Alison Presmanes Hill

Epidemiology of Autism Spectrum Disorders

In this chapter, we review existing prevalence estimates for autism spectrum disorders (ASDs) since 2000 and discuss methodological factors impacting the estimation of prevalence and the interpretation of changes in prevalence estimates over time. Possible explanations for an increase in the prevalence of ASD within and across populations are considered. Increases in ASD diagnostic rates cannot currently be attributed to a true increase in the incidence of ASD due to multiple confounding factors. It remains to be seen how changes to diagnostic criteria introduced in the DSM-5 will impact estimates of ASD prevalence going forward.

Obesity and Autism

OBJECTIVE: Overweight and obesity are increasingly prevalent in the general pediatric population. Evidence suggests that children with autism spectrum disorders (ASDs) may be at elevated risk for unhealthy weight. We identify the prevalence of overweight and obesity in a multisite clinical sample of children with ASDs and explore concurrent associations with variables identified as risk factors for unhealthy weight in the general population. METHODS: Participants were 5053 children with confirmed diagnosis of ASD in the Autism Speaks Autism Treatment Network. Measured values for weight and height were used to calculate BMI percentiles; Centers for Disease Control and Prevention criteria for BMI for gender and age were used to define overweight and obesity (≥85th and ≥95th percentiles, respectively). RESULTS: In children age 2 to 17 years, 33.6% were overweight and 18% were obese. Compared with a general US population sample, rates of unhealthy weight were significantly higher among children with ASDs ages 2 to 5 years and among those of non-Hispanic white origin. Multivariate analyses revealed that older age, Hispanic or Latino ethnicity, lower parent education levels, and sleep and affective problems were all significant predictors of obesity. CONCLUSIONS: Our results indicate that the prevalence of unhealthy weight is significantly greater among children with ASD compared with the general population, with differences present as early as ages 2 to 5 years. Because obesity is more prevalent among older children in the general population, these findings raise the question of whether there are different trajectories of weight gain among children with ASDs, possibly beginning in early childhood.

'It's not that we hate you': understanding children's gender attitudes and expectancies about peer relationships.

Widespread gender segregation, evident throughout elementary school, seems to imply that girls and boys have negative feelings and thoughts about one another, and classic theories of inter-group processes support this idea. However, research has generally overlooked childrens feelings and perceptions about gender-related interpersonal interactions. This paper investigates the nature of childrens attitudes about same- and other-gender peers, and explores how those attitudes relate to the expectancies and beliefs children hold about same- and other-gender peer interactions. Children (N= 98 fifth graders) completed questionnaires assessing their global liking of own- and other-gender peers (Yee & Brown, 1994), positive and negative attitudes about own- and other-gender peers, and outcome expectancies related to interacting with own- and other-gender peers. Results indicated that rather than being characterized by out-group negativity, childrens inter-group gender attitudes are best characterized by an in-group positivity bias. Childrens positive and negative affective attitudes were also significantly associated with outcome expectancies. In contrast, global liking of own- and other-gender peers was less predictive of outcome expectancies. Thus, the greater specificity of the affective attitude measures appeared to be a more predictive and potentially fruitful gauge of childrens feelings about own- and other-gender peers. Results are discussed in terms of the need for finer grained and more extensive studies of childrens gender-related feelings and cognitions about own- and other-gender peers.

Quantifying Repetitive Speech in Autism Spectrum Disorders and Language Impairment

We report on an automatic technique for quantifying two types of repetitive speech: repetitions of what the child says him/herself (self‐repeats) and of what is uttered by an interlocutor (echolalia). We apply this technique to a sample of 111 children between the ages of four and eight: 42 typically developing children (TD), 19 children with specific language impairment (SLI), 25 children with autism spectrum disorders (ASD) plus language impairment (ALI), and 25 children with ASD with normal, non‐impaired language (ALN). The results indicate robust differences in echolalia between the TD and ASD groups as a whole (ALN + ALI), and between TD and ALN children. There were no significant differences between ALI and SLI children for echolalia or self‐repetitions. The results confirm previous findings that children with ASD repeat the language of others more than other populations of children. On the other hand, self‐repetition does not appear to be significantly more frequent in ASD, nor does it matter whether the childs echolalia occurred within one (immediate) or two turns (near‐immediate) of the adults original utterance. Furthermore, non‐significant differences between ALN and SLI, between TD and SLI, and between ALI and TD are suggestive that echolalia may not be specific to ALN or to ASD in general. One important innovation of this work is an objective fully automatic technique for assessing the amount of repetition in a transcript of a childs utterances. Autism Res 2013, ●●: ●●–●●.

Memory in language-impaired children with and without autism

BackgroundA subgroup of young children with autism spectrum disorders (ASD) have significant language impairments (phonology, grammar, vocabulary), although such impairments are not considered to be core symptoms of and are not unique to ASD. Children with specific language impairment (SLI) display similar impairments in language. Given evidence for phenotypic and possibly etiologic overlap between SLI and ASD, it has been suggested that language-impaired children with ASD (ASD + language impairment, ALI) may be characterized as having both ASD and SLI. However, the extent to which the language phenotypes in SLI and ALI can be viewed as similar or different depends in part upon the age of the individuals studied. The purpose of the current study is to examine differences in memory abilities, specifically those that are key “markers” of heritable SLI, among young school-age children with SLI, ALI, and ALN (ASD + language normal).MethodsIn this cross-sectional study, three groups of children between ages 5 and 8 years participated: SLI (n = 18), ALI (n = 22), and ALN (n = 20). A battery of cognitive, language, and ASD assessments was administered as well as a nonword repetition (NWR) test and measures of verbal memory, visual memory, and processing speed.ResultsNWR difficulties were more severe in SLI than in ALI, with the largest effect sizes in response to nonwords with the shortest syllable lengths. Among children with ASD, NWR difficulties were not associated with the presence of impairments in multiple ASD domains, as reported previously. Verbal memory difficulties were present in both SLI and ALI groups relative to children with ALN. Performance on measures related to verbal but not visual memory or processing speed were significantly associated with the relative degree of language impairment in children with ASD, supporting the role of verbal memory difficulties in language impairments among early school-age children with ASD.ConclusionsThe primary difference between children with SLI and ALI was in NWR performance, particularly in repeating two- and three-syllable nonwords, suggesting that shared difficulties in early language learning found in previous studies do not necessarily reflect the same underlying mechanisms.

Quantitative analysis of disfluency in children with autism spectrum disorder or language impairment

Deficits in social communication, particularly pragmatic language, are characteristic of individuals with autism spectrum disorder (ASD). Speech disfluencies may serve pragmatic functions such as cueing speaking problems. Previous studies have found that speakers with ASD differ from typically developing (TD) speakers in the types and patterns of disfluencies they produce, but fail to provide sufficiently detailed characterizations of the methods used to categorize and quantify disfluency, making cross-study comparison difficult. In this study we propose a simple schema for classifying major disfluency types, and use this schema in an exploratory analysis of differences in disfluency rates and patterns among children with ASD compared to TD and language impaired (SLI) groups. 115 children ages 4–8 participated in the study (ASD = 51; SLI = 20; TD = 44), completing a battery of experimental tasks and assessments. Measures of morphological and syntactic complexity, as well as word and disfluency counts, were derived from transcripts of the Autism Diagnostic Observation Schedule (ADOS). High inter-annotator agreement was obtained with the use of the proposed schema. Analyses showed ASD children produced a higher ratio of content to filler disfluencies than TD children. Relative frequencies of repetitions, revisions, and false starts did not differ significantly between groups. TD children also produced more cued disfluencies than ASD children.

Vaccine Potential and Diversity of the Putative Cell Binding Factor (CBF, NMB0345/NEIS1825) Protein of Neisseria meningitidis.

The cbf gene from Neisseria meningitidis strain MC58 encoding the putative Cell Binding Factor (CBF, NMB0345/NEIS1825) protein was cloned into the pRSETA system and a ~36-kDa recombinant (r)CBF protein expressed in Escherichia coli and purified by metal affinity chromatography. High titres of rCBF antibodies were induced in mice following immunization with rCBF-saline, rCBF-Al(OH)3, rCBF-Liposomes or rCBF-Zwittergent (Zw) 3–14 micelles, both with and without incorporated monophosphoryl lipid A (MPLA) adjuvant. Anti-rCBF sera reacted in western blots of meningococcal lysates with a single protein band of molecular mass ~29.5 kDa, indicative of mature CBF protein, but did not react with a lysate of a Δnmb0345 mutant (CBF-), demonstrating specificity of the murine immune responses. CBF protein was produced by all strains of meningococci studied thus far and the protein was present on the surface of MC58 (CBF+) bacteria, but absent on Δnmb0345 mutant (CBF-) bacteria, as judged by FACS reactivity of anti-rCBF sera. Analysis of the NEIS1825 amino acid sequences from 6644 N. meningitidis isolates with defined Alleles in the pubmlst.org/Neisseria database showed that there were 141 ST types represented and there were 136 different allelic loci encoding 49 non-redundant protein sequences. Only 6/6644 (<0.1%) of N. meningitidis isolates lacked the nmb0345 gene. Amongst serogroup B isolates worldwide, ~68% and ~20% expressed CBF encoded by Allele 1 and 18 respectively, with the proteins sharing >99% amino acid identity. Murine antisera to rCBF in Zw 3–14 micelles + MPLA induced significant serum bactericidal activity (SBA) against homologous Allele 1 and heterologous Allele 18 strains, using both baby rabbit serum complement and human serum complement (h)SBA assays, but did not kill strains expressing heterologous protein encoded by Alelle 2 or 3. Furthermore, variable bactericidal activity was induced by murine antisera against different meningococcal strains in the hSBA assay, which may correlate with variable surface exposure of CBF. Regardless, the attributes of amino acid sequence conservation and protein expression amongst different strains and the ability to induce cross-strain bactericidal antibodies indicates that rCBF could be a potential meningococcal vaccine antigen and merits further testing.

Subtyping cognitive profiles in Autism Spectrum Disorder using a Functional Random Forest algorithm

&NA; DSM‐5 Autism Spectrum Disorder (ASD) comprises a set of neurodevelopmental disorders characterized by deficits in social communication and interaction and repetitive behaviors or restricted interests, and may both affect and be affected by multiple cognitive mechanisms. This study attempts to identify and characterize cognitive subtypes within the ASD population using our Functional Random Forest (FRF) machine learning classification model. This model trained a traditional random forest model on measures from seven tasks that reflect multiple levels of information processing. 47 ASD diagnosed and 58 typically developing (TD) children between the ages of 9 and 13 participated in this study. Our RF model was 72.7% accurate, with 80.7% specificity and 63.1% sensitivity. Using the random forest model, the FRF then measures the proximity of each subject to every other subject, generating a distance matrix between participants. This matrix is then used in a community detection algorithm to identify subgroups within the ASD and TD groups, and revealed 3 ASD and 4 TD putative subgroups with unique behavioral profiles. We then examined differences in functional brain systems between diagnostic groups and putative subgroups using resting‐state functional connectivity magnetic resonance imaging (rsfcMRI). Chi‐square tests revealed a significantly greater number of between group differences (p < .05) within the cingulo‐opercular, visual, and default systems as well as differences in inter‐system connections in the somato‐motor, dorsal attention, and subcortical systems. Many of these differences were primarily driven by specific subgroups suggesting that our method could potentially parse the variation in brain mechanisms affected by ASD.