TY - JOUR
T1 - Blunted diurnal interleukin-6 rhythm is associated with amygdala emotional hyporeactivity and depression
T2 - a modulating role of gene-stressor interactions
AU - Hakamata, Yuko
AU - Hori, Hiroaki
AU - Mizukami, Shinya
AU - Izawa, Shuhei
AU - Yoshida, Fuyuko
AU - Moriguchi, Yoshiya
AU - Hanakawa, Takashi
AU - Inoue, Yusuke
AU - Tagaya, Hirokuni
N1 - Publisher Copyright:
Copyright © 2023 Hakamata, Hori, Mizukami, Izawa, Yoshida, Moriguchi, Hanakawa, Inoue and Tagaya.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - basolateral nuclear complex
KW - circadian rhythm
KW - depression
KW - dorsolateral prefrontal cortex
KW - immune system
KW - interleukin-6
KW - magnetic resonance imaging
KW - single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85161887678&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2023.1196235
DO - 10.3389/fpsyt.2023.1196235
M3 - 学術論文
C2 - 37324818
AN - SCOPUS:85161887678
SN - 1664-0640
VL - 14
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
M1 - 1196235
ER -
