Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV

Background: Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serosta...

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Main Authors: Kalen J. Petersen, Xiaoying Yu, Mary Clare Masters, Judith D. Lobo, Tina Lu, Scott Letendre, Ronald J. Ellis, J. Allen McCutchan, Erin Sundermann
Format: Article
Language:English
Published: Elsevier 2023-07-01
Series:Brain, Behavior, & Immunity - Health
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2666354623000583
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author Kalen J. Petersen
Xiaoying Yu
Mary Clare Masters
Judith D. Lobo
Tina Lu
Scott Letendre
Ronald J. Ellis
J. Allen McCutchan
Erin Sundermann
author_facet Kalen J. Petersen
Xiaoying Yu
Mary Clare Masters
Judith D. Lobo
Tina Lu
Scott Letendre
Ronald J. Ellis
J. Allen McCutchan
Erin Sundermann
author_sort Kalen J. Petersen
collection DOAJ
description Background: Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex. Methods: Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities. Results: Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C–C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (β = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (β = −3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected. Interpretation: We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis.
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spelling doaj.art-44782fcca8814338b7d7128611ad22922023-06-22T05:05:26ZengElsevierBrain, Behavior, & Immunity - Health2666-35462023-07-0130100644Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIVKalen J. Petersen0Xiaoying Yu1Mary Clare Masters2Judith D. Lobo3Tina Lu4Scott Letendre5Ronald J. Ellis6J. Allen McCutchan7Erin Sundermann8Department of Neurology, Washington University in St. Louis, St. Louis, Missouri, USADepartment of Biostatistics & Data Science, The University of Texas Medical Branch, Galveston, TX, USADepartment of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USADepartment of Psychiatry, The University of California San Diego, San Diego, CA, USADepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USADepartment of Psychiatry, The University of California San Diego, San Diego, CA, USA; Department of Medicine, The University of California San Diego, San Diego, CA, USADepartment of Psychiatry, The University of California San Diego, San Diego, CA, USADepartment of Medicine, The University of California San Diego, San Diego, CA, USADepartment of Psychiatry, The University of California San Diego, San Diego, CA, USA; Corresponding author. UCSD ACTRI building, office 2W517, 9452 Medical Center Dr. (MC 0875), La Jolla, CA, 92037, USA.Background: Persons with HIV (PWH) have both more frequent depression and higher levels of plasma inflammatory biomarkers compared to persons without HIV (PWoH). Inflammation and depressive symptoms are linked, including in PWH; however, it is unclear whether these associations differ by HIV serostatus and biological sex. Methods: Six plasma inflammatory biomarkers were assessed using samples from PWH and PWoH who participated in six NIH-funded studies through the UCSD HIV Neurobehavioral Research Program (HNRP) from 2011 to 2019. Factor analysis was performed to identify intercorrelated groups of biomarkers. Factors and their components were then examined for relationships with Beck Depression Inventory-II (BDI-II) and modifying effects of sex or HIV serostatus using multivariable linear regression, adjusting for demographics, substance use diagnoses, and relevant co-morbidities. Results: Participants included 150 PWH (age = 48.3 ± 13.1 yr; 88% biologically male) and 138 PWoH (age = 46.3 ± 15.9; 56% male). Two inflammatory factors were identified: Factor 1 loaded on interleukin-6 (IL-6), C-reactive protein (CRP), and D-dimer; Factor 2 loaded on interleukin-8, chemokine C–C ligand 2 (CCL2), and chemokine C-X-C ligand 10 (CXCL10). Sex modified the effect of Factor 1 on BDI-II, with a more positive association for men than women (p = 0.04). No significant association between Factor 2 and BDI-II was found. Of the biomarkers in Factor 1, only IL-6 was significantly associated with BDI-II and was modified by sex (p = 0.003). In sex-stratified analysis, a positive association was found for men (β = 5.42; 95% confidence interval = [1.32, 9.52]) but not women (β = −3.88; 95% C.I. = [-11.02, 3.26]). No HIV-related interactions were detected. Interpretation: We identified a depression-associated inflammatory factor present in both PWH and PWoH, consistent with prior studies of PWH only. The association was driven by a correlation between IL-6 and depression exclusively in men, suggesting that the depression-inflammation link differs by sex. Future studies of depression etiology or treatment, including those on persons with HIV, should consider the impact of biological sex in both design and analysis.http://www.sciencedirect.com/science/article/pii/S2666354623000583DepressionHIV infectionInflammationSex differences
spellingShingle Kalen J. Petersen
Xiaoying Yu
Mary Clare Masters
Judith D. Lobo
Tina Lu
Scott Letendre
Ronald J. Ellis
J. Allen McCutchan
Erin Sundermann
Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
Brain, Behavior, & Immunity - Health
Depression
HIV infection
Inflammation
Sex differences
title Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
title_full Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
title_fullStr Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
title_full_unstemmed Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
title_short Sex-specific associations between plasma interleukin-6 and depression in persons with and without HIV
title_sort sex specific associations between plasma interleukin 6 and depression in persons with and without hiv
topic Depression
HIV infection
Inflammation
Sex differences
url http://www.sciencedirect.com/science/article/pii/S2666354623000583
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