Annelise A Madison1, Rebecca Andridge2, Avelina C Padin1, Stephanie Wilson3, Michael T Bailey4, Catherine M Alfano5, Stephen P Povoski6, Adele M Lipari6, Doreen M Agnese6, William E Carson6, William B Malarkey7, Janice K Kiecolt-Glaser8. 1. Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, United States; Department of Psychology, The Ohio State University, United States. 2. Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, United States; College of Public Health, The Ohio State University, United States. 3. Department of Psychology, Southern Methodist University, United States. 4. Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, United States; Department of Pediatrics, The Ohio State University College of Medicine, United States; Center for Microbial Pathogenesis, Abigail Wexner Research Institute at Nationwide Children's Hospital, United States. 5. Northwell Health Cancer Institute, United States. 6. Comprehensive Cancer Center, The Ohio State University, United States. 7. Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, United States; Department of Internal Medicine, The Ohio State University College of Medicine, United States. 8. Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, United States; Department of Psychiatry and Behavioral Health, The Ohio State University College of Medicine, United States. Electronic address: Janice.Kiecolt-Glaser@osumc.edu.
Abstract
OBJECTIVE: Cross-sectional data have linked gut barrier abnormalities and endotoxemia with depression, even among those without gastrointestinal symptoms. This study examined longitudinal associations between endotoxemia markers and depressive symptoms, as well as the role of inflammation in this relationship. DESIGN: At three annual visits, 315 women (n=209 breast cancer survivors, n = 106 non-cancer patient controls, M=55 years old) completed the Center for Epidemiological Studies Depression questionnaire (CES-D) and provided blood samples to assess inflammatory markers - interleukin-6, tumor necrosis factor-alpha, and C-reactive protein - and endotoxemia markers - lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and their ratio. RESULTS: Adjusting for key demographic variables, health behaviors, visit 1 depressive symptoms, and cancer status and treatment, women with higher visit 1 LBP and LBP/sCD14 had more depressive symptoms at the two subsequent annual visits. Illustrating the notable impact, a woman at the 75th percentile for LBP or LBP/sCD14 at visit 1 was 18 % more likely to report clinically significant depressive symptoms (CES-D ≥16) at follow-up than a woman in the lowest quartile. Cancer status and treatment type did not modulate this relationship. In contrast, visit 1 depressive symptoms did not predict endotoxemia at follow-up. A significant interaction between LBP/sCD14 and inflammatory burden suggested that visit 1 endotoxemia fueled depressive symptoms only in the context of elevated inflammation. CONCLUSION: These results suggest that endotoxemia, combined with systemic inflammation, can drive depressive symptoms. These findings may implicate bacterial endotoxin translocation from the gut to the bloodstream in depression etiology. Interventions that reduce endotoxemia and inflammation may lessen the risk of depression.
OBJECTIVE: Cross-sectional data have linked gut barrier abnormalities and endotoxemia with depression, even among those without gastrointestinal symptoms. This study examined longitudinal associations between endotoxemia markers and depressive symptoms, as well as the role of inflammation in this relationship. DESIGN: At three annual visits, 315 women (n=209 breast cancer survivors, n = 106 non-cancerpatient controls, M=55 years old) completed the Center for Epidemiological Studies Depression questionnaire (CES-D) and provided blood samples to assess inflammatory markers - interleukin-6, tumor necrosis factor-alpha, and C-reactive protein - and endotoxemia markers - lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and their ratio. RESULTS: Adjusting for key demographic variables, health behaviors, visit 1 depressive symptoms, and cancer status and treatment, women with higher visit 1 LBP and LBP/sCD14 had more depressive symptoms at the two subsequent annual visits. Illustrating the notable impact, a woman at the 75th percentile for LBP or LBP/sCD14 at visit 1 was 18 % more likely to report clinically significant depressive symptoms (CES-D ≥16) at follow-up than a woman in the lowest quartile. Cancer status and treatment type did not modulate this relationship. In contrast, visit 1 depressive symptoms did not predict endotoxemia at follow-up. A significant interaction between LBP/sCD14 and inflammatory burden suggested that visit 1 endotoxemia fueled depressive symptoms only in the context of elevated inflammation. CONCLUSION: These results suggest that endotoxemia, combined with systemic inflammation, can drive depressive symptoms. These findings may implicate bacterial endotoxin translocation from the gut to the bloodstream in depression etiology. Interventions that reduce endotoxemia and inflammation may lessen the risk of depression.
Authors: M Rosie Shrout; Annelise A Madison; Megan E Renna; Catherine M Alfano; Stephen P Povoski; Adele M Lipari; Doreen M Agnese; William E Carson; William B Malarkey; Michael T Bailey; Janice K Kiecolt-Glaser Journal: Brain Behav Immun Date: 2021-11-19 Impact factor: 19.227