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Autism spectrum disorder (ASD) is a neurodevelopmental condition that is marked by communication and social difficulties, restricted and repetitive activities, and sensory sensitivity variations. Sleep difficulties, eating disorders, gastrointestinal issues, anxiety, and seizures are frequent co-occurring conditions with ASD.

In a recent study published in Nature Medicine, researchers explore interactions between the lipidome and both environmental and genetic variables in autism.

Study: Interactions between the lipidome and genetic and environmental factors in autism. Image Credit: Dzmitry Sarmont / Shutterstock.com

About the study

In the present study, researchers utilize biological and phenotypic data to evaluate links between the plasma lipidome and autism-related characteristics.

The plasma lipidome was profiled in 765 children according to their class level in the lipid ontology, which was further characterized based on their subclass, domain, and feature. Three crucial neurodevelopmental phenotypes such as ASD diagnosis, sleep disturbances, and intelligence quotient/developmental quotient composite score (IQ/DQ) were also considered. The impact of demographics, batch, food, and medications on neurodevelopmental phenotypes and variables with potential lipidome impacts were also examined.

Omics data-based restricted maximum likelihood (OREML) assessment was used to evaluate the lipidome’s overall correlation with anthropomorphic and neurodevelopmental features in an additive model. Lipidome-wide association studies (LWASs) were performed to detect links between individual lipids and variables like ASD, sleep disorders, IQ/DQ, age, Tanner stage, and body mass index (BMI) that showed significant lipidome correlations in variance component analyses.

The possible impacts of environmental variables on neurodevelopment-related lipidome patterns were explored. Principal component analysis (PCA) was used to assess LWAS relationships, whereas PC1 allowed the researchers to encapsulate a trait’s lipidome characteristics in a single variable.

Results

Although children with greater IQ/DQ were more like to be older, age was well-matched amongst ASD, unrelated children without a diagnosis (UNR), and siblings without a diagnosis (SIB) groups.

Reduced meat consumption was linked to ASD diagnosis and worse IQ/DQ scores after controlling for age and gender. ASD diagnosis was also related to attention deficit hyperactivity disorder (ADHD)/behavioral drugs, anxiolytics/antidepressants, antipsychotics, fish oil/docosahexaenoic acid (DHA) supplements, and sleep medications.

Lower IQ/DQ was correlated to the usage of antiepileptic drugs, sleep medicines, and fish oil/DHA supplements. Furthermore, sleep disruptions were linked to ADHD/behavioral drugs and sleep medications.

ASD diagnosis was associated with lower cholesterol levels that were unrelated to dietary cholesterol, ADHD/behavioral medicines, antipsychotics, or fish oil/DHA consumption. No relationships between IQ/DQ or sleep difficulties and inferred triglycerides or total cholesterol were observed. BMI was related to higher dietary cholesterol, triglycerides, and inferred lipidome cholesterol.

After eliminating storage outliers, lipidome relationships with neurodevelopmental features like IQ/DQ, sleep problems, and ASD diagnosis were more modest. Despite the small sample size, there was a significant association with the adaptive motor domain score of the Vineland Adaptive Behavior Scale (VABS-II). Notably, the lipidome was unrelated to stool consistency.

The researchers also discovered lipid species that were significantly related to ASD diagnosis, sleep disturbance, and IQ/DQ. Multiple species-level relationships with age, BMI, Tanner stage, and gender that corresponded to the associations seen in the variance component analysis were also observed.

Several three-way interactions were also observed between the ASD diagnosis, ASD lipidome profile, and reduced meat consumption in the ASD group. This implies that the ASD lipidome profile may be partially ascribed to lowered meat consumption in the ASD group.

Variations in the ASD lipidomic profile ere associated with certain stool microbiome characteristics such as genetic predisposition for reduced gut microbial acetate synthesis and enhanced pyrimidine ribonucleoside salvage.

Along with positive correlations with sleep disturbances, the lipidomic profile was related to elevated stool microbiome metabolic potential for nicotinamide adenine dinucleotide (NAD) salvage and pyridoxal 5′-phosphate salvage, as well as the reduced metabolic potential for pyruvate fermentation to butanoate, and Clostridium acetobutylicum acidogenic fermentation. ADHD/behavioral therapeutics and fish oil/DHA supplements were inversely linked with the lipidome profile of sleep disturbances.

Conclusions

The current study reported on the intricate connections between neurodevelopment, genetics, physical health, and the environment. These findings indicate that metabolic convergence for sleep problems and poor eating in autistic children has long-term repercussions for their well-being and eventual quality of life.

Future research with longitudinal study designs and enrollments from the general population is needed to gain essential knowledge of the neurodevelopmental lipidome.

Journal reference:

  • Yap, C. X., Henders, A. K., Alvares, G. A., et al. (2023). Interactions between the lipidome and genetic and environmental factors in autism. Nature Medicine 29(4); 936-949. doi:10.1038/s41591-023-02271-1

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