Transcriptomic immaturity inducible by neural hyperexcitation is shared by multiple neuropsychiatric disorders

Area of Science:

• Neuroscience
• Genetics
• Biomarker Discovery

Background:

• Neuropsychiatric disorders often involve imbalances in neural transmission and abnormal brain maturation.
• Improved diagnostic biomarkers are crucial for these complex conditions.

Purpose of the Study:

• To identify shared molecular patterns across various neuropsychiatric disorders.
• To investigate the role of neural hyperexcitation in gene expression changes related to brain maturation.

Main Methods:

• Analysis of gene expression patterns from published studies related to neural hyperexcitation.
• Mapping changes in maturation-related genes, identifying decreases in maturity markers and increases in immaturity markers.
• Transdiagnostic analysis of 87 disease and 12 animal model datasets using identified gene expression patterns.

Main Results:

• Two distinct gene expression patterns were identified: decreased maturity markers (synaptic function-related) and increased immaturity markers (chromosomal modification-related).
• Transcriptomic pseudoimmaturity, induced by neural hyperexcitation, was found to be a shared characteristic across multiple neuropsychiatric disorders.
• This pseudoimmaturity endophenotype was observed in conditions including schizophrenia, Alzheimer disease, and amyotrophic lateral sclerosis.

Conclusions:

• Transcriptomic pseudoimmaturity represents a potential transdiagnostic endophenotype for several neuropsychiatric disorders.
• This finding provides a basis for developing novel diagnostic strategies and understanding sharedPathophysiology across these conditions.