Psychiatric conditions in autistic adolescents: longitudinal stability from childhood and associated risk factors.

Autistic people experience high rates of co-occurring psychiatric diagnoses. Current prevalence estimates vary considerably due to an over-reliance on clinical cohorts and the longitudinal stability of diagnoses from childhood into adolescence is poorly understood. This study aims to provide prevalence rates of co-occurring DSM-5 psychiatric diagnosis for autistic adolescence and investigate, for the first time, the stability of diagnoses from childhood. Using a longitudinal stratified sample of autistic youth (N = 77; 13-17 years; 60% male), selected from a larger community-derived sample of those with pre-existing autism diagnoses (N = 277) weighted prevalence estimates of emotional (anxiety, depression), behavioural (oppositional and conduct disorders) and ADHD diagnoses were calculated based on semi-structured psychiatric interview. Prediction of adolescent psychiatric diagnosis based on childhood diagnostic status, sex, childhood IQ (both assessed at age 4-10 years) was tested. Emotional and behavioural disorders in adolescence were particularly prevalent, and significantly predicted by childhood disorder status. Attention-deficit/hyperactivity-disorder (ADHD) was prevalent but not predicted by childhood ADHD diagnosis. Neither sex nor childhood IQ predicted diagnostic outcomes. Autistic youth have high levels of co-occurring psychiatric conditions, which are broadly persistent across childhood and adolescence. Emotional disorders are particularly prevalent and remain persistent from childhood to adolescence. Greater diagnostic variability was found for ADHD with more adolescents moving across diagnostic thresholds.

Acquisition and loss of best walking skills in children and young people with bilateral cerebral palsy.

AIM: To explore factors predicting acquisition and loss of best walking ability in young people with bilateral cerebral palsy (CP). METHOD: In our population cohort (Study of Hips And Physical Experience) of 338 children (201 males, 137 females) with bilateral CP, age at achieving walking was recorded and walking ability predicted from early motor milestones. Walking was assessed at 5 to 8 years (mean 7y) and in 228 of 278 survivors at 13 to 19 years (mean 16y). Parent carers reported their view of any loss of best achieved walking. Factors potentially associated with loss of best achieved walking were explored: severity and type of motor disorder; intellect and communication; manipulative skill; general health and comorbidity; pain; orthopaedic surgery; musculoskeletal spine and lower limb deformity; weight; fatigue; mood; and presence of regular exercise regime. RESULTS: The ability to walk independently was reliably predicted by the motor milestone 'getting to sit and maintain sitting' by the age of 36 months (without aids) and 55 months (with aids). Forty-five per cent of the cohort never walked 10 steps independently. Not all who achieved walking without aids were still doing so by a mean age of 16 years, which was associated with later age at achieving walking and the degree of musculoskeletal deformity, as was the parent carers' report of loss of best walking. INTERPRETATION: In this study, development of musculoskeletal deformity was a significant factor in not maintaining best achieved walking by mean age 16 years, which is most likely to occur in young people whose walking ability is with aids over short distances or in therapy only. Prediction of future walking ability in a child with bilateral CP can be made from early motor milestones.

Is cognitive inflexibility a missing link? The role of cognitive inflexibility, alexithymia and intolerance of uncertainty in externalising and internalising behaviours in young people with autism spectrum disorder.

BACKGROUND: Internalising (anxiety and low mood) and externalising (aggressive or outburst behaviours, and irritability) difficulties are very common in autism spectrum disorder (ASD) across the life span, relatively stable over time and often associated with poorer quality of life. Understanding the cognitive mechanisms underlying internalising and externalising difficulties in ASD is essential for developing targeted supports and interventions. In the present study, we investigated established and less-researched cognitive factors hypothesised to contribute to internalising and/or externalising difficulties in ASD, namely cognitive inflexibility (CI), intolerance of uncertainty (IU) and alexithymia. Based on previous models and clinical experience, we hypothesised that IU would lead to internalising symptoms, with alexithymia contributing to this pathway, and that CI would have a direct effect on externalising behaviours and may indirectly contribute to internalising symptoms via increasing IU. METHODS: Our sample consisted of 95 5- to 18-year-olds presenting to a specialist neurodevelopmental clinic and receiving a diagnosis of ASD. Parents/caregivers completed questionnaires assessing ASD symptomatology, internalising and externalising difficulties, CI, IU and alexithymia. Structural equation modelling was used to examine the hypothesised pathways and relationships between the main variables of interest. RESULTS: Cognitive Inflexibility played a significant direct role in the pathway from ASD symptoms to externalising symptoms in ASD, and indirect role via IU in the pathway to internalising problems. Relationships between alexithymia and both internalising and externalising symptoms were weaker, with alexithymia predicting internalising difficulties via IU only. CONCLUSIONS: The finding of a direct pathway from CI to externalising behaviours is novel, as is the indirect role of CI in internalising symptomatology. Of the three cognitive mechanisms examined, only CI significantly predicted externalising symptoms. Possible implications for interventions and supports targeting these cognitive processes in ASD are discussed.

Autism spectrum disorder.

Autism spectrum disorder is a term used to describe a constellation of early-appearing social communication deficits and repetitive sensory-motor behaviours associated with a strong genetic component as well as other causes. The outlook for many individuals with autism spectrum disorder today is brighter than it was 50 years ago; more people with the condition are able to speak, read, and live in the community rather than in institutions, and some will be largely free from symptoms of the disorder by adulthood. Nevertheless, most individuals will not work full-time or live independently. Genetics and neuroscience have identified intriguing patterns of risk, but without much practical benefit yet. Considerable work is still needed to understand how and when behavioural and medical treatments can be effective, and for which children, including those with substantial comorbidities. It is also important to implement what we already know and develop services for adults with autism spectrum disorder. Clinicians can make a difference by providing timely and individualised help to families navigating referrals and access to community support systems, by providing accurate information despite often unfiltered media input, and by anticipating transitions such as family changes and school entry and leaving.

Factors associated with pain in adolescents with bilateral cerebral palsy.

AIM: We explored factors associated with pain and its severity in a population cohort of young people with bilateral cerebral palsy, comparing parent/carer and young people self-reports. METHOD: Of 278 survivors (mean age 16y 8mo, SD 1y 4mo, range 13y 8mo-19y 3mo) from the South Thames in the Study of Hips and Physical Experience cohort of 338 young people with bilateral cerebral palsy, 212 parents/carers and 153 young people completed questionnaires on the presence, severity, timing, site, associated factors, impact, and treatment of pain. RESULTS: Seventy per cent of parents/carers reported pain within 3 months, 59% the previous week, and 50% the previous day with 56% reporting 'regularly experienced'. Of young people able to do so, 63% reported pain within 3 months, 50% the previous week, and 42% the previous day, with 48% reporting regular pain. There was strong agreement between the parent/carer and young people, reporting pain severity over the previous 3 months. Pain severity was associated with increased motor impairment and comorbidity, particularly constipation, spasticity, equipment use, and higher emotional score, but not sex, intellectual disability, speech, or maternal education. Multiple sites of musculoskeletal pain were reported in two-thirds of individuals. Pain was associated with voluntary movement in individuals with less motor impairment and with being moved in those with severe motor impairment. Greater pain severity had a negative effect on both physical and psychological quality of life. INTERPRETATION: Increasing awareness of the comorbidities in cerebral palsy may aid effective treatment, reducing pain experienced by young people with cerebral palsy. WHAT THIS STUDY ADDS: Regular moderate or severe pain is reported in young people with bilateral cerebral palsy (CP) in all Gross Motor Function Classification System levels. Pain is reported more frequently in young people who are non-ambulant. General ill health is strongly associated with severity of pain after controlling for severity of CP, especially constipation. Pain occurs most often in ambulant young people during voluntary activity and in those who are non-ambulant when being moved. There is strong agreement between parents/carers and young people about pain presence and severity.

FACTORES ASOCIADOS AL DOLOR EN ADOLESCENTES CON PARÁLISIS CEREBRAL BILATERAL: OBJETIVO: Exploramos los factores asociados con el dolor y su gravedad en una cohorte poblacional de jóvenes con parálisis cerebral bilateral, comparando los autoinformes de padres/cuidadores y jóvenes. MÉTODO: De 278 sobrevivientes (edad media 16 años 8 meses, DS 1 año 4 meses, rango 13 años 8 meses - 19 años 3 meses) del Támesis Meridional, en el Estudio de caderas y experiencia física de 338 jóvenes con parálisis cerebral bilateral, 212 padres/cuidadores y 153 los jóvenes completaron cuestionarios sobre la presencia, la gravedad, el momento, el sitio, los factores asociados, el impacto y el tratamiento del dolor. RESULTADOS: El 70% de los padres/cuidadores reportaron dolor dentro de los 3 meses, el 59% en la semana anterior y el 50% en el día anterior, y el 56% informaron tener dolor "como experiencia regular". De los jóvenes que pueden hacerlo, 63% reportaron dolor dentro de los 3 meses, 50% la semana anterior y 42% el día anterior, con 48% reportando dolor regular. Hubo un fuerte acuerdo entre los padres/cuidadores y los jóvenes, que informaron sobre la gravedad del dolor durante los 3 meses anteriores. La gravedad del dolor se asoció con un aumento del deterioro motor y la comorbilidad, en particular el estreñimiento, la espasticidad, el uso de equipos y una mayor puntuación emocional, pero no el sexo, la discapacidad intelectual, el habla o la educación materna. Se reportaron múltiples sitios de dolor musculoesquelético en dos tercios de los individuos. El dolor se asoció con el movimiento voluntario en individuos con menos discapacidad motora y con el traslado en personas con insuficiencia motora grave. Una mayor gravedad del dolor tuvo un efecto negativo en la calidad de vida tanto física como psicológica. INTERPRETACIÓN: Un mayor conocimiento de las comorbilidades en la parálisis cerebral puede ayudar a un tratamiento eficaz, reduciendo el dolor que experimentan los jóvenes con parálisis cerebral.

FATORES ASSOCIADOS COM DOR EM ADOLESCENTES COM PARALISIA CEREBRAL BILATERAL: OBJETIVO: Exploramos os fatores associados com dor e sua severidade em uma coorte de jovens com paralisia cerebral bilateral, comparando auto-relatos dos jovens e relatos dos pais/cuidadores. MÉTODO: Dos 278 sobreviventes (média de idade 16a 8m, DP 1a 4m, variação 13a 8m-19a 3m) de South Thames, da coorte de 228 jovens com paralisia cerebral bilateral do Estudo dos Quadris e Experiência Física, 212 pais/cuidadores e 153 jovens completaram os questionários de presença, severidade, momento, local, fatores associados, impacto, e tratamento da dor. RESULTADOS: Setenta por cento dos pais/cuidadores relataram dor em 3 meses, 59% na semana anterior, e 50% no dia anterior, com 56% indicando "sente regularmente". Dos jovens capazes de fazê-lo, 63% reportaram dor em 3 meses, 50% na última semana, e 42% no dia anterior, com 48% reportando dor regular. Houve forte concordância entre pais/cuidadores e jovens, relatando severidade da dor nos 3 meses anteriores. A severidade da dor se associou com maior comprometimento motor e comorbidades, particularmente constipação, espasticidade, uso de equipamentos, e maior pontuação emocional, mas não com o sexo, deficiência intelectual, fala, ou educação materna. Múltiplos locais de dor músculo-esquelética foram relatados em dois terços dos indivíduos. A dor foi associada com movimento voluntário em indivíduos com menor comprometimento motor, e com ser movido naqueles com comprometimento severo. Maior severidade da dor teve efeito negativo tanto na qualidade de vida física e psicológica. INTERPRETAÇÃO: Aumentar a conscientização sobre as comorbidades em paralisia cerebral pode ajudar tratamentos efetivos, reduzindo a dor sentida por jovens com paralisia cerebral.

Childhood disintegrative disorder and autism spectrum disorder: a systematic review.

AIM: In an attempt to clarify the debate surrounding the diagnostic validity of childhood disintegrative disorder (CDD), we systematically reviewed its characteristics and compared it with autism spectrum disorder (ASD). METHOD: Four databases were searched (PubMed, PsycINFO, Embase, and Web of Science). Included articles had participants with CDD, as defined by symptoms present in the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision and the International Classification of Diseases, 10th Revision. Comparison groups were those with ASD and ASD with regression. Case studies were excluded. RESULTS: Twenty articles, comprising 96 participants with CDD (80 males, 16 females), were included. Most studies were cross-sectional. The prevalence of CDD was 1.1 to 9.2 per 100 000, with a mean age at regression of 3 years 2 months (SD 1y 1mo), with a range of 2 years to 7 years. In addition to core CDD symptoms, most had intellectual impairment, anxiety, challenging behaviours, and regressed in toileting skills. Participants with CDD and ASD shared core diagnostic and extra-diagnostic features. However, participants with CDD seemed to have more severe symptoms and a different symptom profile, including apparently typical development before regression, faster regression, more affective symptoms, and more global developmental deficit. Possible genetic and autoimmune neurobiological mechanisms were identified. INTERPRETATION: There is limited high-quality evidence describing the aetiology and outcomes of CDD. However, given the qualitative and prognostic differences between ASD and CDD, we recommend that future diagnostic criteria should distinguish late-onset regression.

TRASTORNO DESINTEGRATIVO INFANTIL Y TRASTORNO DEL ESPECTRO AUTISTA: UNA REVISIÓN SISTEMÁTICA: OBJETIVO: En un intento de aclarar el debate que rodea la validez diagnóstica del trastorno desintegrativo infantil (TDI), revisamos sistemáticamente sus características y lo comparamos con el trastorno del espectro autista (TEA). MÉTODO: Se realizaron búsquedas en cuatro bases de datos (PubMed, PsycINFO, Embase y Web of Science). Los artículos incluidos tenían participantes con TDI, según lo definido por los síntomas presentes en los criterios del Manual diagnóstico y estadístico de trastornos mentales, Cuarta edición, Revisión de texto y Clasificación internacional de enfermedades, Décima revisión. Los grupos de comparación fueron aquellos con TEA y TEA con regresión. Se excluyeron los estudios de caso. RESULTADOS: Se incluyeron 20 artículos, con 96 participantes con TDI (80 varones y 16 mujeres). La mayoría de los estudios fueron de corte transversal. La prevalencia de TDI fue de 1,1 a 9,2 por 100.000, con una edad media de regresión de 3 años a 2 meses (DS 1 años 1 mes), con un rango de 2 años a 7 años. Además de los síntomas centrales de la TDI, la mayoría tenía deterioro intelectual, ansiedad, comportamientos desafiantes y regresión en las habilidades para ir al baño. Los participantes con TDI y TEA compartieron funciones básicas comunes de diagnóstico y de diagnóstico adicional. Sin embargo, los participantes con TDI parecían tener síntomas más graves y un perfil de síntomas diferente, incluido un desarrollo aparentemente típico antes de la regresión, una regresión más rápida, síntomas más afectivos y un déficit de desarrollo más global. Se identificaron posibles mecanismos genéticos y autoinmunes neurobiológicos. INTERPRETACIÓN: Existe una evidencia limitada de alta calidad que describe la etiología y los resultados de la TDI. Sin embargo, dadas las diferencias cualitativas y pronósticas entre la TEA y la TDI, recomendamos que los criterios diagnósticos futuros distingan la regresión de inicio tardío.

TRANSTORNO DESINTEGRATIVO DA INFÂNCIA E TRANSTORNO DO ESPECTRO AUTISTA: UMA REVISÃO SISTEMÁTICA: OBJETIVO: Na tentativa de esclarecer o debate em torno da validade diagnóstica do transtorno desintegrativo da infância (TDI), nós revisamos sistematicamente suas características e as comparamos com o transtorno do espectro autista (TEA). MÉTODO: Quatro bases de dados foram pesquisadas (PubMed, PsycINFO, Embase, e Web of Science). Os artigos incluídos tinham participantes com TDI, como definido pelos sintomas presentes nos critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, quarta edição, com revisão do texto, e na Classificação Internacional de Doenças, 10a edição. Grupos de comparação foram aqueles com TEA e TEA com regressão. Estudos de caso foram excluídos. RESULTADOS: Vinte artigos, incluindo 96 participantes com TDI (80 do sexo masculino, 16 do sexo feminino), foram incluídos. A maior parte dos estudos era transversal. A prevalência de TDI foi de 1,1 a 9,2 por 100.000, com idade média de regressão de 3 anos e 2 meses (DP 1a 1m), com variação de 2 anos a 7 anos. Além dos sintomas centrais de TDI, a maioria tinha deficiência intelectual, ansiedade, comportamentos desafiadores, e regressão na habilidade de usar o banheiro. Participantes com TDI e TEA compartilham aspectos diagósticos e extra-diagnósticos centrais. No entanto, os participantes com TDI pareceram ter sintomas mais severos e um perfil diferente de sintomas, incluindo desenvolvimento aparentemente típico antes da regressão, regressão mais rápida, mais sintomas afetivos, e maior déficit global do desenvolvimento. Possíveis mecanismos neurobiológicos genéticos e autoimunes foram identificados. INTERPRETAÇÃO: Há evidência limitada de alta qualidade descrevendo a etiologia dos resultados do TDI. No entanto, dadas as diferenças qualitativas e prognósticas entre TEA e TDI, recomendamos que futuros critérios diagnósticos distinguam a regressão de início tardio.

Exome sequencing in an admixed isolated population indicates NFXL1 variants confer a risk for specific language impairment.

Children affected by Specific Language Impairment (SLI) fail to acquire age appropriate language skills despite adequate intelligence and opportunity. SLI is highly heritable, but the understanding of underlying genetic mechanisms has proved challenging. In this study, we use molecular genetic techniques to investigate an admixed isolated founder population from the Robinson Crusoe Island (Chile), who are affected by a high incidence of SLI, increasing the power to discover contributory genetic factors. We utilize exome sequencing in selected individuals from this population to identify eight coding variants that are of putative significance. We then apply association analyses across the wider population to highlight a single rare coding variant (rs144169475, Minor Allele Frequency of 4.1% in admixed South American populations) in the NFXL1 gene that confers a nonsynonymous change (N150K) and is significantly associated with language impairment in the Robinson Crusoe population (p = 2.04 × 10-4, 8 variants tested). Subsequent sequencing of NFXL1 in 117 UK SLI cases identified four individuals with heterozygous variants predicted to be of functional consequence. We conclude that coding variants within NFXL1 confer an increased risk of SLI within a complex genetic model.

Testing the specificity of executive functioning impairments in adolescents with ADHD, ODD/CD and ASD.

Current diagnostic systems conceptualise attention deficit hyperactivity disorder (ADHD), oppositional defiant/conduct disorder (ODD/CD) and autism spectrum disorder (ASD) as separate diagnoses. However, all three demonstrate executive functioning (EF) impairments. Whether these impairments are trans-diagnostic or disorder-specific remains relatively unexplored. Four groups of 10-16 year-olds [typically developing (TD; N = 43), individuals clinically diagnosed with ADHD (N = 21), ODD/CD (N = 26) and ASD (N = 41)] completed Go/NoGo and Switch tasks. Group differences were tested using analysis of co-variance (ANCOVA) including age, IQ, sex, conduct problems and ADHD symptoms as co-variates. Results indicated some disorder-specificity as only the ASD group demonstrated decreased probability of inhibition in the Go/NoGo task compared to all other groups. However, shared impairments were also found; all three diagnostic groups demonstrated increased reaction time variability (RTV) compared to the TD group, and both the ODD/CD and the ASD group demonstrated increased premature responses. When controlling for ADHD symptoms and conduct problems, group differences in RTV were no longer significant; however, the ASD group continued to demonstrate increased premature responses. No group differences were found in cognitive flexibility in the Switch task. A more varied response style was present across all clinical groups, although this appeared to be accounted for by sub-threshold ODD/CD and ADHD symptoms. Only the ASD group was impaired in response inhibition and premature responsiveness relative to TD adolescents. The findings suggest that some EF impairments typically associated with ADHD may also be found in individuals with ASD.

Commentary: PDA - what's in a name? Dimensions of difficulty in children reported to have an ASD and features of extreme/pathological demand avoidance: a commentary on O'Nions et al. (2017).

Pathological demand avoidance (PDA), a term first used by Elizabeth Newson in the 1980s, refers to a collection of behaviours that children will demonstrate to avoid instructions (and tasks) that they perceive as demands. These children are postulated to be averse to anything that is perceived as a demand placed on them. PDA features are commonly encountered in children with autism but PDA is not a subtype of autism nor a separately diagnosed mental, behavioural or developmental disorder in any of the major classification systems (ICD-10 or DSM-5). Such behaviours are not confined to children with autism and debate continues regarding its existence as a distinct phenomenon and if such a phenotype exists whether it is merely a part of autism or a separate condition. We comment on O'Nions and colleagues' study that explores common themes/behavioural traits in children with autism spectrum disorder (ASD) who also fit the phenotypic description of PDA. We explore how the current classification systems capture features of PDA in autism with diagnoses of common comorbidities in ASD (such as disruptive behaviour/conduct disorders, OCD and anxiety), but to many clinicians and parents this seems an inadequate description. What remains to be explored are the trans-diagnostic temperamental and cognitive traits of children with PDA features, such as cognitive rigidity and intolerance of uncertainty. It is important to understand why some children are demand avoidant and identification of these factors (individual and systemic) helps in management much more than classifying them with an additional label. O'Nions et al. have helpfully provided further insight into several underpinning traits/dimensions of children with PDA features; understanding these will help develop effective strategies for parenting demand-avoidant children.

Language growth in children with heterogeneous language disorders: a population study.

BACKGROUND: Language development has been characterised by significant individual stability from school entry. However, the extent to which trajectories of language growth vary in children with language disorder as a function of co-occurring developmental challenges is a question of theoretical import, with implications for service provision. METHODS: SCALES employed a population-based survey design with sample weighting procedures to estimate growth in core language skills over the first three years of school. A stratified sample (n = 529) received comprehensive assessment of language, nonverbal IQ, and social, emotional and behavioural difficulties at 5-6 years of age and 95% of the sample (n = 499) were assessed again at ages 7-8. Language growth was measured using both raw and standard scores in children with typical development, children with language disorder of unknown origin, and children with language disorders associated with a known clinical condition and/or intellectual disability. RESULTS: Overall, language was stable at the individual level (estimated ICC = 0.95) over the first three years of school. Linear mixed effects models highlighted steady growth in language raw scores across all three groups, including those with multiple developmental challenges. There was little evidence, however, that children with language disorders were narrowing the gap with peers (z-scores). Adjusted models indicated that while nonverbal ability, socioeconomic status and social, emotional and behavioural deficits predicted initial language score (intercept), none predicted language growth (slope). CONCLUSIONS: These findings corroborate previous studies suggesting stable language trajectories after ages 5-6 years, but add considerably to previous work by demonstrating similar developmental patterns in children with additional nonverbal cognitive deficits, social, emotional, and behavioural challenges, social disadvantage or clinical diagnoses.

Younger children experience lower levels of language competence and academic progress in the first year of school: evidence from a population study.

BACKGROUND: The youngest children in an academic year are reported to be educationally disadvantaged and overrepresented in referrals to clinical services. In this study we investigate for the first time whether these disadvantages are indicative of a mismatch between language competence at school entry and the academic demands of the classroom. METHODS: We recruited a population sample of 7,267 children aged 4 years 9 months to 5 years 10 months attending state-maintained reception classrooms in Surrey, England. Teacher ratings on the Children's Communication Checklist-Short (CCC-S), a measure of language competence, the Strengths and Difficulties Questionnaire-Total Difficulties Score (SDQ), a measure of behavioural problems, and the Early Years Foundation Stage Profile (EYFSP), a measure of academic attainment, were obtained at the end of the reception year. RESULTS: The youngest children were rated by teachers as having more language deficits, behaviour problems, and poorer academic progress at the end of the school year. Language deficits were highly associated with behaviour problems; adjusted odds ratio 8.70, 95% CI [7.25-10.45]. Only 4.8% of children with teacher-rated language deficits and 1.3% of those with co-occurring language and behaviour difficulties obtained a 'Good Level of Development' on the EYFSP. While age predicted unique variance in academic attainment (1%), language competence was the largest associate of academic achievement (19%). CONCLUSION: The youngest children starting school have relatively immature language and behaviour skills and many are not yet ready to meet the academic and social demands of the classroom. At a population level, developing oral language skills and/or ensuring academic targets reflect developmental capacity could substantially reduce the numbers of children requiring specialist clinical services in later years.

The impact of nonverbal ability on prevalence and clinical presentation of language disorder: evidence from a population study.

BACKGROUND: Diagnosis of 'specific' language impairment traditionally required nonverbal IQ to be within normal limits, often resulting in restricted access to clinical services for children with lower NVIQ. Changes to DSM-5 criteria for language disorder removed this NVIQ requirement. This study sought to delineate the impact of varying NVIQ criteria on prevalence, clinical presentation and functional impact of language disorder in the first UK population study of language impairment at school entry. METHODS: A population-based survey design with sample weighting procedures was used to estimate population prevalence. We surveyed state-maintained reception classrooms (n = 161 or 61% of eligible schools) in Surrey, England. From a total population of 12,398 children (ages 4-5 years), 7,267 (59%) were screened. A stratified subsample (n = 529) received comprehensive assessment of language, NVIQ, social, emotional and behavioural problems, and academic attainment. RESULTS: The total population prevalence estimate of language disorder was 9.92% (95% CI 7.38, 13.20). The prevalence of language disorder of unknown origin was estimated to be 7.58% (95% CI 5.33, 10.66), while the prevalence of language impairment associated with intellectual disability and/or existing medical diagnosis was 2.34% (95% CI 1.40, 3.91). Children with language disorder displayed elevated symptoms of social, emotional and behavioural problems relative to peers, F(1, 466) = 7.88, p = .05, and 88% did not make expected academic progress. There were no differences between those with average and low-average NVIQ scores in severity of language deficit, social, emotional and behavioural problems, or educational attainment. In contrast, children with language impairments associated with known medical diagnosis and/or intellectual disability displayed more severe deficits on multiple measures. CONCLUSIONS: At school entry, approximately two children in every class of 30 pupils will experience language disorder severe enough to hinder academic progress. Access to specialist clinical services should not depend on NVIQ.

Functional impact of global rare copy number variation in autism spectrum disorders.

The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.

Testing two screening instruments for autism spectrum disorder in UK community child health services.

AIM: The aim of this study was to test the accuracy of two screening instruments in UK Community health services: Modified Checklist for Autism in Toddlers (M-CHAT) and Social Communication Questionnaire (SCQ) for autism spectrum disorder (ASD). A two-stage screening and in-depth assessment procedure, combined with sampling stratification and statistical weighting, allowed the accuracy of the screens to be estimated in the entire population of referred children. METHOD: The study included all referrals of children aged 18 to 48 months to community paediatric and speech and language therapy services in two London districts over a 12-month period between September 2004 and September 2005. Parents of 808 children were approached; screen data were obtained on 543 children (67.2%). A stratified subsample of 120 children received an in-depth assessment for ASD as defined by the International Statistical Classification of Diseases and Related Health Problems, 10th edition. Community clinician judgement of likely ASD was available for 98 out of the 120 children. RESULTS: The sensitivity and specificity were 64% (95% confidence intervals; range 51-80%) and 75% (63-85%) for the SCQ, and 82% (72-92%) and 50% (33-64%) for M-CHAT. There was no evidence that the area under the curve differed between the two screening instruments. There was also no evidence that clinician judgement of likely ASD differed from either of the screening tests. The screening tests did not perform well to confirm preliminary clinical judgement to refer (in series), nor as an alternative indicator for referral (in parallel). INTERPRETATION: While screening tests may provide useful information, their accuracy is moderate. Screening information in isolation should not be used to make referral decisions regarding specialized ASD assessment.

Emotional and behavioural problems in young children with autism spectrum disorder.

AIM: To assess the frequency, pervasiveness, associated features, and persistence of emotional and behavioural problems in a community sample of young children with autism spectrum disorder (ASD). METHOD: Parents (n=277) and teachers (n=228) of 4- to 8-year-olds completed the Developmental Behaviour Checklist (DBC). Intellectual ability and autism symptomatology were also assessed. A subsample repeated the DBC. RESULTS: Three-quarters of the cohort scored above the clinical cut-off on the Developmental Behaviour Checklist Primary Carer Version (DBC-P) questionnaire; almost two-thirds of these scored above cut-off on the Developmental Behaviour Checklist Teacher Version (DBC-T) questionnaire. In 81%, problems persisted above threshold 14 months later. Higher DBC-P scores were associated with greater autism symptomatology, higher deprivation index, parental unemployment, and more children in the home but not with parental education or ethnicity, or child's age or sex. Children with IQ>70 scored higher for disruptive behaviour, depression, and anxiety symptoms; those with IQ<70 scored higher for self-absorption and hyperactivity. INTERPRETATION: The DBC identifies a range of additional behaviour problems that are common in ASD and which could be the focus for specific intervention. The results highlight the potential benefit of systematic screening for co-existing problems.

Quantifying multifaceted needs captured at the point of care. Development of a Disabilities Terminology Set and Disabilities Complexity Scale.

AIMS: To develop a Disabilities Terminology Set and quantify the multifaceted needs of disabled children and their families in a district disability clinic population. METHOD: Data from structured electronic clinic letters of children attending paediatric disability clinics from June 2007 to May 2012 in Sunderland, north-east England collected at the point of clinical care were analysed to determine appropriate terms for consistent recording of each need and issue. Terms were collated to count the number of needs per child. RESULTS: A Systemized Nomenclature of Medicine - Clinical Terms subset of 296 terms was identified and published, and 8392 consultations for 1999 children were reviewed. The required number of clinic appointments correlated strongly with the number of needs identified. Children with intellectual disabilities in addition to cerebral palsy and epilepsy had more than double the number of conditions, technology dependencies, and family-reported issues than those without. Disabled children who subsequently died had the highest burden of needs (p=0.007). INTERPRETATION: Detailed data about needs generated outputs useful for local care pathway development and service planning. Sufficient evidence was provided for successful business cases leading to the appointment of additional paediatric disability consultants. Counting numbers of needs and issues quantifies complexity in a straightforward way. This could underpin needs-based commissioning of services.

Phonological processing in children with specific language impairment with and without reading difficulties.

BACKGROUND: Specific language impairment (SLI) is heterogeneous and identifying subgroups within it may help explain the aetiology of the condition. Phonological processing abilities distinguish between children with SLI who do and do not have reading decoding impairments (RDIs). AIMS: To probe different levels of phonological processing in children with SLI with and without RDI to investigate the cognitive basis of these differences. METHODS & PROCEDURES: A total of 64 children aged 5-17 years were classified using the results of standardized language and single-word reading tests into those with no SLI and no RDI (No SLI/No RDI) (N = 18), no SLI but with RDI (No SLI/RDI) (N = 4, not included in analyses because of the small number), SLI/No RDI (N = 20), and SLI/RDI (N = 22). The groups were compared on a range of tasks engaging different levels of phonological processing (input and output processing and phonological awareness). OUTCOMES & RESULTS: The SLI/RDI group was distinguished from the SLI/No RDI and No SLI/No RDI groups by more errors in the longer items in non-word repetition and by poorer phonological awareness. Non-word discrimination scores indicated a gradient of performance across groups that was not associated with a qualitatively different pattern of performance. CONCLUSIONS & IMPLICATIONS: This is the first study contrasting input and output processes associated with phonological processing. The results suggest that deficits in SLI plus RDI may be associated with impairment in actively maintaining phonological representations for phonological processing, which is not present in those without RDI and which leads to reading decoding difficulties.

Callous-unemotional traits in adolescents with autism spectrum disorder.

BACKGROUND: People with callous-unemotional traits and also those with autism spectrum disorder (ASD) display sociocognitive difficulties. However, the frequency and neurocognitive correlates of callous-unemotional traits within individuals with ASD are unknown. AIMS: To determine the prevalence of callous-unemotional traits in individuals with ASD and test their association with behavioural and cognitive measures. METHOD: Parents of 92 adolescents with ASD completed the Antisocial Processes Screening Device (APSD) for callous-unemotional traits. Adolescents participated in tasks of emotion recognition, theory of mind and cognitive flexibility. RESULTS: In total 51% (n = 47) scored above a cut-off expected to identify the top 6% on the APSD. Of these 17% (n = 8) had concurrent conduct problems. Regression analyses found callous-unemotional traits were associated with specific impairment in fear recognition but not with theory of mind or cognitive flexibility. CONCLUSIONS: Adolescents with ASD show high rates of callous-unemotional traits but, unlike in the general population, these are not strongly associated with conduct problems. The relationship of callous-unemotional traits to impairments in fear recognition suggests similar affective difficulties as in individuals with callous-unemotional traits without ASD.

Development and psychometric properties of the parent version of the Profile of Neuropsychiatric Symptoms (PONS) in children and adolescents.

BACKGROUND: The use of neuropsychiatric Patient Centred Outcome Measures (PCOMs) in routine child mental health and paediatric services is very time consuming and often requires multiple scales being completed as no single scale covers all areas of psychopathology. The use of a web-based programme can overcome these problems and contribute to improved use of PCOMs in clinical practice. We aim to develop a web-based scale (using HealthTracker™) to screen and identify young people with significant neuropsychiatric symptoms to enable early intervention. METHODS: Qualitative development of the Profile of Neuropsychiatric Symptoms (PONS) and quantitative evaluation of the psychometric properties of the PONS scale (parent version). Parents of 929 from the general population and 147 with neuropsychiatric disorders (5-18 years old) completed the PONS online. In addition, those children with neuropsychiatric disorders were assessed for the presence of current and lifetime psychiatric disorders using the Development and Well-Being Assessment (DAWBA). RESULTS: The PONS scale (parent version) consists of 30 symptom domains rated on a 7-point scale for both frequency and impairment. We found an intra-class correlation coefficient for single measures was 0.44 (0.42-0.46 95 % CI, F = 22.84, p ≤ 0.0001) and for average measures was 0.96 (0.95-0.96 95 % CI, F = 22.84, p ≤ 0.0001). The factor analysis showed a 4-factor model: Neurodevelopmental Disability; Behavioural and Emotional Dysregulation; Psychoses and Personality Dysfunction; and Anxiety and Depression. The receiver operating characteristic area for the 4-factors was 0.96 (SE = 0.006; 0.95-0.97 95 % CI). CONCLUSIONS: The PONS scale (parent version) is a web-based PCOM on the HealthTracker™ system that is a rapid, engaging measure that has excellent reliability and validity. The system allows for automated scoring and immediate feedback of statistical cut-off points and assists clinicians with diagnostic decision-making and optimises use of clinician time.

Individual common variants exert weak effects on the risk for autism spectrum disorders.

While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.