Autism spectrum disorders (ASDs) are complex, lifelong, neurodevelopmental conditions of largely unknown cause. They are much more common than previously believed, second in frequency only to mental retardation among the serious developmental disorders. Although a heritable component has been demonstrated in ASD etiology, putative risk genes have yet to be identified. Environmental risk factors may also play a role, perhaps via complex gene-environment interactions, but no specific exposures with significant population effects are known. A number of endogenous biomarkers associated with autism risk have been investigated, and these may help identify significant biologic pathways that, in turn, will aid in the discovery of specific genes and exposures. Future epidemiologic research should focus on expanding population-based descriptive data on ASDs, exploring candidate risk factors in large well-designed studies incorporating both genetic and environmental exposure data and addressing possible etiologic heterogeneity in studies that can stratify case groups and consider alternate endophenotypes.

https://www.annualreviews.org/doi/pdf/10.1146/annurev.publhealth.28.021406.144007

The Epidemiology of Autism Spectrum Disorders

Autism Diagnostic Observation Schedule (ADOS) Modules 1-3 item and domain total distributions were reviewed for 1,630 assessments of children aged 14 months to 16 years with an autism spectrum disorder (ASD) or with heterogeneous non-spectrum disorders. Children were divided by language level and age to yield more homogeneous cells. Items were chosen that best differentiated between diagnoses and were arranged into domains on the basis of multi-factor item-response analysis. Reflecting recent research, the revised algorithm now consists of two new domains, Social Affect and Restricted, Repetitive Behaviors (RRB), combined to one score to which thresholds are applied, resulting in generally improved predictive value.

The Autism Diagnostic Observation Schedule: Revised Algorithms for Improved Diagnostic Validity

OBJECTIVES: The reported increasing prevalence of autism spectrum disorder (ASD) and attendant health and family impact make monitoring of ASD prevalence a public health priority. METHODS: The prevalence of parent-reported diagnosis of ASD among US children aged 3 to 17 years was estimated from the 2007 National Survey of Children9s Health (sample size: 78037). A child was considered to have ASD if a parent/guardian reported that a doctor or other health care provider had ever said that the child had ASD and that the child currently had the condition. The point-prevalence for ASD was calculated for those children meeting both criteria. We examined sociodemographic factors associated with current ASD and with a past (but not current) ASD diagnosis. The health care experiences for children in both ASD groups were explored. RESULTS: The weighted current ASD point-prevalence was 110 per 10,000. We estimate that 673,000 US children have ASD. Odds of having ASD were 4 times as large for boys than girls. Non-Hispanic (NH) black and multiracial children had lower odds of ASD than NH white children. Nearly 40% of those ever diagnosed with ASD did not currently have the condition; NH black children were more likely than NH white children to not have current ASD. Children in both ASD groups were less likely than children without ASD to receive care within a medical home. CONCLUSIONS: The observed point-prevalence is higher than previous US estimates. More inclusive survey questions, increased population awareness, and improved screening and identification by providers may partly explain this finding.

https://texasautism.com/WorkshopFiles/prevalence2009.pdf

Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007.

Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1601-183X.2007.00330.x

Autism-like behavioral phenotypes in BTBR T+tf/J mice

Objectives. We sought to examine racial and ethnic disparities in the recognition of autism spectrum disorders (ASDs).Methods. Within a multisite network, 2568 children aged 8 years were identified as meeting surveillance criteria for ASD through abstraction of evaluation records from multiple sources. Through logistic regression with random effects for site, we estimated the association between race/ethnicity and documented ASD, adjusting for gender, IQ, birthweight, and maternal education.Results. Fifty-eight percent of children had a documented autism spectrum disorder. In adjusted analyses, children who were Black (odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.64, 0.96), Hispanic (OR = 0.76; CI = 0.56, 0.99), or of other race/ethnicity (OR = 0.65; CI = 0.43, 0.97) were less likely than were White children to have a documented ASD. This disparity persisted for Black children, regardless of IQ, and was concentrated for children of other ethnicities when IQ was lower than 70.Conclusions. Signi...

Racial/Ethnic Disparities in the Identification of Children With Autism Spectrum Disorders

Context Autism represents an unusual pattern of development beginning in the infant and toddler years. Objectives To examine the stability of autism spectrum diagnoses made at ages 2 through 9 years and identify features that predicted later diagnosis. Design Prospective study of diagnostic classifications from standardized instruments including a parent interview (Autism Diagnostic Interview–Revised [ADI-R]), an observational scale (Pre-Linguistic Autism Diagnostic Observation Schedule/Autism Diagnostic Observation Schedule [ADOS]), and independent clinical diagnoses made at ages 2 and 9 years compared with a clinical research team's criterion standard diagnoses. Setting Three inception cohorts: consecutive referrals for autism assessment to (1) state-funded community autism centers, (2) a private university autism clinic, and (3) case controls with developmental delay from community clinics. Participants At 2 years of age, 192 autism referrals and 22 developmentally delayed case controls; 172 children seen at 9 years of age. Main Outcome Measures Consensus best-estimate diagnoses at 9 years of age. Results Percentage agreement between best-estimate diagnoses at 2 and 9 years of age was 67, with a weighted κ of 0.72. Diagnostic change was primarily accounted for by movement from pervasive developmental disorder not otherwise specified to autism. Each measure at age 2 years was strongly prognostic for autism at age 9 years, with odds ratios of 6.6 for parent interview, 6.8 for observation, and 12.8 for clinical judgment. Once verbal IQ ( P  = .001) was taken into account at age 2 years, the ADI-R repetitive domain ( P  = .02) and the ADOS social ( P  = .05) and repetitive domains ( P  = .005) significantly predicted autism at age 9 years. Conclusions Diagnostic stability at age 9 years was very high for autism at age 2 years and less strong for pervasive developmental disorder not otherwise specified. Judgment of experienced clinicians, trained on standard instruments, consistently added to information available from parent interview and standardized observation.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/209669/YOA50311.pdf

Autism from 2 to 9 years of age.

Verbal skills were assessed at approximately ages 2, 3, 5, and 9 years for 206 children with a clinical diagnosis of autism (n = 98), pervasive developmental disorders-not otherwise specified (PDD-NOS; n = 58), or nonspectrum developmental disabilities (n = 50). Growth curve analyses were used to analyze verbal skills trajectories over time. Nonverbal IQ and joint attention emerged as strong positive predictors of verbal outcome. The gap between the autism and other 2 groups widened with time as the latter improved at a higher rate. However, there was considerable variability within diagnostic groups. Children with autism most at risk for more serious language impairments later in life can be identified with considerable accuracy at a very young age, while improvement can range from minimal to dramatic.

Pamela S. DiLavore

Papers

Autism from 2 to 9 years of age.

Patterns of growth in verbal abilities among children with autism spectrum disorder.