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.

Child and caregiver predictors of primary caregiver participation in families of school-aged Autistic children.

Engaging in meaningful activities (e.g., leisure, spiritual, fitness) significantly affects caregivers' quality of life (QoL), yet the determinants of participation in caregivers of Autistic children remain largely unknown. The current study examined child and caregiver correlates of primary caregiver participation in meaningful activities. One hundred and six primary caregivers of Autistic children (7-12 years) were recruited from three unique cohorts of Autistic children in this cross-sectional study. Primary caregivers completed online questionnaires measuring occupational gaps (i.e., desired activities caregivers are not participating in), QoL, parenting stress, perceived family outcomes, and social support. In addition to undertaking direct assessments of children's cognition and language, primary caregivers also reported on their child's adaptive behavior, social-emotional skills, and participation. Caregivers reporting fewer occupational gaps (i.e., ≤2 desired activities) were more likely to have Autistic children with no co-occurring conditions, who were older, and with better adaptive behaviors, social-emotional skills, and more frequent home and school participation, compared to caregivers reporting many gaps (i.e., ≥3 desired activities). Caregivers with fewer occupational gaps also reported improved QoL, parenting stress, social support, perceived community inclusiveness, and family outcomes. Logistic regression analysis identified child age, child adaptive behavior, social-emotional skills, home participation, and the caregivers' perceived family outcomes and QoL as important predictors of their occupational gaps. The findings demonstrate that caregiver participation in desired activities was associated with increased functional ability and independence of the child, as well as their perceived capacity to meet their child's needs. Supporting parents' sense of efficacy in meeting their children's needs and building their skills and knowledge will serve to improve both caregiver and child outcomes.

Leisure, community, workforce participation and quality of life in primary and secondary caregivers of autistic children.

Parents of Autistic children often modify their participation in leisure, social, and employment activities to meet the caregiving needs of their child. However, few studies have examined the impact this has on caregiver quality of life (QoL). The aim in the current study was to examine the role of participation in a range of activities on QoL amongst primary and secondary caregivers of school-aged Autistic children. Eighty-eight primary (93% mothers) and 63 secondary (91% fathers) caregivers of Autistic children (aged 7- to 12-years) participated in this cross-sectional study, with time pressure, participation, social support, parenting stress, and QoL measured via an online questionnaire. Compared to secondary caregivers, primary caregivers reported fewer employment hours, increased time pressure, less participation in desired activities, and higher perceived responsibility of domestic and child-rearing tasks. Similar levels of leisure frequency, parenting stress, and QoL were identified by both caregivers. Hierarchical regression revealed caregiver participation as important for QoL in both primary and secondary caregivers. However, when measures of caregiver well-being were added to the model, the unique contribution of participation to QoL was reduced, particularly for secondary caregivers. Overall, the findings demonstrate that despite differences in caregiver roles and responsibilities, participation in meaningful activities was important for QoL in all caregivers.

Stress and well-being in autistic adults: Exploring the moderating role of coping.

The wider stress literature points to negative associations between stress and well-being. Similarly, the use of engagement coping strategies and disengagement coping strategies in the face of stress are related to improved and reduced well-being respectively. However, in the autistic population stress and coping research is limited to date, and the extent to which coping may moderate the relationship between stress and well-being is not known. Using data from an Australian online study, we explored the potential moderating (i.e. buffering or exacerbating) role of coping in the relationship between stress and well-being in a sample of autistic adults (N = 86). Our findings indicated that increased stress was associated with lower well-being. Further, moderation analyses showed that while both engagement coping (e.g. problem solving, positive appraisal) and disengagement coping (e.g., self-distraction, being in denial) strategies had significant positive and negative direct effects on well-being respectively; engagement coping also moderated the relationship between stress and well-being, buffering the impact of stress on well-being. Our results illustrate the different underlying mechanisms by which coping strategies may be associated with stress and well-being. They also highlight the potential protective role of engagement coping strategies, which can be incorporated into the promotion and maintenance of well-being in autistic adults.

Brief Report: Longitudinal Role of Coping Strategies on Mental Health Outcomes in Autistic Youth and Adults.

The stress literature suggests that coping strategies are implicated in mental health outcomes. However, the longitudinal relationship between coping strategies and mental health in the autistic adult population has not yet been examined. This 2-year longitudinal study examined the predictive role of both baseline and change in coping strategy use over time (i.e., an increase or decrease) on anxiety, depression, and well-being after 2-years in 87 autistic adults aged 16 to 80 years. Controlling for baseline mental health, both baseline and increase in disengagement coping strategies (e.g., denial, self-blame) predicted higher anxiety and depression, and lower well-being, while an increase in engagement coping strategies (e.g., problem solving, acceptance) predicted higher well-being. These findings extend the current coping literature in autistic adults, offering insight into mental health support and intervention options.

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.

Coping-resilience profiles and experiences of stress in autistic adults.

Emerging studies allude to high stress in autistic adults. Considering the detrimental impact of stress on health outcomes, examining individual resources which may influence the extent to which stress is experienced (e.g., coping and resilience) is vital. Using a person-focused approach, this study aimed to identify coping-resilience profiles, and examine their relations to general perceived stress and daily hassles in a sample of autistic adults (N = 86; aged 19-74 years). Cluster analysis identified four coping-resilience profiles (i.e., high cope/ low resilience, low cope/ high resilience, engage cope/ high resilience, and disengage cope/ low resilience). The high cope/ low resilience and disengage cope/ low resilience groups had significantly higher general perceived stress than the remaining groups. No significant group differences were noted in relation to daily hassles. Jointly addressing coping and resilience may be beneficial on the perceived stress experienced in autistic adults. The use of coping-resilience profiles may also allow for the personalization of stress management and support options in the autistic adult population.

Associations between coping strategies and mental health outcomes in autistic adults.

Compared to the general population, mental health difficulties are commonly reported in autistic adults. However, the ways in which coping strategies are associated with mental health and well-being in this population remain unknown. Further, we do not know if, and if so, how these associations might differ to that of non-autistic adults. In this study, we hypothesized that in both our autistic (N = 255) and non-autistic (N = 165) adult samples, disengagement coping strategies (e.g., denial) would relate to poorer mental health and well-being, while engagement coping strategies (e.g., problem solving) would relate to better mental health and well-being. Regression analyses revealed that higher use of disengagement coping strategies was significantly associated with higher levels of anxiety and depression, and lower levels of well-being in both samples. In contrast, increased use of engagement coping strategies was associated with better well-being, but only in the autistic sample. Our results contribute to the characterization of negative and positive mental health outcomes in autistic adults from a coping perspective, with potential to offer novel information regarding coping strategies to consider when addressing support options for mental health difficulties in the autistic adult population. LAY SUMMARY: Mental health conditions (such as anxiety and depression) and poor well-being are commonly reported in autistic adults. Research suggests that how one copes with stress is associated with one's mental health and well-being. However, we have little information about how coping strategies relate to the mental health of autistic adults, and whether this might be different in non-autistic adults. In this study, we examined the relationship between coping strategies and mental health in a large group of autistic individuals aged 15-80 years. We then compared this with similar aged non-autistic individuals. We found that in both the autistic and non-autistic individuals, using more disengagement coping strategies (such as being in denial, blaming oneself) was related to poorer mental health and well-being. Additionally, using more engagement coping strategies (such as problem solving, acceptance) was related to better mental health and well-being, but only in the autistic individuals. These results can help inform support services, as they highlight the coping strategies that may need to be focused on (i.e., developing engagement coping strategies and reducing disengagement coping strategies) in order to better support the mental health of autistic individuals.

Inter-relationships between trait resilience, coping strategies, and mental health outcomes in autistic adults.

Resilience has been depicted as a key characteristic in the promotion of mental health in the face of stress and adversity. Despite high levels of stress encountered in the autistic population, resilience studies remain scarce. Using data from an Australian longitudinal adult study, this study explored the inter-relationships between trait resilience, coping, and mental health in a sample of autistic adults (N = 78). In particular, we examined the relationship between resilience and use of coping strategies, and the potential mediating role of coping strategies in the relationship between resilience and mental health outcomes. Our findings suggested that increased use of engagement coping (e.g., problem-solving, positive appraisal) and decreased use of disengagement coping (e.g., self-blame, being in denial) strategies were associated with higher levels of resilience. Further, mediation analysis results suggest that disengagement coping mediated the associations between resilience and all three mental health outcomes (i.e., depression, anxiety, and well-being), while engagement coping strategies mediated the relationship between resilience and well-being only. Our results illustrate that coping strategies may be an important mechanism in explaining the resilience-mental health relationship in autistic adults, highlighting the importance of considering stress-related constructs together (i.e., trait resilience and coping) when addressing support and intervention options for mental health difficulties in the autistic adult population. LAY SUMMARY: This research explored how resilience and coping strategies influence the mental health and well-being of autistic adults. We found that resilient autistic adults used more engagement coping strategies, less disengagement coping strategies, and reported better mental health and well-being. Considering stress-related factors together (i.e., resilience and coping) offers a novel perspective to mental health difficulties in autistic adults and may be a vital step in the development of support options in this population.

Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.

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).