The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia's Etiology
Autor(a) principal: | |
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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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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 |
_version_ |
1824718304528302080 |