Role of cortical excitatory/inhibitory imbalance in autism spectrum disorders from a symptom severity trajectories framework: a study protocol.

Researchers are planning a study to understand how brain activity balance affects autism symptoms over time. They will follow children with autism for up to 4 years, using brain scans and other tests to see how brain chemistry relates to autism behaviors. This research could help identify biological markers and lead to more personalized treatments for autism.

This study protocol outlines a longitudinal investigation into the excitatory/inhibitory (E/I) cortical imbalance theory in autism spectrum disorders. The research will follow at least 98 participants with ASD from 12-72 months of age over an 18-48 month period, using multiple approaches to measure E/I balance including electrophysiology, magnetic resonance imaging, and genetics. The study aims to examine how E/I imbalance relates to autism symptom severity trajectories over time, addressing previous inconsistencies in the field through comprehensive assessment methods and longitudinal design. This multisystemic approach could potentially contribute to autism biomarker research and inform more personalized treatment approaches.

If successful, this research could contribute to autism biomarker identification and support development of personalized treatments based on individual E/I balance profiles. However, as this is only a protocol, clinical applications await actual study results and validation.

This is a study protocol only - no actual findings or results are reported. The research has not yet been conducted, so effectiveness of the proposed methodology remains to be demonstrated.

There is considerable evidence reporting an excitatory/inhibitory (E/I) cortical imbalance in autism spectrum disorders (ASD). However, previous findings on the direction of this imbalance and its relationship to ASD symptomatology are heterogeneous. Some factors contributing to these mixed results might be the methodological differences between studies assessing the E/I ratio and the intrinsic variability within the autistic spectrum. Studying the evolution of ASD symptoms and the factors that modulate it might help to explain and reduce this variability.

Here we present a study protocol to explore the longitudinal role of E/I imbalance in ASD symptoms, combining different approaches to measure the E/I ratio and using the trajectories of symptom severity as a framework. This observational two time-point prospective study assesses the E/I ratio and the evolution of the behavioural symptoms in a sample of at least 98 participants with ASD. Participants are enrolled at 12 to 72 months of age and followed from 18 to 48 months after. A comprehensive battery of tests is applied to evaluate ASD clinical symptoms.

The E/I ratio is approached from electrophysiology, magnetic resonance, and genetics. We will calculate the individual change for the main ASD symptoms and, based on that, we will define the trajectories of symptom severity. Then, we will investigate the correlation between measures of excitation/inhibition balance and autistic symptomatology cross-sectionally, as well as the ability of these measurements to predict changes in symptoms over time. This study presents a robust multisystemic approach to the E/I imbalance theory in autism and its relation to divergent symptom trajectories.

That setting will allow us to relate and compare the neurobiological information coming from different sources and its impact on behavioural symptoms while accounting for the high variability in ASD. The findings derived from this study could contribute to the ASD biomarkers research and might provide valuable evidence for the development of more personalized treatments in ASD.