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Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions
BACKGROUND: The immune system has major roles in the brain and related psychopathology. Disrupted interleukin-6 secretion and aberrant amygdala emotional reactivity are well-documented in stress-related mental disorders. The amygdala regulates psychosocial stress-related interleukin-6 affected by re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262086/ https://www.ncbi.nlm.nih.gov/pubmed/37324818 http://dx.doi.org/10.3389/fpsyt.2023.1196235 |
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author | Hakamata, Yuko Hori, Hiroaki Mizukami, Shinya Izawa, Shuhei Yoshida, Fuyuko Moriguchi, Yoshiya Hanakawa, Takashi Inoue, Yusuke Tagaya, Hirokuni |
author_facet | Hakamata, Yuko Hori, Hiroaki Mizukami, Shinya Izawa, Shuhei Yoshida, Fuyuko Moriguchi, Yoshiya Hanakawa, Takashi Inoue, Yusuke Tagaya, Hirokuni |
author_sort | Hakamata, Yuko |
collection | PubMed |
description | BACKGROUND: The immune system has major roles in the brain and related psychopathology. Disrupted interleukin-6 secretion and aberrant amygdala emotional reactivity are well-documented in stress-related mental disorders. The amygdala regulates psychosocial stress-related interleukin-6 affected by related genes. These led us to comprehensively examine the relationship between interleukin-6, amygdala activity, and stress-related mental symptoms under gene-stressor interactions. METHODS: One hundred eight nonclinical participants with various levels of anxiety/depression underwent magnetic resonance imaging scans during an emotional face task for amygdala activity and saliva collection (at 10-time points across 2 days) for the total output and diurnal patterns of interleukin-6. Gene-stressor interactions between rs1800796 (C/G) and rs2228145 (C/A) and stressful life events for the biobehavioral measures were explored. RESULTS: The blunting of interleukin-6 diurnal pattern was associated with hypoactivation of the basolateral amygdala in response to fearful (vs. neutral) faces (t = 3.67, FWE-corrected p = 0.003), and was predominantly observed in individuals with rs1800796 C-allele homozygotes and negative life changes in the past year (F = 19.71, p < 0.001). When considered in a comprehensive model, the diminished diurnal pattern predicted greater depressive symptoms (β = −0.40), modulated by the amygdala hypoactivity (β = 0.36) and rs1800796-stressor interactions (β = −0.41; all p < 0.001). CONCLUSION: Here we show that the blunted interleukin-6 diurnal rhythm predicts depressive symptoms, modulated by amygdala emotional hyporeactivity and gene-stressor interactions. These findings indicate a potential mechanism underlying vulnerability to depressive disorders, suggesting their early detection, prevention, and treatment through the understanding of immune system dysregulation. |
format | Online Article Text |
id | pubmed-10262086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102620862023-06-15 Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions Hakamata, Yuko Hori, Hiroaki Mizukami, Shinya Izawa, Shuhei Yoshida, Fuyuko Moriguchi, Yoshiya Hanakawa, Takashi Inoue, Yusuke Tagaya, Hirokuni Front Psychiatry Psychiatry BACKGROUND: The immune system has major roles in the brain and related psychopathology. Disrupted interleukin-6 secretion and aberrant amygdala emotional reactivity are well-documented in stress-related mental disorders. The amygdala regulates psychosocial stress-related interleukin-6 affected by related genes. These led us to comprehensively examine the relationship between interleukin-6, amygdala activity, and stress-related mental symptoms under gene-stressor interactions. METHODS: One hundred eight nonclinical participants with various levels of anxiety/depression underwent magnetic resonance imaging scans during an emotional face task for amygdala activity and saliva collection (at 10-time points across 2 days) for the total output and diurnal patterns of interleukin-6. Gene-stressor interactions between rs1800796 (C/G) and rs2228145 (C/A) and stressful life events for the biobehavioral measures were explored. RESULTS: The blunting of interleukin-6 diurnal pattern was associated with hypoactivation of the basolateral amygdala in response to fearful (vs. neutral) faces (t = 3.67, FWE-corrected p = 0.003), and was predominantly observed in individuals with rs1800796 C-allele homozygotes and negative life changes in the past year (F = 19.71, p < 0.001). When considered in a comprehensive model, the diminished diurnal pattern predicted greater depressive symptoms (β = −0.40), modulated by the amygdala hypoactivity (β = 0.36) and rs1800796-stressor interactions (β = −0.41; all p < 0.001). CONCLUSION: Here we show that the blunted interleukin-6 diurnal rhythm predicts depressive symptoms, modulated by amygdala emotional hyporeactivity and gene-stressor interactions. These findings indicate a potential mechanism underlying vulnerability to depressive disorders, suggesting their early detection, prevention, and treatment through the understanding of immune system dysregulation. Frontiers Media S.A. 2023-05-30 /pmc/articles/PMC10262086/ /pubmed/37324818 http://dx.doi.org/10.3389/fpsyt.2023.1196235 Text en Copyright © 2023 Hakamata, Hori, Mizukami, Izawa, Yoshida, Moriguchi, Hanakawa, Inoue and Tagaya. 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 Hakamata, Yuko Hori, Hiroaki Mizukami, Shinya Izawa, Shuhei Yoshida, Fuyuko Moriguchi, Yoshiya Hanakawa, Takashi Inoue, Yusuke Tagaya, Hirokuni Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
title | Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
title_full | Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
title_fullStr | Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
title_full_unstemmed | Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
title_short | Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
title_sort | blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression: a modulating role of gene-stressor interactions |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10262086/ https://www.ncbi.nlm.nih.gov/pubmed/37324818 http://dx.doi.org/10.3389/fpsyt.2023.1196235 |
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