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Greater facial asymmetry has been consistently found in children with autism spectrum disorder (ASD) relative to children without ASD. There is substantial evidence that both facial structure and the recurrence of ASD diagnosis are highly heritable within a nuclear family. Furthermore, sub-clinical levels of autistic-like behavioural characteristics have also been reported in first-degree relatives of individuals with ASD, commonly known as the 'broad autism phenotype'. Therefore, the aim of the current study was to examine whether a broad autism phenotype expresses as facial asymmetry among 192 biological parents of autistic individuals (134 mothers) compared to those of 163 age-matched adults without a family history of ASD (113 females). Using dense surface-modelling techniques on three dimensional facial images, we found evidence for greater facial asymmetry in parents of autistic individuals compared to age-matched adults in the comparison group (p = 0.046, d = 0.21 [0.002, 0.42]). Considering previous findings and the current results, we conclude that facial asymmetry expressed in the facial morphology of autistic children may be related to heritability factors. LAY ABSTRACT: In a previous study, we showed that autistic children presented with greater facial asymmetry than non-autistic children. In the current study, we examined the amount of facial asymmetry shown on three-dimensional facial images of 192 parents of autistic children compared to a control group consisting of 163 similarly aged adults with no known history of autism. Although parents did show greater levels of facial asymmetry than those in the control group, this effect is statistically small. We concluded that the facial asymmetry previously found in autistic children may be related to genetic factors.

Alcohol exposure during pregnancy has been associated with altered brain development and facial dysmorphology. While autism spectrum disorder (ASD) is not specifically related to distinct facial phenotypes, recent studies have suggested certain facial characteristics—increased facial masculinity and asymmetry—may be associated with ASD and its clinical presentations. In the present study, we conducted a preliminary investigation to examine the effects of prenatal alcohol exposure on facial morphology in autistic children with (n = 37; mean age = 8.21 years, SD = 2.72) and without (n = 100; mean age = 8.37 years, SD = 2.47) prenatal alcohol exposure. Using three-dimensional facial scans and principal component analysis, we identified a facial shape associated with prenatal alcohol exposure in autistic children. However, variations in the alcohol-related facial shape were generally not associated with behavioural and cognitive measures. These findings suggest that while early exposure to alcohol may influence the development of facial structures, it is does not appear to be associated with ASD phenotypic variability. Importantly, although these findings do not implicate a role for prenatal alcohol exposure in the etiology of ASD, further research is warranted to investigate the link between prenatal alcohol exposure and facial morphology differences among neurodevelopmental conditions.

This study aimed to explore the rates of motor difficulties in children from the Australian Autism Biobank, and how early motor concerns impacted on children functionally. Children with autism aged 2-7 years, including 441 with a Vineland Adaptive Behavior Scale (VABS-II) motor subscale and 385 with a Mullen Scales of Early Learning (MSEL) fine motor subscale were included (n total = 514; 80% male). Approximately 60% of children on the MSEL and ~ 25% on the VABS-II had clinically significant motor impairments. More children with delayed sitting and walking motor milestones had early childhood parent reported motor difficulties (p 0.001). Early motor delays or concerns may assist identifying individuals who will likely benefit from early ongoing developmental monitoring and early support.

Key Points Question Does preemptive intervention compared with usual care reduce the severity of autism symptoms and the likelihood of an autism spectrum disorder (ASD) diagnosis in infants showing early signs of ASD? Findings In this randomized clinical trial of 103 infants showing early behavioral signs of ASD, preemptive intervention led to a statistically significant reduction in the severity of ASD behaviors across early childhood. Infants who received the preemptive intervention had lower odds of meeting diagnostic criteria for ASD (7%) than those who received usual care (21%) at age 3 years, with a number needed to treat of 7 participants. Meaning This study found that a preemptive intervention reduced ASD diagnostic behaviors when used at the time atypical development first emerges during infancy., 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., This randomized clinical trial examines whether preemptive intervention compared with usual care reduces the severity of autism symptoms and the odds of an autism spectrum disorder diagnosis among infants showing early signs of autism.

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 score70), 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.

BackgroundGreat 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.MethodsIn 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.FindingsBetween 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.InterpretationA 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.FundingWestern Australia Children's Research Fund, Autism Cooperative Research Centre, La Trobe University, and Angela Wright Bennett Foundation.

‘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.

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 aim of this study was to understand the challenges experienced by families obtaining a diagnosis and therapy for developmental coordination disorder (DCD).Parents of 435 children aged 4-18 years with persistent motor difficulties consistent with a diagnosis of DCD completed an online survey. Diagnostic timeline and diagnostic label/s received were examined, along with therapies accessed.There was inconsistent diagnostic terminology (nine separate terms) with more children diagnosed with dyspraxia (64.7%) than DCD (48.8%). Even though most parents (87.0%) reported that receiving a diagnosis was helpful, children did not receive a diagnosis until years after seeking help (mean 2.8 ± 2.3 years). Many children were diagnosed with at least one co-occurring neurodevelopmental, language or learning disorder (70.0%). Almost all families had accessed therapy for their child's movement difficulties (93.9%), but more than half did not have access to funding to support therapy costs (57.8%) and reported that the costs caused financial strain (52.6%). Two out of every three families reported that they did not feel the current level of therapy was sufficient.This critical advocacy research highlights inconsistent and incorrect terminology and the challenges families experience in obtaining a diagnosis and adequate access to therapy for their child's movement difficulties.This is the first comprehensive study to examine the challenges families experience gaining a diagnosis and therapy for their child with DCD. Families regularly experienced prolonged diagnosis; 45% waited between 2 and 4 years. There is no clear diagnostic pathway, with children more likely to be diagnosed with dyspraxia than the correct clinical diagnosis of DCD. More extensive implementation of the diagnostic guidelines into clinical practice is needed.

Atypical facial morphology, particularly increased facial asymmetry, has been identified in some individuals with Autism Spectrum Conditions (ASC). Many cognitive, behavioural and biological features associated with ASC also occur on a continuum in the general population. The aim of the present study was to examine subthreshold levels of autistic traits and facial morphology in non-autistic individuals. Facial asymmetry was measured using three-dimensional facial photogrammetry, and the Autism-spectrum Quotient was used to measure autistic-like traits in a community-ascertained sample of young adults (n = 289). After accounting for covariates, there were no significant associations observed between autistic-like traits and facial asymmetry, suggesting that any potential facial morphology differences linked to ASC may be limited to the clinical condition.

Reduced cardiac autonomic function is associated with increased risk of cardiovascular disease (CVD), with heart rate variability (HRV) providing an accessible index of cardiac autonomic function. HRV may provide a candidate physiological mechanism linking reduced cardiac autonomic function to increased risk for CVD in schizophrenia illness. This study examines whether HRV is also reduced in a community sample of treatment-seeking participants experiencing early psychosis (n = 48) compared to healthy volunteers (n = 48) and social anxiety control groups (n = 48) matched by gender and age. HRV was assessed during a five-minute interbeat interval recording at rest. Participants also completed self-report psychiatric symptom measures. Early psychosis participants showed significant reductions in HRV compared to social anxiety and healthy control groups. Reductions in HRV were also observed in early psychosis participants taking anticholinergic medications compared to both control groups taking cardio-benign medications or who were non-medicated. Lastly, whether or not early psychosis participants were taking anticholinergic medications was not associated with reductions in HRV. Findings provide preliminary evidence that early psychosis is associated with reduced HRV. This study supports further research with larger sample sizes to precisely determine the influence of anticholinergic drugs on HRV in early psychosis populations.

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-1β, IL-8, MIP-1β, 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. Electronic supplementary material The online version of this article (10.1186/s13229-017-0176-2) contains supplementary material, which is available to authorized users.

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.

A key research priority in the study of autism spectrum conditions (ASC) is the discovery of biological markers that may help to identify and elucidate etiologically distinct subgroups. One physical marker that has received increasing research attention is facial structure. Although there remains little consensus in the field, findings relating to greater facial asymmetry (FA) in ASC exhibit some consistency. As there is growing recognition of the importance of replicatory studies in ASC research, the aim of this study was to investigate the replicability of increased FA in autistic children compared to nonautistic peers. Using three-dimensional photogrammetry, this study examined FA in 84 autistic children, 110 typically developing children with no family history of the condition, and 49 full siblings of autistic children. In support of previous literature, significantly greater depth-wise FA was identified in autistic children relative to the two comparison groups. As a further investigation, increased lateral FA in autistic children was found to be associated with greater severity of ASC symptoms on the Autism Diagnostic Observation Schedule, second edition, specifically related to repetitive and restrictive behaviors. These outcomes provide an important and independent replication of increased FA in ASC, as well as a novel contribution to the field. Having confirmed the direction and areas of increased FA in ASC, these findings could motivate a search for potential underlying brain dysmorphogenesis. Autism Res 2019, 12: 1774-1783. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study looked at the amount of facial asymmetry (FA) in autistic children compared to typically developing children and children who have siblings with autism. The study found that autistic children, compared to the other two groups, had greater FA, and that increased FA was related to greater severity of autistic symptoms. The face and brain grow together during the earliest stages of development, and so findings of facial differences in autism might inform future studies of early brain differences associated with the condition.

Aim To determine the incidence of and risk factors for psychiatric disorders in early adulthood in patients with childhood onset type 1 diabetes (T1D). Methods In this retrospective-cohort study, we identified a population-based childhood onset T1D cohort and an age and sex matched (5:1) non-diabetic comparison cohort. Data linkage was used to access inpatient hospitalization data, mental health support service data, and mortality data to follow-up both cohorts into early adulthood. Results The mean age of T1D diagnosis was 9.5 years (SD 4.1), with a mean age at end of follow-up of 26.4 years (SD 5.2, max 37.7). The diagnosis of any psychiatric disorder was observed for 187 of 1302 (14.3%) in the T1D cohort and 400 of 6422 (6.2%) in the comparison cohort [adjusted hazard ratio (HR) 2.3; 95% CI 1.9, 2.7]. Anxiety, eating, mood, and personality and behaviour disorders were observed at higher rates within the T1D cohort. Comorbid psychiatric disorders were more frequent, at the cohort level, within the T1D cohort (2-3 disorders 3.76% vs 1.56%) and service utilization was higher (15+ contacts 6.8% vs 2.8%); though these differences did not remain when restricted to only those individuals diagnosed during follow-up. A history of poor glycaemic control was associated with an increased risk of anxiety, mood, and ‘any’ disorder (HR ranging from 1.35 to 1.42 for each 1% increase in mean paediatric HbA1c). Conclusion Our findings highlight the need for access to mental health support services as part of routine patient care for young adults with T1D, and for better predictive tools to facilitate targeting at-risk patients with early intervention programs.

A growing body of research has suggested heart rate variability (HRV) may be reduced in autism spectrum disorder (ASD) in comparison to neurotypical cohorts. While there have been several studies investigating HRV in children diagnosed with ASD, few studies have been conducted in adults. The objective of the current study was to investigate autonomic nervous system activity as assessed by HRV in adults diagnosed with ASD. We hypothesized that adults with ASD would show a reduction in HRV compared to neurotypical participants. Participants diagnosed with ASD (n = 55) were recruited from the Autism Clinic for Translational Research at the Brain and Mind Centre (University of Sydney) between 2013 and 2017. Neurotypical participants were recruited from advertisements and online media. Resting state heart rate was measured for 5 min while participants sat in an upright position. Results showed there was an overall significant difference in resting-state HRV between adults diagnosed with ASD compared to the neurotypical control group. Logarithmically transformed high frequency (HF) and root mean square of successive differences were particularly decreased in the ASD group, suggesting lower parasympathetic activity. The use of psychotropic medications and comorbidities were associated with reductions in low frequency of HRV. Our data suggest an overall dysregulation in resting autonomic activity in adults with ASD. This may represent an important physiological mechanism leading to potential cardiovascular risk in ASD, which warrants further investigation. Autism Res 2019, 12: 922-930. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: ASD is commonly associated with a range of physical and mental health comorbidities. Autonomic disruptions underlying reductions in heart rate variability (HRV) have been linked to a range of mental and physical health conditions. We assessed resting-state HRV in adults diagnosed with ASD in comparison to healthy individuals. Our results showed reduced heart rate variability in people diagnosed with ASD compared to adults without ASD. These findings implicate a role for autonomic activity as a potentially modifiable risk factor for ASD.

Background Nausea and vomiting during pregnancy (NVP) is thought to be caused by changes in maternal hormones during pregnancy. Differences in hormone exposure during prenatal life have been implicated in the causal pathways for some cases of autism spectrum disorder (ASD). However, no study has investigated whether the presence and severity of NVP may be related to symptom severity in offspring with ASD. Methods A large sample of children with ASD (227 males and 60 females, aged 2 to 18 years) received a clinical assessment, during which parents completed questionnaires regarding their child’s social (Social Responsiveness Scale, SRS) and communication (Children’s Communication Checklist–2nd edition, CCC-2) symptoms. Parents also reported on a 5-point scale the frequency and severity of NVPs during the pregnancy of the child being assessed: (1) no NVP during the pregnancy, (2) occasional nausea, but no vomiting, (3) daily nausea, but no vomiting, (4) occasional vomiting, with or without nausea, and (5) daily nausea and vomiting. Results Impairments in social responsiveness in offspring, as indexed by SRS total score, significantly increased as a function of the frequency and severity of their mothers’ NVP, as did the level of language difficulties as indexed by the Global Communication Composite of the CCC-2. Conclusions The strong, positive association between increasing frequency and severity of NVP and ASD severity in offspring provides further evidence that exposure to an atypical hormonal environment during prenatal life may affect neurodevelopment and contribute to the ASD phenotype. Given that the measure of NVP symptoms in the current study was based on retrospective recall, replication of this finding is required before strong conclusions can be drawn. Electronic supplementary material The online version of this article (10.1186/s13229-018-0223-7) contains supplementary material, which is available to authorized users.

Background: The effectiveness of psychotherapies for social anxiety disorder (SAD) is typically evaluated using self- and clinician-reported symptom change, while biomarkers of treatment response are rarely measured. The current study aimed to compare biomarkers of response following two brief group interventions for SAD. Methods: This randomized controlled trial evaluated the effectiveness of single-session group interventions for SAD (n = 58) – imagery rescripting (IR) and verbal restructuring (VR) versus waitlist control (WC). The IR intervention guided participants to rescript autobiographical memories through visualization whilst the VR intervention focused on thought challenging. Trial outcomes included change in psychophysiological reactivity (heart rate variability (HRV) and electrodermal responding) to social stress, and symptom-based measures (social interaction anxiety, negative self-portrayal, cognitive avoidance, repetitive negative thinking, memory modification, anxious behaviors). Results: Psychophysiological reactivity was selectively attenuated following IR treatment, compared to VR and WC groups. The specific influence of the imagery-based intervention in modulating autonomic reactivity was evident across HRV parameters, including the standard deviation of intervals between heartbeats (IR vs. WC, d = 0.67, p = 0.021; IR vs. VR, d = 0.58, p = 0.041), and high frequency power – an indicator of parasympathetically mediated emotion regulation (IR vs. WC, d = 0.75, p = 0.034; IR vs. VR, d = 0.95, p = 0.006). Few group differences were observed across self-report measures. Conclusion: The current study highlights the specificity of brief imagery-based interventions in influencing psychophysiological reactivity in SAD and establishes the sensitivity of objective markers of treatment response in quantifying change over symptom-based measurements.

Reduced social attention is a hallmark feature in autism spectrum disorder (ASD), emerging as early as the first year of life. This difference represents a possible mechanism impacting upon the development of more complex social-communicative behaviors. The aim of this study was to develop and test the efficacy of a novel attention bias modification paradigm to alter social attention, specifically orienting to faces. Children with ASD (n = 66), aged between 5 and 12 years, were randomized to play either a social attention training or control game for 15 min. Children playing the training game were reinforced for attending to and engaging with social characters, whereas children in the control group were equally rewarded for attending to both social and non-social characters. Eye-tracking measures were obtained before and after gameplay. There was a significant increase in the percentage of first fixations to faces, relative to objects, after social attention training compared to a control group, associated with a medium effect size (partial η = 0.15). The degree of social attention change in the training group was inversely associated with restricted and repetitive behaviors and moderated by comorbid attention deficit hyperactivity disorder diagnoses, suggestive of differential training effects based on individual symptom profiles. By using the principles of attention bias modification, we demonstrated that social attention can be acutely modified in children with ASD, with an increased tendency to orient attention toward faces after brief social attention training. Modifying attentional biases may therefore represent a potential novel mechanism to alter the development of social communication trajectories. Autism Res 2019, 12: 527-535 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Some children with autism spectrum disorder (ASD) do not look at faces or eyes as much as their non-ASD peers do. Using a game where players have to pay attention to characters with faces to score points, we found that children playing the game began to look more at faces, even outside of the game. Looking at faces is an important prerequisite to many social interactions, telling us about others' emotions and states of attention-things that become harder to understand when they are not seen. If children with ASD could use games to help train looking at faces in real life, then they may be in a better position to understand and participate in social exchanges.

Background: The nature of sleep-wake abnormalities in individuals with mental disorders remains unclear. The present study aimed to exam ine the differences in objective ambulatory measures of the sleep-wake and activity cycles across young people with anxiety, mood or psychotic disorders. Methods: Participants underwent several days of actigraphy monitoring. We divided participants into 5 groups (control, anxiety disorder, unipolar depression, bipolar disorder, psychotic disorder) according to primary diagnosis. Results: We enrolled 342 participants aged 12–35 years in our study: 41 healthy controls, 56 with anxiety disorder, 135 with unipolar depression, 80 with bipolar disorder and 30 with psychotic disorders. Compared with the control group, sleep onset tended to occur later in the anxiety, depression and bipolar groups; sleep offset occurred later in all primary diagnosis groups; the sleep period was longer in the anxiety, bipolar and psychosis groups; total sleep time was longer in the psychosis group; and sleep efficiency was lower in the depression group, with a similar tendency for the anxiety and bipolar groups. Sleep parameters were significantly more variable in patient subgroups than in controls. Cosinor analysis revealed delayed circadian activity profiles in the anxiety and bipolar groups and abnormal circadian curve in the psychosis group. Limitations: Although statistical analyses controlled for age, the sample included individuals from preadolescence to adulthood. Most participants from the primary diagnosis subgroups were taking psychotropic medications, and a large proportion had other comorbid mental disorders. Conclusion: Our findings suggest that delayed and disorganized sleep offset times are common in young patients with various mental disorders. However, other sleep-wake cycle disturbances appear to be more prominent in broad diagnostic categories.

Background Technology-based interventions for Autism Spectrum Disorder (ASD) have proliferated, but few have been evaluated within the context of a randomised controlled trial (RCT). This RCT evaluated the efficacy of one technology-based early intervention programme (Therapy Outcomes By You; TOBY) in young children with ASD. Methods TOBY is an app-based learning curriculum designed for children and parents as a complement to early behavioural intervention. Eighty children (16 female) were recruited to this RCT within 12 months of receiving a diagnosis of ASD (M age = 3.38; SD = 0.69) and randomised to receive either treatment-as-usual (community-based intervention, n = 39) or the TOBY therapy (at least 20 min/day) plus treatment-as-usual (n = 41) for a period of 6 months. Outcomes were assessed at 3 and 6 months postbaseline. (Australian New Zealand Clinical Trials Registry: ACTRN12614000738628; www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365463). Results Children in the TOBY intervention group averaged 19 min/day engaging with the app in the first 3 months, but only 2 min/day during the second 3 months. There was no group difference in scores on the primary outcome, the Autism Treatment Evaluation Checklist, at either the 3- or 6-month follow-up. However, significant improvements at the 6-month follow-up were observed in the TOBY intervention group relative to the treatment-as-usual group on three secondary outcomes: the Fine Motor and Visual Reception subscales of the Mullen Scale of Early Learning and the Total Words Understood scale of the MacArthur-Bates Communicative Development Index. Statistical trends towards improvement in the TOBY intervention group were observed on measures of adaptive function, although these decreased in magnitude from the 3- to 6-month follow-up. Conclusions This study provides evidence that technology-based interventions may provide a relatively low-cost addition to existing therapist-delivered interventions for children with ASD. However, sustained use of the app over the full 6-month period was a challenge for most families.

There is significant heterogeneity amongst individuals with Autism Spectrum Disorder (ASD) in symptom presentation and severity. An understanding of the factors that contribute to and modulate symptom severity are critical to informing prognosis, stratification, and treatment decisions. Maternal prenatal stress exposure is a nonspecific risk factor for a wide array of neurodevelopmental outcomes in subsequent offspring. Emerging evidence suggests that prenatal maternal stress may increase ASD risk and contribute to variability in autism-like traits in the general population. In the current study, we aimed to determine whether prenatal maternal exposure to stressful life events is associated with symptom severity amongst individuals with ASD. We performed multiple regression analyses to examine associations between retrospectively recalled maternal prenatal stressful life events and the severity of ASD-associated symptoms in 174 children with ASD (Mage = 9.09 years; SD = 3.81). ASD-related symptom severity was measured using the Social Responsiveness Scale and communication abilities were measured using the Children's Communication Checklist. Exposure to prenatal stressful life events was a significant predictor of ASD-related symptom severity (t = 2.014; P = .048) and communication abilities (t = -2.925; P = .004) amongst children with ASD, even after controlling for a range of sociodemographic and obstetric variables. Follow-up analyses demonstrated significant increases in symptom severity only in the context of multiple (two or more) prenatal stressful life events. Together, these findings indicate that ASD, in the context of prenatal maternal stress exposure, may be associated with a more severe phenotype, particularly when there are multiple prenatal exposures. Autism Res 2017, 10: 1866-1877. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.There is emerging evidence that prenatal maternal stress may increase the risk for Autism Spectrum Disorder (ASD) and contribute to variability in autism-like traits in the general population. Here, we found that more stressful life events experienced during pregnancy was associated with more severe ASD-related symptoms and poorer communication abilities amongst children with ASD. The results from this study suggest that prenatal maternal stress exposure and its sequelae may contribute to variability in symptom severity amongst children with ASD.

Social-cognitive deficits contribute to poor functional outcomes in early psychosis; however, no effective pharmacological treatments exist for these problems. This study was the first to investigate the efficacy of an extended treatment of oxytocin nasal spray combined with social cognition training (SCT) to improve social cognition, clinical symptoms, and social functioning in early psychosis. In a double-blind, randomized, placebo-controlled, between-subjects trial, 52 individuals (aged 16–35 years) diagnosed with an early psychosis schizophrenia-spectrum illness were recruited. Participants received oxytocin (24 International Units) or placebo nasal spray twice-daily for 6 weeks, combined with group SCT (2 × 1 hour weekly sessions for 6 weeks). An additional dose of oxytocin was administered before each weekly session. Assessments were conducted at baseline, post-treatment, and at 3-month follow-up. Primary outcomes included the Reading the Mind in the Eyes Test, the Scale for the Assessment of Positive and Negative Symptoms, and the Social Functioning Scale. Secondary outcomes included self-report and behavioral assessments of social cognition, symptom severity, and social functioning. Results showed that on all primary and secondary outcomes, there was no benefit of oxytocin nasal spray treatment in comparison to placebo. Exploratory post hoc analysis suggested that increased use of nasal spray was, however, associated with reductions in negative symptoms in the oxytocin condition only. This study represents the first evaluation of oxytocin treatment for early psychosis. Although results suggest no benefit of oxytocin treatment, results also highlight an urgent need to consider nasal spray delivery and dose-related variables for future clinical trials.

This study explored the relationships between the later age of achievement of early motor milestones, current motor atypicalities (toe walking), and the severity of restricted and repetitive behaviors (RRBs) in individuals with autism spectrum disorder (ASD). Parents of 147 children and adolescents with ASD (M

Atypical facial characteristics have been observed in many disorders associated with developmental disability. While autism spectrum conditions (ASC) have not previously been thought to be associated with a distinct facial phenotype, an emerging research literature is casting doubt on this assumption. The identification of differences in the facial phenotype of individuals with ASC may contribute to efforts to promote early identification of the condition and help elucidate etiological pathways. With the aim of identifying facial phenotypes associated with ASC, this commentary evaluated facial features purported to distinguish ASC from typical development. Although there is little consensus across the reviewed studies for the majority of facial characteristics described, preliminary evidence suggests increased facial asymmetry may be more common in ASC. There is also evidence to suggest that there are morphologically distinct subgroups within ASC that correspond with different cognitive and behavioral symptomatology. However, in light of the various inconsistencies in the reported literature, and based on an accumulating understanding of etiological pathways proposed to be associated with ASC, we propose an alternative paradigm for investigating facial phenotypes in ASC. A series of studies are outlined to demonstrate the promise of a research program that has taken a hypothesis-driven approach to examine facial phenotypes associated with increased exposure to prenatal testosterone and to ASC. Autism Res 2017, 10: 1910-1918. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.This commentary reviewed studies that found differences in the facial features of individuals with autism spectrum conditions (ASC) compared to typically developing individuals. While there is little agreement between studies, there is some support for asymmetrical facial features associated with ASC, and preliminary evidence that particular facial features relate to specific patterns of cognitive and behavioral symptoms. However, in light of inconsistencies between studies and based on accumulating understanding of etiological pathways, we propose an alternative approach to investigating facial differences in ASC.

BackgroundPolyvagal theory emphasizes that autonomic nervous system functioning plays a key role in social behavior and emotion. The theory predicts that psychiatric disorders of social dysfunction are associated with reduced heart rate variability, an index of autonomic control, as well as social inhibition and avoidance. The purpose of this study was to examine whether heart rate variability was reduced in treatment-seeking patients diagnosed with social anxiety disorder, a disorder characterized by social fear and avoidance.MethodsSocial anxiety patients (n = 53) were recruited prior to receiving psychological therapy. Healthy volunteers were recruited through the University of Sydney and the general community and were matched by gender and age (n = 53). Heart rate variability was assessed during a five-minute recording at rest, with participants completing a range of self-report clinical symptom measures.ResultsCompared to controls, participants with social anxiety exhibited significant reductions across a number of heart rate variability measures. Reductions in heart rate variability were observed in females with social anxiety, compared to female controls, and in patients taking psychotropic medication compared to non-medicated patients. Finally, within the clinical group, we observed significant associations between reduced heart rate variability and increased social interaction anxiety, psychological distress, and harmful alcohol use.ConclusionsThe results of this study confirm that social anxiety disorder is associated with reduced heart rate variability. Resting state heart rate variability may therefore be considered a marker for social approach-related motivation and capacity for social engagement. Additionally, heart rate variability may provide a useful biomarker to explain underlying difficulties with social approach, impaired stress regulation, and behavioral inhibition, especially in disorders associated with significant impairments in these domains.

The hormone and neuropeptide oxytocin is believed to buffer against social stress and reduce social-threat perception. We employed a widely used ostracism paradigm, Cyberball, to investigate whether oxytocin ameliorated the acute behavioral and affective consequences of social rejection. In a double-blind, randomized, between-subjects design, 74 healthy male and female participants were administered intranasal oxytocin or placebo and subsequently ostracized or included during this virtual ball-tossing game. Ostracized participants reported negative affective and attachment-related reactions, as well as a significant motivational change in increased desire to be involved in the game; these effects were not influenced by oxytocin. Intranasal oxytocin did, however, increase included participants' desire to play again with the same participants, suggesting oxytocin enhanced desire for future social engagement following inclusion. These findings are argued to provide evidence that the effects of oxytocin in promoting social approach behavior may be context specific and sensitive to positive social cues. The results suggest that in an explicitly aversive context, oxytocin does not buffer against the immediate impact of blunt social rejection.

Social anxiety disorder is characterized by excessive fear and habitual avoidance of social situations. Decision-making models suggest that patients with anxiety disorders may fail to exhibit goal-directed control over actions. We therefore investigated whether such biases may also be associated with social anxiety and to examine the relationship between such behavior with outcomes from cognitive-behavioral therapy. Patients diagnosed with social anxiety and controls completed an instrumental learning task in which two actions were performed to earn food outcomes. After outcome devaluation, where one outcome was consumed to satiety, participants were re-tested in extinction. Results indicated that, as expected, controls were goal-directed, selectively reducing responding on the action that previously delivered the devalued outcome. Patients with social anxiety, however, exhibited no difference in responding on either action. This loss of a devaluation effect was associated with greater symptom severity and poorer response to therapy. These findings indicate that variations in goal-directed control in social anxiety may represent both a behavioral endophenotype and may be used to predict individuals who will respond to learning-based therapies.