Parent-Child Interactions May Help to Explain Relations Between Parent Characteristics and Clinically Observed Child Autistic Behaviours.

The importance of supporting parent-child interactions has been noted in the context of prodromal autism, but little consideration has been given to the possible contributing role of parental characteristics, such as psychological distress. This cross-sectional study tested models in which parent-child interaction variables mediated relations between parent characteristics and child autistic behaviour in a sample of families whose infant demonstrated early signs of autism (N = 103). The findings suggest that associations between parent characteristics (psychological distress; aloofness) and child autistic behaviours may be mediated by the child's inattentiveness or negative affect during interactions. These findings have important implications in developing and implementing interventions in infancy which target the synchrony of parent-child interaction with the goal to support children's social communication development.

The effect of oxytocin nasal spray on social interaction in young children with autism: a randomized clinical trial.

Early supports to enhance social development in children with autism are widely promoted. While oxytocin has a crucial role in mammalian social development, its potential role as a medication to enhance social development in humans remains unclear. We investigated the efficacy, tolerability, and safety of intranasal oxytocin in young children with autism using a double-blind, randomized, placebo-controlled, clinical trial, following a placebo lead-in phase. A total of 87 children (aged between 3 and 12 years) with autism received 16 International Units (IU) of oxytocin (n = 45) or placebo (n = 42) nasal spray, morning and night (32 IU per day) for twelve weeks, following a 3-week placebo lead-in phase. Overall, there was no effect of oxytocin treatment over time on the caregiver-rated Social Responsiveness Scale (SRS-2) (p = 0.686). However, a significant interaction with age (p = 0.028) showed that for younger children, aged 3-5 years, there was some indication of a treatment effect. Younger children who received oxytocin showed improvement on caregiver-rated social responsiveness ( SRS-2). There was no other evidence of benefit in the sample as a whole, or in the younger age group, on the clinician-rated Clinical Global Improvement Scale (CGI-S), or any secondary measure. Importantly, placebo effects in the lead-in phase were evident and there was support for washout of the placebo response in the randomised phase. Oxytocin was well tolerated, with more adverse side effects reported in the placebo group. This study suggests the need for further clinical trials to test the benefits of oxytocin treatment in younger populations with autism.Trial registration www.anzctr.org.au (ACTRN12617000441314).

Exploring the Experience of Seeking an Autism Diagnosis as an Adult.

Background: Emerging research suggests that seeking an autism diagnosis as an adult is usually difficult and time-consuming but brings relief once a diagnosis is made. This study explored the experience of the pathway to an autism diagnosis during adulthood for adults living in Australia. Methods: We conducted a qualitative phenomenological study and interviewed 13 adults who identified as autistic about their pathway to autism diagnosis in their mode of choice. Spoken interviews were transcribed verbatim, and transcripts were analyzed by using a thematic approach. Results: Data analysis resulted in 6 themes and 20 meaning units that described the experiences of adults seeking an autism diagnosis in Australia. These themes involved two interwoven journeys that spanned before, during, and after the diagnostic process. The personal journey involved feeling different, considering autism, and living as autistic, whereas the clinical journey involved missed opportunities, varied diagnostic experiences, and absent supports. Conclusions: Given the potential benefits for adults obtaining a formal autism diagnosis and accessing post-diagnostic supports, it is important that health professionals and governments collaborate to reduce access barriers and ensure adequate services are available. The findings from this study informed the development of Australia's national guideline for autism diagnosis.

Why is this an important issue?: The experience of being diagnosed as autistic as an adult is not well understood, particularly in Australia. Research from other places, such as New Zealand and the United Kingdom, suggests that receiving an autism diagnosis in adulthood is difficult and time-consuming, but brings relief. We do not know whether this is the same for adults in Australia. What was the purpose of this study?: This study aimed at exploring the experience of seeking an autism diagnosis during adulthood in Australia. What did the researchers do?: We conducted interviews with 13 adults who identified as autistic about their pathway to an autism diagnosis. Three sets of interview questions were used, depending on whether they had already obtained an autism diagnosis, were going through the assessment process, or were self-diagnosed. Adults completed the interview in their mode of choice. Spoken interviews were transcribed word-for-word, and the transcripts were analyzed to identify common themes. What were the results of the study?: We identified six themes that described the experiences of adults seeking an autism diagnosis in Australia. These themes involved two related journeys that spanned before, during, and after the diagnostic process. The personal journey involved feeling different, considering autism, and living as autistic. The clinical journey involved missed opportunities, varied diagnostic experiences, and absent supports. Before starting the diagnostic process in adulthood, participants described always feeling different and many missed opportunities to receive an autism diagnosis in their younger years.During the diagnostic process, participants described beginning to consider whether they were autistic and the varied pathways they underwent to confirm this. After the diagnostic process, participants described their experiences of living as autistic and a lack of post-diagnostic supports tailored to their needs. What do these findings add to what was already known?: Our findings were similar to previous research findings from other countries, including the complex journey to diagnosis, relief and understanding on identifying as autistic, and lack of post-diagnostic services. However, to our knowledge, this is the first qualitative study to explore the experiences of adults seeking an autism diagnosis in Australia. Further, we included participants who did not have a formal diagnosis of autism. This group of people is often excluded from autism research, and their experiences of seeking an autism diagnosis are largely unknown. What are potential weaknesses in the study?: The weaknesses of our study included recruiting a relatively small sample of mostly Caucasian females, and we did not consult with our study participants or other autistic adults to see whether our final themes aligned well with their experience. However, no new findings emerged in later interviews and our findings were similar to international literature. Future research should recruit more diverse groups of autistic adults and involve greater levels of autistic input. How will these findings help autistic adults now or in the future?: Our findings informed the development of the "National Guideline for the Assessment and Diagnosis of Autism Spectrum Disorder in Australia," a first step toward improving autism diagnosis in Australia.

Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis.

Importance: Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date. Objective: To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period. Design, Setting, and Participants: This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020. Interventions: Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians. Main Outcomes and Measures: Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05. Results: Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group. Conclusions and Relevance: Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years. Trial Registration: http://anzctr.org.au identifier: ACTRN12616000819426.

Randomised Controlled Trial of a Therapeutic Playgroup for Children with Developmental Delays.

A single-blind randomised control trial investigated the effectiveness of the Learn, Engage and Play (LEaP) playgroup. Seventy-one children with developmental delay were randomly allocated to an 8-week LEaP playgroup or control group and followed up at 12 and 28 weeks. On the primary outcome measure, LEaP demonstrated significant within group changes at 28 weeks (parenting distress p = 0.018) but no between group changes. On secondary outcome measures, at 12 weeks LEaP produced significantly better outcomes than control in goal achievement (performance p = 0.022; function p = 0.008) and family-support (p = 0.024), with LEaP continuing to demonstrate significantly better goal achievement (child performance p = 0.042; function p = 0.012) at 28 weeks. Findings indicate LEaP may assist in improving family-support and goal achievement outcomes for children with developmental delays.

Investigating associations between birth order and autism diagnostic phenotypes.

BACKGROUND: Birth order effects have been linked to variability in intelligence, educational attainment and sexual orientation. First- and later-born children have been linked to an increased likelihood of an Autism Spectrum Disorder (ASD) diagnosis, with a smaller body of evidence implicating decreases in cognitive functioning with increased birth order. The present study investigated the potential association between birth order and ASD diagnostic phenotypes in a large and representative population sample. METHODS: Data were obtained from an ongoing prospective diagnostic registry, collected between 1999 and 2017, including children (1-18 years of age, n = 5,404) diagnosed with ASD in the state of Western Australia. Children with ASD were ranked relative to sibling's birth to establish birth order within families at time of ASD diagnosis. Information reported to the registry by health professionals at the time of diagnostic evaluation included demographic and family characteristics, functional abilities and intellectual capacity. RESULTS: Adaptive functioning and intelligence scores decreased with increasing birth order, with later-born children more likely to have an intellectual disability. Compared to first-born children with siblings, first-born children without siblings at the time of diagnosis also exhibited decreased cognitive functioning. CONCLUSIONS: These findings demonstrate for the first time an association between increasing birth order and variability in ASD clinical phenotypes at diagnosis, with potential evidence of reproductive curtailment in children without siblings. Taken together, these findings have significant implications for advancing understanding about the potential mechanisms that contribute to heterogeneity in ASD clinical presentations as a function of birth order and family size.

The Power of Playgroups: Key components of supported and therapeutic playgroups from the perspective of parents.

INTRODUCTION: Playgroups are community-based programs for children and families aiming to improve child outcomes, enhance family and community networks and increase parenting capacity. Despite the prevalence of playgroups in Australian communities there is a lack of research clearly articulating the key components of playgroups, specifically from the perspective of parents attending these groups. This study aimed to identify the key components of supported and therapeutic playgroups impacting on perceived effectiveness from the perspective of parents with a child with a developmental delay and/or disability. METHODS: This study explored the experiences of 23 parents attending supported or therapeutic playgroups using a qualitative interpretive phenomenological approach. Data were collected through three focus groups and seven individual interviews and analysed using Colaizzi's (1978) qualitative method of data analysis. RESULTS: Findings indicated playgroup components that most strongly impacted on perceived effectiveness were feeling accepted; providing opportunities for child development, socialisation and enjoyment; and enhancing parental knowledge and skills. Findings reinforced the importance of family centred practice and facilitating peer support for families of children with developmental delay and/or disability. CONCLUSION: Supported and therapeutic playgroups emerged as a valuable model for parents of children with developmental delays and/or disabilities but require an interplay of specific facilitator, parent and child characteristics to be effective. This study contributes to the understanding of key components of successful supported and therapeutic playgroup models, highlighting the importance of engaging consumers in developing evidence-based meaningful interventions for children with developmental delay and/or disabilities and their families.

Deconstructing the repetitive behaviour phenotype in autism spectrum disorder through a large population-based analysis.

OBJECTIVE: Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD. METHOD: Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM-IV-TR criteria on a 4-point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms. RESULTS: The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non-significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests. CONCLUSIONS: The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions.

Prevalence of Motor Difficulties in Autism Spectrum Disorder: Analysis of a Population-Based Cohort.

Motor impairment is not currently included in the diagnostic criteria or evaluation of autism. This reflects the lack of large-scale studies demonstrating its prominence to advocate for change. We examined the prevalence of motor difficulties at the time of diagnosis in a large sample of children with autism utilizing standardized assessment, and the relationship between motor difficulties, core autism symptomology, and other prominent clinical features. Vineland Adaptive Behavior Scales were administered to children from the Western Australian Register for Autism Spectrum Disorders aged ≤6 years (N = 2,084; 81.2% males, 18.8% females). Prevalence of motor difficulties was quantified based on scores from the motor domain of the Vineland and then compared to other domains of functioning within the Vineland (communication, daily living, and socialization), the DSM criteria, intellectual level, age, and gender. Scores on the Vineland indicated that 35.4% of the sample met criteria for motor difficulties (standard score <70), a rate almost as common as intellectual impairment (37.7%). Motor difficulties were reported by diagnosing clinicians in only 1.34% of cases. Motor difficulties were common in those cases meeting diagnostic criteria for impairments in nonverbal behavior and the presence of restricted and repetitive behaviors. The prevalence of motor difficulties also increased with increasing age of diagnosis (P < 0.001). Findings from the present study highlight the need for further consideration of motor difficulties as a distinct specifier within the diagnostic criteria for ASD. Autism Res 2020, 13: 298-306. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this population-based cohort that included 2,084 children with autism aged ≤6 years, over one-third met the criteria for motor difficulties, a rate almost as common as intellectual disability. This study demonstrates that motor difficulties are a prominent feature of the autism phenotype requiring further consideration in both the diagnostic criteria and evaluation of autism.

The misnomer of 'high functioning autism': Intelligence is an imprecise predictor of functional abilities at diagnosis.

'High functioning autism' is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants (n = 2225, 1-18 years of age) were notified at diagnosis to a prospective register and grouped by presence (n = 1041) or absence (n = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group's adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that 'high functioning autism' is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice.

Effect of Fluoxetine on Obsessive-Compulsive Behaviors in Children and Adolescents With Autism Spectrum Disorders: A Randomized Clinical Trial.

Importance: Selective serotonin receptor inhibitors are prescribed to reduce the severity of core behaviors of autism spectrum disorders, but their efficacy remains uncertain. Objective: To determine the efficacy of fluoxetine for reducing the frequency and severity of obsessive-compulsive behaviors in autism spectrum disorders. Design, Setting, and Participants: Multicenter, randomized, placebo-controlled clinical trial. Participants aged 7.5-18 years with autism spectrum disorders and a total score of 6 or higher on the Children's Yale-Brown Obsessive Compulsive Scale, modified for pervasive developmental disorder (CYBOCS-PDD) were recruited from 3 tertiary health centers across Australia. Enrollment began November 2010 and ended April 2017. Follow-up ended August 2017. Interventions: Participants were randomized to receive fluoxetine (n = 75) or placebo (n = 71). Study medication was commenced at 4 or 8 mg/d for the first week, depending on weight, and then titrated to a maximum dose of 20 or 30 mg/d over 4 weeks. Treatment duration was 16 weeks. Main Outcomes and Measures: The primary outcome was the total score on the CYBOCS-PDD (scores range from 0-20; higher scores indicate higher levels of maladaptive behaviors; minimal clinically important difference, 2 points) at 16 weeks postrandomization, analyzed with a linear regression model adjusted for stratification factors (site, age at baseline, and intellectual disability), with an additional prespecified model that included additional adjustment for baseline score, sex, communication level, and imbalanced baseline and demographic variables. Results: Among the 146 participants who were randomized (85% males; mean age, 11.2 years), 109 completed the trial; 31 in the fluoxetine group and 21 in the placebo group dropped out or did not complete treatment. The mean CYBOCS-PDD score from baseline to 16 weeks decreased in the fluoxetine group from 12.80 to 9.02 points (3.72-point decrease; 95% CI, -4.85 to -2.60) and in the placebo group from 13.13 to 10.89 points (2.53-point decrease; 95% CI, -3.86 to -1.19). The between-group mean difference at 16 weeks was -2.01 (95% CI, -3.77 to -0.25; P = .03) (adjusted for stratification factors), and in the prespecified model with further adjustment, it was -1.17 (95% CI, -3.01 to 0.67; P = .21). Conclusions and Relevance: In this preliminary study of children and adolescents with autism spectrum disorders, treatment with fluoxetine compared with placebo resulted in significantly lower scores for obsessive-compulsive behaviors at 16 weeks. Interpretation is limited by the high dropout rate, null findings of prespecified analyses that accounted for potentially confounding factors and baseline imbalances, and CIs for the treatment effect that included the minimal clinically important difference. Trial Registration: anzctr.org.au Identifier: ACTRN12608000173392.

Pre-emptive intervention versus treatment as usual for infants showing early behavioural risk signs of autism spectrum disorder: a single-blind, randomised controlled trial.

BACKGROUND: Great interest exists in the potential efficacy of prediagnostic interventions within the autism spectrum disorder prodrome, but available evidence relates to children at high familial risk. We aimed to test the efficacy of a pre-emptive intervention designed for infants showing early behavioural signs of autism spectrum disorder. METHODS: In this single-blind, randomised controlled trial done at two specialist centres in Australia, infants aged 9-14 months were enrolled if they were showing at least three early behavioural signs of autism spectrum disorder on the Social Attention and Communication Surveillance-Revised (SACS-R) 12-month checklist. Infants were randomly assigned (1:1) to receive a parent-mediated video-aided intervention (iBASIS-VIPP) or treatment as usual. Group allocation was done by minimisation, stratified by site, sex, age, and the number of SACS-R risk behaviours. Assessments were done at baseline (before treatment allocation) and at the 6 month endpoint. The primary outcome was Autism Observation Scale for Infants (AOSI), which measures early behavioural signs associated with autism spectrum disorder. Secondary outcomes were a range of infant and caregiver outcomes measured by Manchester Assessment of Caregiver-Infant interaction (MACI), Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd edition (VABS-2), MacArthur-Bates Communicative Development Inventory (MCDI), and Parenting Sense of Competence (PSOC) scale. This trial is registered with Australian New Zealand Clinical Trials Registry, number ANZCTR12616000819426. FINDINGS: Between June 9, 2016, and March 30, 2018, 103 infants were randomly assigned, 50 to the iBASIS-VIPP group and 53 to the treatment-as-usual group. After the intervention, we observed no significant differences between groups on early autism spectrum disorder behavioural signs measured by the AOSI (difference estimate -0·74, 95% CI -2·47 to 0·98). We also observed no significant differences on secondary outcomes measuring caregiver non-directiveness (0·16, -0·33 to 0·65), caregiver sensitive responding (0·24, -0·15 to 0·63), and infant attentiveness (-0·19, -0·63 to 0·25) during parent-child interactions (MACI), as well as on researcher-administered measures of receptive (1·30, -0·48 to 3·08) and expressive language (0·54, -0·73 to 1·80), visual reception (0·31, -0·77 to 1·40), and fine motor skills (0·55, -0·32 to 1·41) using the MSEL. Compared with the treatment-as-usual group, the iBASIS-VIPP group had lower infant positive affect (-0·69, -1·27 to -0·10) on the MACI, but higher caregiver-reported receptive (37·17, 95% CI 10·59 to 63·75) and expressive vocabulary count (incidence rate ratio 2·31, 95% CI 1·22 to 4·33) on MCDI, and functional language use (difference estimate 6·43, 95% CI 1·06 to 11·81) on VABS. There were no significant group differences on caregiver-reported measures of MCDI infant gesture use (3·22, -0·60 to 7·04) and VABS social behaviour (3·28, -1·43 to 7·99). We observed no significant differences between groups on self-reported levels of parenting satisfaction (difference estimate 0·21, 95% CI -0·09 to 0·52), interest (-0·23, -0·62 to 0·16) and efficacy (-0·08, -0·38 to 0·22) on PSOC. INTERPRETATION: A pre-emptive intervention for the autism spectrum disorder prodrome had no immediate treatment effect on early autism spectrum disorder symptoms, the quality of parent-child interactions, or researcher-administered measures of developmental skills. However, we found a positive effect on parent-rated infant communication skills. Ongoing follow-up of this infant cohort will assess longer-term developmental effects. FUNDING: Western Australia Children's Research Fund, Autism Cooperative Research Centre, La Trobe University, and Angela Wright Bennett Foundation.

Atypical nested 22q11.2 duplications between LCR22B and LCR22D are associated with neurodevelopmental phenotypes including autism spectrum disorder with incomplete penetrance.

BACKGROUND: Chromosome 22q11.2 is susceptible to genomic rearrangements and the most frequently reported involve deletions and duplications between low copy repeats LCR22A to LCR22D. Atypical nested deletions and duplications are rarer and can provide a valuable opportunity to investigate the dosage effects of a smaller subset of genes within the 22q11.2 genomic disorder region. METHODS: We describe thirteen individuals from six families, each with atypical nested duplications within the central 22q11.2 region between LCR22B and LCR22D. We then compared the molecular and clinical data for patients from this study and the few reported atypical duplication cases, to the cases with larger typical duplications between LCR22A and LCR22D. Further, we analyzed genes with the nested region to identify candidates highly enriched in human brain tissues. RESULTS: We observed that atypical nested duplications are heterogeneous in size, often familial, and associated with incomplete penetrance and highly variable clinical expressivity. We found that the nested atypical duplications are a possible risk factor for neurodevelopmental phenotypes, particularly for autism spectrum disorder (ASD), speech and language delay, and behavioral abnormalities. In addition, we analyzed genes within the nested region between LCR22B and LCR22D to identify nine genes (ZNF74, KLHL22, MED15, PI4KA, SERPIND1, CRKL, AIFM3, SLC7A4, and BCRP2) with enriched expression in the nervous system, each with unique spatiotemporal patterns in fetal and adult brain tissues. Interestingly, PI4KA is prominently expressed in the brain, and this gene is included either partially or completely in all of our subjects. CONCLUSION: Our findings confirm variable expressivity and incomplete penetrance for atypical nested 22q11.2 duplications and identify genes such as PI4KA to be directly relevant to brain development and disorder. We conclude that further work is needed to elucidate the basis of variable neurodevelopmental phenotypes and to exclude the presence of a second disorder. Our findings contribute to the genotype-phenotype data for atypical nested 22q11.2 duplications, with implications for genetic counseling.

What makes playgroups therapeutic? A scoping review to identify the active ingredients of therapeutic and supported playgroups.

BACKGROUND: Supported and therapeutic playgroups aim to support and strengthen vulnerable children and families by increasing parenting capacity, parent-child interaction, enhancing child outcomes and promoting community networks. This review aimed to comprehensively scope the literature to identify the "active ingredients" of supported and therapeutic playgroups. METHOD: A systematic search of grey and scholarly literature was conducted using Medline, PyschINFO, EMBASE, ERIC, CINAHL, MedNar, Informit, Scopus, Libraries of Australia and Trove. Articles were included if they: i) defined playgroup as a group of children and actively involved caregivers; ii) described a therapeutic playgroup or supported playgroup model; iii) targeted children prior to school age; and iv) measured the impact of playgroups. A total of 36 articles met the inclusion criteria. Qualitative data was synthesised using a meta-ethnography approach with findings charted against a conceptual model of engagement. Quantitative data was synthesised using descriptive statistics. RESULTS: The findings identified that emotional, practical and informational components of playgroups strongly reflect family centred practice, self-efficacy theory and peer-support principles. CONCLUSION: Therapeutic and supported playgroups are complex interventions, with numerous interacting components that make them beneficial for children and families. This review is the first to identify the "active ingredients" of playgroups with findings informing the design of future playgroups for vulnerable children and families.

Cytokine levels and associations with symptom severity in male and female children with autism spectrum disorder.

Background: Autism spectrum disorders (ASDs) are complex, pervasive, and heterogeneous neurodevelopmental conditions with varying trajectories, significant male bias and largely unknown etiology. However, an understanding of the biological mechanisms driving pathophysiology is evolving. Immune system aberrations, as identified through cytokine profiles, are believed to have a role in ASD. Altered cytokine levels may facilitate identification of ASD subtypes as well as provide biological markers of response to effective treatments. Research exploring the relationship between cytokine profiles and ASD symptoms is, however, in its infancy. The objective of this study was to explore relationships between cytokine levels and the severity of ASD and other clinical traits. Methods: Multiplex assay techniques were used to measure levels of 27 cytokines in plasma samples from a cohort of 144 children diagnosed with ASD. Results: Overall, results showed a significant negative association between platelet-derived growth factor (PDGF)-BB, and the severity of ASD symptoms. Furthermore, a significant interaction with sex suggested a different immune profile for females compared to males. ASD symptom severity was negatively associated with levels of 4 cytokines, IL-1ß, IL-8, MIP-1ß, and VEGF, in females, but not in males. Conclusions: Results of the present study suggest that an altered cytokine response or profile is associated with the severity of ASD-related symptoms, with sex a potential modifier of this relationship. Further research in larger populations which recognizes the importance of sex comparisons and longitudinal assessments are now required to extend and further describe the role of the immune system in ASD.

Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses.

The increasing prevalence of Autism Spectrum Disorders (ASD) may in part be due to a shift in the diagnostic threshold that has led to individuals with a less severe behavioral phenotype receiving a clinical diagnosis. This study examined whether there were changes over time in the qualitative and quantitative phenotype of individuals who received the diagnosis of Autistic Disorder. Data were from a prospective register of new diagnoses in Western Australia (n = 1252). From 2000 to 2006, we examined differences in both the percentage of newly diagnosed cases that met each criterion as well as severity ratings of the behaviors observed (not met, partially met, mild/moderate and extreme). Linear regression determined there was a statistically significant reduction from 2000 to 2006 in the percentage of new diagnoses meeting two of 12 criteria. There was also a reduction across the study period in the proportion of new cases rated as having extreme severity on six criteria. There was a reduction in the proportion of individuals with three or more criteria rated as extreme from 2000 (16.0%) to 2006 (1.6%), while percentage of new cases with no "extreme" rating on any criteria increased from 58.5% to 86.6% across the same period. This study provides the first clear evidence of a reduction over time in the behavioral severity of individuals diagnosed with Autistic Disorder during a period of stability in diagnostic criteria. A shift toward diagnosing individuals with less severe behavioral symptoms may have contributed to the increasing prevalence of Autistic Disorder diagnoses. Autism Res 2017, 10: 179-187. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Obesity and associated factors in youth with an autism spectrum disorder.

Weight status on children and youth with autism spectrum disorder is limited. We examined the prevalence of overweight/obesity in children and youth with autism spectrum disorder, and associations between weight status and range of factors. Children and youth with autism spectrum disorder aged 2-16 years (n = 208) and their parents participated in this study. Body mass index was calculated using the Centers for Disease Control and Prevention growth charts and the International Obesity Task Force body mass index cut-offs. The Autism Diagnostic Observation Schedule was administered. Parents completed questionnaires about socio-demographics, diagnosed comorbidities, sleep disturbances, social functioning and medication of youth with autism spectrum disorder. The prevalence of overweight/obesity in participants with autism spectrum disorder was 35%. One quarter of obese children and youth (25.6%) had obese parents. There was a significant association between children and youth's body mass index and maternal body mass index (r = 0.25, n = 199, p < 0.001). The gender and age, parental education, family income, ethnicity, autism spectrum disorder severity, social functioning, psychotropic and complementary medication use of children and youth with autism spectrum disorder were not statistically associated with their weight status. Findings suggest the need for clinical settings to monitor weight status of children and youth with autism spectrum disorder in a bid to manage or prevent overweight/obesity in this population. Incorporating a family system approach to influence health behaviours among children and youth with autism spectrum disorder especially for specific weight interventions is warranted and should be further explored.

Fluoxetine for Autistic Behaviors (FAB trial): study protocol for a randomized controlled trial in children and adolescents with autism.

BACKGROUND: Serotonin reuptake inhibitors (SSRIs) are commonly prescribed off-label for children with autism. To date, clinical trials examining the use of SSRIs in autism have been limited by small sample sizes and inconclusive results. The efficacy and safety of SSRIs for moderating autistic behaviors is yet to be adequately examined to provide evidence to support current clinical practice. The aim of the Fluoxetine for Autistic Behaviors (FAB) study is to determine the efficacy and safety of low dose fluoxetine compared with placebo, for reducing the frequency and severity of repetitive stereotypic behaviors in children and adolescents with an autism spectrum disorder (ASD). The relationship between the effectiveness of fluoxetine treatment and serotonin transporter genotype will also be explored. METHODS/DESIGN: The FAB study is a multicenter, double-blinded, randomized controlled trial, funded by the Australian Government's National Health and Medical Research Council (NHMRC) grant. Participants will be aged between 7.5 and 17 years with a confirmed diagnosis of ASD. Eligible participants will be randomized to either placebo or fluoxetine for a 16-week period. Medication will be titrated over the first four weeks. Reponses to medication will be monitored fortnightly using the Clinical Global Impressions Scale (CGI). The primary outcome measure is the Children's Yale-Brown Obsessive Compulsive Scale-Modified for Pervasive Developmental Disorders (CYBOCS-PDD), administered at baseline and 16 weeks. Secondary outcome measures include the Aberrant Behaviour Scale (ABC), the Spence Children's Anxiety Scale Parent Report (SCAS-P), and the Repetitive Behaviors Scale (RBS-R), measured at baseline and 16 weeks. Participants will be invited to undergo genetic testing for SLC6A4 allele variants using a cheek swab. Continuous outcomes, including the primary outcome will be compared between the active and placebo groups using unadjusted linear regression. Binary outcomes will be compared using unadjusted logistic regression. DISCUSSION: The FAB study is a large clinical trial to specifically investigate the efficacy of low dose fluoxetine for restricted, repetitive, and stereotyped behaviors in ASD. The outcomes of this study will contribute to evidence-based interventions used in clinical practice to assist children with ASD. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12608000173392; registered on 9 April, 2008.

A "bottom-up" approach to aetiological research in autism spectrum disorders.

Autism spectrum disorders (ASD) are currently diagnosed in the presence of impairments in social interaction and communication, and a restricted range of activities and interests. However, there is considerable variability in the behaviors of different individuals with an ASD diagnosis. The heterogeneity spans the entire range of IQ and language abilities, as well as other behavioral, communicative, and social functions. While any psychiatric condition is likely to incorporate a degree of heterogeneity, the variability in the nature and severity of behaviors observed in ASD is thought to exceed that of other disorders. The current paper aims to provide a model for future research into ASD subgroups. In doing so, we examined whether two proposed risk factors - low birth weight (LBW), and in utero exposure to selective serotonin reuptake inhibitors (SSRIs) - are associated with greater behavioral homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively. The findings from this "proof of principle" paper provide support for this "bottom-up" approach as a feasible method for creating homogenous groups.

Brief report: do the nature of communication impairments in autism spectrum disorders relate to the broader autism phenotype in parents?

Extensive empirical evidence indicates that the lesser variant of Autism Spectrum Disorders (ASD) involves a communication impairment that is similar to, but milder than, the deficit in clinical ASD. This research explored the relationship between the broader autism phenotype (BAP) among parents, an index of genetic liability for ASD, and proband communication difficulties. ASD probands with at least one BAP parent (identified using the Autism Spectrum Quotient) had greater structural and pragmatic language difficulties (assessed using the Children's Communication Checklist-2) than ASD probands with no BAP parent. This finding provides support for the position that genetic liability for ASD is associated with increased communication difficulties across structural and pragmatic domains.