Nucifora LG, MacDonald ML, Lee BJ, et al. - Given the possibility for common pathophysiological pathways for subtypes of schizophrenia, researchers examined if increased protein insolubility and ubiquitination underlie the pathophysiology for a subtype of schizophrenia. From postmortem brains of individuals with and without schizophrenia, they subjected prefrontal cortex and superior temporal gyrus to cold sarkosyl fractionation, separating proteins into soluble and insoluble fractions. Observations revealed an increase in protein insolubility and ubiquitination in the insoluble fraction in a subset of the brains of schizophrenics. The proteins that were significantly altered in the insoluble fraction were enriched for pathways relating to axon target recognition as well as nervous system development and function. Findings thereby support that a subset of patients with schizophrenia had a pathological process related to protein insolubility. The investigators recommend determining the molecular mechanism of this subtype of schizophrenia in order to enhance the understanding of the pathways underlying the clinical phenotype in some patients with major mental illness, as well as to improve nosology and identification of novel therapeutic targets.