NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?

Joseph C. Masdeu; Josep Dalmau; Karen F. Berman

doi:10.1016/j.tins.2016.02.006

NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?

Joseph C. Masdeu, Josep Dalmau, Karen F. Berman

Research output: Contribution to journal › Review article › peer-review

66 Scopus citations

Abstract

Since the early 1990s it has been postulated that hypofunction of N-methyl-. d-aspartate (NMDA) receptors in brain networks supporting perception and cognition underlies schizophrenic psychosis. Recently, NMDA receptor hypofunction was described in patients with psychotic manifestations who exhibited autoantibodies binding the GluN1 subunit of the receptor, and who improved when the level of these antibodies was lowered by immunomodulation. In this disorder, NMDA receptor antibodies decrease the availability of NMDA receptors by internalizing them. In this opinion article, we review this mechanism as well as data supporting or refuting the possibility that this disorder or similar autoimmune disorders affecting synaptic proteins, which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis. We also suggest methodological approaches to clarify this issue.

Original language	English (US)
Pages (from-to)	300-310
Number of pages	11
Journal	Trends in Neurosciences
Volume	39
Issue number	5
DOIs	https://doi.org/10.1016/j.tins.2016.02.006
State	Published - May 1 2016

Keywords

Antibodies
Immunotherapy
NMDA receptor
Psychosis
Schizophrenia
Synapsis

ASJC Scopus subject areas

Neuroscience(all)

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10.1016/j.tins.2016.02.006

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title = "NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?",

abstract = "Since the early 1990s it has been postulated that hypofunction of N-methyl-. d-aspartate (NMDA) receptors in brain networks supporting perception and cognition underlies schizophrenic psychosis. Recently, NMDA receptor hypofunction was described in patients with psychotic manifestations who exhibited autoantibodies binding the GluN1 subunit of the receptor, and who improved when the level of these antibodies was lowered by immunomodulation. In this disorder, NMDA receptor antibodies decrease the availability of NMDA receptors by internalizing them. In this opinion article, we review this mechanism as well as data supporting or refuting the possibility that this disorder or similar autoimmune disorders affecting synaptic proteins, which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis. We also suggest methodological approaches to clarify this issue.",

keywords = "Antibodies, Immunotherapy, NMDA receptor, Psychosis, Schizophrenia, Synapsis",

author = "Masdeu, {Joseph C.} and Josep Dalmau and Berman, {Karen F.}",

note = "Funding Information: J.C.M. and K.F.B. were supported by the Houston Methodist Research Institute and by the National Institute of Mental Health (NIMH) Intramural Research Program, respectively; J.D. by NIH grants RO1NS077851, RO1MH094741, FIS, 11/01780, Fundaci{\'o} la Marat{\'o} de TV3, a McKnight Neuroscience of Brain Disorders award and a research grant from Euroimmun Inc. Dr Isabel P{\'e}rez Ota{\~n}o provided valuable comments on the manuscript. Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",

year = "2016",

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doi = "10.1016/j.tins.2016.02.006",

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T2 - A Reversible Mechanism Underlying Psychosis?

AU - Masdeu, Joseph C.

AU - Dalmau, Josep

AU - Berman, Karen F.

N1 - Funding Information: J.C.M. and K.F.B. were supported by the Houston Methodist Research Institute and by the National Institute of Mental Health (NIMH) Intramural Research Program, respectively; J.D. by NIH grants RO1NS077851, RO1MH094741, FIS, 11/01780, Fundació la Marató de TV3, a McKnight Neuroscience of Brain Disorders award and a research grant from Euroimmun Inc. Dr Isabel Pérez Otaño provided valuable comments on the manuscript. Publisher Copyright: © 2016 Elsevier Ltd. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Since the early 1990s it has been postulated that hypofunction of N-methyl-. d-aspartate (NMDA) receptors in brain networks supporting perception and cognition underlies schizophrenic psychosis. Recently, NMDA receptor hypofunction was described in patients with psychotic manifestations who exhibited autoantibodies binding the GluN1 subunit of the receptor, and who improved when the level of these antibodies was lowered by immunomodulation. In this disorder, NMDA receptor antibodies decrease the availability of NMDA receptors by internalizing them. In this opinion article, we review this mechanism as well as data supporting or refuting the possibility that this disorder or similar autoimmune disorders affecting synaptic proteins, which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis. We also suggest methodological approaches to clarify this issue.

AB - Since the early 1990s it has been postulated that hypofunction of N-methyl-. d-aspartate (NMDA) receptors in brain networks supporting perception and cognition underlies schizophrenic psychosis. Recently, NMDA receptor hypofunction was described in patients with psychotic manifestations who exhibited autoantibodies binding the GluN1 subunit of the receptor, and who improved when the level of these antibodies was lowered by immunomodulation. In this disorder, NMDA receptor antibodies decrease the availability of NMDA receptors by internalizing them. In this opinion article, we review this mechanism as well as data supporting or refuting the possibility that this disorder or similar autoimmune disorders affecting synaptic proteins, which are therefore treatable with immunomodulation, could account for some cases of idiopathic psychosis. We also suggest methodological approaches to clarify this issue.

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NMDA Receptor Internalization by Autoantibodies: A Reversible Mechanism Underlying Psychosis?

Abstract

Keywords

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