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September 1999

Connecting the "Dots" of Brain Dysfunction in Schizophrenia: What Does the Picture Look Like?

Arch Gen Psychiatry. 1999;56(9):791-793. doi:10.1001/archpsyc.56.9.791

IN THIS issue of the ARCHIVES, Dr Nancy Andreasen1 proposes a "unitary" neural circuit–cognitive dysfunction model for understanding schizophrenia. This commentary will review Andreasen's scholarly article with a focus on (1) the continued search for specific neural circuit abnormalities in schizophrenia and their associated "signature" cognitive deficits; (2) how these neural circuit dysfunctions and cognitive deficits relate to the heterogeneity of schizophrenia disorder(s); and (3) the problem of the testing and falsifiability of the cortico-cerebellar-thalamic-cortical circuit (CCTCC) cognitive dysmetria model and whether any single unitary model is likely to account for the widespread functional and structural deficits of schizophrenia. At the end of the exercise of connecting the "dots" of brain dysfunction, will we end up with one or multiple (potentially overlapping) pictures of abnormal neural circuits in schizophrenia? I believe that the answer is the latter—that no single unitary model of neural circuit–cognitive dysfunction will be validated for this heterogeneous disorder. It is, of course, possible that a unitary view will prevail, and that is why I agree with Andreasen that much more research is needed in this complex area of inquiry.