Molecular Signatures of Schizophrenia and Insights into Potential Biological Convergence

Schizophrenia is a chronic, polygenic psychiatric disorder marked by considerable clinical and biological heterogeneity. Despite its established heritability, the molecular basis of its onset and development continue to present a major scientific challenge. New developments of multiscale molecular structure including GWAS, rare variant analyses, epi-genetic regulation, transcriptomic alterations, and proteomic profiling in the study of schizophrenia can be used to dissect the molecular biology involved in the disorder. These observed molecular signatures of schizophrenia, ranging from shared SNPs, CNVs, to differential DNA methylation, non-coding RNA regulation and post-translational modification, suggest that at the molecular level upstream perturbations often converge onto a limited number of core biological pathways: synaptic signaling, immune activation, mitochondrial function, cell-adhesion molecules and neurodevelopmental regulation. At a systems level studies have combined genetic risk with transcriptional and epigenomic networks elucidating mechanisms underlying pathogenesis and heterogeneity. Furthermore patient-derived cellular models and studies of biological markers underpin the translation potential of these respective mechanisms for precise psychiatry. Together, these findings point toward a conceptual framework of convergence in psychiatric re-search, wherein diverse molecular alterations, frequently implicate a limited set of bio-logical pathways. Our literature search suggests a recurrent involvement of synaptic, immune, mitochondrial, neurodevelopmental, and adhesion-related mechanisms across multiple studies suggests these may represent shared axes of dysfunction worthy of further systematic investigation.