Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

The NMDA Receptor as a Site for Psychopathology: Primary or Secondary Role?

The NMDA Receptor as a Site for Psychopathology: Primary or Secondary Role? Abstract 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 References 1. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia . Arch Gen Psychiatry . 1995;52:998-1007.Crossref 2. DeLisi LE. The significance of age of onset for schizophrenia . Schizophr Bull . 1992;18:209-215.Crossref 3. Kovelman JA, Scheibel AB. A neurohistological correlate of schizophrenia . Biol Psychiatry . 1984;191:1601-1621. 4. Jakob H, Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenia . J Neural Transm . 1986;65:303-326.Crossref 5. Farber N, Wozniak DF, Price MT, Labruyere J, Huss J, Peter H, Olney JW. Age-specific neurotoxicity in rat associated with NMDA receptor blockade: potential relevance to schizophrenia? Biol Psychiatry . In press. 6. Tsai G, Gastfriend DR, Coyle JT. The glutaminergic basis of human alcoholism . Am J Psychiatry . 1995;152:332-340. 7. Nowak G, Paul IA, Popik P, Young A, Skolnick O. Ca++ antagonists effect an antidepressantlike adaptation of the NMDA receptor complex . Eur J Pharmacol . 1993;247:101-102.Crossref 8. Cotman CW, Monaghan DT. Chemistry and anatomy of excitatory amino acid systems . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:197-211. 9. Allen RM, Young SJ. Phencyclidine-induced psychosis . Am J Psychiatry . 1978;135:1081-1084. 10. Rothman SM, Olney JW. Excitotoxicity and the NMDA receptor . Trends Neurosci . 1987;10:299-302.Crossref 11. Lipska B, Weinberger D. Phenotypic variations in responses to neonatal excitotoxic hippocampal damage . Abstr Am Coll Neuropsychopharmacol . 1994;178. 12. Feinberg I. Schizophrenia: caused by a fault inprogrammed synaptic elimination during adolescence? J Psychiatr Res . 1982;17:319-334.Crossref 13. Walker E, Lewine RJ. Prediction of adult-onset schizophrenia from childhood home movies of the patients . Am J Psychiatry . 1990;147:1052-1056. 14. Fish B, Marcus J, Hans SL, Auerbach JG, Perdue S. Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect: a review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study . Arch Gen Psychiatry . 1992;49:221-235.Crossref 15. Luisada PV, Brown BL. Clinical management of phencyclidine psychosis . Clin Toxicol . 1976;9:539-545.Crossref 16. Carpenter WT, Buchanan RW. Schizophrenia . N Engl J Med . 1994;330:681-690.Crossref 17. Häfner H, Maurer K, Löffler W, Riecher-Rössler A. The influence of age and sex on the onset and early course of schizophrenia . Br J Psychiatry . 1993;162:80-86.Crossref 18. Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP. Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics . J Neurosci . 1992;12:924-929. 19. Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients . Arch Gen Psychiatry . 1991;48:996-1001.Crossref 20. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE, Jones EG. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics . Arch Gen Psychiatry . 1995;52:258-266.Crossref 21. Beckwith JP, Stefanis NC, McLaughlin DP, Kerwin RW. The expression of NMDA receptor subunits in schizophrenic post-mortem hippocampus . Schizophr Res . 1995;15:54.Crossref 22. Selemon LD, Rajkowska G, Goldman-Rakic PS. Cytologic abnormalities in area 9 of the schizophrenic cortex . Soc Neurosci Abstr . 1993;19:200. 23. Pakkenberg B. Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical disectors . Biol Psychiatry . 1993;34:768-772.Crossref 24. Tandon R, Greden JF, Silk KR. Treatment of negative schizophrenic symptoms with trihexyphenidyl . J Clin Psychopharmacol . 1988;8:212-215. 25. Wolkowitz OM, Pickar D. Benzodiazepines in the treatment of schizophrenia: a review and reappraisal . Am J Psychiatry . 1991;148:714-726. 26. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP. Amelioration of negative symptoms in schizophrenia by glycine . Am J Psychiatry . 1994;151:1234-1236. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

The NMDA Receptor as a Site for Psychopathology: Primary or Secondary Role?

Archives of General Psychiatry , Volume 52 (12) – Dec 1, 1995

Loading next page...
 
/lp/american-medical-association/the-nmda-receptor-as-a-site-for-psychopathology-primary-or-secondary-cxlPnt9XC6
Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1995.03950240026005
Publisher site
See Article on Publisher Site

Abstract

Abstract 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 References 1. Olney JW, Farber NB. Glutamate receptor dysfunction and schizophrenia . Arch Gen Psychiatry . 1995;52:998-1007.Crossref 2. DeLisi LE. The significance of age of onset for schizophrenia . Schizophr Bull . 1992;18:209-215.Crossref 3. Kovelman JA, Scheibel AB. A neurohistological correlate of schizophrenia . Biol Psychiatry . 1984;191:1601-1621. 4. Jakob H, Beckmann H. Prenatal developmental disturbances in the limbic allocortex in schizophrenia . J Neural Transm . 1986;65:303-326.Crossref 5. Farber N, Wozniak DF, Price MT, Labruyere J, Huss J, Peter H, Olney JW. Age-specific neurotoxicity in rat associated with NMDA receptor blockade: potential relevance to schizophrenia? Biol Psychiatry . In press. 6. Tsai G, Gastfriend DR, Coyle JT. The glutaminergic basis of human alcoholism . Am J Psychiatry . 1995;152:332-340. 7. Nowak G, Paul IA, Popik P, Young A, Skolnick O. Ca++ antagonists effect an antidepressantlike adaptation of the NMDA receptor complex . Eur J Pharmacol . 1993;247:101-102.Crossref 8. Cotman CW, Monaghan DT. Chemistry and anatomy of excitatory amino acid systems . In: Meltzer HY, ed. Psychopharmacology: The Third Generation of Progress . New York, NY: Raven Press; 1987:197-211. 9. Allen RM, Young SJ. Phencyclidine-induced psychosis . Am J Psychiatry . 1978;135:1081-1084. 10. Rothman SM, Olney JW. Excitotoxicity and the NMDA receptor . Trends Neurosci . 1987;10:299-302.Crossref 11. Lipska B, Weinberger D. Phenotypic variations in responses to neonatal excitotoxic hippocampal damage . Abstr Am Coll Neuropsychopharmacol . 1994;178. 12. Feinberg I. Schizophrenia: caused by a fault inprogrammed synaptic elimination during adolescence? J Psychiatr Res . 1982;17:319-334.Crossref 13. Walker E, Lewine RJ. Prediction of adult-onset schizophrenia from childhood home movies of the patients . Am J Psychiatry . 1990;147:1052-1056. 14. Fish B, Marcus J, Hans SL, Auerbach JG, Perdue S. Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect: a review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study . Arch Gen Psychiatry . 1992;49:221-235.Crossref 15. Luisada PV, Brown BL. Clinical management of phencyclidine psychosis . Clin Toxicol . 1976;9:539-545.Crossref 16. Carpenter WT, Buchanan RW. Schizophrenia . N Engl J Med . 1994;330:681-690.Crossref 17. Häfner H, Maurer K, Löffler W, Riecher-Rössler A. The influence of age and sex on the onset and early course of schizophrenia . Br J Psychiatry . 1993;162:80-86.Crossref 18. Benes FM, Vincent SL, Alsterberg G, Bird ED, SanGiovanni JP. Increased GABAA receptor binding in superficial layers of cingulate cortex in schizophrenics . J Neurosci . 1992;12:924-929. 19. Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL. Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients . Arch Gen Psychiatry . 1991;48:996-1001.Crossref 20. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE, Jones EG. Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics . Arch Gen Psychiatry . 1995;52:258-266.Crossref 21. Beckwith JP, Stefanis NC, McLaughlin DP, Kerwin RW. The expression of NMDA receptor subunits in schizophrenic post-mortem hippocampus . Schizophr Res . 1995;15:54.Crossref 22. Selemon LD, Rajkowska G, Goldman-Rakic PS. Cytologic abnormalities in area 9 of the schizophrenic cortex . Soc Neurosci Abstr . 1993;19:200. 23. Pakkenberg B. Total nerve cell number in neocortex in chronic schizophrenics and controls estimated using optical disectors . Biol Psychiatry . 1993;34:768-772.Crossref 24. Tandon R, Greden JF, Silk KR. Treatment of negative schizophrenic symptoms with trihexyphenidyl . J Clin Psychopharmacol . 1988;8:212-215. 25. Wolkowitz OM, Pickar D. Benzodiazepines in the treatment of schizophrenia: a review and reappraisal . Am J Psychiatry . 1991;148:714-726. 26. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP. Amelioration of negative symptoms in schizophrenia by glycine . Am J Psychiatry . 1994;151:1234-1236.

Journal

Archives of General PsychiatryAmerican Medical Association

Published: Dec 1, 1995

References