Anne O'Hare

CMIP and ATP2C2 modulate phonological short-term memory in language impairment

Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition.

Prosody and its relationship to language in school-aged children with high-functioning autism

BACKGROUND Disordered expressive prosody is a widely reported characteristic of individuals with autism. Despite this, it has received little attention in the literature and the few studies that have addressed it have not described its relationship to other aspects of communication. AIMS To determine the nature and relationship of expressive and receptive language, phonology, pragmatics, and non-verbal ability in school-aged children with high-functioning autism and to determine how prosody relates to these abilities and which aspects of prosody are most affected. METHODS & PROCEDURES A total of 31 children with high-functioning autism and 72 typically developing children matched for verbal mental age completed a battery of speech, language, and non-verbal assessments and a procedure for assessing receptive and expressive prosody. OUTCOMES & RESULTS Language skills varied, but the majority of children with high-functioning autism had deficits in at least one aspect of language with expressive language most severely impaired. All of the children with high-functioning autism had difficulty with at least one aspect of prosody and prosodic ability correlated highly with expressive and receptive language. The children with high-functioning autism showed significantly poorer prosodic skills than the control group, even after adjusting for verbal mental age. CONCLUSIONS Investigating prosody and its relationship to language in autism is clinically important because expressive prosodic disorders add an additional social and communication barrier for these children and problems are often life-long even when other areas of language improve. Furthermore, a receptive prosodic impairment may have implications not only for understanding the many functions of prosody but also for general language comprehension.

Absence of urinary opioid peptides in children with Autism

Objective: It has been claimed for a number of years that the urine of children with autism contains exogenously derived opioid peptides. This finding is said to reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic marker for autism and predict treatment response to a diet excluding gluten and casein. The aim of the present study was to determine whether exogenous or endogenous peptides were present in the urine of children with autism or of control children. Design: Case-control study Setting: Cases were recruited from two tertiary referral centres specialising in autistic spectrum disorders, while controls were recruited from mainstream primary and secondary schools in the same geographical area. Participants: 65 boys with autism, mean age 7.4 years (range 5–11) and 158 control boys, mean age 7.8 years (range 4.2–11). Investigations: Urine samples were examined by high pressure liquid chromatography (HPLC) and matrix assisted laser desorbtion ionisation-time of flight mass spectrometry (MALDI-TOF MS) for the presence of a number of putative opioid peptides. Outcomes: There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found, MALDI-TOF established that these peaks did not, in fact, represent opioid peptides. Conclusions: Given the lack of evidence for any opioid peptiduria in children with autism, opioid peptides can neither serve as a biomedical marker for autism nor be employed to predict or monitor response to a casein- and gluten-free diet.

A Clinical Assessment Tool for Advanced Theory of Mind Performance in 5 to 12 Year Olds

One hundred forty typically developing 5- to 12-year-old children were assessed with a test of advanced theory of mind employing Happé’s strange stories. There was no significant difference in performance between boys and girls. The stories discriminated performance across the different ages with the lowest performance being in the younger children who nevertheless managed to achieve a third of their potential total. However, some of the individual mentalising concepts such as persuasion were too difficult for these younger children. This normative data provides a useful clinical tool to measure mentalising ability in more able children with autism spectrum disorder.

The fatty acid compositions of erythrocyte and plasma polar lipids in children with autism, developmental delay or typically developing controls and the effect of fish oil intake.

The erythrocyte and plasma fatty acid compositions of children with autism were compared in a case-control study with typically developing (TD) children and with children showing developmental delay (DD). Forty-five autism subjects were age-matched with TD controls and thirty-eight with DD controls. Fatty acid data were compared using paired t tests. In addition, blood fatty acids from treatment-naive autism subjects were compared with autism subjects who had consumed fish oil supplements by two-sample t tests. Relatively few differences were seen between erythrocyte fatty acids in autism and TD subjects although the former had an increased arachidonic acid (ARA):EPA ratio. This ratio was also increased in plasma samples from the same children. No changes in n-3 fatty acids or ARA:EPA ratio were seen when comparing autism with DD subjects but some SFA and MUFA were decreased in the DD subjects, most notably 24 : 0 and 24 : 1, which are essential components of axonal myelin sheaths. However, if multiple comparisons are taken into account, and a stricter level of significance applied, most of these values would not be significant. Autism subjects consuming fish oil showed reduced erythrocyte ARA, 22 : 4n-6, 22 : 5n-6 and total n-6 fatty acids and increased EPA, 22 : 5n-3, 22 : 6n-3 and total n-3 fatty acids along with reduced n-6:n-3 and ARA:EPA ratios. Collectively, the autism subjects did not have an underlying phospholipid disorder, based on erythrocyte fatty acid compositions, although the increased ARA:EPA ratio observed suggested that an imbalance of essential highly unsaturated fatty acids may be present in a cohort of autism subjects.

Phonetic and phonological errors in children with high functioning autism and Asperger syndrome

This study involved a qualitative analysis of speech errors in children with autism spectrum disorders (ASDs). Participants were 69 children aged 5–13 years; 30 had high functioning autism and 39 had Asperger syndrome. On a standardized test of articulation, the minority (12%) of participants presented with standard scores below the normal range, indicating a speech delay/disorder. Although all the other children had standard scores within the normal range, a sizeable proportion (33% of those with normal standard scores) presented with a small number of errors. Overall 41% of the group produced at least some speech errors. The speech of children with ASD was characterized by mainly developmental phonological processes (gliding, cluster reduction and final consonant deletion most frequently), but non-developmental error types (such as phoneme specific nasal emission and initial consonant deletion) were found both in children identified as performing below the normal range in the standardized speech test and in those who performed within the normal range. Non-developmental distortions occurred relatively frequently in the children with ASD and previous studies of adolescents and adults with ASDs shows similar errors, suggesting that they do not resolve over time. Whether or not speech disorders are related specifically to ASD, their presence adds an additional communication and social barrier and should be diagnosed and treated as early as possible in individual children.

Prevalence of autistic spectrum disorders in Lothian, Scotland: an estimate using the “capture–recapture” technique

Aims: To determine the prevalence of autistic spectrum disorder in a geographically defined population for children receiving services and compare this to the estimated prevalence based on a two source “capture–recapture” technique previously employed in biological populations to give a “true” prevalence with full ascertainment. Methods: Information on gender, age, and postcode sector was determined from nine different datasets maintained for children with autistic spectrum disorder and point prevalence was calculated. Data from the diagnostic services and the Special Needs System were entered into the two source “capture–recapture” calculation. Results: Of a total population of 134 661 under 15 year olds resident in Lothian in southeast Scotland, 443 were known to autism services, with a point prevalence of 32.9 per 10 000 (95% CI 29.8 to 36.0). The estimated prevalence using a capture–recapture method was 44.2 (95% CI 39.5 to 48.9), which suggests that 74% of affected children were registered with services in some way. The age distribution was similar to that of the background population under the age of 12 years and there was no indication of a rising prevalence. The ratio of boys to girls was 7:1. Conclusions: The prevalence of autistic spectrum disorder in a geographically based population employing two source capture–recapture analysis is comparable to that quoted for the best active ascertainment studies. This technique offers a tool for establishing the prevalence of this condition in health service populations to assist in planning clinical services.

Impairments in Sensory Modulation in Children with Autistic Spectrum Disorder

The Short Sensory Profile was used to measure a caregiver report of sensory reactivity in a group of children with an autistic spectrum disorder (ASD). Fifty-six of 78 (72%) families invited to participate returned the questionnaires and the data were complete for 44 children. These 44 children represented a stratified sample out of a total of 443 children, identified through nine different data sets maintained for children affected by ASD from a total geographical region in South East Scotland. Clinical information was collected retrospectively from contemporaneous paediatric community child health medical notes and also cross-sectionally from caregivers. Sensory reactivity was outside normal limits in over 70% of the children, with the highest percentage of sensitivities occurring in the auditory filtering and the underresponsiveness and seeking sensation domains. Logistic regression analysis showed no significant relationship between sensory reactivity and the childs age at presentation with autism or parental report of regression. The severity of autism was measured by the Gilliam Autism Rating Scale and related to the Short Sensory Profile (r = 0.39, p = 0.001). These findings suggest that all children affected by ASD, regardless of clinical features or age, may potentially be affected by sensory reactivities and may benefit from appropriate occupational therapy assessment and management. ASDs are relatively common among neurodevelopmental conditions and confer lifelong disabilities. As the majority of affected children will have sensory modulation difficulties, this has significant implications for paediatric occupational therapy services.

Gender ratio in a clinical population sample, age of diagnosis and duration of assessment in children and adults with autism spectrum disorder

This article reports on gender ratio, age of diagnosis and the duration of assessment procedures in autism spectrum disorder diagnosis in a national study which included all types of clinical services for children and adults. Findings are reported from a retrospective case note analysis undertaken with a representative sample of 150 Scottish children and adults recently diagnosed with autism spectrum disorder. The study reports key findings that the gender ratio in this consecutively referred cohort is lower than anticipated in some age groups and reduces with increasing age. The gender ratio in children, together with the significant difference in the mean age of referral and diagnosis for girls compared to boys, adds evidence of delayed recognition of autism spectrum disorder in younger girls. There was no significant difference in duration of assessment for males and females suggesting that delays in diagnosis of females occur prior to referral for assessment. Implications for practice and research are considered.2

A trial of an iPad™ intervention targeting social communication skills in children with autism

This study evaluated a technology-based early intervention for social communication skills in pre-schoolers in a randomised controlled trial. Participants were 54 children aged under 6 years with a diagnosis of autism, assigned to either intervention or control conditions. The app engaged children, who played consistently, regardless of developmental level, and was rated highly by parents. There were no significant group differences in parent-report measures post-intervention, nor in a measure of parent–child play at follow-up. Therefore, this intervention did not have an observable impact on real-world social communication skills and caution is recommended about the potential usefulness of iPad™ apps for amelioration of difficulties in interaction. However, positive attitudes among participants, lack of harms and the potential of apps to deliver therapeutic content at low economic cost suggest this approach is worth pursuing further, perhaps targeting other skill domains.