Journal ArticleDOI
The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia
Donald C. Goff,Joseph T. Coyle +1 more
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TLDR
Dysfunction of glutamatergic neurotransmission may play an important role in the pathophysiology of schizophrenia, especially of the negative symptoms and cognitive impairments associated with the disorder, and is a promising target for drug development.Abstract:
OBJECTIVE: Research has implicated dysfunction of glutamatergic neurotransmission in the pathophysiology of schizophrenia. This review evaluates evidence from preclinical and clinical studies that brain glutamatergic neurotransmission is altered in schizophrenia, may affect symptom expression, and is modulated by antipsychotic drugs. METHOD: A comprehensive review of scientific articles published over the last decade that address the role of glutamate in the pathophysiology of schizophrenia was carried out. RESULTS: Glutamatergic neurons are the major excitatory pathways linking the cortex, limbic system, and thalamus, regions that have been implicated in schizophrenia. Postmortem studies have revealed alterations in pre- and postsynaptic markers for glutamatergic neurons in several brain regions in schizophrenia. The N-methyl-d-aspartic acid (NMDA) subtype of glutamate receptor may be particularly important as blockade of this receptor by the dissociative anesthetics reproduces in normal subjects the sym...read more
Citations
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Journal ArticleDOI
Psychosis as a state of aberrant salience: A framework linking biology, phenomenology, and pharmacology in schizophrenia.
TL;DR: A heuristic framework for linking the psychological and biological in psychosis is provided and it is proposed that a dysregulated, hyperdopaminergic state, at a "brain" level of description and analysis, leads to an aberrant assignment of salience to the elements of one's experience, at an "mind" level.
Journal ArticleDOI
Neuregulin 1 and Susceptibility to Schizophrenia
Hreinn Stefansson,Engilbert Sigurdsson,Valgerdur Steinthorsdottir,Soley Bjornsdottir,Thordur Sigmundsson,Shyamali Ghosh,J Brynjolfsson,Steinunn Gunnarsdottir,Omar Ivarsson,Thomas T. Chou,Omar Hjaltason,Birgitta Birgisdottir,Helgi Jonsson,Vala G. Gudnadottir,Elsa Gudmundsdottir,Asgeir Björnsson,Brynjolfur Ingvarsson,Andres Ingason,Sigmundur Sigfusson,Hronn Hardardottir,Richard P. Harvey,Richard P. Harvey,Donna Lai,Mingdong Zhou,Daniela Brunner,Vincent Mutel,Acuna Gonzalo,Greg Lemke,Jesus Sainz,Gardar Johannesson,Thorkell Andresson,Daniel F. Gudbjartsson,Andrei Manolescu,Michael L. Frigge,Mark E. Gurney,Augustine Kong,Jeffrey R. Gulcher,Hannes Petursson,Kari Stefansson +38 more
TL;DR: The results of a genomewide scan of schizophrenia families in Iceland show that schizophrenia maps to chromosome 8p, and extensive fine-mapping of the 8p locus and haplotype-association analysis identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia.
Journal ArticleDOI
Dysconnection in Schizophrenia: From Abnormal Synaptic Plasticity to Failures of Self-monitoring
TL;DR: It is argued that this neurobiological mechanism can explain failures of self-monitoring, leading to a mechanistic explanation for first-rank symptoms as pathognomonic features of schizophrenia, and may provide a basis for future diagnostic classifications with physiologically defined patient subgroups.
Journal ArticleDOI
Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs
TL;DR: A brief review and critique of the current therapeutic armamentarium for treating schizophrenia and drug development strategies and theories of mechanisms of action of antipsychotic drugs is provided, and focuses on novel targets for therapeutic agents for future drug development.
Journal ArticleDOI
Oxidative stress in psychiatric disorders : evidence base and therapeutic implications
TL;DR: Multi-dimensional data support the role of oxidative stress in diverse psychiatric disorders and suggest that oxidative mechanisms may form unifying common pathogenic pathways in psychiatric disorders, but also introduce new targets for the development of therapeutic interventions.
References
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A synaptic model of memory: long-term potentiation in the hippocampus
TL;DR: The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.
Journal ArticleDOI
Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans: Psychotomimetic, perceptual, cognitive, and neuroendocrine responses.
John H. Krystal,Laurence P. Karper,John Seibyl,Glenna K. Freeman,Richard C. Delaney,J. Douglas Bremner,George R. Heninger,Malcolm B. Bowers,Dennis S. Charney +8 more
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Journal ArticleDOI
Recent advances in the phencyclidine model of schizophrenia.
TL;DR: It was found that PCP-induced psychotomimetic effects are associated with submicromolar serum concentrations of PCP and the findings suggest that endogenous dysfunction of NMDA receptor-mediated neurotransmission might contribute to the pathogenesis of schizophrenia.
Journal ArticleDOI
Molecular diversity of glutamate receptors and implications for brain function.
TL;DR: The molecular and functional diversity of the glutamate receptors is reviewed and their implications for integrative brain function are discussed.
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