The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology

Detalhes bibliográficos
Autor(a) principal: Dias, Alvaro Machado [UNIFESP]
Data de Publicação: 2012
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.2174/157015912799362742
http://repositorio.unifesp.br/handle/11600/43455
Resumo: Background: schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e. g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time.Objectives: This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia's etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification.Highlights: Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e. g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.
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spelling The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's EtiologySchizophreniamolecular psychiatryconnectivityglutamatewhite matterBackground: schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e. g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time.Objectives: This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia's etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification.Highlights: Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e. g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.Univ Sao Paulo, Sch Med, Dept Neuroimaging Psychiat LIM 21, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of ScienceBentham Science Publ LtdUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Dias, Alvaro Machado [UNIFESP]2018-06-15T17:05:13Z2018-06-15T17:05:13Z2012-03-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion2-11http://dx.doi.org/10.2174/157015912799362742Current Neuropharmacology. Sharjah: Bentham Science Publ Ltd, v. 10, n. 1, p. 2-11, 2012.10.2174/1570159127993627421570-159Xhttp://repositorio.unifesp.br/handle/11600/43455WOS:000300637600002engCurrent Neuropharmacologyinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-05-02T13:59:32Zoai:repositorio.unifesp.br/:11600/43455Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-05-02T13:59:32Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
title The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
spellingShingle The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
Dias, Alvaro Machado [UNIFESP]
Schizophrenia
molecular psychiatry
connectivity
glutamate
white matter
title_short The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
title_full The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
title_fullStr The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
title_full_unstemmed The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
title_sort The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
author Dias, Alvaro Machado [UNIFESP]
author_facet Dias, Alvaro Machado [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Dias, Alvaro Machado [UNIFESP]
dc.subject.por.fl_str_mv Schizophrenia
molecular psychiatry
connectivity
glutamate
white matter
topic Schizophrenia
molecular psychiatry
connectivity
glutamate
white matter
description Background: schizophrenia's endophenotipic profile is not only generally complex, but often varies from case to case. The perspective of trying to define specific anatomic correlates of the syndrome has led to disappointing results. In that context, neurophysiologic hypotheses (e. g. glutamatergic hypothesis) and connectivity hypotheses became prominent. Nevertheless, despite their commitment to the principle of denying 'localist' views and approaching the syndrome's endophenotype from a whole brain perspective, efforts to integrate both have not flourished at this moment in time.Objectives: This paper aims to introduce a new etiological model that integrates the glutamatergic and the WM (WM) hypotheses of schizophrenia's etiology. This model proposes to serve as a framework in order to relate to patterns of brain abnormalities from the onset of the syndrome to stages of advanced chronification.Highlights: Neurotransmitter abnormalities forego noticeable WM abnormalities. The former, chiefly represented by NMDAR hypo-function and associated molecular cascades, is related to the first signs of cell loss. This process is both directly and indirectly integrated to the underpinning of WM structural abnormalities; not only is the excess of glutamate toxic to the WM, but its disruption is associated to the expression of known genetic risk factors (e. g., NRG-1). A second level of the model develops the idea that abnormal neurotransmission within specific neural populations ('motifs') impair particular cognitive abilities, while subsequent WM structural abnormalities impair the integration of brain functions and multimodality. As a result of this two-stage dynamic, the affected individual progresses from experiencing specific cognitive and psychological deficits, to a condition of cognitive and existential fragmentation, linked to hardly reversible decreases in psychosocial functioning.
publishDate 2012
dc.date.none.fl_str_mv 2012-03-01
2018-06-15T17:05:13Z
2018-06-15T17:05:13Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.2174/157015912799362742
Current Neuropharmacology. Sharjah: Bentham Science Publ Ltd, v. 10, n. 1, p. 2-11, 2012.
10.2174/157015912799362742
1570-159X
http://repositorio.unifesp.br/handle/11600/43455
WOS:000300637600002
url http://dx.doi.org/10.2174/157015912799362742
http://repositorio.unifesp.br/handle/11600/43455
identifier_str_mv Current Neuropharmacology. Sharjah: Bentham Science Publ Ltd, v. 10, n. 1, p. 2-11, 2012.
10.2174/157015912799362742
1570-159X
WOS:000300637600002
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Current Neuropharmacology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 2-11
dc.publisher.none.fl_str_mv Bentham Science Publ Ltd
publisher.none.fl_str_mv Bentham Science Publ Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
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