Calibrated Severity Scores Research Articles

The Autism Diagnostic Observation Schedule, Toddler Module: Standardized Severity Scores.

Standardized calibrated severity scores (CSS) have been created for Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) Modules 1-4 as a metric of the relative severity of autism-specific behaviors. Total and domain CSS were created for the Toddler Module to facilitate comparison to other modules. Analyses included 388 children with ASD age 12-30 months and were replicated on 435 repeated assessments from 127 children with ASD. Compared to raw scores, associations between total and domain CSS and participant characteristics were reduced in the original sample. Verbal IQ effects on Social Affect-CSS were not reduced in the replication sample. Toddler Module CSS increases comparability of ADOS-2 scores across modules and allows studies of symptom trajectories to extend to earlier ages.

Replication of Standardized ADOS Domain Scores in the Simons Simplex Collection.

Raw totals from diagnostic and screening measures for autism spectrum disorder (ASD) are frequently used as dimensional measures of autism symptom severity without appropriate correction for confounding factors, such as developmental level or non-ASD-specific behavior problems. Although these associated features are important to consider when diagnosing ASD and developing intervention plans, both researchers and clinicians sometimes need metrics of ASD severity that are not influenced by these factors. The Autism Diagnostic Observation Schedule (ADOS) domain calibrated severity scores (CSS) were created to provide separate estimates of social affect (SA-CSS) and restricted, repetitive behaviors (RRB-CSS) that are relatively independent of child characteristics (Hus et al., 2014). Using a sample of 2,509 probands with ASD from the Simons Simplex Collection (SSC), this study provides the first replication of the ADOS domain CSS in an independent sample. Consistent with the original standardization study, when applied to existing SSC data, the ADOS domain CSS were less influenced by age and cognitive ability compared to raw domain totals. Domain CSS were also relatively independent of behavior problems. Use of the ADOS domain CSS to assess relationships between ASD symptoms and genetic risk factors will increase confidence that associations reflect domain-specific relationships. Scores also offer less developmentally-influenced estimates of ASD severity for future phenotypic explorations in the SSC. This independent replication provides support for the application of the ADOS domain CSS in other samples, though further replication in population-based samples will be an important next step.

Longitudinal study of symptom severity and language in minimally verbal children with autism.

A significant minority of children with autism spectrum disorder (ASD) are considered 'minimally verbal' due to language development stagnating at a few words. Recent developments allow for the severity of ASD symptoms to be examined using Autism Diagnostic Observation Schedule (ADOS) Social Affect (SA) and Restricted and Repetitive Behaviors (RRB) domain severity scores. The aim of the current study was to explore language outcomes in a cohort of minimally verbal children with autism evaluated through the preschool years and determine if and how ASD symptom severity in core domains predicts the development of spoken language by age 5. The sample consisted of 70 children with autism aged 1-5 years at the first evaluation who were examined at least 1 year later, during their fifth year of age. The ADOS overall level of language item was used to categorize children as minimally verbal or having phrase speech, and the Mullen Scales of Early Learning was used as a continuous measure of expressive language. At Time 1, 65% (n = 47) of children in the sample were minimally verbal and by Time 2, 36% (n = 17 of 47) of them had developed phrase speech. While the Time 1 ADOS calibrated severity scores did not predict whether or not a child remained minimally verbal at Time 2, change in the SA calibrated severity score (but not RRB) was predictive of the continuous measure of expressive language. However, change in SA severity no longer predicted continuous expressive language when nonverbal cognitive ability was added to the model. Findings indicate that the severity of SA symptoms has some relationship with continuous language outcome, but not categorical. However, the omnipresent influence of nonverbal cognitive ability was confirmed in the current study, as the addition of it to the model rendered null the predictive utility of SA severity.

The Autism Diagnostic Observation Schedule, Module 4: Revised Algorithm and Standardized Severity Scores

The recently published Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) includes revised diagnostic algorithms and standardized severity scores for modules used to assess younger children. A revised algorithm and severity scores are not yet available for Module 4, used with verbally fluent adults. The current study revises the Module 4 algorithm and calibrates raw overall and domain totals to provide metrics of autism spectrum disorder (ASD) symptom severity. Sensitivity and specificity of the revised Module 4 algorithm exceeded 80% in the overall sample. Module 4 calibrated severity scores provide quantitative estimates of ASD symptom severity that are relatively independent of participant characteristics. These efforts increase comparability of ADOS scores across modules and should facilitate efforts to examine symptom trajectories from toddler to adulthood.

Trajectories of Autism Severity in Early Childhood

Relatively little is known about trajectories of autism severity using calibrated severity scores (CSS) from the Autism Diagnostic Observation Schedule, but characterizing these trajectories has important theoretical and clinical implications. This study examined CSS trajectories during early childhood. Participants were 129 children with autism spectrum disorder evaluated annually from ages 2½ to 5½. The four severity trajectory classes that emerged--Persistent High (n = 47), Persistent Moderate (n = 54), Worsening (n = 10), and Improving (n = 18)-were strikingly similar to those identified by Gotham et al. (Pediatrics 130(5):e1278-e1284, 2012). Children in the Persistent High trajectory class had the most severe functional skill deficits in baseline nonverbal cognition and daily living skills and in receptive and expressive language growth.

The Interstitial Duplication 15q11.2‐q13 Syndrome Includes Autism, Mild Facial Anomalies and a Characteristic EEG Signature

Chromosomal copy number variants (CNV) are the most common genetic lesion found in autism. Many autism-associated CNVs are duplications of chromosome 15q. Although most cases of interstitial (int) dup(15) that present clinically are de novo and maternally derived or inherited, both pathogenic and unaffected paternal duplications of 15q have been identified. We performed a phenotype/genotype analysis of individuals with interstitial 15q duplications to broaden our understanding of the 15q syndrome and investigate the contribution of 15q duplication to increased autism risk. All subjects were recruited solely on the basis of interstitial duplication 15q11.2-q13 status. Comparative array genome hybridization was used to determine the duplication size and boundaries while the methylation status of the maternally methylated small nuclear ribonucleoprotein polypeptide N gene was used to determine the parent of origin of the duplication. We determined the duplication size and parental origin for 14 int dup(15) subjects: 10 maternal and 4 paternal cases. The majority of int dup(15) cases recruited were maternal in origin, most likely due to our finding that maternal duplication was coincident with autism spectrum disorder. The size of the duplication did not correlate with the severity of the phenotype as established by Autism Diagnostic Observation Scale calibrated severity score. We identified phenotypes not comprehensively described before in this cohort including mild facial dysmorphism, sleep problems and an unusual electroencephalogram variant. Our results are consistent with the hypothesis that the maternally expressed ubiquitin protein ligase E3A gene is primarily responsible for the autism phenotype in int dup(15) since all maternal cases tested presented on the autism spectrum.

Commentary: Advancing measurement of ASD severity and social competence: a reply to Constantino and Frazier (2013)

Commentary: Advancing measurement of ASD severity and social competence: a reply to Constantino and Frazier (2013)

Beyond Autism: A Baby Siblings Research Consortium Study of High-Risk Children at Three Years of Age

ObjectiveFirst-degree relatives of persons with an autism spectrum disorder (ASD) are at increased risk for ASD-related characteristics. As little is known about the early expression of these characteristics, this study characterizes the non-ASD outcomes of 3-year-old high-risk (HR) siblings of children with ASD. MethodTwo groups of children without ASD participated: 507 HR siblings and 324 low-risk (LR) control subjects (no known relatives with ASD). Children were enrolled at a mean age of 8 months, and outcomes were assessed at 3 years. Outcome measures were Autism Diagnostic Observation Schedule (ADOS) calibrated severity scores, and Mullen Verbal and Non-Verbal Developmental Quotients (DQ). ResultsAt 3 years, HR siblings without an ASD outcome exhibited higher mean ADOS severity scores and lower verbal and non-verbal DQs than LR controls. HR siblings were over-represented (21% HR versus 7% LR) in latent classes characterized by elevated ADOS severity and/or low to low-average DQs. The remaining HR siblings without ASD outcomes (79%) belonged to classes in which they were not differentially represented with respect to LR siblings. ConclusionsHaving removed a previously identified 18.7% of HR siblings with ASD outcomes from all analyses, HR siblings nevertheless exhibited higher mean levels of ASD severity and lower levels of developmental functioning than LR children. However, the latent class membership of four-fifths of the HR siblings was not significantly different from that of LR control subjects. One-fifth of HR siblings belonged to classes characterized by higher ASD severity and/or lower levels of developmental functioning. This empirically derived characterization of an early-emerging pattern of difficulties in a minority of 3-year-old HR siblings suggests the importance of developmental surveillance and early intervention for these children.

The ADOS Calibrated Severity Score: Relationship to Phenotypic Variables and Stability over Time

Measurement of the severity of autism at a single time point, and over time, is a widespread challenge for researchers. Recently, Gotham, Pickles, and Lord published a severity metric (calibrated severity scores; CSS) that takes into account age and language level and is based on raw total scores of the Autism Diagnostic Observation Schedule (ADOS), a standardized measure commonly used in autism diagnosis. The present study examined psychometric characteristics of the CSS compared to raw scores in an independent sample of 368 children aged 2 to 12 years with autism, pervasive developmental disorder-not otherwise specified (PDD-NOS), non-spectrum delay, or typical development. Reflecting the intended calibration, the CSS were more uniformly distributed within clinical diagnostic category and across ADOS modules than were raw scores. Cross-sectional analyses examining raw and severity scores and their relationships to participant characteristics revealed that verbal developmental level was a significant predictor of raw score but accounted for significantly less variance in the CSS. Longitudinal analyses indicated overall stability of the CSS over 12 to 24 months in children with autism. Findings from this study support the use of the CSS as a more valid indicator of autism severity than the ADOS raw total score, and extend the literature by examining the stability over 12 to 24 months of the CSS in children with ASD.

Standardized ADOS Scores: Measuring Severity of Autism Spectrum Disorders in a Dutch Sample

The validity of the calibrated severity scores on the ADOS as reported by Gotham et al. (J Autism Dev Disord 39: 693–705, 2009), was investigated in an independent sample of 1248 Dutch children with 1455 ADOS administrations (modules 1, 2 and 3). The greater comparability between ADOS administrations at different times, ages and in different modules, as reached by Gotham et al. with the calibrated severity measures, seems to be corroborated by the current study for module 1 and to a lesser extent for module 3. For module 2, the calibrated severity scores need to be further investigated within a sample that resembles Gotham’s sample in age and level of verbal functioning.

Standardizing ADOS Scores for a Measure of Severity in Autism Spectrum Disorders

The aim of this study is to standardize Autism Diagnostic Observation Schedule (ADOS) scores within a large sample to approximate an autism severity metric. Using a dataset of 1,415 individuals aged 2-16 years with autism spectrum disorders (ASD) or nonspectrum diagnoses, a subset of 1,807 assessments from 1,118 individuals with ASD were divided into narrow age and language cells. Within each cell, severity scores were based on percentiles of raw totals corresponding to each ADOS diagnostic classification. Calibrated severity scores had more uniform distributions across developmental groups and were less influenced by participant demographics than raw totals. This metric should be useful in comparing assessments across modules and time, and identifying trajectories of autism severity for clinical, genetic, and neurobiological research.