Shared molecular dysregulation across neuropsychiatric disorders reveals candidate therapeutic targets

Autism Spectrum Disorder (ASD), Bipolar Disorder (BD), and Schizophrenia (SCZ) are major neuropsychiatric conditions that contribute substantially to global disability. Although traditionally considered distinct disorders, increasing evidence suggests overlapping molecular mechanisms across these conditions. In this study, we applied a cross-disorder transcriptomic framework to identify shared molecular dysregulation across ASD, BD, and SCZ. Publicly available RNA-sequencing datasets for each disorder were analysed independently using disorder-specific case-control comparisons. Differentially expressed genes were ranked within each disorder using a composite magnitude-confidence score integrating effect size and statistical significance, and the top 500 ranked genes per disorder were selected for cross-disorder analysis. Genes recurrently dysregulated in at least two disorders were prioritised based on their mean cross-disorder score. This approach identified 20 high-confidence recurrent genes, with pronounced transcriptional convergence observed between BD and SCZ. Notably, genes such as TPRX1, NPC1L1, and SLC12A3 emerged among the highest-ranked cross-disorder candidates, reflecting consistent and robust dysregulation across disorders. Directionality analysis revealed predominantly concordant expression patterns, with limited disorder-specific divergence. Functional annotation highlighted biological processes related to cellular homeostasis, immune regulation, metabolic pathways, and signal transduction. Overall, this study provides a systematic and quantitative framework for identifying shared molecular signatures across major neuropsychiatric disorders. The prioritised genes identified here represent promising candidates for further functional investigation and contribute to a deeper understanding of transdiagnostic disease biology.