Emma Woodhouse

Heritability of Autism Spectrum Disorder in a UK Population-Based Twin Sample

IMPORTANCE Most evidence to date highlights the importance of genetic influences on the liability to autism and related traits. However, most of these findings are derived from clinically ascertained samples, possibly missing individuals with subtler manifestations, and obtained estimates may not be representative of the population. OBJECTIVES To establish the relative contributions of genetic and environmental factors in liability to autism spectrum disorder (ASD) and a broader autism phenotype in a large population-based twin sample and to ascertain the genetic/environmental relationship between dimensional trait measures and categorical diagnostic constructs of ASD. DESIGN, SETTING, AND PARTICIPANTS We used data from the population-based cohort Twins Early Development Study, which included all twin pairs born in England and Wales from January 1, 1994, through December 31, 1996. We performed joint continuous-ordinal liability threshold model fitting using the full information maximum likelihood method to estimate genetic and environmental parameters of covariance. Twin pairs underwent the following assessments: the Childhood Autism Spectrum Test (CAST) (6423 pairs; mean age, 7.9 years), the Development and Well-being Assessment (DAWBA) (359 pairs; mean age, 10.3 years), the Autism Diagnostic Observation Schedule (ADOS) (203 pairs; mean age, 13.2 years), the Autism Diagnostic Interview-Revised (ADI-R) (205 pairs; mean age, 13.2 years), and a best-estimate diagnosis (207 pairs). MAIN OUTCOMES AND MEASURES Participants underwent screening using a population-based measure of autistic traits (CAST assessment), structured diagnostic assessments (DAWBA, ADI-R, and ADOS), and a best-estimate diagnosis. RESULTS On all ASD measures, correlations among monozygotic twins (range, 0.77-0.99) were significantly higher than those for dizygotic twins (range, 0.22-0.65), giving heritability estimates of 56% to 95%. The covariance of CAST and ASD diagnostic status (DAWBA, ADOS and best-estimate diagnosis) was largely explained by additive genetic factors (76%-95%). For the ADI-R only, shared environmental influences were significant (30% [95% CI, 8%-47%]) but smaller than genetic influences (56% [95% CI, 37%-82%]). CONCLUSIONS AND RELEVANCE The liability to ASD and a more broadly defined high-level autism trait phenotype in this large population-based twin sample derives primarily from additive genetic and, to a lesser extent, nonshared environmental effects. The largely consistent results across different diagnostic tools suggest that the results are generalizable across multiple measures and assessment methods. Genetic factors underpinning individual differences in autismlike traits show considerable overlap with genetic influences on diagnosed ASD.

Exploring the cognitive features in children with autism spectrum disorder, their co-twins, and typically developing children within a population-based sample

BACKGROUND The behavioural symptoms of autism spectrum disorder (ASD) are thought to reflect underlying cognitive deficits/differences. The findings in the literature are somewhat mixed regarding the cognitive features of ASD. This study attempted to address this issue by investigating a range of cognitive deficits and the prevalence of multiple cognitive atypicalities in a large population-based sample comprising children with ASD, their unaffected co-twins, and typically developing comparison children. METHODS Participants included families from the Twins Early Development Study (TEDS) where one or both children met diagnostic criteria for ASD. Overall, 181 adolescents with a diagnosis of ASD and 73 unaffected co-twins were included, plus an additional 160 comparison control participants. An extensive cognitive battery was administered to measure IQ, central coherence, executive function, and theory of mind ability. RESULTS Differences between groups (ASD, co-twin, control) are reported on tasks assessing theory of mind, executive function, and central coherence. The ASD group performed atypically in significantly more cognitive tasks than the unaffected co-twin and control groups. Nearly a third of the ASD group presented with multiple cognitive atypicalities. CONCLUSIONS Multiple cognitive atypicalities appear to be a characteristic, but not universal feature, of ASD. Further work is needed to investigate whether specific cognitive atypicalities, either alone or together, are related to specific behaviours characteristic of ASD.

Does sex influence the diagnostic evaluation of autism spectrum disorder in adults

It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x2 = 4.09; p = 0.04). In high-functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered.

Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire

Background Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear. Method We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments. Results Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72–0.82] and positive predictive value of 0.76 (95% CI 0.70–0.80), the specificity of 0.29 (95% CI 0.20–0.38) and negative predictive value of 0.36 (95% CI 0.22–0.40) were low. Thus, 64% of those who scored below the AQ cut-off were ‘false negatives’ who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may ‘mimic’ ASD and inflate AQ scores, leading to false positives. Conclusions The AQs utility for screening referrals was limited in this sample. Recommendations supporting the AQs role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.

Diagnosing Autism Spectrum Disorder in community settings using the development and well-being assessment: validation in a UK population-based twin sample

Background Increasing numbers of people are being referred for the assessment of autism spectrum disorder (ASD). The NICE (UK) and the American Academy of Pediatrics recommend gathering a developmental history using a tool that operationalises ICD/DSM criteria. However, the best‐established diagnostic interview instruments are time consuming, costly and rarely used outside national specialist centres. What is needed is a brief, cost‐effective measure validated in community settings. We tested the Development and Well‐Being Assessment (DAWBA) for diagnosing ASD in a sample of children/adolescents representative of those presenting in community mental health settings. Methods A general population sample of twins (TEDS) was screened and 276 adolescents were selected as at low (CAST score < 12; n = 164) or high risk for ASD (CAST score ≥ 15 and/or parent reported that ASD suspected/previously diagnosed; n = 112). Parents completed the ASD module of the DAWBA interview by telephone or online. Families were visited at home: the ADI‐R and autism diagnostic observation schedule (ADOS) were completed to allow a best‐estimate research diagnosis of ASD to be made. Results Development and Well‐Being Assessment ASD symptom scores correlated highly with ADI‐R algorithm scores (ρ = .82, p < .001). Good sensitivity (0.88) and specificity (0.85) were achieved using DAWBA computerised algorithms. Clinician review of responses to DAWBA questions minimally changed sensitivity (0.86) and specificity (0.87). Positive (0.82–0.95) and negative (0.90) predictive values were high. Eighty‐six per cent of children were correctly classified. Performance was improved by using it in conjunction with the ADOS. Conclusions The DAWBA is a brief structured interview that showed good sensitivity and specificity in this general population sample. It requires little training, is easy to administer (online or by interview) and diagnosis is aided by an algorithm. It holds promise as a tool for assisting with assessment in community settings and may help services implement the recommendations made by NICE and the American Academy of Pediatrics regarding diagnosis of young people on the autism spectrum.

Autism Spectrum Disorders and Other Mental Health Problems: Exploring Etiological Overlaps and Phenotypic Causal Associations

OBJECTIVE Recent studies have highlighted the impact of coexisting mental health problems in autism spectrum disorders (ASD). No twin studies to date have reported on individuals meeting diagnostic criteria of ASD. This twin study reports on the etiological overlap between the diagnosis of ASD and emotional symptoms, hyperactivity, and conduct problems measured with the Strengths and Difficulties Questionnaire. METHOD Genetic and environmental influences on the covariance between ASD and coexisting problems were estimated, in line with the correlated risks model prediction. Phenotypic causality models were also fitted to explore alternative explanations of comorbidity: namely, that coexisting problems are the result of or result in ASD symptoms; that they increase recognition of ASD; or that they arise due to an over-observation bias/confusion when differentiating between phenotypes. RESULTS More than 50% of twins with broad spectrum/ASD met the borderline/abnormal levels cut-off criteria for emotional symptoms or hyperactivity, and approximately 25% met these criteria for the 3 reported problems. In comparison, between 13% and 16% of unaffected twins scored above the cut-offs. The phenotypic correlation between ASD and emotional symptoms was explained entirely by genetic influences and accompanied by a moderate genetic correlation (0.42). The opposite was true for the overlap with conduct problems, as nonshared-environmental factors had the strongest impact. For hyperactivity, the best-fitting model suggested a unidirectional phenotypic influence of hyperactivity on ASD. CONCLUSION Our findings suggest a possible effect of hyperactivity on identification of ASD. The lack of genetic influences on conduct problems-ASD overlap further supports the genetic independence of these 2 phenotypes. Finally, the co-occurrence of emotional symptoms in ASD, compared to other co-occurring problems, is completely explained by common genetic effects.

Screening for co-occurring conditions in adults with autism spectrum disorder using the Strengths and Difficulties Questionnaire: a pilot study

Adolescents and adults with autism spectrum disorder (ASD) are at elevated risk of co‐occurring mental health problems. These are often undiagnosed, can cause significant impairment, and place a very high burden on family and carers. Detecting co‐occurring disorders is extremely important. However, there is no validated screening tool for this purpose. The aim of this pilot study is to test the utility of the strengths and difficulties questionnaire (SDQ) to screen for co‐occurring emotional disorders and hyperactivity in adolescents and adults with ASD. The SDQ was completed by 126 parents and 98 individuals with ASD (in 79 cases both parent and self‐report were available from the same families). Inter‐rater reliability, test‐retest stability, internal consistency, and construct validity were examined. SDQ subscales were also compared to clinically utilized measures of emotional disorders and hyperactivity to establish the ability to predict risk of disorder. Inter‐rater reliability (r = 0.42), test‐retest stability (r = 0.64), internal consistency (α = 0.52–0.81) and construct validity (r = 0.42–0.57) for the SDQ subscales were comparable to general population samples. Parent‐ and self‐report SDQ subscales were significantly associated with measures of anxiety, depression and hyperactivity (62–74% correctly classified). Parent‐report performed significantly better than self‐report; adults with ASD under‐reported difficulties. The SDQ shows promise as a simple and efficient way to screen for emotional disorders and hyperactivity in adolescents and adults with ASD that could help reduce the impact of these disorders on individuals and their families. However, further more systematic attempts at validation are warranted. Autism Res 2016, 9: 1353–1363.

Guidelines for identification and treatment of individuals with attention deficit/hyperactivity disorder and associated fetal alcohol spectrum disorders based upon expert consensus

BackgroundThe association of attention deficit/hyperactivity disorder (ADHD) and fetal alcohol spectrum disorders (FASD) results in a complex constellation of symptoms that complicates the successful diagnosis and treatment of the affected individual. Current literature lacks formal guidelines, randomized control trials, and evidence-based treatment plans for individuals with ADHD and associated FASD. Therefore, a meeting of professional experts was organized with the aim of producing a consensus on identification and treatment guidelines that will aid clinicians in caring for this unique patient population.MethodsExperts from multiple disciplines in the fields of ADHD and FASD convened in London, United Kingdom, for a meeting hosted by the United Kingdom ADHD Partnership (UKAP; www.UKADHD.com) in June 2015. The meeting provided the opportunity to address the complexities of ADHD and FASD from different perspectives and included presentations, discussions, and group work. The attendees worked towards producing a consensus for a unified approach to ADHD and associated FASD.ResultsThe authors successfully came to consensus and produced recommended guidelines with specific regards to identification and assessment, interventions and treatments, and multiagency liaisons and care management, highlighting that a lifespan approach to treatment needs to be adopted by all involved. Included in the guidelines are: 1) unique ‘red flags’, which when identified in the ADHD population can lead to an accurate associated FASD diagnosis, 2) a treatment decision tree, and 3) recommendations for multiagency care management.ConclusionsWhile clinically useful guidelines were achieved, more research is still needed to contribute to the knowledge base about the diagnosis, treatment, and management of those with ADHD and associated FASD.

The assessment of autism spectrum disorders in adults

Purpose – The purpose of this paper is to explore and highlight the main elements of an autism spectrum disorder assessment in adults. It features significant challenges for the clinical teams responsible to undertake the assessment. This paper aims to explain the importance of the wider needs assessment in accordance to the Autism Act and Autism Strategy. Design/methodology/approach – The paper describes the main symptom domains for an ASD diagnosis, according to the two basic diagnostic manuals. It provides compendious summary of the available diagnostic tools and the significant comorbidities people with ASD present with including other neurodevelopmental disorders, mental or physical health problems, challenging behaviour and risk issues. Findings – The paper proposes that all National Health System professionals should be able to recognise possible signs of ASD and accordingly refer individuals for a comprehensive assessment to secondary services. It highlights the importance of a wider needs assessm...