Publications and outputs
Interactions between the lipidome and genetic and environmental factors in autism
This study looked at interactions between the lipidome and genetic and environmental factors in autism. Lipids are fat molecules that play important roles in neurodevelopment and metabolism. We explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism) within the Australian Autism Biobank. We found that various plasma lipids were associated with autism diagnosis, IQ and sleep disturbances. Sleep problems had the strongest lipid associations, whereas autism had weaker associations with lipids. Notably, lower levels of some long-chain polyunsaturated fatty acids appeared to contribute to sleep problems.
Yap, C.X., Henders, A.K., Alvares, G.A. et al. Interactions between the lipidome and genetic and environmental factors in autism. Nat Med 29, 936–949 (2023).
Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles
In this study of dietary differences linked to autism, children, and teenagers on the spectrum ate fewer different foods and were less likely to eat recommended amounts of fruits and vegetables when compared to non-autistic siblings and unrelated children and teenagers. There were also family differences, in that those on the spectrum and their siblings ate more unhealthy foods and less dairy. Among those on the spectrum, dietary differences were linked to age, sex, autistic traits and sensory processing styles.
Mathew, N.E., Mallitt, K.A., Masi, A., Katz, T., Walker, A.K., Morris & M.J., Ooi, C.Y. (2022). Dietary intake in children on the autism spectrum is altered and linked to differences in autistic traits and sensory processing styles. Autism Res. doi: 10.1002/aur.2798.
Sleep difficulties in children on the autism spectrum: Understanding the biological and behavioural attributes leading to sleep difficulties in children on the autism spectrum
Sleep is now recognised as a fundamental factor contributing to the quality of life. By understanding the biological and behavioural attributes of sleep difficulties as a comorbidity in children on the autism spectrum, we can provide the right supports to improve quality of life. The project team examined a range of clinical and behavioural data from 969 children on the autism spectrum, 188 siblings and 111 non-related, non-autistic children (controls) from the Australian Autism Biobank. Results from this project showed that children and adolescents with a diagnosis of autism were more likely to have greater severity of sleep difficulties compared to both siblings and unrelated children without an autism diagnosis. Specifically, children on the autism spectrum had more bedtime resistance, greater sleep onset delay, reduced sleep duration, increased levels of sleep anxiety, more night awakenings and parasomnias and greater levels of daytime sleepiness than both siblings and unrelated children without an autism diagnosis. A range of other findings and recommendations can be found in the Final Report.
Masi, A., Eapen, V., Lin, P-I., Moni, M.A., Heussler, H. (2022). Sleep difficulties in children on the autism spectrum: Understanding the biological and behavioural attributes leading to sleep difficulties in children on the autism spectrum. Final Report. Brisbane: Autism CRC
Genetic pathways associated with sleep problems in children with autism spectrum disorder
The goal of study was to identify genetic variants associated with sleep disturbance and melatonin levels in autistic children. The data from this study indicated that urine melatonin levels were positively associated with Children's Sleep Habits Questionnaire (CSHQ) scores, suggesting that autistic children with a poorer sleep quality could have higher melatonin level. Furthermore, genetic association studies suggest that genetic pathways involved in pro-inflammatory responses might be involved in sleep disturbance. Taken together, our findings indicate that sleep disturbance and melatonin metabolism could be attributable to distinct biological mechanisms in autistic children since they might not share genetic contributors.
Lin, P.I., Masi, A., Moni, M.A., Kummerfeld, S. & Eapen, V. (2022). Genetic pathways associated with sleep problems in children with autism spectrum disorder. Front Psychiatry. Jul 8;13:904091. doi: 10.3389/fpsyt.2022.904091.
Inflammation and neuromodulation in autism: Defining an immune-mediated subgroup of children in the Australian Autism Biobank
Autism is a condition that is widely known to be associated with a large amount of diversity in relation to behavioural traits, associated challenges, co-occurring conditions, and underlying biology. This diversity is referred to as ‘heterogeneity.’ Heterogeneity poses challenges when studying the usefulness of specific supports or when studying underlying biological processes in autistic populations, because these are believed to vary between subgroups on the spectrum. To improve outcomes for children and adults on the autism spectrum, we need to understand which supports work best for different subgroups of autistic individuals. Our study identified four subgroups of children on the autism spectrum within the Australian Autism Biobank.
Montgomery, A., Masi, A., Silove, N., Karlov, L., Whitehouse, A., Eapen, V. (2022). Defining an immune-mediated subgroup of children in the Australian Autism Biobank [Executive summary]. Final Report. Brisbane: Autism CRC.
Patterns of sensory modulation by age and sex in young people on the autism spectrum
We studied sensory symptoms such as over-responding, under-responding and sensation seeking behaviours in 919 autistic children and adolescents. We found that 6–12-year-olds and females displayed the most sensory over-responding symptoms. Autistic children could be grouped into mild, moderate, and severe levels of sensory symptoms, however, children differed in the type of strategies used to cope with their sensory symptoms meaning that they may require different intervention approaches.
Lane, A.E., Simpson, K., Masi, A., Grove, R., Moni, M.A., Montgomery, A., Roberts, J., Silove, N., Whalen, O., Whitehouse, A.J.O. & Eapen, V. (2022). Patterns of sensory modulation by age and sex in young people on the autism spectrum. Autism Research. 1-15. doi: 10.1002/aur.2762.
Dental care experiences and clinical phenotypes in children on the autism spectrum
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. This project investigated parental reports of oral health and dental service needs of children diagnosed with autism and explored relationships with clinical phenotypes. Data was sourced from the parents of 140 children on the spectrum who had participated in the Australian Autism Biobank. Parents completed 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 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. 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.
Alvares, G. A., Mekertichian, K., Rose, F., Vidler, S., & Whitehouse, A. (2022). Dental care experiences and clinical phenotypes in children on the autism spectrum. Special Care in Dentistry. Early online. doi: 10.1111/scd.12746.
Clinical and behavioural attributes leading to sleep disorders in children on the autism spectrum
Autistic children generally have co-occurring conditions. Sleep disorders impact approximately 50%–80% of autistic children. The impact on the quality of life for both the children and their families can be significant. This study compares sleep problems in autistic children and adolescents with their siblings and children without a diagnosis of autism, and investigates the relationship between specific autistic traits, daily life behaviours and sleep problems. The findings highlight the importance of a holistic assessment for autistic children and matching appropriate sleep intervention and supports where indicated.
Masi, A., Moni, M.A., Azim, S.I., Choi, B., Heussler, H., Lin, P.I., Diaz, A.M. & Eapen, V. (2022). Clinical and behavioural attributes leading to sleep disorders in children on the autism spectrum. Autism Research. 1274-1287. doi: 10.1002/aur.2745.
Parent-reported atypical development in the first year of life and age of autism diagnosis
Parents are often the first to notice and report developmental differences in their children. However, it remains unclear how these differences affect children who will later receive a diagnosis of autism. Greater understanding of early developmental differences may help find new ways to achieve an earlier diagnosis. Using data from 423 children who participated in the Australian Autism Biobank, this study sought to understand at what age parents noticed developmental differences in their children, and how and when this led to specialist consultation and autism diagnosis. The study found there was a significant diagnostic delay and that clinicians may benefit from greater education regarding the breadth of developmental areas related to autism.
Waddington, H., Macaskill, E., Whitehouse, A.J.O., Billingham, W. & Alvares, G.A. (2022, April 20). Parent-reported atypical development in the first year of life and age of autism diagnosis. J Autism Dev Disord. doi: 10.1007/s10803-022-05506-1
Sensory subtypes in children on the autism spectrum
A major research goal is to better understand the variation in autistic traits in order to assist with identifying which practices and supports may be most effective for which children. Sensory traits including hyper-reactivity, hypo-reactivity and unusual sensory interests are behavioural characteristics of autism that may provide insights into clinically meaningful subtypes. Within the autism field, however, most sensory features are measured using tools that focus on sensory reactivity only. This project aimed to identify sensory subtypes in children and adolescents on the autism spectrum aged 3-15 years and to evaluate the relationship between sensory subtypes and autistic traits and characteristics. Participants were recruited via the Australian Autism Biobank, the Longitudinal study of Australian Students with Autism (LASA) and from the NSW KU Autism Specific Early Learning and Care Centre (ASELCC). The study revealed differences that were largely linked to severity gradient in terms of sensory responsivity. A sensory subtype characterised predominantly by emotional regulation and attentional difficulties was also identified. The long term objective is to utilise the results of these analyses to identify homogeneous subgroups and to inform whether supports for young children on the autism spectrum based on their sensory profile optimise outcomes in school participation, and independent daily living.
Masi, A., Eapen, V., Lane, A., Simpson, K. & Roberts, J. (2021). Sensory subtypes in children on the autism spectrum: Final Report. Brisbane: Autism CRC
Autism-related dietary preferences mediate autism-gut microbiome associations
Gut complaints commonly affect autistic people. Some researchers have even suggested that bacteria within our gut – the gut microbiome – affect the brain and ‘cause’ autism. These claims have rapidly progressed to early clinical trials, spin-off companies marketing microbiome-based interventions, and widespread reporting by popular media. However, the evidence to support these claims is not strong, because studies have been small and have not accounted for important factors such as diet. This means earlier results have been difficult to reproduce. To investigate claims of relationships between autism and the gut microbiome, in the largest and ricest autism microbiome dataset to date. 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 autism diagnosis and the gut microbiome. Instead, our data support a model whereby autism-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to autism diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in autism may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in autism.
Yap, C.X., Henders, A.K., Alvares, G.A, Wood, D., Krause, L., Tyson, G.W., Restaudi, R., Wallace, L., McLaren, T., Hansell, N.K., Cleary, D., Grove, R., Hafekost, C., Harun, A., Holdsworth, H., Jellett, R., Khan, F., Lawson, L.P., Leslie, J., Frenk, M.L., Masi, A., Mathew, N.E., Muniandy, M., Nothard, M., Miller, J., Nunn, L., Holtmann, G., Strike, L., de Zubricaray, G. Thompson, P.M., McMahon, K., Wright, M.J., Visscher, P.M., Dawson, P.A., Dissanayake, C., Eapen, V…Gratten, J. (2021, November 11). Autism-related dietary preferences mediate autism-gut microbiome associations. Cell. doi:10.1016/j.cell.2021.10.015
Characterising the early presentation of motor difficulties in autistic children
This study aimed to explore the rates of motor difficulties in children from the Australian Autism Biobank, and how early motor concerns impacted on children functionally. Children with autism aged 2-7 years, including 441 with a Vineland Adaptive Behavior Scale (VABS-II) motor subscale and 385 with a Mullen Scales of Early Learning (MSEL) fine motor subscale were included (n total = 514; 80% male). Approximately 60% of children on the MSEL and ~ 25% on the VABS-II had clinically significant motor impairments. More children with delayed sitting and walking motor milestones had early childhood parent reported motor difficulties (p < 0.001). Early motor delays or concerns may assist identifying individuals who will likely benefit from early ongoing developmental monitoring and early support.
Montgomery, A., Masi, A., Silove, N., Karlov, L., Whitehouse, A., Eapen, V. (2022). Characterising the early presentation of motor difficulties in autistic children. J Autism Dev Disord. doi: 10.1007/s10803-021-05333-w
Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.
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.
Yap, C.X., Alvares, G.A., Henders, A.K. et al. (2021). Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank. Molecular Autism 12, 12 (2021). doi: 10.1186/s13229-020-00407-5
Demographic and Clinical Characteristics of Participants in the Australian Autism Biobank
There is enormous clinical (phenotypic) and genetic heterogeneity within individuals diagnosed with Autism Spectrum Disorder (ASD). Alongside significant advances in genetic and biological research have been increasing imperatives to establish large bio-resources to support discovery research. The Australian Autism Biobank was initiated in 2014 by the Autism CRC. The objectives of this project was to describe the demographic and clinical characteristics of participants in the Australian Autism Biobank.
Alvares, G.A., Australian Autism Biobank team. (2019) Demographic and clinical characteristics of participants in the Australian Autism Biobank [Poster]. International Society for Autism Research 2019 Annual Meeting, 1-4 May, Canada. International Society for Autism Research.
Study protocol for the Australian Autism Biobank: an international resource to advance autism discovery research
The phenotypic (clinical) and genetic heterogeneity of autism presents considerable challenges in understanding the condition, selecting effective supports, 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 autism. 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 autism to facilitate future discovery research.
Alvares, G.A., Dawson, P.A., Dissanayake, C., Eapen, V., Gratten, J., Grove, R., Henders, A., Heussler, H., Lawson, L., Masi, A., Raymond, E., Rose, F., Wallace, L., Wray, N.R., Whitehouse, A.J.O.; Australian Autism Biobank team (2018). Study protocol for the Australian Autism Biobank: an international resource to advance autism discovery research. BMC Pediatr. Aug 27;18(1):284. doi: 10.1186/s12887-018-1255-z