Long-term social skills group training for children and adolescents with autism spectrum disorder: a randomized controlled trial.

Social skills group training (SSGT) is widely used for intellectually able children and adolescents with autism spectrum disorder (ASD). Previous studies indicate small to moderate effects on social communication capacities. The duration of most available programs is relatively short, and extended training might lead to further improvement. This randomized controlled trial compared an extended 24-week version of the SSGT program KONTAKT with standard care. The weekly sessions gradually shifted in content from acquisition of new skills to real-world application of the acquired skills. A total of 50 participants with ASD (15 females; 35 males) aged 8-17 years were included. The study was conducted at two child and adolescent psychiatry outpatient units in Sweden. The primary outcome was the Social Responsiveness Scale-Second Edition (SRS-2) rated by parents and blinded teachers. Secondary outcomes included parent- and teacher-rated adaptive behaviors, trainer-rated global functioning and clinical severity, and self-reported child and caregiver stress. Assessments were made at baseline, posttreatment, and at 3-months follow-up. Parent-rated SRS-2 scores indicated large effects posttreatment [- 19.2; 95% CI - 29.9 to - 8.5; p < .001, effect size (ES) = 0.76], which were maintained at follow-up (- 20.7; 95% CI - 31.7 to - 9.7; p < .0001, ES = 0.82). These estimates indicate substantially larger improvement than previously reported for shorter SSGT. However, the effects on teacher-rated SRS-2 and most secondary outcomes did not reach statistical significance. Our results suggest added benefits of extended SSGT training, implying that service providers might reach better results by optimizing the delivery of SSGT.

Copy Number Variation Analysis of 100 Twin Pairs Enriched for Neurodevelopmental Disorders.

Hundreds of penetrant risk loci have been identified across different neurodevelopmental disorders (NDDs), and these often involve rare (<1% frequency) copy number variations (CNVs), which can involve one or more genes. Monozygotic (MZ) twin pairs are long thought to share 100% of their genomic information. However, genetic differences in the form of postzygotic somatic variants have been reported recently both in typically developing (TD) and in clinically discordant MZ pairs. We sought to investigate the contribution of rare CNVs in 100 twin pairs enriched for NDD phenotypes with a particular focus on postzygotic CNVs in MZ pairs discordant for autism spectrum disorder (ASD) using the Illumina Infinium PsychArray. In our sample, no postzygotic de novo CNVs were found in 55 MZ twin pairs, including the 13 pairs discordant for ASD. We did detect a higher rate of CNVs overlapping genes involved in disorders of the nervous system, such as a rare deletion affecting HNRNPU, in MZ pairs discordant and concordant for ASD in comparison with TD pairs (p = .02). Our results are in concordance with earlier findings that postzygotic de novo CNV events are typically rare in genomic DNA derived from saliva or blood, and suggests that the discordance of NDDs in our sample of twins is not explained by discordant CNVs. Still, studies investigating postzygotic variation in MZ discordant twins using DNA from different tissues and single cells and higher resolution genomics are needed in the future.

Standardization and cross-cultural comparisons of the Swedish Conners 3® rating scales.

PURPOSE: The Conners Rating Scales are widely used in research and clinical practice for measuring attention deficit/hyperactivity disorder (ADHD) and associated problem behaviors, but country-specific norms are seldom collected. The current study presents the standardization of the Swedish Conners 3® Rating Scales. In addition, we compared the Swedish norms to those collected in the U.S. and Germany. MATERIAL AND METHODS: The study included altogether 3496 ratings of children and adolescents aged 6-18 years from population-based samples. RESULTS: The scores obtained for the Swedish Conners 3® showed satisfactory to excellent internal consistency for most subscales and excellent test-retest reliability. Across-informant correlations were modest. Cross-country comparisons revealed that aggression symptoms rated by teachers and ADHD symptoms rated by parents differed between Sweden, Germany and the U.S. Executive functioning deficits also varied as a function of rater and country, with German and Swedish teachers reporting increasing behavior problems with age, whereas a decrease was observed in the U.S. For some subscales, the observed cross-cultural differences were large enough for a child to be classified as being within the normal range (t-score <60) in one country and within the clinical range (t-score > 70) in another country. CONCLUSION: The present study shows that the Swedish adaptation of the Conners 3® provides consistent and reproducible scores. However, across-informant ratings were only modest and significant cross-cultural differences in scoring were observed. This emphasizes the need for multi-informant assessment as well as for national norms for rating instruments commonly used within child and adolescent psychiatry research and clinical settings.

The Interrater Reliability of the Autism Diagnostic Interview-Revised (ADI-R) in Clinical Settings.

BACKGROUND: The Autism Diagnostic Interview-Revised (ADI-R) is considered a first choice assessment tool in autism spectrum disorder. Nevertheless, despite its wide use in psychiatric practice and recommendations by various clinical guidelines, its interrater reliability has predominantly been confirmed in research settings by specially trained, research reliability interviewers. The reliability of ADI-R assessments among clinicians has not yet been established. Therefore, this study examined the spontaneous interrater reliability of the ADI-R in a naturalistic clinical multicenter setting. SAMPLING AND METHODS: Ten video-recorded ADI-R administrations were rated by 5 different raters each from a pool of 11 raters affiliated to 8 different clinical sites. RESULTS: The interrater reliability for the 12 diagnostic criteria operationalizing autism spectrum disorders according to DSM-IV/ICD-10 in the ADI-R algorithms ranged between G(q,k) (analogous to intraclass correlations) = 0.96 and 0.99 for reciprocal social interaction, 0.96 and 1.00 for communication, and 0.91 and 0.97 for repetitive and restricted behavior. Reliability of diagnostic classification was ĸCohen 0.83. CONCLUSIONS: The findings endorse the psychometric properties of ADI-R in terms of interrater reliability previously reported from research settings and support their generalization to common clinical settings. Limitations of this study include an unbalanced sample composition.

Facial affect recognition in autism, ADHD and typical development.

INTRODUCTION: Autism spectrum disorder (ASD) and Attention-Deficit Hyperactivity Disorder (ADHD) have been associated with facial affect recognition (FAR) alterations. METHODS: This study examined accuracy and response times for general and specific FAR in whole face and eye-region stimuli. FAR was assessed in matched samples of children and adolescents with ASD (n = 35), ADHD (n = 32), and typical development (TD) (n = 32) aged 8.6-15.9 years (M = 11.6; SD = 2.0). RESULTS: Compared to TD, the ASD group performed less accurate and showed longer response times for general and specific FAR, mostly driven by problems in neutral and happy face identification. The ADHD group responded faster than the ASD group for global FAR. No differences between ADHD and TD were found. Attentional distractibility had a significant effect on FAR performance in ASD and ADHD. CONCLUSIONS: Findings confirm FAR alterations in ASD, but not ADHD, and endorse effects of attentional distractibility on FAR in ASD and ADHD. FAR and attention function training is clinically meaningful in ASD. Future studies should include control for visual attention and facial configuration skills, use naturalistic FAR material and also investigate implicit FAR.

The objectivity of the Autism Diagnostic Observation Schedule (ADOS) in naturalistic clinical settings.

The Autism Diagnostic Observation Schedule (ADOS) is a first-choice diagnostic tool in autism spectrum disorder (ASD). Excellent interpersonal objectivity (interrater reliability) has been demonstrated for the ADOS under optimal conditions, i.e., within groups of highly trained "research reliable" examiners in research setting. We investigated the spontaneous interrater reliability among clinically trained ADOS users across multiple sites in clinical routine. Forty videotaped administrations of the ADOS modules 1-4 were rated by five different raters each from a pool of in total 15 raters affiliated to 13 different clinical sites. G(q,k) coefficients (analogous to intraclass correlations), kappas (ĸ) and percent agreement (PA) were calculated. The median interrater reliability for items across the four modules was G(q,k) = .74-.83, with the single ADOS items ranging from .23 to .94. G(q,k) for total scores was .85-.92. For diagnostic classification (ASD/non-spectrum), PA was 64-82 % and Fleiss' ĸ .19-.55. Objectivity was lower for pervasive developmental disorder not otherwise specified and non-spectrum diagnoses as compared to autism. Interrater reliabilities of the ADOS items and domain totals among clinical users across multiple sites were in the same range as previously reported for research reliable users, while the one for diagnostic classification was lower. Differences in sample characteristics, rater skills and statistics compared with previous studies are discussed. Findings endorse the objectivity of the ADOS in naturalistic clinical settings, but also pinpoint its limitations and the need and value of adequate and continuous rater training.

The EU-Emotion Stimulus Set: A validation study.

The EU-Emotion Stimulus Set is a newly developed collection of dynamic multimodal emotion and mental state representations. A total of 20 emotions and mental states are represented through facial expressions, vocal expressions, body gestures and contextual social scenes. This emotion set is portrayed by a multi-ethnic group of child and adult actors. Here we present the validation results, as well as participant ratings of the emotional valence, arousal and intensity of the visual stimuli from this emotion stimulus set. The EU-Emotion Stimulus Set is available for use by the scientific community and the validation data are provided as a supplement available for download.

The Roots of Autism and ADHD Twin Study in Sweden (RATSS).

Neurodevelopmental disorders affect a substantial minority of the general population. Their origins are still largely unknown, but a complex interplay of genetic and environmental factors causing disturbances of the central nervous system's maturation and a variety of higher cognitive skills is presumed. Only limited research of rather small sample size and narrow scope has been conducted in neurodevelopmental disorders using a twin-differences design. The Roots of Autism and ADHD Twin Study in Sweden (RATSS) is an ongoing project targeting monozygotic twins discordant for categorical or dimensional autistic and inattentive/hyperactive-impulsive phenotypes as well as other neurodevelopmental disorders, and typically developing twin controls. Included pairs are 9 years of age or older, and comprehensively assessed for psychopathology, medical history, neuropsychology, and dysmorphology, as well as structural, functional, and molecular brain imaging. Specimens are collected for induced pluripotent (iPS) and neuroepithelial stem cells, genetic, gut bacteria, protein-/monoamine, and electron microscopy analyses. RATSS's objective is to generate a launch pad for novel surveys to understand the complexity of genotype-environment-phenotype interactions in autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD). By October 2013, RATSS had collected data from 55 twin pairs, among them 10 monozygotic pairs discordant for autism spectrum disorder, seven for ADHD, and four for other neurodevelopmental disorders. This article describes the design, recruitment, data collection, measures, collected pairs' characteristics, as well as ongoing and planned analyses in RATSS. Potential gains of the study comprise the identification of environmentally mediated biomarkers, the emergence of candidates for drug development, translational modeling, and new leads for prevention of incapacitating outcomes.

Inclusive practice for students with neurodevelopmental disorders in Sweden.

'Inclusion' aims to achieve adaptation of the environment to the diverse prerequisites and needs of individuals, instead of demanding of individuals to cope with the challenges of a given context themselves exclusively. All Scandinavian countries have made formal decisions to enhance inclusive practice for children and adolescents with disabilities in educational settings, seeking to implement international conventions. We investigated current inclusive practice for students with neurodevelopmental disorders (NDDs) in Swedish primary, secondary and high-schools using the 61-item INCLUSIO scale among N=4778 school staff with educational responsibilities in 68 public and private schools across 11 municipalities. Overall, school staff reported not to be well prepared to teach students with NDDs and that their school's implementation of concrete inclusive practice was limited. Findings indicate a gap between inclusive educational ambitions and current practice for students with NDDs. Enriched teacher education and supervision for NDDs, a shift in pedagogical views of NDDs and better collaboration between community services, as well as systematic evidence-based implementation plans driven by policy makers and educational authorities may help improve inclusive practice.

Proof of concept: The TRANSITION program for young adults with autism spectrum disorder and/or attention deficit hyperactivity disorder.

BACKGROUND: The support needs of people with neurodevelopmental disorders are not sufficiently met during the initial years of adulthood. AIM: To evaluate feasibility and preliminary effects of a novel programme designed to empower young adults with autism spectrum disorder (ASD) and/or attention deficit hyperactivity disorder (ADHD) to make progress within significant life domains (i.e. work, education, finance, housing/household management, health, leisure/participation in society, and relationships/social network). MATERIAL AND METHOD: TRANSITION is a 24-week programme that combines group-based workshops with personalised support based on goal attainment scaling. The study enrolled 26 young adults (50% females; age 17-24 years) in the normative intellectual range, diagnosed with ASD (n = 8), ADHD (n = 4), or both (n = 14). The intervention was delivered by the regular staff of publicly funded psychiatric services in Stockholm, Sweden. RESULTS: The programme was possible to implement with minor deviations from the manual. Participants and staff generally viewed the intervention positively, but also provided feedback to guide further improvement. There was a high degree of attendance throughout, with 21 participants (81%) completing the programme. All completers exceeded their predefined goal expectations within at least one domain. CONCLUSIONS: The TRANSITION-programme is a promising concept that deserves further evaluation.

Enhanced social learning of threat in adults with autism.

BACKGROUND: Recent theories have linked autism to challenges in prediction learning and social cognition. It is unknown, however, how autism affects learning about threats from others "demonstrators" through observation, which contains predictive learning based on social information. The aims of this study are therefore to investigate social fear learning in individual with autism spectrum disorder (ASD) and to examine whether typically developing social cognition is necessary for successful observational learning. METHODS: Adults with ASD (n = 23) and neurotypical controls (n = 25) completed a social fear learning (SFL) procedure in which participants watched a "demonstrator" receiving electrical shocks in conjunction with a previously neutral conditioned stimulus (CS+), but never with a safe control stimulus (CS-). Skin conductance was used to measure autonomic responses of learned threat responses to the CS+ versus CS-. Visual attention was measured during learning using eye tracking. To establish a non-social learning baseline, each participant also underwent a test of Pavlovian conditioning. RESULTS: During learning, individuals with ASD attended less to the demonstrator's face, and when later tested, displayed stronger observational, but not Pavlovian, autonomic indices of learning (skin conductance) compared to controls. In controls, both higher levels of attention to the demonstrator's face and trait empathy predicted diminished expressions of learning during test. LIMITATIONS: The relatively small sample size of this study and the typical IQ range of the ASD group limit the generalizability of our findings to individuals with ASD in the average intellectual ability range. CONCLUSIONS: The enhanced social threat learning in individuals with ASD may be linked to difficulties using visual attention and mental state attributions to downregulate their emotion.

Association between Copy Number Variation and Response to Social Skills Training in Autism Spectrum Disorder.

Challenges in social communication and interaction are core features of autism spectrum disorder (ASD) for which social skills group training (SSGT) is a commonly used intervention. SSGT has shown modest and heterogeneous effects. One of the major genetic risk factors in ASD is rare copy number variation (CNV). However, limited information exists whether CNV profiles could be used to aid intervention decisions. Here, we analyzed the rare genic CNV carrier status for 207 children, of which 105 received SSGT and 102 standard care as part of a randomized clinical trial for SSGT. We found that being a carrier of rare genic CNV did not have an impact on the SSGT outcome measured by the parent-report Social Responsiveness Scale (SRS). However, when stratifying by pathogenicity and size of the CNVs, we identified that carriers of clinically significant and large genic CNVs (>500 kb) showed inferior SRS outcomes at post-intervention (P = 0.047 and P = 0.036, respectively) and follow-up (P = 0.008 and P = 0.072, respectively) when adjusting for standard care effects. Our study provides preliminary evidence that carriers of clinically significant and large genic CNVs might not benefit as much from SSGT as non-carriers. Our results indicate that genetic information might help guide the modifications of interventions in ASD.

Emotion recognition training in autism spectrum disorder: A systematic review of challenges related to generalizability.

PURPOSE: To assess the generalizability of findings from randomized controlled trials (RCTs) evaluating emotion recognition (ER) training for children and adolescents with autism spectrum disorder (ASD). METHODS: We present a systematic review and narrative synthesis of the determinants of external validity in RCTs on ER training. Generalizability of the findings across situations, populations, settings, treatment delivery, and intervention formats was considered. RESULTS: We identified 13 eligible studies. Participants were predominantly boys with ASD in the normative IQ range (IQ > 70), with an age span from 4 to 18 years across studies. Interventions and outcome measures were highly variable. Several studies indicated that training may improve ER, but it is still largely unknown to what extent training effects are translated to daily social life. CONCLUSION: The generalizability of findings from currently available RCTs remains unclear. This underscores the importance of involving children with ASD and their caregivers in informed treatment decisions.

Dynamical features in fetal and postnatal zinc-copper metabolic cycles predict the emergence of autism spectrum disorder.

Metals are critical to neurodevelopment, and dysregulation in early life has been documented in autism spectrum disorder (ASD). However, underlying mechanisms and biochemical assays to distinguish ASD cases from controls remain elusive. In a nationwide study of twins in Sweden, we tested whether zinc-copper cycles, which regulate metal metabolism, are disrupted in ASD. Using novel tooth-matrix biomarkers that provide direct measures of fetal elemental uptake, we developed a predictive model to distinguish participants who would be diagnosed with ASD in childhood from those who did not develop the disorder. We replicated our findings in three independent studies in the United States and the UK. We show that three quantifiable characteristics of fetal and postnatal zinc-copper rhythmicity are altered in ASD: the average duration of zinc-copper cycles, regularity with which the cycles recur, and the number of complex features within a cycle. In all independent study sets and in the pooled analysis, zinc-copper rhythmicity was disrupted in ASD cases. In contrast to controls, in ASD cases, the cycle duration was shorter (F = 52.25, P < 0.001), regularity was reduced (F = 47.99, P < 0.001), and complexity diminished (F = 57.30, P < 0.001). With two distinct classification models that used metal rhythmicity data, we achieved 90% accuracy in classifying cases and controls, with sensitivity to ASD diagnosis ranging from 85 to 100% and specificity ranging from 90 to 100%. These findings suggest that altered zinc-copper rhythmicity precedes the emergence of ASD, and quantitative biochemical measures of metal rhythmicity distinguish ASD cases from controls.

Social Skills Training for Children and Adolescents With Autism Spectrum Disorder: A Randomized Controlled Trial.

OBJECTIVE: Social skills group training (SSGT) for children and adolescents with autism spectrum disorder (ASD) is widely applied, but effectiveness in real-world practice has not yet been properly evaluated. This study sought to bridge this gap. METHOD: This 12-week pragmatic randomized controlled trial of SSGT compared to standard care alone was conducted at 13 child and adolescent psychiatry outpatient units in Sweden. Twelve sessions of manualized SSGT ("KONTAKT") were delivered by regular clinical staff. Participants (N = 296; 88 females and 208 males) were children (n = 172) and adolescents (n = 124) aged 8 to 17 years with ASD without intellectual disability. The primary outcome was the Social Responsiveness Scale rating by parents and blinded teachers. Secondary outcomes included parent- and teacher-rated adaptive behaviors, trainer-rated global functioning and clinical severity, and self-reported child and caregiver stress. Assessments were made at baseline, posttreatment, and 3-month follow-up. Moderator analyses were conducted for age and gender. RESULTS: Significant treatment effects on the primary outcome were limited to parent ratings for the adolescent subgroup (posttreatment: -8.3; 95% CI = -14.2 to -1.9; p = .012, effect size [ES] = 0.32; follow-up: -8.6; 95% CI = -15.4 to -1.8; p = .015, ES = 0.33) and females (posttreatment: -8.9; 95% CI = -16.2 to -1.6; p = .019, ES = 0.40). Secondary outcomes indicated moderate effects on adaptive functioning and clinical severity. CONCLUSION: SSGT for children and adolescents with ASD in regular mental health services is feasible and safe. However, the modest and inconsistent effects underscore the importance of continued efforts to improve SSGT beyond current standards. CLINICAL TRIAL REGISTRATION INFORMATION: Social Skills Group Training ("KONTAKT") for Children and Adolescent With High-functioning Autism Spectrum Disorders; https://clinicaltrials.gov/; NCT01854346.

Fetal and postnatal metal dysregulation in autism.

Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.

Basic and complex emotion recognition in children with autism: cross-cultural findings.

BACKGROUND: Children with autism spectrum conditions (ASC) have emotion recognition deficits when tested in different expression modalities (face, voice, body). However, these findings usually focus on basic emotions, using one or two expression modalities. In addition, cultural similarities and differences in emotion recognition patterns in children with ASC have not been explored before. The current study examined the similarities and differences in the recognition of basic and complex emotions by children with ASC and typically developing (TD) controls across three cultures: Israel, Britain, and Sweden. METHODS: Fifty-five children with high-functioning ASC, aged 5-9, were compared to 58 TD children. On each site, groups were matched on age, sex, and IQ. Children were tested using four tasks, examining recognition of basic and complex emotions from voice recordings, videos of facial and bodily expressions, and emotional video scenarios including all modalities in context. RESULTS: Compared to their TD peers, children with ASC showed emotion recognition deficits in both basic and complex emotions on all three modalities and their integration in context. Complex emotions were harder to recognize, compared to basic emotions for the entire sample. Cross-cultural agreement was found for all major findings, with minor deviations on the face and body tasks. CONCLUSIONS: Our findings highlight the multimodal nature of ER deficits in ASC, which exist for basic as well as complex emotions and are relatively stable cross-culturally. Cross-cultural research has the potential to reveal both autism-specific universal deficits and the role that specific cultures play in the way empathy operates in different countries.