# Transcriptional and neurotransmitter signatures associated with regional gray matter alterations in juvenile myoclonic epilepsy

## TL;DR

This study identifies brain structure changes in juvenile myoclonic epilepsy and links them to specific genes and neurotransmitters involved in brain development and function.

## Contribution

The study integrates brain imaging with gene and neurotransmitter data to reveal molecular mechanisms underlying gray matter changes in JME.

## Key findings

- GM decreases in sensorimotor areas and increases in emotion and cognition regions were consistently observed in JME.
- 926 genes linked to GM changes are enriched in ion channels, synaptic function, and neurodevelopmental pathways.
- GM alterations correlate with serotonin, dopamine, and acetylcholine neurotransmitter systems.

## Abstract

The neurobiological basis of gray matter (GM) alterations in juvenile myoclonic epilepsy (JME) remains poorly understood. This study aimed to identify robust GM changes and their underlying molecular signatures.

We performed an updated coordinate-based meta-analysis of 15 voxel-based morphometry studies (394 JME patients, 448 healthy controls) and integrated the resulting GM alteration map with data from the Allen Human Brain Atlas and neurotransmitter atlases using advanced spatial correlation, gene enrichment, and network analysis approaches.

Our analysis revealed a consistent pattern of GM decreases in the sensorimotor areas and increases in regions implicated in emotion and cognition. These structural changes were spatially correlated with a set of 926 genes enriched for pathways related to ion channel activity, synaptic function, neuronal processes, and cellular metabolism, which showed peak expression during neurodevelopmental periods coinciding with JME onset. Protein–protein interaction analysis identified hub genes from two key functional classes: transcriptional regulators linked to circadian rhythms, and cellular signaling molecules including established monogenic epilepsy genes. Furthermore, the GM map correlated significantly with the spatial distributions of the serotonin, dopamine, and acetylcholine neurotransmitter systems.

While these associations are based on data from healthy donors and require further validation, our findings bridge the gap between macroscopic brain alterations and their underlying molecular architecture in JME. This provides an integrated model of its pathophysiology and highlights potential therapeutic avenues.