Schizophrenia, "just the facts": what we know in 2008 Part 3: neurobiology.

Investigating the neurobiological basis of schizophrenia is a critical step toward establishing its diagnostic validity, predicting outcome, delineating causative mechanisms and identifying objective targets for treatment research. Over the past two decades, there have been several advances in this field, principally related to developments in neuroimaging, electrophysiological and neuropathological approaches. Several neurobiological alterations in domains of brain structure, physiology and neurochemistry have been documented that may reflect diverse pathophysiological pathways from the "genome to the phenome". While none of the observed abnormalities are likely to qualify as diagnostic markers at this time, many can serve as potential intermediate phenotypes for elucidating etiological factors including susceptibility genes, and as therapeutic targets for novel drug discovery. Despite several challenges including the substantial phenotypic, pathophysiologic and etiological heterogeneity of schizophrenia, technological limitations, and the less than ideal animal models, considerable progress has been made in characterizing the neurobiological substrate of schizophrenia. The accumulating fact-base on the neurobiology of schizophrenia calls for novel integrative model(s) that may generate new, testable predictions.