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Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents

Animal models of stress and related conditions, including depression, have shown that elevated peripheral levels of inflammatory cytokines have downstream consequences on glutamate (Glu) in the brain. Although studies in human adults with depression have reported evidence of higher inflammation but...

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Autores principales: Ho, Tiffany C., Teresi, Giana I., Segarra, Jillian R., Ojha, Amar, Walker, Johanna C., Gu, Meng, Spielman, Daniel M., Sacchet, Matthew D., Jiang, Fei, Rosenberg-Hasson, Yael, Maecker, Holden, Gotlib, Ian H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081972/
https://www.ncbi.nlm.nih.gov/pubmed/33935833
http://dx.doi.org/10.3389/fpsyt.2021.642976
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author Ho, Tiffany C.
Teresi, Giana I.
Segarra, Jillian R.
Ojha, Amar
Walker, Johanna C.
Gu, Meng
Spielman, Daniel M.
Sacchet, Matthew D.
Jiang, Fei
Rosenberg-Hasson, Yael
Maecker, Holden
Gotlib, Ian H.
author_facet Ho, Tiffany C.
Teresi, Giana I.
Segarra, Jillian R.
Ojha, Amar
Walker, Johanna C.
Gu, Meng
Spielman, Daniel M.
Sacchet, Matthew D.
Jiang, Fei
Rosenberg-Hasson, Yael
Maecker, Holden
Gotlib, Ian H.
author_sort Ho, Tiffany C.
collection PubMed
description Animal models of stress and related conditions, including depression, have shown that elevated peripheral levels of inflammatory cytokines have downstream consequences on glutamate (Glu) in the brain. Although studies in human adults with depression have reported evidence of higher inflammation but lower Glu in the anterior cingulate cortex (ACC), the extent to which peripheral inflammation contributes to glutamatergic abnormalities in adolescents with depression is not well-understood. It is also unclear whether antioxidants, such as ascorbate (Asc), may buffer against the effects of inflammation on Glu metabolism. Fifty-five depressed adolescents were recruited in the present cross-sectional study and provided blood samples, from which we assayed pro-inflammatory cytokines, and underwent a short-TE proton magnetic spectroscopy scan at 3T, from which we estimated Glu and Asc in the dorsal ACC. In the 31 adolescents with usable cytokine and Glu data, we found that IL-6 was significantly positively associated with dorsal ACC Glu (β = 0.466 ± 0.199, p = 0.029). Of the 16 participants who had usable Asc data, we found that at higher levels of dorsal ACC Asc, there was a negative association between IL-6 and Glu (interaction effect: β = −0.906 ± 0.433, p = 0.034). Importantly, these results remained significant when controlling for age, gender, percentage of gray matter in the dorsal ACC voxel, BMI, and medication (antidepressant and anti-inflammatory) usage. While preliminary, our results underscore the importance of examining both immune and neural contributors to depression and highlight the potential role of anti-inflammatory compounds in mitigating the adverse effects of inflammation (e.g., glutamatergic neuroexcitotoxicity). Future studies that experimentally manipulate levels of inflammation, and of ascorbate, and that characterize these effects on cortical glutamate concentrations and subsequent behavior in animals and in humans are needed.
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spelling pubmed-80819722021-04-30 Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents Ho, Tiffany C. Teresi, Giana I. Segarra, Jillian R. Ojha, Amar Walker, Johanna C. Gu, Meng Spielman, Daniel M. Sacchet, Matthew D. Jiang, Fei Rosenberg-Hasson, Yael Maecker, Holden Gotlib, Ian H. Front Psychiatry Psychiatry Animal models of stress and related conditions, including depression, have shown that elevated peripheral levels of inflammatory cytokines have downstream consequences on glutamate (Glu) in the brain. Although studies in human adults with depression have reported evidence of higher inflammation but lower Glu in the anterior cingulate cortex (ACC), the extent to which peripheral inflammation contributes to glutamatergic abnormalities in adolescents with depression is not well-understood. It is also unclear whether antioxidants, such as ascorbate (Asc), may buffer against the effects of inflammation on Glu metabolism. Fifty-five depressed adolescents were recruited in the present cross-sectional study and provided blood samples, from which we assayed pro-inflammatory cytokines, and underwent a short-TE proton magnetic spectroscopy scan at 3T, from which we estimated Glu and Asc in the dorsal ACC. In the 31 adolescents with usable cytokine and Glu data, we found that IL-6 was significantly positively associated with dorsal ACC Glu (β = 0.466 ± 0.199, p = 0.029). Of the 16 participants who had usable Asc data, we found that at higher levels of dorsal ACC Asc, there was a negative association between IL-6 and Glu (interaction effect: β = −0.906 ± 0.433, p = 0.034). Importantly, these results remained significant when controlling for age, gender, percentage of gray matter in the dorsal ACC voxel, BMI, and medication (antidepressant and anti-inflammatory) usage. While preliminary, our results underscore the importance of examining both immune and neural contributors to depression and highlight the potential role of anti-inflammatory compounds in mitigating the adverse effects of inflammation (e.g., glutamatergic neuroexcitotoxicity). Future studies that experimentally manipulate levels of inflammation, and of ascorbate, and that characterize these effects on cortical glutamate concentrations and subsequent behavior in animals and in humans are needed. Frontiers Media S.A. 2021-04-15 /pmc/articles/PMC8081972/ /pubmed/33935833 http://dx.doi.org/10.3389/fpsyt.2021.642976 Text en Copyright © 2021 Ho, Teresi, Segarra, Ojha, Walker, Gu, Spielman, Sacchet, Jiang, Rosenberg-Hasson, Maecker and Gotlib. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Ho, Tiffany C.
Teresi, Giana I.
Segarra, Jillian R.
Ojha, Amar
Walker, Johanna C.
Gu, Meng
Spielman, Daniel M.
Sacchet, Matthew D.
Jiang, Fei
Rosenberg-Hasson, Yael
Maecker, Holden
Gotlib, Ian H.
Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents
title Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents
title_full Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents
title_fullStr Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents
title_full_unstemmed Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents
title_short Higher Levels of Pro-inflammatory Cytokines Are Associated With Higher Levels of Glutamate in the Anterior Cingulate Cortex in Depressed Adolescents
title_sort higher levels of pro-inflammatory cytokines are associated with higher levels of glutamate in the anterior cingulate cortex in depressed adolescents
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081972/
https://www.ncbi.nlm.nih.gov/pubmed/33935833
http://dx.doi.org/10.3389/fpsyt.2021.642976
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