Schizophrenia and glutamatergic transmission

Research output: Contribution to journalArticle

328 Citations (Scopus)

Abstract

Schizophrenia is a human brain disease with well-defined symptoms and a lifelong disease course, but without a current biological explanation. Several observations implicate brain glutamatergic abnormalities in the pathophysiology of this illness. This evidence includes both human neurochemical and clinical pharmacologic data. Furthermore the psychotomimetic action of phencyclidine, the noncompetitive NMDA-sensitive glutamate receptor antagonist, suggests the association between human psychosis and NMDA receptor blockade. This paper reviews basic aspects of glutamatergic transmission in animal and human brain with particular attention to its putative role in schizophrenia. Consideration is given to other glutamate-related human brain diseases and their purported mechanisms. Evidence of glutamatergic abnormalities in schizophrenia is critically reviewed, including data using postmortem neurochemistry, in vivo human brain imaging, clinical pharmacology, and animal models. The current theoretical formulations based on these studies are articulated. We propose a 'working' glutamate hypothesis of schizophrenia which postulates a diminished glutamatergic transmission in the hippocampal glutamate-mediated efferent pathways and cerebral dysfunction in the hippocampus and its target areas, especially the anterior cingulate cortex. Considerable work remains to be done in this area to formulate and test a comprehensive hypothesis.

Original languageEnglish (US)
Pages (from-to)21-36
Number of pages16
JournalCritical Reviews in Neurobiology
Volume12
Issue number1-2
StatePublished - 1998

Fingerprint

Schizophrenia
Glutamic Acid
Brain Diseases
Neurochemistry
Efferent Pathways
Phencyclidine
Excitatory Amino Acid Antagonists
Clinical Pharmacology
Gyrus Cinguli
Brain
N-Methylaspartate
N-Methyl-D-Aspartate Receptors
Neuroimaging
Psychotic Disorders
Hippocampus
Animal Models

Keywords

  • Brain imaging
  • Glutamate receptor
  • Ketamine
  • NMDA
  • PCP
  • Postmortem
  • Psychosis
  • Schizophrenia

ASJC Scopus subject areas

  • Clinical Neurology
  • Physiology
  • Neuroscience(all)

Cite this

Schizophrenia and glutamatergic transmission. / Tamminga, Carol A.

In: Critical Reviews in Neurobiology, Vol. 12, No. 1-2, 1998, p. 21-36.

Research output: Contribution to journalArticle

@article{3c09a8e36b8642bda39ea89885bfcef3,
title = "Schizophrenia and glutamatergic transmission",
abstract = "Schizophrenia is a human brain disease with well-defined symptoms and a lifelong disease course, but without a current biological explanation. Several observations implicate brain glutamatergic abnormalities in the pathophysiology of this illness. This evidence includes both human neurochemical and clinical pharmacologic data. Furthermore the psychotomimetic action of phencyclidine, the noncompetitive NMDA-sensitive glutamate receptor antagonist, suggests the association between human psychosis and NMDA receptor blockade. This paper reviews basic aspects of glutamatergic transmission in animal and human brain with particular attention to its putative role in schizophrenia. Consideration is given to other glutamate-related human brain diseases and their purported mechanisms. Evidence of glutamatergic abnormalities in schizophrenia is critically reviewed, including data using postmortem neurochemistry, in vivo human brain imaging, clinical pharmacology, and animal models. The current theoretical formulations based on these studies are articulated. We propose a 'working' glutamate hypothesis of schizophrenia which postulates a diminished glutamatergic transmission in the hippocampal glutamate-mediated efferent pathways and cerebral dysfunction in the hippocampus and its target areas, especially the anterior cingulate cortex. Considerable work remains to be done in this area to formulate and test a comprehensive hypothesis.",
keywords = "Brain imaging, Glutamate receptor, Ketamine, NMDA, PCP, Postmortem, Psychosis, Schizophrenia",
author = "Tamminga, {Carol A.}",
year = "1998",
language = "English (US)",
volume = "12",
pages = "21--36",
journal = "Critical Reviews in Neurobiology",
issn = "0892-0915",
publisher = "Begell House Inc.",
number = "1-2",

}

TY - JOUR

T1 - Schizophrenia and glutamatergic transmission

AU - Tamminga, Carol A.

PY - 1998

Y1 - 1998

N2 - Schizophrenia is a human brain disease with well-defined symptoms and a lifelong disease course, but without a current biological explanation. Several observations implicate brain glutamatergic abnormalities in the pathophysiology of this illness. This evidence includes both human neurochemical and clinical pharmacologic data. Furthermore the psychotomimetic action of phencyclidine, the noncompetitive NMDA-sensitive glutamate receptor antagonist, suggests the association between human psychosis and NMDA receptor blockade. This paper reviews basic aspects of glutamatergic transmission in animal and human brain with particular attention to its putative role in schizophrenia. Consideration is given to other glutamate-related human brain diseases and their purported mechanisms. Evidence of glutamatergic abnormalities in schizophrenia is critically reviewed, including data using postmortem neurochemistry, in vivo human brain imaging, clinical pharmacology, and animal models. The current theoretical formulations based on these studies are articulated. We propose a 'working' glutamate hypothesis of schizophrenia which postulates a diminished glutamatergic transmission in the hippocampal glutamate-mediated efferent pathways and cerebral dysfunction in the hippocampus and its target areas, especially the anterior cingulate cortex. Considerable work remains to be done in this area to formulate and test a comprehensive hypothesis.

AB - Schizophrenia is a human brain disease with well-defined symptoms and a lifelong disease course, but without a current biological explanation. Several observations implicate brain glutamatergic abnormalities in the pathophysiology of this illness. This evidence includes both human neurochemical and clinical pharmacologic data. Furthermore the psychotomimetic action of phencyclidine, the noncompetitive NMDA-sensitive glutamate receptor antagonist, suggests the association between human psychosis and NMDA receptor blockade. This paper reviews basic aspects of glutamatergic transmission in animal and human brain with particular attention to its putative role in schizophrenia. Consideration is given to other glutamate-related human brain diseases and their purported mechanisms. Evidence of glutamatergic abnormalities in schizophrenia is critically reviewed, including data using postmortem neurochemistry, in vivo human brain imaging, clinical pharmacology, and animal models. The current theoretical formulations based on these studies are articulated. We propose a 'working' glutamate hypothesis of schizophrenia which postulates a diminished glutamatergic transmission in the hippocampal glutamate-mediated efferent pathways and cerebral dysfunction in the hippocampus and its target areas, especially the anterior cingulate cortex. Considerable work remains to be done in this area to formulate and test a comprehensive hypothesis.

KW - Brain imaging

KW - Glutamate receptor

KW - Ketamine

KW - NMDA

KW - PCP

KW - Postmortem

KW - Psychosis

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0031979134&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031979134&partnerID=8YFLogxK

M3 - Article

C2 - 9444480

AN - SCOPUS:0031979134

VL - 12

SP - 21

EP - 36

JO - Critical Reviews in Neurobiology

JF - Critical Reviews in Neurobiology

SN - 0892-0915

IS - 1-2

ER -