Nucifora LG, MacDonald ML, Lee BJ, et al. - Researchers examined if the pathophysiology for a subtype of schizophrenia involve increased protein insolubility and ubiquitination. They performed cold sarkosyl fractionation on the prefrontal cortex and superior temporal gyrus from postmortem brains of individuals with and without schizophrenia, separating proteins into soluble and insoluble fractions. They quantified protein insolubility and ubiquitin levels for each insoluble fraction, with normalization to total homogenate protein. Then they identified the protein contents of the insoluble fractions via performing mass spectrometry analysis. They used Gene Ontology enrichment analysis and Ingenuity Pathway Analysis to assess the potential biological relevance of the detected proteins. An increase in protein insolubility and ubiquitination in the insoluble fraction was evident in a subset of the schizophrenia brains. Outcomes imply that a subset of patients with schizophrenia indicates a pathological process related to protein insolubility. Determining the molecular mechanism of this subtype of schizophrenia may help in ascertaining the pathways underlying the clinical phenotype in some patients with major mental illness as well as in improving nosology and identification of novel therapeutic targets.