The emerging role of glutamate in the pathophysiology and treatment of schizophrenia

American Journal of Psychiatry

Volumn 158, Issue 9, 2001, Pages 1367-1377

  Goff, D C ^a   Coyle, J T ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 QUINOXALINECARBOXYLIC ACID PIPERIDIDE; ALPHA (2,3 DIMETHOXYPHENYL) 1 [2 (4 FLUOROPHENYL)ETHYL] 4 PIPERIDINEMETHANOL; ANESTHETIC AGENT; CHLORPROMAZINE; CLOZAPINE; CYCLOSERINE; DEXTRO SERINE; DIZOCILPINE; DOPAMINE; GLUTAMATE RECEPTOR; GLUTAMATE RECEPTOR ANTAGONIST; GLUTAMIC ACID; GLYCINE; HALOPERIDOL; KETAMINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR BLOCKING AGENT; NEUROLEPTIC AGENT; OLANZAPINE; PHENCYCLIDINE; QUETIAPINE; REMOXIPRIDE; RISPERIDONE;

BRAIN CORTEX; BRAIN REGION; COGNITIVE DEFECT; DOPAMINE RELEASE; HUMAN; LIMBIC CORTEX; NEGATIVE SYNDROME; NEUROTRANSMISSION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SCHIZOPHRENIA; THALAMUS;

ANIMALS; ANTIPSYCHOTIC AGENTS; BRAIN; CEREBRAL CORTEX; COGNITION DISORDERS; CORPUS STRIATUM; GLUTAMATES; HUMANS; LIMBIC SYSTEM; RATS; RECEPTORS, GLUTAMATE; SCHIZOPHRENIA; SCHIZOPHRENIC PSYCHOLOGY; SYNAPTIC TRANSMISSION; THALAMUS;

EID: 0034843738     PISSN: 0002953X     EISSN: None     Source Type: Journal    
DOI: 10.1176/appi.ajp.158.9.1367     Document Type: Review

References (148)

1. NMDA agonists and antagonists as probes of glutamatergic dysfunction and pharmacotherapies for neuropsychiatric disorders
2. Glutamate receptors in schizophrenia and antipsychotic drugs
3. Glutamate receptor expression in schizophrenic brain
4. Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: Effects of schizophrenia
5. Ionotropic glutamate receptor binding and subunit mRNA expression in thalamic nuclei in schizophrenia
6. Functional imaging of memory retrieval in deficit vs nondeficit schizophrenia
7. Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia
8. Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development
9. Distorted distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase neurons in temporal lobe of schizophrenics implies anomalous cortical development
10. Schizophrenia as a disorder of developmentally reduced synaptic connectivity
11. Physiological and pathophysiological roles of excitatory amino acids during central nervous system development
12. Glutamate receptor, microtubule associated proteins and developmental anomaly in schizophrenia: An hypothesis
13. Modulation of neuronal migration by NMDA receptors
14. Glutamate neurotoxicity and diseases of the nervous system
15. New mechanisms of excitatory transmitter neurotoxicity
16. Interactions between glutamatergic and monoaminergic systems within the basal ganglia - Implications for schizophrenia and Parkinson's disease
17. Molecular diversity of glutamate receptors and implications for brain function
18. Nitric oxide: Cellular regulation and neuronal injury
19. The neuropsychopharmacology of phencyclidine: From NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia
20. Competitive antagonism of glycine at the N-methyl-D-aspartate (NMDA) receptor
21. Modulation of N-methyl-D-aspartate receptor function by glycine transport
22. Glycine and N-methyl-D-aspartate receptors: Physiological significance and possible therapeutic applications
23. Reversal of the behavioral and neurochemical effects of phencyclidine by glycine and glycine transport inhibitors
24. A synaptic model of memory: Long-term potentiation in the hippocampus
25. 2+ block in NMDA receptor channels
26. NMDA-dependent modulation of CA1 local circuit inhibition
27. Regulation of cortical and subcortical glutamate receptor subunit expression by antipsychotic drugs
28. Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers
29. Low cerebrospinal glutamate in schizophrenic patients and a new hypothesis on schizophrenia
30. Plasma amino acids in relation to cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy controls
31. Amino acid patterns in schizophrenia: Some new findinss
32. Glutamate in schizophrenics and healthy controls
33. Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutamatersic neuronal dysfunction
34. Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia
35. Abnormal excitatory neurotransmitter metabolism in schizophrenic brains
36. The nagging question of the function of N-acetylaspartylglutamate
37. In vivo neurochemistry of brain in schizophrenia as revealed by magnetic resonance spectroscopy
38. N-Acetylaspartate in neuropsychiatric disorders
39. Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia
40. 3H] kainic acid binding in the prefrontal cortex in schizophrenia
41. Asymmetrical loss of glutamate receptor subtype in left hippocampus in schizophrenia
42. Quantitative autoradiosraphic analysis of glutamate binding sites in the hippocampal formation in normal and schizophrenic brain post mortem
43. NMDA-associated glycine binding site increases in schizophrenic brains
44. Increases in strychnine-insensitive glycine binding sites in cerebral cortex of chronic schizophrenics: Evidence for glutamate hypothesis
45. Regionally selective deficits in uptake sites for glutamate and gamma-aminobutyric acid in the basal ganglia in schizophrenia
46. Decreased hippocampal expression of a glutamate receptor gene in schizophrenia
47. Decreased expression of mRNAs encoding non-NMDA glutamate receptors GluR1 and GluR2 in medial temporal lobe neurons in schizophrenia
48. Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics
49. Mice with reduced NMDA receptor expression display behaviors related to schizophrenia
50. Study of a new schizophrenomimetic drug - Sernyl
51. Recent advances in the phencyclidine model of schizophrenia
52. Effect of phencyclidine in chronic schizophrenics
53. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses
54. Comparison of phencyclidine hydrochloride (sernyl) with other drugs: Simulation of schizophrenic performance with phencyclidine hydrochloride (sernyl), lysergic acid diethylamide (LSD-25), and amobarbital (Amytal) sodium, II: Symbolic and sequential thinking
55. The initial prodrome in schizophrenia: Searching for core dimensions of experience and behavior
56. NMDA receptor function and human cognition: The effects of ketamine in healthy volunteers
57. Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis
58. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia
59. Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics
60. Therapeutic implications of the hyperglutamatergic effects of NMDA antagonists
61. Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers
62. Ketamine activates psychosis and alters limbic blood flow in schizophrenia
63. Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)
64. 18F] fluorodeoxyglucose (FDG)
65. Single photon emission computed tomography in phencyclidine and related drug abuse
66. Positron emission tomography study of phencyclidine users as a possible drug model of schizophrenia
67. Enduring cognitive deficits and cortical dopamine dysfunction in monkeys after long-term administration of phencyclidine
68. Mesolimbic and mesocortical dopamine activation induced by phencyclidine: Contrasting pattern to striatal response
69. Activation of forebrain dopamine systems by phencyclidine and footshock stress: Evidence for distinct mechanisms
70. NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: Modulation by dopamine
71. Activation of glutamatergic neurotransmission by ketamine: A novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex
72. 1-adrenoreceptor antagonism
73. 11C-raclopride in normal human subjects
74. Effects of NMDA antagonism on striatal dopamine release in healthy subjects: Application of a novel PET approach
75. 11C]raclopride PET study of a model psychosis in humans
76. 11C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: Multiparametric PET studies combined with microdialysis analysis
77. Subchronic phencyclidine administration reduces mesoprefrontal dopamine utilization and impairs prefrontal cortical-dependent cognition in the rat
78. Reduced prefrontal dopamine, but not acetylcholine, release in vivo after repeated, intermittent phencyclidine administration to rats
79. Differential effects of single and repeated ketamine administration on dopamine, serotonin, and GABA transmission in rat prefrontal cortex
80. Differential regulation, by MK-801, of dopamine receptor gene expression in rat nigrostriatal and mesocorticolimbic systems
81. Dopamine receptor gene expression in hippocampus is differentially regulated by the NMDA receptor antagonist MK-801
82. 1 dopamine receptors in prefrontal cortex: Involvement in working memory
83. Dopamine in schizophrenia: A review and reconceptualization
84. Phencyclidine increases forebrain monoamine metabolism in rats and monkeys: Modulation by the isomers of HA966
85. The ontogeny of behavioral sensitization to phencyclidine
86. Low-dose bromocriptine in neuroleptic-resistant schizophrenia: A pilot study
87. Phencyclidine-induced behavioral sensitization
88. Behavioral, pharmacological, and biochemical effects of acute and chronic administration of ketamine in the rat
89. Subchronic phencyclidine administration increases mesolimbic dopamine system responsivity and augments stress and amphetamine-induced hyperlocomotion
90. Neurochemical sensitization in the pathophysiology of schizophrenia: Deficits and dysfunction in neuronal regulation and plasticity
91. Sensorimotor gating and schizophrenia
92. Clozapine antagonizes phencyclidine-induced deficits in sensorimotor gating of the startle response
93. Antagonism of phencyclidine-induced deficits in prepulse inhibition by the putative atypical antipsychotic drug olanzapine
94. Seroquel restores sensorimotor gating in phencyclidine-treated rats
95. The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat
96. Seroquel, clozapine and chlorpromazine restore sensorimotor gating in ketamine-treated rats
97. Reversal of phencyclidine-induced deficits in prepulse inhibition by prazosin, an alpha-1 adrenergic antagonist
98. Differential effects of clozapine and haloperidol on ketamine-induced brain metabolic activation
99. Comparison of the effects of clozapine, risperidone, and olanzapine on ketamine-induced alterations in regional brain metabolism
100. Antipsychotic agents antagonize non-competitive N-methyl-D-aspartate antagonist-induced behaviors
101. Efficacy of clozapine compared with other antipsychotics in preventing NMDA-antagonist neurotoxicity
102. Olanzapine and fluperlapine mimic clozapine in preventing MK-801 neurotoxicity
103. Antipsychotic drugs block phencyclidine receptor-mediated neurotoxicity
104. Glutamate receptor dysfunction and schizophrenia
105. Intracellular modulation of NMDA receptor function by antipsychotic drugs
106. Regulation of phosphorylation of the GluR1 AMPA receptor in the neostriatum by dopamine and stimulants in vivo
107. Differential effects of chronic antipsychotic drug treatment on extracellular glutamate and dopamine concentrations
108. Brain region effects of clozapine on amino acid and monoamine transmission
109. Duration-dependent increase in striatal glutamate following prolonged fluphenazine administration in rats
110. Chronic neuroleptic treatment alters expression of glial glutamate transporter GLT-1 mRNA in the striatum
111. Tardive dyskinesia and substrates of energy metabolism in CSF
112. Markers of glutamatergic neurotransmission and oxidative stress associated with tardive dyskinesia
113. Effects of subchronic clozapine and haloperidol on striatal glutamatergic synapses
114. Antiglutamatergic effects of clozapine
115. Clozapine and haloperidol modulate N-methyl-D-aspartate and non-N-methyl-D-aspartate receptor-mediated neurotransmission in rat prefrontal cortical neurons in vitro
116. M100907 and clozapine, but not haloperidol or raclopride, prevent phencyclidine-induced blockade of NMDA responses in pyramidal neurons of the rat medial prefrontal cortical slice
117. Glutamate agonist activity: Implications for antipsychotic drug action and schizophrenia
118. Antipsychotic drug effects on glutamatergic activity
119. Haloperidol interacts with the strychnine-insensitive glycine site at the NMDA receptor in cultured mouse hippocampal neurones
120. Chronic antipsychotic treatment alters glycine-stimulated NMDA receptor binding in rat brain
121. Clozapine and haloperidol differentially affect AMPA and kainate receptor subunit mRNA levels in rat cortex and striatum
122. Regulation of NMDA receptor subunit messenger RNA levels in the rat brain following acute and chronic exposure to antipsychotic drugs
123. Differential regulation of hippocampal AMPA and kainate receptor subunit expression by haloperidol and clozapine
124. Does modulation of glutamatergic function represent a viable therapeutic strategy in Alzheimer's disease?
125. Glycine therapy of schizophrenia
126. Glycine adjuvant therapy to conventional neuroleptic treatment in schizophrenia: An open-label, pilot study
127. An open trial of glycine as an adjunct to neuroleptics in chronic treatment-refractory schizophrenics
128. Glycine site agonists of the NMDA receptor: A review
129. Amelioration of negative symptoms in schizophrenia by glycine
130. Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia
131. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia
132. D-Serine added to antipsychotics for the treatment of schizophrenia
133. D-Cycloserine acts as a partial agonist at the glycine modulatory site of the NMDA receptor expressed in Xenopus oocytes
134. Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia
135. Efficacy and tolerance of D-cycloserine in drug-free schizophrenic patients
136. A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia
137. D-cycloserine adjuvant therapy to molindone in the treatment of schizophrenia
138. D-cycloserine added to clozapine for patients with schizophrenia
139. A placebo-controlled crossover trial of D-cycloserine added to clozapine in patients with schizophrenia
140. Effect of clozapine and adjunctive high-dose glycine in treatment-resistant schizophrenia
141. D-Serine added to clozapine for the treatment of schizophrenia
142. Placebo-controlled trial of glycine added to clozapine in schizophrenia
143. Effects of a memory-enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus
144. Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo
145. Effects of pharmacologically facilitating glutamatergic transmission in the trisynaptic intrahippocampal circuit
146. Facilitation of glutamate receptors enhances memory
147. Synergistic interactions between ampakines and antipsychotic drugs
148. A preliminary dose escalation trial of CX516 (Ampakine) added to clozapine in schizophrenia