias, item response theory, differential item functioning, ADOS

Background: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be useful in clinical trials as an endpoint or predictor of treatment response. However, seizures and antiepileptic medications also affect resting neural oscillatory activity and could undermine the utility of resting state EEG features as biomarkers in neurodevelopmental disorders such as TSC. Methods: This paper compares resting state EEG features in a cross-sectional cohort of young children with TSC (n = 49, ages 12–37 months) to 49 age- and sex-matched typically developing controls. Within children with TSC, associations were examined between resting state EEG features, seizure severity composite score, and use of GABA agonists. Results: Compared to matched typically developing children, children with TSC showed significantly greater beta power in permutation cluster analyses. Children with TSC also showed significantly greater aperiodic offset (reflecting nonoscillatory neuronal firing) after power spectra were parameterized using SpecParam into aperiodic and periodic components. Within children with TSC, both greater seizure severity and use of GABAergic antiepileptic medication were significantly and independently associated with increased periodic peak beta power. Conclusions: The elevated peak beta power observed in children with TSC compared to matched typically developing controls may be driven by both seizures and GABA agonist use. It is recommended to collect seizure and medication data alongside EEG data for clinical trials. These results highlight the challenge of using resting state EEG features as biomarkers in trials with neurodevelopmental disabilities when epilepsy and anti-epileptic medication are common.

Restricted and repetitive behaviors (RRBs) are an early-emerging and defining feature of autism spectrum disorder (ASD). This longitudinal study examined developmental trajectories of RRBs as measured by the Repetitive Behavior Scale-Revised (RBS-R) in 12-36-month-old infants (n = 207), including those with elevated likelihood of ASD due to familial history (ELSib) or early social communication concerns (ELScreen), and low-likelihood infants (LL), with observations at 12, 18, 24, and 36 months. Across these two years, the development of RRBs was non-linear, with a peak in RBS-R Overall Scores at 27 months in typically developing infants (those with no developmental concerns). The ASD group (those who received an ASD diagnosis) showed significantly faster increases in RRBs than all groups of infants not diagnosed with ASD, regardless of initial likelihood status. Among participants diagnosed with ASD, RRB trajectories were similar between ELSib-ASD and ELScreen-ASD, suggesting findings are generalizable across simplex and multiplex families. ASD infants demonstrated faster growth in RRBs than infants with non-ASD developmental delays (e.g., speech or global delays). Significant group differences in levels of RRBs did not emerge until 24-months of age, suggesting RRBs may lack specificity earlier in development. These results underscore the potential of RRBs as an early marker of ASD, as elevations compared to typically developing infants are evident by 12-months of age and increase in the following two years. However, clinicians and parents should be aware that smaller transient increases in RRBs are normative, and that early (<2 years) RRB elevations may not be specific to ASD.