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The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia’s Etiology
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. glutamaterg...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Bentham Science Publishers
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286845/ https://www.ncbi.nlm.nih.gov/pubmed/22942875 http://dx.doi.org/10.2174/157015912799362742 |
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author | Dias, Alvaro Machado |
author_facet | Dias, Alvaro Machado |
author_sort | Dias, Alvaro Machado |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3286845 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-32868452012-09-01 The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia’s Etiology Dias, Alvaro Machado Curr Neuropharmacol Article 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. Bentham Science Publishers 2012-03 2012-03 /pmc/articles/PMC3286845/ /pubmed/22942875 http://dx.doi.org/10.2174/157015912799362742 Text en ©2012 Bentham Science Publishers http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.5/), which permits unrestrictive use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Dias, Alvaro Machado 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 |
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_short | The Integration of the Glutamatergic and the White Matter Hypotheses of Schizophrenia’s Etiology |
title_sort | integration of the glutamatergic and the white matter hypotheses of schizophrenia’s etiology |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286845/ https://www.ncbi.nlm.nih.gov/pubmed/22942875 http://dx.doi.org/10.2174/157015912799362742 |
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