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Article
October 1993

Schizophrenia as a Brain Disease

Arch Neurol. 1993;50(10):1096-1097. doi:10.1001/archneur.1993.00540100081021
Abstract

It is now widely accepted that schizophrenia is a brain disease, yet the pathophysiology of this illness is still obscure. In some ways, we are at the same point in understanding the symptoms of this illness that medicine was in understanding the symptoms of heart failure before the circulatory system was discovered.

The last two decades have been dominated by the dopamine hypothesis of schizophrenia. This is not surprising, as conventional antipsychotic medications act on dopamine receptors and their effectiveness is related directly to this ability.1 However, more recent studies have failed to provide unequivocal evidence of dopamine hyperactivity in vivo or in postmortem brain tissue. The absence of a linkage between the D2 dopamine receptor gene region and the presence of schizophrenia in a large Swedish and a California pedigree has been even more disappointing.2 While the role of other receptor subtypes has not been fully

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