S Melanie Lee1, Silena Te2, Elizabeth C Breen1,3, Richard Olmstead1,3, Michael R Irwin1,3, Joshua H Cho1,3. 1. Department of Psychiatry and Behavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. 2. Keck School of Medicine of University of Southern California, Los Angeles, CA, USA. 3. Cousins Center for Psychoneuroimmunology, UCLA Semel Institute for Neuroscience, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Abstract
Objectives: Circulating cytokines have been associated with depression, but their detection has limitations, which may be overcome by direct detection of intracellular cytokines (ICCs) after lipopolysaccharide (LPS) stimulation in vitro. This study compared circulating versus LPS-induced inflammatory markers as correlates of subthreshold depressive symptoms. Methods: Secondary data analysis of a cross-sectional insomnia study in healthy community-dwelling older adults was conducted. In 117 participants (≥55 years), plasma tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and in vitro LPS-induced monocyte production of IL-6 and TNF-α were assayed. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). Multivariate linear regression was conducted to test the associations between inflammatory markers and subthreshold depressive symptoms in the entire sample as well as in subgroups stratified into higher and lower inflammation levels. Results: LPS-induced TNF-α (adjusted β = 0.28, p = .04), IL-6 (0.29, p = .03) and TNF-α + IL-6 (0.43, p = .001) significantly positively correlated with subthreshold depressive symptoms only in higher inflammation subgroups. No circulating biomarkers positively correlated in any subgroups. In the entire sample, no biomarkers were significantly associated with subthreshold depressive symptoms.Conclusions: LPS-induced cytokines may be more sensitive correlates of subthreshold depressive symptoms than circulating cytokines, particularly in older adults with higher systemic inflammation.Clinical Trials Registry: ClinicalTrials.gov NCT00280020.
Objectives: Circulating cytokines have been associated with depression, but their detection has limitations, which may be overcome by direct detection of intracellular cytokines (ICCs) after lipopolysaccharide (LPS) stimulation in vitro. This study compared circulating versus LPS-induced inflammatory markers as correlates of subthreshold depressive symptoms. Methods: Secondary data analysis of a cross-sectional insomnia study in healthy community-dwelling older adults was conducted. In 117 participants (≥55 years), plasma tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and in vitro LPS-induced monocyte production of IL-6 and TNF-α were assayed. Depressive symptoms were assessed using the clinician-rated Inventory of Depressive Symptomatology (IDS-C). Multivariate linear regression was conducted to test the associations between inflammatory markers and subthreshold depressive symptoms in the entire sample as well as in subgroups stratified into higher and lower inflammation levels. Results:LPS-induced TNF-α (adjusted β = 0.28, p = .04), IL-6 (0.29, p = .03) and TNF-α + IL-6 (0.43, p = .001) significantly positively correlated with subthreshold depressive symptoms only in higher inflammation subgroups. No circulating biomarkers positively correlated in any subgroups. In the entire sample, no biomarkers were significantly associated with subthreshold depressive symptoms.Conclusions: LPS-induced cytokines may be more sensitive correlates of subthreshold depressive symptoms than circulating cytokines, particularly in older adults with higher systemic inflammation.Clinical Trials Registry: ClinicalTrials.gov NCT00280020.
Authors: Michael R Irwin; Richard Olmstead; Carmen Carrillo; Nina Sadeghi; Elizabeth C Breen; Tuff Witarama; Megumi Yokomizo; Helen Lavretsky; Judith E Carroll; Sarosh J Motivala; Richard Bootzin; Perry Nicassio Journal: Sleep Date: 2014-09-01 Impact factor: 5.849
Authors: Yekta Dowlati; Nathan Herrmann; Walter Swardfager; Helena Liu; Lauren Sham; Elyse K Reim; Krista L Lanctôt Journal: Biol Psychiatry Date: 2009-12-16 Impact factor: 13.382
Authors: Frank M Schmidt; Thomas Schröder; Kenneth C Kirkby; Christian Sander; Thomas Suslow; Lesca M Holdt; Daniel Teupser; Ulrich Hegerl; Hubertus Himmerich Journal: Psychiatry Res Date: 2016-02-23 Impact factor: 3.222
Authors: Erik L Knight; Marzieh Majd; Jennifer E Graham-Engeland; Joshua M Smyth; Martin J Sliwinski; Christopher G Engeland Journal: Physiol Behav Date: 2021-11-25