Potential impact of DSM-5 criteria on autism spectrum disorder prevalence estimates

Importance: The DSM-5 contains revised diagnostic criteria for autism spectrum disorder (ASD) from the DSM-IV-TR. Potential impacts of the new criteria on ASD prevalence are unclear.

Objective: To assess potential effects of the DSM-5 ASD criteria on ASD prevalence estimation by retrospectively applying the new criteria to population-based surveillance data collected for previous ASD prevalence estimation.

Design, setting, and participants: Cross-sectional, population-based ASD surveillance based on clinician review of coded behaviors documented in children’s medical and educational evaluations from 14 geographically defined areas in the United States participating in the Autism and Developmental Disabilities Monitoring (ADDM) Network in 2006 and 2008. This study included 8-year-old children living in ADDM Network study areas in 2006 or 2008, including 644 883 children under surveillance, of whom 6577 met surveillance ASD case status based on the DSM-IV-TR.

Main outcomes and measures: Proportion of children meeting ADDM Network ASD criteria based on the DSM-IV-TR who also met DSM-5 criteria; overall prevalence of ASD using DSM-5 criteria.

Results: Among the 6577 children classified by the ADDM Network as having ASD based on the DSM-IV-TR, 5339 (81.2%) met DSM-5 ASD criteria. This percentage was similar for boys and girls but higher for those with than without intellectual disability (86.6% and 72.5%, respectively; P < .001). A total of 304 children met DSM-5 ASD criteria but not current ADDM Network ASD case status. Based on these findings, ASD prevalence per 1000 for 2008 would have been 10.0 (95% CI, 9.6-10.3) using DSM-5 criteria compared with the reported prevalence based on DSM-IV-TR criteria of 11.3 (95% CI, 11.0-11.7).

Conclusions and relevance: Autism spectrum disorder prevalence estimates will likely be lower under DSM-5 than under DSM-IV-TR diagnostic criteria, although this effect could be tempered by future adaptation of diagnostic practices and documentation of behaviors to fit the new criteria.

Although social impairments are considered the hallmark deficit of autism, many behavioral intervention studies rely on cognitive functioning as a primary outcome. Fewer studies have examined whether changes in cognition are associated with changes in social functioning. This study examined whether cognitive gains among 192 students from 47 kindergarten-through-second-grade autism support classrooms participating in a year-long behavioral intervention study were associated with gains in social functioning. Children’s gains in cognitive ability were modestly associated with independent assessors’ and teachers’ evaluations of social functioning but were not associated with changes in parent ratings. Observed social gains were not commensurate with gains in cognition, suggesting the need both for interventions that directly target social functioning and relevant field measures of social functioning.

Keywords: autism spectrum disorder; intervention; social deficits.

Most recent estimates indicate that 1 in 68 children are affected by an autism spectrum disorder (ASD). Though decades of research have uncovered much about these disorders, the pathological mechanism remains unknown. Hampering efforts is the seeming inability to integrate findings over the micro to macro scales of study, from changes in molecular, synaptic and cellular function to large-scale brain dysfunction impacting sensory, communicative, motor and cognitive activity. In this review, we describe how studies focusing on neuronal circuit function provide unique context for identifying common neurobiological disease mechanisms of ASD. We discuss how recent EEG and MEG studies in subjects with ASD have repeatedly shown alterations in ensemble population recordings (both in simple evoked related potential latencies and specific frequency subcomponents). Because these disease-associated electrophysiological abnormalities have been recapitulated in rodent models, studying circuit differences in these models may provide access to abnormal circuit function found in ASD. We then identify emerging in vivo and ex vivo techniques, focusing on how these assays can characterize circuit level dysfunction and determine if these abnormalities underlie abnormal clinical electrophysiology. Such circuit level study in animal models may help us understand how diverse genetic and environmental risks can produce a common set of EEG, MEG and anatomical abnormalities found in ASD.

Keywords: ASD; EEG; MEG; VSDi; circuit; gamma; neurophysiology; translational.

Approximately 30% of hearing children with autism spectrum disorder (ASD) do not acquire expressive language, and those who do often show impairments related to their social deficits, using language instrumentally rather than socially, with a poor understanding of pragmatics and a tendency toward repetitive content. Linguistic abnormalities can be clinically useful as diagnostic markers of ASD and as targets for intervention. Studies have begun to document how ASD manifests in children who are deaf for whom signed languages are the primary means of communication. Though the underlying disorder is presumed to be the same in children who are deaf and children who hear, the structures of signed and spoken languages differ in key ways. This article describes similarities and differences between the signed and spoken language acquisition of children on the spectrum. Similarities include echolalia, pronoun avoidance, neologisms, and the existence of minimally verbal children. Possible areas of divergence include pronoun reversal, palm reversal, and facial grammar.

Background: SCN2A 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 presentation: We 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.

Conclusion: This 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.