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Brain Behav Immun. 2018 Oct;73:725-730. doi: 10.1016/j.bbi.2018.07.026. Epub 2018 Aug 1.

Inflammation negatively correlates with amygdala-ventromedial prefrontal functional connectivity in association with anxiety in patients with depression: Preliminary results.

Author information

1
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States; Neuroscience Graduate Program, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA 30322, United States.
2
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States; Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States.
3
School of Psychology and Sociology, Shenzhen University, Shenzhen, Guangdong, 518060, China; Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen, Guangdong, 518060, China.
4
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States.
5
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States; School of Psychology and Sociology, Shenzhen University, Shenzhen, Guangdong, 518060, China; Shenzhen Key Laboratory of Affective and Social Cognitive Science, Shenzhen University, Shenzhen, Guangdong, 518060, China. Electronic address: zhihao_li@szu.edu.cn.
6
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, United States; Winship Cancer Institute, Emory University, Atlanta, GA 30322, United States. Electronic address: jfelger@emory.edu.

Abstract

Biomarkers of inflammation, including inflammatory cytokines and the acute-phase reactant C-reactive protein (CRP), are reliably increased in a subset of patients with depression, anxiety disorders and post-traumatic stress disorder (PTSD). Administration of innate immune stimuli to laboratory subjects and the associated release of inflammatory cytokines has been shown to affect brain regions involved in fear, anxiety and emotional processing such as the amygdala. However, the role of inflammation in altered circuitry involving amygdala and other brain regions and its subsequent contribution to symptom severity in depression, anxiety disorders and PTSD is only beginning to be explored. Herein, medically-stable, currently unmedicated outpatients with a primary diagnosis of major depressive disorder (MDD; n = 48) underwent resting-state functional MRI (rfMRI) to determine whether altered connectivity between the amygdala and whole brain was observed in a subset of patients with high inflammation and symptoms of anxiety. Whole-brain, voxel-wise functional connectivity analysis of the right and left amygdala as a function of inflammation (plasma CRP concentrations) revealed that increased CRP predicted decreased functional connectivity between right amygdala and left ventromedial prefrontal cortex (vmPFC) (corrected p < 0.05). Amygdala-vmPFC connectivity was, in turn, negatively correlated with symptoms of anxiety (r = -0.33, df = 46, p = 0.022). In exploratory analyses, relationships between low amygdala-vmPFC connectivity and high anxiety were only observed in patients with a secondary diagnosis of an anxiety disorder or PTSD (r = -0.54 to -0.87, p < 0.05). More work is needed to understand the role of inflammation and its effects on amygdala-vmPFC circuitry and symptoms of anxiety in MDD patients with comorbid anxiety disorders or PTSD.

KEYWORDS:

Amygdala; Anxiety; C-reactive protein; Depression; Functional connectivity; Inflammation; Post-traumatic stress disorder; fMRI

PMID:
30076980
PMCID:
PMC6129411
[Available on 2019-10-01]
DOI:
10.1016/j.bbi.2018.07.026
[Indexed for MEDLINE]

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