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Despite their high prevalence and clinical importance in autism, unusual and restricted interests remain under-researched and poorly understood. This study aimed to characterize the frequency and type of interests in autism by coding caregivers’ open-ended responses in a sample of 237 autistic children and adolescents ( Mage = 8.27 years, SDage = 4.07; range: 2.08–18.25 years). It further aimed to explore the effects of age, sex, cognitive functioning and social and communication deficits on the number and type of interests. We found that 75% of autistic youth had at least one interest and that 50% of those children showed two or more different interests. The most frequent interests were sensory-based (43%), with a majority of these interests relating to the visual modality. Interest within vehicles/transportation, fictional characters, television/digital versatile disk/movies, computers, and video games, constructive, mechanical objects, animals and plants, and attachment to specific objects were also prevalent. Logistic regression showed that being male, having a co-occurring intellectual disability and having more severe social and communication impairments were associated with a higher probability of having one or more restricted interests. Sex was significantly associated with the type (χ2 = 37.52, Phi = 0.37, p = 0.021) of restricted interests, with females showing a significantly higher percentage of creative interests and males significantly higher percentage of interest in characters, vehicles/transportation, computers/video games, mechanical objects and constructive interests. Theoretical and measurement implications are discussed. Lay abstract Despite being highly prevalent among people with autism, restricted and unusual interests remain under-researched and poorly understood. This article confirms that restricted interests are very frequent and varied among children and adolescents with autism. It also further extends current knowledge in this area by characterizing the relationship between the presence, number, and type of restricted interests with chronological age, sex, cognitive functioning, and social and communication symptoms.

Background The aim of this study was to understand the challenges experienced by families obtaining a diagnosis and therapy for developmental coordination disorder (DCD). Methods 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. Results 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. Conclusions 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. Impact 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.

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 examined whether parent-reported atypical development in their child’s first year was associated with age of diagnosis and age when parents first needed to consult a specialist about their child’s development. It involved 423 children who participated in the Australian Autism Biobank. Most parents retrospectively identified ≥ 1 domain of atypical child development. Atypical development in most domains was associated with an earlier age when parents felt specialist consultation was needed. Atypical development in the “gaze abnormalities”, “lack of response to social stimuli”, and “no social communication” subdomains within the social domain was associated with an earlier age of diagnosis, as was atypical development in the “hypo/hypersensitivity” and “preoccupation with parts of objects” subdomains within the stereotyped/restricted behavior domain.

Background Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism. Methods Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain. Results The ASD (p = 6.1e−13), sibling (p = 4.9e−3) and unrelated (p = 3.0e−3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height—a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e−3) and parents (r = 0.17, p = 8.0e−7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e−3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants. Limitations This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered. Conclusions We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).

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.

Background: Children on the autism spectrum may be at higher likelihood of poorer oral health or experience difficulties with dental health care. However, which children may be more vulnerable is still unknown. Aim: To investigate parental reports of oral health and dental service needs of children diagnosed with autism and explore relationships with clinical phenotypes. Design: Participants (n=140) were parents of children on the spectrum who had participated in a large biobank, the Australian Autism Biobank, and completed additional surveys about oral health, service use, and barriers to care. Results: One third of parents reported their child’s oral health was worse than other children the same age, with 26% reporting untreated dental problems. A third of children had undergone general anaesthesia at least once for dental procedures. Children who had undergone general anaesthesia were more likely to have intellectual impairments and greater functional difficulties. Parents of children with greater functional limitations and sensory challenges reported experiencing barriers to accessing dental care more frequently. Conclusions: These results have important implications for paediatric dentists working with children on the spectrum with co-occurring intellectual, functional, and sensory challenges. Findings may inform the development of more personalised supports for individuals on the autism spectrum.

IntroductionThere are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD.Methods and analysisThis study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14–40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024.Ethics and disseminationThe study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia’s National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12620000890932).

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.

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 A balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app—Sun Safe—through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). Objective The aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. Methods Young teenagers (aged 12-13 years; N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. Results Of the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most (>50%) reporting that they used a smartphone to access their designated app either “once a fortnight” or “once/twice in total.” Improved sun health knowledge—particularly about the UV Index—was observed in participants who were given access to Sun Safe compared with those who used the placebo (−6.2 [percentage correct] difference in predicted means, 95% CI –12.4 to –0.03; P=.049; 2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8; P=.02; Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic–related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by >100 minutes per day (–105 minutes per day difference in predicted means, 95% CI –150 to –59 minutes per day; P=.002; paired 2-tailed Student t test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). Conclusions Access to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger sample sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.

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.

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.

Altered trajectories of brain growth are often reported in Autism Spectrum Disorder (ASD), particularly during the first year of life. However, less is known about prenatal head growth trajectories, and no study has examined the relation with postnatal autistic symptom severity. The current study prospectively examined the association between fetal head growth and the spectrum of autistic symptom severity in two large population-based cohorts, including a sample of individuals with clinically diagnosed ASD. This study included 3,820 children from two longitudinal prenatal cohorts in The Netherlands and Australia, comprising 60 individuals with a confirmed diagnosis of ASD. Latent growth curve models were used to examine the relationship between fetal head circumference measured at three different time points and autistic traits measured in postnatal life using either the Social Responsiveness Scale or the Autism-Spectrum Quotient. While lower initial prenatal HC was weakly associated with increasing autistic traits in the Dutch cohort, this relationship was not observed in the Australian cohort, nor when the two cohorts were analysed together. No differences in prenatal head growth were found between individuals with ASD and controls. This large population-based study identified no consistent association across two cohorts between prenatal head growth and postnatal autistic traits. Our mixed findings suggest that further research in this area is needed. Autism Res 2018, 11: 602-612. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay summary It is not known whether different patterns of postnatal brain growth in Autism Spectrum Disorder (ASD) also occurs prenatally. We examined fetal head growth and autistic symptoms in two large groups from The Netherlands and Australia. Lower initial prenatal head circumference was associated with autistic traits in the Dutch, but not the Australian, group. No differences in head growth were found in individuals with ASD and controls when the data was combined. Our mixed findings suggest that more research in this area is needed.

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.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Maternal immune activation has been highlighted as a factor that might increase the risk and severity of autism spectrum disorder (ASD) in children. Preclinical animal evidence shows that immune activation in mothers during pregnancy causes ASD-like behavioural traits in offspring. To this point, there has been no investigation of whether immune system activation in human mothers during pregnancy is associated with more severe symptoms in children with ASD. In this study, data from an existing ASD cohort (N=220) were analysed to investigate whether immune conditions in the mother were associated with greater severity of autism-related symptoms. Results showed that children whose mothers reported a history of immune activation (allergies and asthma) had significantly higher scores on the Social Responsiveness Scale (SRS; P=0.016), suggesting more severe social impairment symptoms in these children. This increasing severity of social impairment symptoms was further shown on the SRS cognition (P=0.007) and mannerisms (P=0.002) subscales. While immune history was associated with an increase in the severity of social impairment symptoms, history of autoimmune conditions in the mother did not have any effect in this cohort. To the best of our knowledge, this study is the first to show an association between immune activation history in the mother and increased ASD symptom severity in children with ASD. These findings support the idea of an immune system-mediated subtype in ASD, where the immune history of the mother may be an important factor.

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. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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 (Mage = 8.09 years, SD = 4.28; 119 males) completed an early developmental milestones questionnaire and the Social Responsiveness Scale as a measure of Insistence on Sameness (IS) and Repetitive Mannerisms (RM). Two hierarchical regression analyses were conducted to test whether RM and IS behaviors were predicted by early motor milestones, or current toe walking. The final model predicting RM accounted for 15% of the variance (F = 3.02, p = .009), with toe walking as a unique and independent predictor of RM scores (t = 3.568, p = .001). The final model predicting IS accounted for 19.1% of variance in IS scores (F = 4.045, p = .001), with chronological age (CA) (t = 2.92, p = .004), age when first standing (t = 2.09, p = .038), and toe walking (t = 2.53, p = .013) as unique independent predictors. Toe walking (t = 2.4, p = .018) and age when first sitting (t = 2.08, p = .04) predicted the severity of RRBs on the Autism Diagnostic Observation Schedule (F = 2.334, p = .036). Our study replicates previous findings on the relationship between concurrent motor impairments and RRBs, and provides the first evidence for the association between RRBs and age of attainment of early motor milestones. Autism Res 2017. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2017, 10: 1163-1168. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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.

Extensive research efforts in the last decade have been expended into understanding whether intranasal oxytocin may be an effective therapeutic in treating social communication impairments in individuals with autism spectrum disorder (ASD). After much hyped early findings, subsequent clinical trials of longer-term administration have yielded more conservative and mixed evidence. However, it is still unclear at this stage whether these more disappointing findings reflect a true null effect or are mitigated by methodological differences masking true effects. In this review, we comprehensively evaluate the rationale for oxytocin as a therapeutic, evaluating evidence from randomized controlled trials, case reports, and open-label studies of oxytocin administration in individuals with ASD. The evidence to date, including reviews of preregistered trials, suggests a number of critical considerations for the design and interpretation of research in this area. These include considering the choice of ASD outcome measures, dosing and nasal spray device issues, and participant selection. Despite these limitations in the field to date, there remains significant potential for oxytocin to ameliorate aspects of the persistent and debilitating social impairments in individuals with ASD. Given the considerable media hype around new treatments for ASD, as well as the needs of eager families, there is an urgent need for researchers to prioritise considering such factors when conducting well-designed and controlled studies to further advance this field. Autism Res 2017, 10: 25-41. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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 phenotypic and genetic heterogeneity of autism spectrum disorder (ASD) presents considerable challenges in understanding etiological pathways, selecting effective therapies, providing genetic counselling, and predicting clinical outcomes. With advances in genetic and biological research alongside rapid-pace technological innovations, there is an increasing imperative to access large, representative, and diverse cohorts to advance knowledge of ASD. To date, there has not been any single collective effort towards a similar resource in Australia, which has its own unique ethnic and cultural diversity. The Australian Autism Biobank was initiated by the Cooperative Research Centre for Living with Autism (Autism CRC) to establish a large-scale repository of biological samples and detailed clinical information about children diagnosed with ASD to facilitate future discovery research. Methods The primary group of participants were children with a confirmed diagnosis of ASD, aged between 2 and 17 years, recruited through four sites in Australia. No exclusion criteria regarding language level, cognitive ability, or comorbid conditions were applied to ensure a representative cohort was recruited. Both biological parents and siblings were invited to participate, along with children without a diagnosis of ASD, and children who had been queried for an ASD diagnosis but did not meet diagnostic criteria. All children completed cognitive assessments, with probands and parents completing additional assessments measuring ASD symptomatology. Parents completed questionnaires about their child’s medical history and early development. Physical measurements and biological samples (blood, stool, urine, and hair) were collected from children, and physical measurements and blood samples were collected from parents. Samples were sent to a central processing site and placed into long-term storage. Discussion The establishment of this biobank is a valuable international resource incorporating detailed clinical and biological information that will help accelerate the pace of ASD discovery research. Recruitment into this study has also supported the feasibility of large-scale biological sample collection in children diagnosed with ASD with comprehensive phenotyping across a wide range of ages, intellectual abilities, and levels of adaptive functioning. This biological and clinical resource will be open to data access requests from national and international researchers to support future discovery research that will benefit the autistic community.

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.

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.

There is growing interest in the role of the oxytocin system in social cognition and behavior. Peripheral oxytocin concentrations are regularly used to approximate central concentrations in psychiatric research. This methodological approach has obvious appeal given the invasiveness of cerebrospinal fluid collection. However, the validity of this approach and potential moderators of the association between central and peripheral levels are unclear. Thus, we conducted a pre-registered systematic search and meta-analysis of correlations between central and peripheral oxytocin concentrations. A search of databases yielded 17 eligible studies for effect size synthesis and moderator analysis, resulting in a total sample size of 516 participants and subjects. Overall, a positive association between central and peripheral oxytocin concentrations was revealed [r=0.29, 95% CI (0.15, 0.42), pr=0.67, pp=.0002) than the equivalent association under baseline conditions (r=0.08, p=.31). These results support the use of peripheral levels of oxytocin as a marker of central levels, but only after exogenous oxytocin administration. Despite the popularity of using peripheral OT levels to approximate central levels during baseline conditions, this approach is not supported by the present results.

The structurally similar neuropeptides and hormones oxytocin (OT) and arginine vasopressin (AVP) play significant and complex roles in modulating a range of social behaviours, including social recognition and bond formation. Although OT has well-known roles in facilitating prosocial behaviors and enhancing emotion recognition, AVP has received increasing interest for diverging effects on social cognition behaviour most notably in males. The current study aimed to determine whether AVP also modulates the ability to understand emotion. Using a randomised double blind procedure, 45 healthy young males received either an AVP or placebo nasal spray and completed the Reading the Mind in the Eyes Test (RMET). In contrast to previous findings, there were no significant differences observed in performance on the RMET between AVP and placebo groups, even after examining items separated by task difficulty, emotional valence, and gender. This study provides diverging evidence from previous findings and adds to the growing body of research exploring the influence of neuropeptide hormones in social behaviour. It demonstrates that in this sample of participants, AVP does not enhance the ability to understand higher order emotion from others. Implications and suggestions for future AVP administration studies are discussed.

Neuropeptides are small molecules that act as messengers between different brain regions. There are roughly 100 neuropeptides that are important for various functions, including hunger, memory, and learning. Oxytocin is a neuropeptide that plays a crucial role in childbirth and breastfeeding. More recently, oxytocin has been shown to be essential for our social behaviors. When given to people in the form of a nasal spray, oxytocin can change key aspects of social behavior, such as how easily we can recognize emotions in others. People with autism often have difficulties in understanding and using social information, and scientists have been testing oxytocin nasal spray as a potential treatment. But how does oxytocin nasal spray travel from the nose to the brain, and how does it change how we behave socially?

Background Research examining the effects of oxytocin (OT) interventions on psychiatric, social-behavioral, and social-cognitive outcomes regularly collect peripheral levels of OT as markers of central bioavailability. Such inferences rest on the assumption that central and peripheral levels of OT are directly associated. However, conflicting evidence from coordinated sampling of central and peripheral OT question the validity of this assumption. The purpose of this meta-analysis is to evaluate the correlation between central and peripheral OT, as well as to account for potential heterogeneity in the literature. Methods/design Studies that report coordinated sampling of central and peripheral OT in humans and animals will be identified. Research investigating concentrations in both basal states and after exogenous administration will be considered. PubMed and Embase databases will be searched, along with citation lists of retrieved articles. Peer-reviewed studies written in English published from 1971 onwards will be included in the meta-analysis. Data will be extracted from eligible studies for a random-effects meta-analysis. For each study, a summary effect size, heterogeneity, risk of bias, publication bias, and the effect of categorical and continuous moderator variables will be determined. Discussion This systematic review and meta-analysis will identify and synthesize evidence to determine if there is an association between central and peripheral OT concentrations. If significant associations are observed, evidence would provide a rationale for future research to use peripheral measures as a proxy for central OT concentrations. Systematic review registration PROSPERO CRD42015027864

The number of publications investigating heart rate variability (HRV) in psychiatry and the behavioral sciences has increased markedly in the last decade. In addition to the significant debates surrounding ideal methods to collect and interpret measures of HRV, standardized reporting of methodology in this field is lacking. Commonly cited recommendations were designed well before recent calls to improve research communication and reproducibility across disciplines. In an effort to standardize reporting, we propose the Guidelines for Reporting Articles on Psychiatry and Heart rate variability (GRAPH), a checklist with four domains: participant selection, interbeat interval collection, data preparation and HRV calculation. This paper provides an overview of these four domains and why their standardized reporting is necessary to suitably evaluate HRV research in psychiatry and related disciplines. Adherence to these communication guidelines will help expedite the translation of HRV research into a potential psychiatric biomarker by improving interpretation, reproducibility and future meta-analyses.

Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental conditions associated with persistent, stereotyped or repetitive actions, and patterns of interest that are maintained in spite of possible negative outcomes. The aim of the present study was to investigate whether impairments in the ability to execute flexible goal-directed actions may be an underlying feature in ASD contributing to these symptoms. Young adults diagnosed with ASD were recruited along with controls and adults with social anxiety disorder (SAD). Participants were trained to make keyboard actions for food outcomes and then subsequently allowed to consume one outcome till satiety. As expected, this outcome devaluation procedure reduced subsequent responding for actions predicting the devalued outcome, while maintaining responding on the other still-valued action, in controls. However, both ASD and SAD participants were unable to demonstrate flexible goal-directed actions, and were insensitive to the change in outcome value on subsequent action control. This behavioral deficit was not due to impairments in appropriate contingency awareness, as all groups rated the devalued food outcome as less pleasant after devaluation. A lack of control over actions may underlie persistent and habitual actions in anxiety-inducing contexts typical in both ASD and SAD, such as avoidance and safety behaviors. Using a translational behavioral paradigm, this study demonstrated that individuals with ASD are unable to use changes in the environment to flexibly update their behavior in the same context. This reduced behavioral control may underlie persistence of intrusive actions and restricted inflexible cognition, representing a specific area for targeted behavioral interventions. Autism Res 2016. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. Autism Res 2016, 9: 1285-1293. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Cumulative evidence over the last decade indicates that intranasally administered oxytocin (OT) has a major impact on social behavior and cognition. In parallel, researchers have also highlighted the effects of OT on cardiovascular (CV) and autonomic nervous system (ANS) regulation. Taken at face value, these two streams of research appear largely unrelated. However, another line of evidence highlights a key role for autonomic cardiac control in social behavior and cognition. In this review, we suggest that autonomic cardiac control may moderate the relationship between OT and social behavior. We also highlight the importance of autonomic cardiac control in psychiatric disorders of social dysfunction and suggest that heart rate variability (HRV)—an index of autonomic cardiac control—may play a key role in patient response in treatment trials of OT.

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.

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.