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Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation

The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample...

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Autores principales: Lewis, Charles P., Port, John D., Blacker, Caren J., Sonmez, A. Irem, Seewoo, Bhedita J., Leffler, Jarrod M., Frye, Mark A., Croarkin, Paul E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181616/
https://www.ncbi.nlm.nih.gov/pubmed/32327639
http://dx.doi.org/10.1038/s41398-020-0792-z
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author Lewis, Charles P.
Port, John D.
Blacker, Caren J.
Sonmez, A. Irem
Seewoo, Bhedita J.
Leffler, Jarrod M.
Frye, Mark A.
Croarkin, Paul E.
author_facet Lewis, Charles P.
Port, John D.
Blacker, Caren J.
Sonmez, A. Irem
Seewoo, Bhedita J.
Leffler, Jarrod M.
Frye, Mark A.
Croarkin, Paul E.
author_sort Lewis, Charles P.
collection PubMed
description The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy ((1)H-MRS) at 3 T, utilizing a 2-dimensional J-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluid-corrected ACC metabolite concentrations were compared between healthy control (HC, n = 16), depressed without SI (Dep/SI−, n = 13), and depressed with SI (Dep/SI+, n = 11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and the N-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI− and Dep/SI+ adolescents. Dep/SI+ adolescents had higher Glx than Dep/SI− participants (p(adj) = 0.012) and had lower NAA/Glx than both Dep/SI− (p(adj) = 0.002) and HC adolescents (p(adj) = 0.039). There were significant relationships between SI intensity and Glx (p(FDR) = 0.026), SI severity and NAA/Glx (p(FDR) = 0.012), and SI intensity and NAA/Glx (p(FDR) = 0.004). ACC Glx and NAA/Glx discriminated Dep/SI− from Dep/SI+ participants. Uncoupled NAA−glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior.
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spelling pubmed-71816162020-04-29 Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation Lewis, Charles P. Port, John D. Blacker, Caren J. Sonmez, A. Irem Seewoo, Bhedita J. Leffler, Jarrod M. Frye, Mark A. Croarkin, Paul E. Transl Psychiatry Article The anterior cingulate cortex (ACC) is involved in emotion regulation and salience processing. Prior research has implicated ACC dysfunction in suicidal ideation (SI) and suicidal behavior. This study aimed to quantify ACC glutamatergic concentrations and to examine relationships with SI in a sample of healthy and depressed adolescents. Forty adolescents underwent clinical evaluation and proton magnetic resonance spectroscopy ((1)H-MRS) at 3 T, utilizing a 2-dimensional J-averaged PRESS sequence sampling a medial pregenual ACC voxel. Cerebrospinal fluid-corrected ACC metabolite concentrations were compared between healthy control (HC, n = 16), depressed without SI (Dep/SI−, n = 13), and depressed with SI (Dep/SI+, n = 11) youth using general linear models covarying for age, sex, and psychotropic medication use. Relationships between ACC metabolites and continuous measures of SI were examined using multiple linear regressions. ROC analysis was used to determine the ability of glutamate+glutamine (Glx) and the N-acetylaspartate (NAA)/Glx ratio to discriminate Dep/SI− and Dep/SI+ adolescents. Dep/SI+ adolescents had higher Glx than Dep/SI− participants (p(adj) = 0.012) and had lower NAA/Glx than both Dep/SI− (p(adj) = 0.002) and HC adolescents (p(adj) = 0.039). There were significant relationships between SI intensity and Glx (p(FDR) = 0.026), SI severity and NAA/Glx (p(FDR) = 0.012), and SI intensity and NAA/Glx (p(FDR) = 0.004). ACC Glx and NAA/Glx discriminated Dep/SI− from Dep/SI+ participants. Uncoupled NAA−glutamatergic metabolism in the ACC may play a role in suicidal ideation and behavior. Longitudinal studies are needed to establish whether aberrant glutamatergic metabolism corresponds to acute or chronic suicide risk. Glutamatergic biomarkers may be promising targets for novel risk assessment and interventional strategies for suicidal ideation and behavior. Nature Publishing Group UK 2020-04-23 /pmc/articles/PMC7181616/ /pubmed/32327639 http://dx.doi.org/10.1038/s41398-020-0792-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lewis, Charles P.
Port, John D.
Blacker, Caren J.
Sonmez, A. Irem
Seewoo, Bhedita J.
Leffler, Jarrod M.
Frye, Mark A.
Croarkin, Paul E.
Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
title Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
title_full Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
title_fullStr Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
title_full_unstemmed Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
title_short Altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
title_sort altered anterior cingulate glutamatergic metabolism in depressed adolescents with current suicidal ideation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181616/
https://www.ncbi.nlm.nih.gov/pubmed/32327639
http://dx.doi.org/10.1038/s41398-020-0792-z
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