Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 73, Issue -, Pages 725-730Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2018.07.026
Keywords
Inflammation; Amygdala; Functional connectivity; fMRI; C-reactive protein; Anxiety; Depression; Post-traumatic stress disorder
Categories
Funding
- National Institutes of Mental Health [R01MH109637, R21MH106904, K23MH091254]
- Brain and Behavioral Research Foundation
- Dana Foundation [BBRF22296, CADF49143]
- Natural Science Foundation of China/Shenzhen [31671169, 31530031/000099]
- PHS from the Clinical and Translational Science Award program [UL1TR000454, KL2TR000455]
- NIH/NCI [P30CA138292]
- NATIONAL CANCER INSTITUTE [P30CA138292] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [KL2TR000455, UL1TR002378, UL1TR000454] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH109637, R01MH112076, R21MH106904, K23MH091254, R01MH107033] Funding Source: NIH RePORTER
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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 urnnedicated 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 co morbid anxiety disorders or PTSD.
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