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

Biomarkers are needed to improve the diagnosis of neuropsychiatric disorders, which are often associated to excitatory/inhibitory imbalances in neural transmission and abnormal maturation. Here, we characterized different disease conditions by mapping changes in the expression patterns of maturation-related genes whose expression was altered by experimental neural hyperexcitation in published studies. This analysis revealed two gene expression patterns: decreases in maturity markers and increases in immaturity markers. These two groups of genes were characterized by the over-representation of genes related to synaptic function and chromosomal modification, respectively. Using these two groups in a transdiagnostic analysis of 87 disease datasets for eight neuropsychiatric disorders and 12 datasets from corresponding animal models, we found that transcriptomic pseudoimmaturity inducible by neural hyperexcitation is shared by multiple neuropsychiatric disorders, such as schizophrenia, Alzheimer disorders, and amyotrophic lateral sclerosis. Our results indicate that this endophenotype serves as a basis for the transdiagnostic characterization of these disorders.