Biomarkers for Epilepsy Development and the Effect of Physical Exercise in Children With Autism

Biomarkers for Epilepsy Development and the Effect of Physical Exercise in Children With Autism

This study aims to identify novel biomarkers for epilepsy development in children with autism and to evaluate the effects of physical exercise on these biomarkers and clinical outcomes. Very little is known about epilepsy biomarkers in children with autism, and the risk of developing epilepsy in this population ranges from 5% to 47%. The project focuses on potential signaling pathways, including immunological factors, synaptic proteins, circadian rhythm genes, sleep architecture, and cognitive function.

Children with autism, with or without epilepsy, as well as children with epilepsy, will undergo genetic analyses (exome sequencing) of synaptic and circadian rhythm-related genes, immunological protein profiling, EEG or polysomnography, actigraphy, neuropsychological testing, and physical assessments including coordination, balance, and body awareness. Participants will also engage in a three-month structured physical exercise program. Follow-up assessments will examine the effects of exercise on seizure frequency, biomarker expression, sleep, cognition, and physical abilities.

The study addresses two key research questions: 1) whether biomarkers and physiological measures correlate with seizure occurrence in children with autism, and 2) whether regular physical activity can modulate seizure frequency, biomarker expression, circadian rhythm, sleep, cognitive performance, and physical skills. The findings are expected to improve understanding of the mechanisms underlying epilepsy in autism and inform potential interventions.

The project aims to explore novel biomarkers for the development of epilepsy in children with autism and to evaluate how physical exercise may influence the expression of these biomarkers as well as the severity of epilepsy and autism. Currently, limited knowledge exists within this research field, and the risk of developing epilepsy in individuals with autism varies considerably. One hypothesis is that autism and epilepsy may partly arise from similar genetic alterations in synaptic proteins and exhibit comparable variations in immunological protein levels. Children with autism as well as children with epilepsy also have an increased risk of disrupted circadian rhythm and sleep disturbances, as well as dysfunction in genes regulating circadian rhythms. Physical exercise has been associated with changes in inflammatory responses, epilepsy development, cognitive brain functions, and circadian rhythm/sleep patterns.

The project includes children with autism with or without epilepsy, as well as children with epilepsy, who will:

1. Provide blood samples for genetic analyses (exome sequencing) focusing on synaptic proteins and circadian clock genes. Blood samples will also be collected from both biological parents for comparison. Immunological protein levels will be analyzed in a separate blood sample from the children.
2. Undergo electroencephalography (EEG) or polysomnography (PSG) to assess brain electrical activity during sleep, as well as actigraphy to evaluate circadian rhythm.
3. Undergo neuropsychological testing, including assessments of memory, executive function, and attention, as well as physical tests focusing primarily on coordination, balance, and body awareness.
4. Participate in a physical exercise program for approximately three months.
5. After completion of the physical exercise program, provide follow-up blood samples for immunological protein analyses and undergo repeat EEG or PSG with actigraphy, as well as cognitive and physical testing.

The aim of this study is to explore biomarkers for the development of epilepsy in children with autism and to evaluate the extent to which these signaling pathways, as well as the severity of epilepsy and autism, can be influenced by physical activity. Very little has been published on biomarkers for epilepsy in children with autism. According to previous studies, the risk of developing epilepsy in children with autism ranges from 5% to 47%.

In the present research project, the investigators focus on identifying potential signaling pathways that may serve as biomarkers. These include primarily immunological factors, synaptic proteins, circadian clock genes, sleep architecture, and circadian rhythm. The research group also investigate whether physical exercise can influence the expression of these biomarkers, sleep architecture, cognitive function, physical abilities such as coordination, balance, and body awareness, as well as seizure frequency.

Scientific Research Questions:

1. Can the expression of immunological factors in blood, alterations in synaptic and circadian rhythm genes, circadian rhythm patterns, cognitive function, or EEG changes be correlated with the occurrence of epileptic seizures in children with autism?
2. Can regular physical exercise in children with autism, with or without epilepsy, influence the onset or frequency of epileptic seizures, the expression of immunological factors, circadian rhythm, sleep architecture, cognitive abilities, and physical skills such as balance, coordination, and body awareness?

Inclusion Criteria:

• Children aged 10-15 years
• Diagnosed with mild-to-moderate autism spectrum disorder and/or diagnosed with epilepsy

Exclusion Criteria:

• Severe autism spectrum disorder
• Severe cognitive impairment
• Severe ADHD
• Active systemic inflammatory or neurodegenerative disease
• Traumatic brain injury within the past 6 months