Olney and Farber1 present a "unified hypothesis" based on N-methyl-D-aspartate (NMDA) receptor hypofunction, which they claim accounts for "major clinical and pathophysiological aspects of schizophrenia." Although, as I shall show, there are elements of interest in thishypothesis, it is flawed in that it depends on an erroneous account of etiology, predicts neurological symptoms that are not present in schizophrenia, and is inconsistent with the known epidemiological characteristics of the disease. A comparison of this hypothesis with previous hypotheses of the same type ("neurohumoral" theories) and with two other classes of hypotheses of pathogenesis ("focal damage" and "connectionist" theories) in their ability to explain known drug effects, phenomenological characteristics, brain changes, and epidemiological characteristics, reveals constraints on the type of theory that we may entertain and a pattern of strengths and weaknesses that points the way to a more incisive theory.
See also pages 998, 1008, 1015, and 1019
Crow TJ. Constraints on Concepts of Pathogenesis: Language and the Speciation Process as the Key to the Etiology of Schizophrenia. Arch Gen Psychiatry. 1995;52(12):1011–1014. doi:10.1001/archpsyc.1995.03950240029006
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