Autism-related dietary preferences mediate autism-gut microbiome associations.

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.

An investigation of a novel broad autism phenotype: increased facial masculinity among parents of children on the autism spectrum.

The broad autism phenotype commonly refers to sub-clinical levels of autistic-like behaviour and cognition presented in biological relatives of autistic people. In a recent study, we reported findings suggesting that the broad autism phenotype may also be expressed in facial morphology, specifically increased facial masculinity. Increased facial masculinity has been reported among autistic children, as well as their non-autistic siblings. The present study builds on our previous findings by investigating the presence of increased facial masculinity among non-autistic parents of autistic children. Using a previously established method, a 'facial masculinity score' and several facial distances were calculated for each three-dimensional facial image of 192 parents of autistic children (58 males, 134 females) and 163 age-matched parents of non-autistic children (50 males, 113 females). While controlling for facial area and age, significantly higher masculinity scores and larger (more masculine) facial distances were observed in parents of autistic children relative to the comparison group, with effect sizes ranging from small to medium (0.16 ≤ d ≤ .41), regardless of sex. These findings add to an accumulating evidence base that the broad autism phenotype is expressed in physical characteristics and suggest that both maternal and paternal pathways are implicated in masculinized facial morphology.

The unmet clinical needs of children with developmental coordination disorder.

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.

Investigating associations between birth order and autism diagnostic phenotypes.

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

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

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

Attenuated Psychophysiological Reactivity following Single-Session Group Imagery Rescripting versus Verbal Restructuring in Social Anxiety Disorder: Results from a Randomized Controlled Trial.

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.

Study protocol for the Australian autism biobank: an international resource to advance autism discovery research.

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.

Autonomic nervous system dysfunction in psychiatric disorders and the impact of psychotropic medications: a systematic review and meta-analysis.

BACKGROUND: Autonomic nervous system (ANS) dysfunction is a putative underlying mechanism for increased cardiovascular disease risk in individuals with psychiatric disorders. Previous studies suggest that this risk may be related to psychotropic medication use. In the present study we systematically reviewed and analyzed published studies of heart rate variability (HRV), measuring ANS output, to determine the effect of psychiatric illness and medication use. METHODS: We searched for studies comparing HRV in physically healthy adults with a diagnosed psychiatric disorder to controls and comparing HRV pre- and post-treatment with a psychotropic medication. RESULTS: In total, 140 case-control (mood, anxiety, psychosis, dependent disorders, k = 151) and 30 treatment (antidepressants, antipsychotics; k = 43) studies were included. We found that HRV was reduced in all patient groups compared to controls (Hedges g = -0.583) with a large effect for psychotic disorders (Hedges g = -0.948). Effect sizes remained highly significant for medication-free patients compared to controls across all disorders. Smaller and significant reductions in HRV were observed for specific antidepressants and antipsychotics. LIMITATIONS: Study quality significantly moderated effect sizes in case-control analyses, underscoring the importance of assessing methodological quality when interpreting HRV findings. CONCLUSION: Combined findings confirm substantial reductions in HRV across psychiatric disorders, and these effects remained significant even in medication-free individuals. Reductions in HRV may therefore represent a significant mechanism contributing to elevated cardiovascular risk in individuals with psychiatric disorders. The negative impact of specific medications on HRV suggest increased risk for cardiovascular disease in these groups, highlighting a need for treatment providers to consider modifiable cardiovascular risk factors to attenuate this risk.

The effects of a course of intranasal oxytocin on social behaviors in youth diagnosed with autism spectrum disorders: a randomized controlled trial.

BACKGROUND: There is increasing interest in oxytocin as a therapeutic to treat social deficits in autism spectrum disorders (ASD). The aim of this study was to investigate the efficacy of a course of oxytocin nasal spray to improve social behavior in youth with ASD. METHODS: In a double-blind, placebo-controlled trial across two Australian university sites between February 2009 and January 2012, 50 male participants aged between 12 and 18 years, with Autistic or Asperger's Disorder, were randomized to receive either oxytocin (n = 26) or placebo (n = 24) nasal sprays (either 18 or 24 International Units), administered twice-daily for 8 weeks. Participants were assessed at baseline, after 4- and 8-weeks of treatment, and at 3-month follow-up. Primary outcomes were change in total scores on the caregiver-completed Social Responsiveness Scale and clinician-ratings on the Clinical Global Impressions-Improvement scale. Secondary assessments included caregiver reports of repetitive and other developmental behaviors and social cognition. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry www.anzctr.org.au ACTRN12609000513213. RESULTS: Participants who received oxytocin showed no benefit following treatment on primary or secondary outcomes. However, caregivers who believed their children received oxytocin reported greater improvements compared to caregivers who believed their child received placebo. Nasal sprays were well tolerated and there was no evidence of increased side effects resulting from oxytocin administration. CONCLUSIONS: This is the first evaluation of the efficacy for a course of oxytocin treatment for youth with ASD. Although results did not suggest clinical efficacy, further research is needed to explore alternative delivery methods, earlier age of intervention, and the influence of caregiver expectation on treatment response.

Ambulatory sleep-wake patterns and variability in young people with emerging mental disorders.

BACKGROUND: The nature of sleep-wake abnormalities in individuals with mental disorders remains unclear. The present study aimed to examine 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.

Psychosocial wellbeing, parental concerns, and familial impact of children with developmental coordination disorder.

BACKGROUND: Developmental Coordination Disorder (DCD) is a neurodevelopmental condition impacting motor skill acquisition and competence. While previous studies have identified adverse psychosocial outcomes in DCD, they are limited by small or population-screened, community-based samples. AIMS: To understand the psychosocial difficulties, parental concerns, and familial impacts of childhood DCD in a large population-based sample. METHODS AND PROCEDURES: Parents of 310 children aged 4 - 18 years with a diagnosis of DCD (or synonymous term) completed the Impact for DCD survey. Parent-rated measures of emotional problems, peer problems, and prosocial behaviour were compared to normative data. Parental concerns for the impact of DCD on participation, interaction, emotional well-being, and the family system were examined. OUTCOMES AND RESULTS: Compared to typically developing children, children with DCD were rated significantly higher for emotional and peer problems, and significantly lower for prosocial behaviours. Parents most commonly reported concerns for their child's future and withdrawal from physical activity. The presence of one or more co-occurring disorders did not significantly influence outcomes. CONCLUSION AND IMPLICATIONS: Findings highlight the poor psychosocial outcomes for children with DCD. Crucially, poor psychosocial outcomes were just as likely in those with a single diagnosis of DCD as those with DCD and multiple co-occurring diagnoses. Parents reported concerns for their child (i.e., non-participation and social withdrawal) that are not targeted in existing DCD intervention modalities and emphasised the impact of DCD on the whole family unit. WHAT THIS PAPER ADDS: This paper presents data from the largest parent-reported survey of children with a known diagnosis of DCD (or synonymous labels). It highlights the significant impact of DCD on psychosocial outcomes in children across age groups. The children in this study were rated by their parents to have significantly higher levels of emotional and peer problems, and lower prosocial behaviours, than similarly aged Australian children without DCD. It also challenges the misconception that poor psychosocial outcomes in DCD are the result of co-occurring disorders, with outcomes observed to be as poor in children with a sole diagnosis of DCD in this sample. Furthermore, findings highlighted the significant worry and concern that parents with DCD face, particularly around their child's participation and their emotional health. Finally, parents reported on the considerable impact that DCD had on their family unit, regularly causing worry and concern, influencing their choice of activities, and causing financial strain. These concerns and impacts are not addressed in current intervention models for DCD and highlight the need for support mechanisms moving forward.

Investigating the impact of developmental coordination difficulties across home, school, and community settings: Findings from the Australian Impact for DCD survey.

AIM: To evaluate the participation difficulties experienced by children with developmental coordination disorder (DCD) in home, school, and community environments. METHODS: The Impact for DCD survey was completed by primary caregivers of 4-18-year-old children with DCD (or synonymous diagnosis) (n = 429). OUTCOMES AND RESULTS: The greatest participation difficulties experienced at home included dressing, eating with utensils, self-care tasks and drawing/writing reported by over 70% of families. At school, fine motor difficulties were also frequently reported, with additional difficulties keeping up or completing tasks, and not feeling supported at school. Socialisation challenges and bullying were also commonly reported (34.9%). As a result of participation difficulties at school, 5.4% were home schooled. Many children engaged in community activity, with 72.0% currently engaged in at least one organised sports-based activity. CONCLUSIONS AND IMPLICATIONS: Increased recognition of the widespread impact of DCD in a child's life is crucial at an individual and societal level. Parents reported their children experiencing significant participation restrictions and difficulties. The findings of this large-scale study have revealed that most children with DCD are not receiving the support they need to thrive, especially at school. This largely reflects a lack of understanding and recognition of the condition and its associated challenges.

Parent-reported atypical development in the first year of life and age of autism diagnosis.

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.

Dental care experiences and clinical phenotypes in children on the autism spectrum.

AIMS: Children diagnosed with autism spectrum disorder may be at higher likelihood of experiencing poorer oral health and difficulties accessing dental health care. However, identifying which children on the autism spectrum may be more vulnerable to experiencing dental care difficulties is still unknown. This study investigated parental reports of oral health and dental service needs of children diagnosed with autism and explored relationships with clinical phenotypes. METHODS AND RESULTS: Participants (n = 140) were parents of children on the autism spectrum who had participated in a large national biobank study, the Australian Autism Biobank, invited to complete additional surveys about oral health, service use, and barriers to care. 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 were reported to have undergone general anaesthesia at least once for dental procedures. Children who had undergone general anaesthesia were more likely to have intellectual disability and greater functional difficulties. Parents of children with greater functional limitations and sensory challenges reported experiencing barriers to accessing dental care more frequently. CONCLUSION: These results have important implications for paediatric dentists working with children diagnosed with autism with co-occurring intellectual, functional, and sensory challenges. Findings may inform the development of more personalised autism-specific supports.

Characterizing restricted and unusual interests in autistic youth.

A broad range of interests characterized by unusual content and/or intensity, labeled as circumscribed interests (CI), are a core diagnostic feature of autism. Recent evidence suggests that a distinction can be drawn between interests that, although characterized by unusually high intensity and/or inflexibility, are otherwise common in terms of their content (e.g., an interest in movies or animals), labeled as restricted interests (RI), and interests that are generally not salient outside of autism (e.g., an interest in traffic lights or categorization), labeled as unusual interests (UI). The current study aimed to further characterize RI and UI by exploring their association with age, sex, IQ, and social motivation, as well as to examine differences in the adaptive benefits and negative impacts of these two subdomains. Parents of 1892 autistic children and adolescents (Mage  = 10.82, SDage  = 4.14; 420 females) completed an online survey including the Dimensional Assessment of Restricted and Repetitive Behaviors and the Social Communication Questionnaire. Both RI and UI were found to be highly frequent. Sex-based differences were observed in the content, but not intensity, of CI such that females were more likely to show interests with a social component. Finally, RI and UI showed distinct patterns of association with age, sex, IQ, and social motivation, as well as metrics of adaptive benefits and negative impacts. Findings afford a more nuanced understanding of sex-based differences in CI and, crucially, provide preliminary evidence that RI and UI represent distinct constructs that should be studied independently in future research.

Profiles of circumscribed interests in autistic youth.

Circumscribed interests (CI) encompass a range of different interests and related behaviors that can be characterized by either a high intensity but otherwise usual topic [referred to as restricted interests (RI)] or by a focus on topics that are not salient outside of autism [referred to as unusual interests (UI)]. Previous research has suggested that there is pronounced variability across individuals in terms of the endorsement of different interests, however, this variability has not been quantified using formal subtyping approaches. Therefore, using Latent Profile Analysis in a sample of 1,892 autistic youth (Mage = 10.82, SDage = 4.14; 420 females), this study aimed to identify subgroups based on the RU and UI profiles. Three profiles of autistic individuals were identified. They were characterized as Low CI, Predominantly RI, and Predominantly UI. Importantly, profiles differed on several key demographic and clinical variables, including age, sex composition, IQ, language level, social and communication abilities, anxiety, and obsessive-compulsive behaviors. Although replication across other samples is needed, the profiles identified in this study are potentially promising for future research given their distinct profiles of RI and UI and unique patterns of associations with key cognitive and clinical variables. Therefore, this study represents an important initial step towards more individualized assessment and support for diverse presentations of CI in autistic youth.

Reliability of the Commonly Used and Newly-Developed Autism Measures.

PURPOSE: The aim of the present study was to compare scale and conditional reliability derived from item response theory analyses among the most commonly used, as well as several newly developed, observation, interview, and parent-report autism instruments. METHODS: When available, data sets were combined to facilitate large sample evaluation. Scale reliability (internal consistency, average corrected item-total correlations, and model reliability) and conditional reliability estimates were computed for total scores and for measure subscales. RESULTS: Generally good to excellent scale reliability was observed for total scores for all measures, scale reliability was weaker for RRB subscales of the ADOS and ADI-R, reflecting the relatively small number of items for these measures. For diagnostic measures, conditional reliability tended to be very good (> 0.80) in the regions of the latent trait where ASD and non-ASD developmental disability cases would be differentiated. For parent-report scales, conditional reliability of total scores tended to be excellent (> 0.90) across very wide ranges of autism symptom levels, with a few notable exceptions. CONCLUSIONS: These findings support the use of all of the clinical observation, interview, and parent-report autism symptom measures examined, but also suggest specific limitations that warrant consideration when choosing measures for specific clinical or research applications.

Interactions between the lipidome and genetic and environmental factors in autism.

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.

Toward better characterization of restricted and unusual interests in youth with autism.

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.