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Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide
Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340369/ https://www.ncbi.nlm.nih.gov/pubmed/22558144 http://dx.doi.org/10.1371/journal.pone.0035367 |
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author | Sequeira, Adolfo Morgan, Ling Walsh, David M. Cartagena, Preston M. Choudary, Prabhakara Li, Jun Schatzberg, Alan F. Watson, Stanley J. Akil, Huda Myers, Richard M. Jones, Edward G. Bunney, William E. Vawter, Marquis P. |
author_facet | Sequeira, Adolfo Morgan, Ling Walsh, David M. Cartagena, Preston M. Choudary, Prabhakara Li, Jun Schatzberg, Alan F. Watson, Stanley J. Akil, Huda Myers, Richard M. Jones, Edward G. Bunney, William E. Vawter, Marquis P. |
author_sort | Sequeira, Adolfo |
collection | PubMed |
description | Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P≤0.01 and fold change±1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain. |
format | Online Article Text |
id | pubmed-3340369 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33403692012-05-03 Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide Sequeira, Adolfo Morgan, Ling Walsh, David M. Cartagena, Preston M. Choudary, Prabhakara Li, Jun Schatzberg, Alan F. Watson, Stanley J. Akil, Huda Myers, Richard M. Jones, Edward G. Bunney, William E. Vawter, Marquis P. PLoS One Research Article Suicidal behaviors are frequent in mood disorders patients but only a subset of them ever complete suicide. Understanding predisposing factors for suicidal behaviors in high risk populations is of major importance for the prevention and treatment of suicidal behaviors. The objective of this project was to investigate gene expression changes associated with suicide in brains of mood disorder patients by microarrays (Affymetrix HG-U133 Plus2.0) in the dorsolateral prefrontal cortex (DLPFC: 6 Non-suicides, 15 suicides), the anterior cingulate cortex (ACC: 6NS, 9S) and the nucleus accumbens (NAcc: 8NS, 13S). ANCOVA was used to control for age, gender, pH and RNA degradation, with P≤0.01 and fold change±1.25 as criteria for significance. Pathway analysis revealed serotonergic signaling alterations in the DLPFC and glucocorticoid signaling alterations in the ACC and NAcc. The gene with the lowest p-value in the DLPFC was the 5-HT2A gene, previously associated both with suicide and mood disorders. In the ACC 6 metallothionein genes were down-regulated in suicide (MT1E, MT1F, MT1G, MT1H, MT1X, MT2A) and three were down-regulated in the NAcc (MT1F, MT1G, MT1H). Differential expression of selected genes was confirmed by qPCR, we confirmed the 5-HT2A alterations and the global down-regulation of members of the metallothionein subfamilies MT 1 and 2 in suicide completers. MTs 1 and 2 are neuro-protective following stress and glucocorticoid stimulations, suggesting that in suicide victims neuroprotective response to stress and cortisol may be diminished. Our results thus suggest that suicide-specific expression changes in mood disorders involve both glucocorticoids regulated metallothioneins and serotonergic signaling in different regions of the brain. Public Library of Science 2012-04-30 /pmc/articles/PMC3340369/ /pubmed/22558144 http://dx.doi.org/10.1371/journal.pone.0035367 Text en Sequeira et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sequeira, Adolfo Morgan, Ling Walsh, David M. Cartagena, Preston M. Choudary, Prabhakara Li, Jun Schatzberg, Alan F. Watson, Stanley J. Akil, Huda Myers, Richard M. Jones, Edward G. Bunney, William E. Vawter, Marquis P. Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide |
title | Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide |
title_full | Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide |
title_fullStr | Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide |
title_full_unstemmed | Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide |
title_short | Gene Expression Changes in the Prefrontal Cortex, Anterior Cingulate Cortex and Nucleus Accumbens of Mood Disorders Subjects That Committed Suicide |
title_sort | gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340369/ https://www.ncbi.nlm.nih.gov/pubmed/22558144 http://dx.doi.org/10.1371/journal.pone.0035367 |
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