Autism Diagnostic Instruments Research Articles

Commentary: Best practices and processes for assessment of autism spectrum disorder - the intended role of standardized diagnostic instruments.

Development of standardized diagnostic instruments has facilitated the systematic characterization of individuals with autism spectrum disorders (ASD) in clinical and research settings. However, overemphasis on scores from specific instruments has significantly detracted from the original purpose of these tools. Rather than provide a definitive "answer," or even a confirmation of diagnosis, standardized diagnostic instruments were designed to aid clinicians in the process of gathering information about social communication, play, and repetitive and sensory behaviors relevant to diagnosis and treatment planning. Importantly, many autism diagnostic instruments are not validated for certain patient populations, including those with severe vision, hearing, motor, and/or cognitive impairments, and they cannot be administered via a translator. In addition, certain circumstances, such as the need to wear personal protective equipment (PPE), or behavioral factors (e.g., selective mutism) may interfere with standardized administration or scoring procedures, rendering scores invalid. Thus, understanding the uses and limitations of specific tools within specific clinical or research populations, as well as similarities or differences between these populations and the instrument validation samples, is paramount. Accordingly, payers and other systems must not mandate the use of specific tools in cases when their use would be inappropriate. To ensure equitable access to appropriate assessment and treatment services, it is imperative that diagnosticians be trained in best practice methods for the assessment of autism, including if, how, and when to appropriately employ standardized diagnostic instruments.

PEAK Pre-Assessments: Preliminary Evidence Establishing Internal Consistency and Construct Validity.

Promoting the Emergence of Advanced Knowledge (PEAK) is a behavior-analytic tool that assesses and teaches language and cognitive abilities. PEAK preassessment total scores showed statistically significant correlations with measures of intelligence (r = .703, p = .023) and adaptive behavior (r = .618, p = .018), whereas no significant correlations were found between PEAK and age, autism diagnostic instruments, or aggression scales in a sample (N = 18) receiving behavior-analytic assessment in an autism clinic. Statistically significant correlations were found between all modules within the PEAK system (p ≤ .001). Results provide preliminary evidence of the construct validity and internal consistency of the PEAK preassessments.

Clinical characteristics and problems diagnosing autism spectrum disorder in girls

BackgroundAutism is a neurodevelopmental disorder with various clinical presentations. It has been historically considered a male disorder. An increasing number of authors stress the existence of sex/gender bias in prevalence and the need to define sex/gender differences in the clinical presentation. ReviewRecently, an increasing number of authors have studied the impact of sex/gender on autism's clinical presentation. The sex ratio of four boys to one girl commonly reported in literature is questioned. Sociocultural and familial influences can impact female clinical presentation as well as the way the difficulties of girls with autism are perceived. Issues of autism diagnostic instruments such as sex/gender bias are also studied since they have an impact on the access to diagnosis for girls. Clinical variability is a part of autism spectrum disorder, but some traits appear to be more specific of the female phenotype: existence of a “camouflage” phenomenon and less unusual play or restricted interests. DiscussionBetter understanding and diagnosis of females with autism is required to ensure the access to the support and treatment they need. Professionals must apprehend the sex/gender clinical differences to prevent the frequent misdiagnosis or missed diagnosis of females with autism. ConclusionPursuing research on sex/gender differences seems necessary to ensure appropriate support and diagnosis of undiagnosed females.

The influence of parental concern on the utility of autism diagnostic instruments.

The parental report-based Autism Diagnostic Interview-Revised (ADI-R) and the clinician observation-based Autism Diagnostic Observation Schedule (ADOS) have been validated primarily in U.S. clinics specialized in autism spectrum disorder (ASD), in which most children are referred by their parents because of ASD concern. This study assessed diagnostic agreement of the ADOS-2 and ADI-R toddler algorithms in a more broadly based sample of 679 toddlers (age 35-47 months) from the Norwegian Mother and Child Cohort. We also examined whether parental concern about ASD influenced instrument performance, comparing toddlers identified based on parental ASD concern (n = 48) and parent-reported signs of developmental problems (screening) without a specific concern about ASD (n = 400). The ADOS cutoffs showed consistently well-balanced sensitivity and specificity. The ADI-R cutoffs demonstrated good specificity, but reduced sensitivity, missing 43% of toddlers whose parents were not specifically concerned about ASD. The ADI-R and ADOS dimensional scores agreed well with clinical diagnoses (area under the curve ≥ 0.85), contributing additively to their prediction. On the ADI-R, different cutoffs were needed according to presence or absence of parental ASD concern, in order to achieve comparable balance of sensitivity and specificity. These results highlight the importance of taking parental concern about ASD into account when interpreting scores from parental report-based instruments such as the ADI-R. While the ADOS cutoffs performed consistently well, the additive contributions of ADI-R and ADOS scores to the prediction of ASD diagnosis underscore the value of combining instruments based on parent accounts and clinician observation in evaluation of ASD. Autism Res 2017, 10: 1672-1686. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Identifying High Ability Children with DSM-5 Autism Spectrum or Social Communication Disorder: Performance on Autism Diagnostic Instruments.

This study was a replication of Mazefsky et al.'s (Journal of Autism and Developmental Disabilities 43:1236-1242, 2013) investigation among a sample of 45 high ability children and adolescents diagnosed with ASD under DSM-IV-TR. Items from the ADOS and ADI-R were mapped onto DSM-5 diagnostic criteria for ASD and SCD to determine whether participants would meet either diagnosis under DSM-5. If the ADOS were administered alone, 62% of individuals diagnosed with ASD would no longer meet criteria under DSM-5; however, when the ADI-R and ADOS scores were combined, 100% of individuals would continue to meet ASD diagnosis. The ADOS was determined to be an insufficient measure for SCD due to the small number of algorithm items measuring SCD diagnostic criteria, suggesting the development of SCD measures is required.

Development, behavior, and biomarker characterization of Smith-Lemli-Opitz syndrome: an update.

BackgroundSmith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive inborn error of cholesterol metabolism syndrome with neurocognitive manifestations. SLOS is the result of mutations in the gene encoding the 7-dehydrocholesterol reductase, which results in the elevation of the cholesterol precursor 7-dehydrocholesterol (7-DHC). Previous reports indicate that intellectual disability, behavioral disturbances, and autism symptoms are frequently part of the SLOS behavioral phenotype. In the current study, we characterize the developmental history and current behavior of 33 individuals with SLOS aged 4 to 23 years and report on biomarkers 7-DHC and 8-DHC in relation to cognition and behavior.MethodsThis was an observational case series, wherein participants with SLOS underwent extensive behavioral evaluation of cognitive function, adaptive function, autism symptoms, and problem behaviors, in addition to parent report of developmental milestones. Serum and CSF were contemporaneously obtained from the majority of participants.ResultsDevelopmental milestones such as walking, talking, and toileting were uniformly delayed. Overall levels of cognitive and adaptive functioning were low; no participant received adaptive behavior scores in the average range, and the mean level of cognitive functioning in the full sample was in the moderate range of impairment. Aggressive behavior was present in nearly half of participants. Although the majority of participants had elevated scores on the gold standard autism diagnostic instruments, only about half of participants received a clinical diagnosis of autism spectrum disorder. Finally, while CSF cholesterol was not found to correlate with cognitive or adaptive functioning, both serum and CSF 7-DHC and 8-DHC (and their ratios with cholesterol) were moderately and negatively correlated with functioning in this group.ConclusionsA history of developmental delay, followed by intellectual disability, is common in individuals with SLOS. Although autism spectrum disorder appears to be a frequent diagnosis in this population, it is apparent that the low level of functioning observed in SLOS may artificially inflate scores on standard autism assessments. Our findings further support that cholesterol precursors 7-DHC and 8-DHC are important biomarkers of the level of functioning in SLOS, especially regarding cognitive abilities, and thus may be to explore as mediators within the context of treatment trials.Trial registrationClinicalTrials.gov, NCT00001721, NCT00064792Electronic supplementary materialThe online version of this article (doi:10.1186/s11689-016-9145-x) contains supplementary material, which is available to authorized users.

De novo SCN2A splice site mutation in a boy with Autism spectrum disorder

BackgroundSCN2A is a gene that codes for the alpha subunit of voltage-gated, type II sodium channels, and is highly expressed in the brain. Sodium channel disruptions, such as mutations in SCN2A, may play an important role in psychiatric disorders. Recently, de novo SCN2A mutations in autism spectrum disorder (ASD) have been identified. The current study characterizes a de novo splice site mutation in SCN2A that alters mRNA and protein products.Case presentationWe describe results from clinical and genetic characterizations of a seven-year-old boy with ASD. Psychiatric interview and gold standard autism diagnostic instruments (ADOS and ADI-R) were used to confirm ASD diagnosis, in addition to performing standardized cognitive and adaptive functioning assessments (Leiter-R and Vineland Adaptive Behavior Scale), and sensory reactivity assessments (Sensory Profile and Sensory Processing Scales). Genetic testing by whole exome sequencing revealed four de novo events, including a splice site mutation c.476 + 1G > A in SCN2A, a missense mutation (c.2263G > A) causing a p.V755I change in the TLE1 gene, and two synonymous mutations (c.2943A > G in the BUB1 gene, and c.1254 T > A in C10orf68 gene). The de novo SCN2A splice site mutation produced a stop codon 10 amino acids downstream, possibly resulting in a truncated protein and/or a nonsense-mediated mRNA decay. The participant met new DSM-5 criteria for ASD, presenting with social and communication impairment, repetitive behaviors, and sensory reactivity issues. The participant’s adaptive and cognitive skills fell in the low range of functioning.ConclusionThis report indicates that a splice site mutation in SCN2A might be contributing to the risk of ASD. Describing the specific phenotype associated with SCN2A mutations might help to reduce heterogeneity seen in ASD.

Autism spectrum disorders in 24 children who are deaf or hard of hearing

ObjectivesApproximately 4% of children who are deaf or hard of hearing have co-occurring autism spectrum disorder (ASD). Making an additional diagnosis of ASD in this population can be challenging, given the complexities of determining whether speech/language and social delays can be accounted for by their hearing loss, or whether these delays might be indicative of a comorbid ASD diagnosis. This exploratory study described a population of 24 children with the dual diagnosis of ASD and hearing loss. MethodsChildren completed a comprehensive ASD evaluation using standardized autism diagnostic instruments (Autism Diagnostic Observation Schedule, language and psychological testing). Children with permanent hearing loss who had a developmental evaluation between 2001 and 2011 and were diagnosed with an ASD based on the results of that evaluation were included. Information on communication modality, language and cognitive abilities was collected. ResultsThe median age of diagnosis was 14 months (range 1–71) for hearing loss and 66.5 months (range 33–106) for ASD. Only 25% (n=6) children were diagnosed with ASD ≤48 months of age and 46% by ≤6 years. Twelve (50%) children were diagnosed with ASD, 11 were diagnosed with pervasive developmental disorder not otherwise specified and 1 child had Asperger's. Most (67%) had profound degree of hearing loss. Fourteen (58%) children had received a cochlear implant, while 3 children had no amplification for hearing loss. Nine (38%) of the 24 children used speech as their mode of communication (oral communicators). ConclusionsCommunication delays in children who are deaf or hard of hearing are a serious matter and should not be assumed to be a direct consequence of the hearing loss. Children who received cochlear implants completed a multidisciplinary evaluation including a developmental pediatrician, which may have provided closer monitoring of speech and language progression and subsequently an earlier ASD diagnosis. Because children who are deaf or hard of hearing with ASD are challenging to evaluate, they may receive a diagnosis of ASD at older ages.

The Use of the Autism Diagnostic Interview-Revised with a Latino Population of Adolescents and Adults with Autism

Research shows that Latinos are less likely to be diagnosed with autism than their non-Latino counterparts. One factor that may contribute to these differences is that autism diagnostic instruments have not been adapted for the Latino population. The present study compared scores from the Autism Diagnostic Interview-Revised for two groups: 48 Latino adolescents and adults with autism and a matched sample of 96 non-Latino Whites. There were no significant differences between the two groups in total impairments in social reciprocity or communication. However, lower levels of restrictive-and-repetitive behaviors were found among Latino adolescents and adults with autism compared to Whites. Findings suggest that there may be cultural equivalency in some domains, but others may warrant further exploration.

Autism spectrum conditions in individuals with Möbius sequence, CHARGE syndrome and oculo-auriculo-vertebral spectrum: Diagnostic aspects

As part of multidisciplinary surveys of three Behavioural Phenotype Conditions (BPCs); Möbius sequence (Möbius), CHARGE syndrome (CHARGE) and oculo-auriculo-vertebral spectrum (OAV), autism spectrum conditions (ASCs) was diagnosed in 45%, 68% and 42% of the individuals, respectively. Diagnostic difficulties due to additional dysfunctions such as mental retardation (MR), impaired vision, reduced hearing and cranial nerve dysfunction, were experienced in all three BPC groups. The applicability of current autism diagnostic instruments, such as the Autism Diagnostic Interview-Revised (ADI-R), the Childhood Autism Rating Scale (CARS) and the Autistic Behaviour Checklist (ABC), in individuals with ASCs and Möbius/CHARGE/OAV was analysed. Use of an extensive battery of diagnostic instruments, including both observational schedules and parent interviews, and, if possible, independent judgements from two clinicians, is essential in the diagnostics of ASCs in these individuals. Further, in individuals who are deaf and blind the applicability of current autism diagnostic instruments is highly questionable.