The Article by Olney and Farber1 elaborates a hypothesis concerning the role of decreased N-methyl-D-aspartate (NMDA) receptor function as an etiological factor in schizophrenia. The novel feature of this hypothesis is that the postulated structural lesion, due to attenuated NMDA receptor function, can potentially reconcile the age of onset data2 with the hypothesis that early neurodevelopmental disturbances underlie schizophrenic symptom production.3,4 The fact that the psychotic phase of the disorder is usually initially manifest in the early adult years is at variance with the hypothesis that the lesion leading to psychosis may occur as early as the second trimester of pregnancy. A potential solution is suggested through results of animal studies reported by Farber et al,5 showing that structural damage due to NMDA antagonists such as phencyclidine hydrochloride (PCP) is not found experimentally until after puberty. These results and the psychotomimetic effect of PCP prompted Olney
Henn FA. The NMDA Receptor as a Site for Psychopathology: Primary or Secondary Role? Arch Gen Psychiatry. 1995;52(12):1008–1010. doi:10.1001/archpsyc.1995.03950240026005
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