5 These definitions may plausibly represent several distinct diseases and/or a spectrum of disease6; we return to this important point in the discussion, but for now we assume — as do most current investigators — that schizophrenia is a single entity. Our current understanding of the causes of schizophrenia

emphasizes interactions between diverse genetic and environmental Inhibitors,research,lifescience,medical factors.2,7 Conceptually, these diverse causes should converge on a small set of brain abnormalities pathognomonic of the disorder. Modern neuroimaging methods reveal a wide range of brain abnormalities in schizophrenia, including reductions in whole brain volume, increases in ventricular volume, reductions in frontal, temporal, limbic, and thalamic grey matter, and abnormalities Inhibitors,research,lifescience,medical in frontal and temporal white matter.8-10 Despite these promising findings, the abnormalities are insufficiently sensitive or specific to be individually or collectively diagnostic or prognostic of the

disease in the clinical setting. In addition, the abnormalities have yet to be integrated into Inhibitors,research,lifescience,medical a clinically validated model of schizophrenia; such a model would for instance allow a rational approach to the search for treatment and prevention of the disorder.

Clinical Inhibitors,research,lifescience,medical neuroscientists increasingly postulate that schizophrenia is a disorder of integration of information between specialized brain regions. The emergence of complex perceptual, behavioral, and cognitive functions — the functions predominantly affected in schizophrenia — is contingent on such Inhibitors,research,lifescience,medical integration11,12; the binding of visual and other sensory stimuli into a unified perceptual whole is a well-studied instance of this phenomenon.13 Abnormality of integration hence represents an intuitive Sepantronium Bromide mouse unifying hypothesis of schizophrenia. An early version of this hypothesis was posited by psychiatrists in the 19th century; modern versions of this hypothesis — including the constructs of dysconnection and much cognitive dysmetria — have emerged in the last 20 years,14-19 driven by advances in neuroimaging and the consequent possibility of the study of integration in living humans. As part of the same broader trend, investigators recently proposed a roadmap towards reclassification of schizophrenia and other psychiatric disorders from entities based on subjective clinical diagnoses towards entities based on objective abnormalities of integration or brain networks.20 The study of integration is the study of brain networks.