Regionally diverse cortical pathology in schizophrenia: clues to the etiology of the disease

Abstract

Perhaps the most surprising revelation that has emerged from recent pathologic studies of schizophrenia is the marked cortical regional heterogeneity of the disease. Areal specific alterations of many parameters have been reported (e.g., neuronal density, density of gamma-aminobutyric acid [GABA]-immunoreactive cells, and concentration of synapse-associated proteins and messenger ribonucleic acid [mRNA]s). In the past 5 years, as a flood of seemingly contradictory findings have been published, divergent findings often have been regarded as further evidence of the irreplicability and futility of postmortem studies. Although some discrepancies in findings may be due to methodological differences or to the study of different cohorts of patients, a growing number of laboratories are examining the same parameter(s) in multiple cortical areas in a single brain cohort and finding regionally specific abnormalities. These findings provide compelling evidence that cortical pathology in schizophrenia is nonuniform and complex. A major challenge in contemporary schizophrenia research is to make sense of the patterning of whole brain pathology in schizophrenia, as the mosaic of neuropathologic alterations may provide clues to the disease etiology.