Understanding anxiety experienced by young males with Duchenne muscular dystrophy: a qualitative focus group study.

In this multi-methods study we explored the characteristics, causes and impact of anxiety in Duchenne muscular dystrophy (DMD) from the perspective of young males with DMD and their parents. Eight young males with DMD (7-18 years) and 14 parents participated in separate focus groups. Perspectives on anxiety were explored using semi-structured interview schedules. Themes were identified using Framework Analysis. Neurodevelopmental, emotional and behavioural symptom scores were obtained using standard instruments including the Strengths and Difficulties Questionnaire and Revised Children's Anxiety and Depression Scale. We identified six common anxiety characteristics: Catastrophic conclusions; Rigidly-held anxieties; Extreme distress; Social anxieties; Physical changes/needs; Unexpected/unfamiliar. Four further themes described influential systemic factors: Individual, Family, and Social responses and Physical environment and service contexts. All DMD participants had significantly higher total difficulties, emotional problems and impact scores than population norms. The Revised Children's Anxiety and Depression Scale showed low sensitivity in identifying anxiety symptoms. Fifty-seven percent (8/14) of parents who had wanted help for their son's anxiety were dissatisfied with the available support. In conclusion, anxiety can severely impact wellbeing and functioning of individuals with DMD. There are important nuances to consider when managing DMD-associated anxiety. We highlight the importance of multimodal assessment considering the multiple contexts within which anxiety arises.

Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations.

AIM: Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders. The aim of the study was to characterize the DMD neuropsychiatric profile fully and to explore underlying genotype/phenotype associations. METHOD: One hundred and thirty males with DMD (mean age 9y 10mo, range 5-17y) in four European centres were included and completed IQ assessment and a neurodevelopmental-screening questionnaire. Of these, 87 underwent comprehensive neuropsychiatric assessment using structured diagnostic interview and parent-reported questionnaires. RESULTS: The overall mean score on the neurodevelopmental questionnaire was significantly abnormal compared with the general population of children (p<0.001). On average, intelligence was below the population mean, with intellectual disability observed in 34 males (26%). Autistic spectrum disorder was identified in 18 (21%), hyperactivity in 21 (24%), and inattention in 38 (44%). Clinical levels of internalizing and externalizing problems were observed in 21 (24%) and 13 (15%) respectively. Over a third of males scored more than two measures of emotional, behavioural, or neurodevelopmental problems. Males with mutations at the 3' end of the DMD gene affecting all protein isoforms had higher rates of intellectual disability and clusters of symptoms. INTERPRETATION: Males with DMD are at very high risk of neuropsychiatric disturbance, and this risk appears to increase with mutations at the 3' end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which may require prompt evaluation and early intervention.

Variability in the common genetic architecture of social-communication spectrum phenotypes during childhood and adolescence.

BACKGROUND: Social-communication abilities are heritable traits, and their impairments overlap with the autism continuum. To characterise the genetic architecture of social-communication difficulties developmentally and identify genetic links with the autistic dimension, we conducted a genome-wide screen of social-communication problems at multiple time-points during childhood and adolescence. METHODS: Social-communication difficulties were ascertained at ages 8, 11, 14 and 17 years in a UK population-based birth cohort (Avon Longitudinal Study of Parents and Children; N ≤ 5,628) using mother-reported Social Communication Disorder Checklist scores. Genome-wide Complex Trait Analysis (GCTA) was conducted for all phenotypes. The time-points with the highest GCTA heritability were subsequently analysed for single SNP association genome-wide. Type I error in the presence of measurement relatedness and the likelihood of observing SNP signals near known autism susceptibility loci (co-location) were assessed via large-scale, genome-wide permutations. Association signals (P ≤ 10-5) were also followed up in Autism Genetic Resource Exchange pedigrees (N = 793) and the Autism Case Control cohort (Ncases/Ncontrols = 1,204/6,491). RESULTS: GCTA heritability was strongest in childhood (h2(8 years) = 0.24) and especially in later adolescence (h2(17 years) = 0.45), with a marked drop during early to middle adolescence (h2(11 years) = 0.16 and h2(14 years) = 0.08). Genome-wide screens at ages 8 and 17 years identified for the latter time-point evidence for association at 3p22.2 near SCN11A (rs4453791, P = 9.3 × 10-9; genome-wide empirical P = 0.011) and suggestive evidence at 20p12.3 at PLCB1 (rs3761168, P = 7.9 × 10-8; genome-wide empirical P = 0.085). None of these signals contributed to risk for autism. However, the co-location of population-based signals and autism susceptibility loci harbouring rare mutations, such as PLCB1, is unlikely to be due to chance (genome-wide empirical Pco-location = 0.007). CONCLUSIONS: Our findings suggest that measurable common genetic effects for social-communication difficulties vary developmentally and that these changes may affect detectable overlaps with the autism spectrum.

Testing the construct validity of proposed criteria for DSM-5 autism spectrum disorder.

OBJECTIVE: To use confirmatory factor analysis to test the construct validity of the proposed DSM-5 symptom model of autism spectrum disorder (ASD), in comparison to alternative models, including that described in DSM-IV-TR. METHOD: Participants were 708 verbal children and young persons (mean age, 9.5 years) with mild to severe autistic difficulties. Autistic symptoms were measured using the Developmental, Dimensional and Diagnostic interview (3Di). The fit of the two-factor DSM-5 model, which has a social communication and a restricted, repetitive behavior (RRB) factor, was compared with that of alternative models. In one half of the sample, properties of the DSM-5 model were examined to investigate the validity of specific diagnostic criteria, informing the development of a better fitting DSM-5 model. This was then cross-validated in the remaining "hold-out" half of the sample; and its stability was tested across groups defined by age, sex, and symptom severity. RESULTS: The DSM-5 model was superior to the three-factor DSM-IV-TR model. It was improved by the removal of items measuring "play and imagination" and "stereotyped and repetitive use of language." A scale measuring sensory abnormalities was added to the model, and loaded onto its RRB factor. This DSM-5 model fit well in the hold-out sample; was stable across age and sex; and fit adequately in those with clinical and sub-threshold autistic presentations. CONCLUSIONS: Among higher-functioning individuals, ASD is a dyad, not a triad, with distinct social communication and repetitive behavior dimensions. As suggested in the proposed DSM-5 criteria, sensory abnormalities are part of the RRB symptom cluster.

High-functioning autism and Asperger's disorder: utility and meaning for families.

We used framework analysis to investigate the utility of pervasive developmental disorder diagnoses, interviewing young people (aged 9-16 years) with high-functioning autistic disorder (AD) and Asperger's disorder (AsD), and their parents. Twenty two participants from ten families described both gains and costs resulting from diagnosis. Perceived advantages of AD and AsD diagnosis were increased understanding and practical support, and parental empowerment. Disadvantages included the effects of stigma and concerns about validity. Participants tended to consider AsD and AD as interchangeable terms. Findings suggest that the utility of AD and AsD depends upon both their validity and how these diagnoses are received in their cultural, economic and legislative context. Improvement of post-diagnostic services will improve the utility of AD and AsD.

Links between co-occurring social-communication and hyperactive-inattentive trait trajectories.

OBJECTIVE: There is overlap between an autistic and hyperactive-inattentive symptomatology when studied cross-sectionally. This study is the first to examine the longitudinal pattern of association between social-communication deficits and hyperactive-inattentive symptoms in the general population, from childhood through adolescence. We explored the interrelationship between trajectories of co-occurring symptoms, and sought evidence for shared prenatal/perinatal risk factors. METHOD: Study participants were 5,383 singletons of white ethnicity from the Avon Longitudinal Study of Parents and Children (ALSPAC). Multiple measurements of hyperactive-inattentive traits (Strengths and Difficulties Questionnaire) and autistic social-communication impairment (Social Communication Disorder Checklist) were obtained between 4 and 17 years. Both traits and their trajectories were modeled in parallel using latent class growth analysis (LCGA). Trajectory membership was subsequently investigated with respect to prenatal/perinatal risk factors. RESULTS: LCGA analysis revealed two distinct social-communication trajectories (persistently impaired versus low-risk) and four hyperactive-inattentive trait trajectories (persistently impaired, intermediate, childhood-limited and low-risk). Autistic symptoms were more stable than those of attention-deficit/hyperactivity disorder (ADHD) behaviors, which showed greater variability. Trajectories for both traits were strongly but not reciprocally interlinked, such that the majority of children with a persistent hyperactive-inattentive symptomatology also showed persistent social-communication deficits but not vice versa. Shared predictors, especially for trajectories of persistent impairment, were maternal smoking during the first trimester, which included familial effects, and a teenage pregnancy. CONCLUSIONS: Our longitudinal study reveals that a complex relationship exists between social-communication and hyperactive-inattentive traits. Patterns of association change over time, with corresponding implications for removing exclusivity criteria for ASD and ADHD, as proposed for DSM-5.

Social cognition and conduct problems: a developmental approach.

OBJECTIVE: To estimate associations between trajectories of conduct problems and social-cognitive competences through childhood into early adolescence. METHOD: A prospective population-based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC) recruited in the prenatal period (13,988 children alive at 12 months) formed the basis for the current study. Socio-emotional and pragmatic language competences were examined in relation to conduct problem development in a group of 6,047 children with no known autistic-spectrum disorders. Specifically, conduct problem trajectories (low, childhood-limited, adolescent-onset, and early-onset persistent) identified using maternal prospective reports (Strengths and Difficulties Questionnaire: ages 4 through 13 years) were contrasted. Demographic confounders, child verbal IQ and other psychopathologies were controlled. RESULTS: In contrast to individuals with low conduct problem levels, all conduct problem groups presented with difficulties in both social-cognitive domains. Deficits among those with early-onset persistent conduct problems were particularly apparent: 40.6% of boys and 24.3% of girls with persistent conduct problems met impairment criteria for one or other social-cognitive domain. Associations remained robust after controlling for demographic confounders (maternal age at birth, low SES, maternal education), child verbal IQ, and internalizing and inattention symptoms. For boys, results indicated that overlaps with overactivity symptoms may contribute problems with pragmatic language; this was not the case for girls or for socio-emotional difficulties. CONCLUSIONS: Findings have far-reaching implications for children with conduct problems, particularly those with early onset and persistent difficulties. Traditional parent training interventions are likely to be bolstered by strategies that help to develop the social competences of these children.

The construction and validation of a short form of the developmental, diagnostic and dimensional interview.

We aimed to construct and validate a shortened form of the developmental, diagnostic and dimensional interview (3Di), a parent report interview for assessing and diagnosing autistic spectrum disorders (ASDs). Data from 879 children and young people were used. In half of the sample (n = 440) reliability analysis was used to identify 3Di items that best measured each dimension of the autism triad. This informed the construction of a shortened (53 item) 3Di, which was then validated on subjects not used in the reliability analysis (n = 439). This involved comparison with scores from the original 3Di algorithm and, in a subsample (n = 29), with the autism diagnostic interview-revised (ADI-R). Agreement of the new shortened 3Di with the 3Di's original algorithm was excellent in both dimensional and categorical terms. Agreement on caseness (27 out of 29) with the ADI-R was also strong. The new 3Di short version is less than half as long as the original version and outputs very similar scores. It will be useful to clinicians and researchers for obtaining a dimensional autism assessment in less than 45 minutes.

Research review: What is the association between the social-communication element of autism and repetitive interests, behaviours and activities?

Autism is currently conceptualised as a unitary disorder, in which social-communication impairments are found alongside repetitive interests, behaviours and activities (RIBAs). This relies upon the validity of the assumption that social-communication impairments and RIBAs co-occur at an above chance level as a result of sharing underlying causes. In the current review it is argued that the evidence for this assumption is scarce: the very great majority of RIBA research has not been intended for or suited to its examination. In fact only three studies are fit to address directly the question of the relationship between social-communication impairment and RIBAs, and these contradict each other. In consequence, further relevant evidence was sought in the behavioural and genetic literature. This approach suggested that the correlation between social-communication impairments and RIBAs has been exaggerated in the current consensus about the autism syndrome, and that these aspects of autism may well share largely independent underlying causes. Some clinical and research implications are discussed.

Measuring autistic traits: heritability, reliability and validity of the Social and Communication Disorders Checklist.

BACKGROUND: Autistic traits are widely distributed in the general population, but the boundaries of the autistic spectrum are unclear. Whole-population surveys of unselected samples of children are hampered by the lack of appropriate screening instruments. AIMS: To assess whether the Social and Communication Disorders Checklist (SCDC) fulfils the need for a sensitive measure of autistic traits, which can be completed in a few minutes and which measures heritable characteristics in both males and females. METHOD: A12-item scale, the SCDC, was completed by three independent samples drawn from a twin register, a group with Turner syndrome and children with a diagnosis of autistic-spectrum disorder attending clinics. The data were used to establish the heritability, reliability and validity of the checklist. RESULTS: Traits measured by the SCDC were highly heritable in both genders (0.74). Internal consistency was excellent (0.93) and test - retest reliability high (0.81). Discriminant validity between pervasive developmental disorder and other clinical groups was good, discrimination from non-clinical samples was better; sensitivity (0.90), specificity (0.69). CONCLUSIONS: The SCDC is a unique and efficient first-level screening questionnaire for autistic traits.