TY - JOUR
T1 - Higher levels of plasma inflammation biomarkers are associated with depressed mood and quality of life in aging, virally suppressed men, but not women, with HIV
AU - Ellis, Ronald J.
AU - Letendre, Scott L.
AU - Atkinson, J. Hampton
AU - Clifford, David
AU - Collier, Ann C.
AU - Gelman, Benjamin B.
AU - Marra, Christina
AU - McCutchan, J. Allen
AU - Morgello, Susan
AU - Sacktor, Ned
AU - Tang, Bin
AU - Heaton, Robert K.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/8
Y1 - 2020/8
N2 - Background and objectives: People with HIV (PWH) often suffer from depressive symptoms which have a deleterious impact on numerous domains including antiretroviral adherence and quality of life. In the general population, a treatment-resistant phenotype of depression is associated with systemic inflammation, which is of considerable importance as it responds favorably to anti-inflammatory medications. Aging PWH experience increasing inflammation. We sought to evaluate the impact of chronic inflammation in aging PWH on depressed mood. Methods: PWH were recruited at 6 U.S. academic medical centers. Depressed mood was assessed using the Beck Depression Inventory (BDI)-II. Inflammatory biomarkers measured at the 12-year follow-up visit in blood plasma using immunoassays were neopterin, sTNFRII, d-dimer, IL-6, CRP, MCP-1, sCD14 and sCD40L. Factor analyses with oblique Equamax rotation were employed to reduce the dimensionality of the biomarkers. Results: Participants were 78 PWH, 14 (17.9%) women, 40 (51.3%) non-White, mean age 55.3 (±SD 8.29), with a nadir and current CD4 of 134 (IQR 36, 204) and 567 (316, 797), respectively. 80.5% were virally suppressed. A factor analysis of the eight inflammatory biomarkers in plasma at the 12-year follow-up visit yielded 3 Factors, with Factor 1 loading on neopterin and sTNFRII, Factor 2 loading on d-dimer, IL-6 and CRP, and Factor 3 loading on sCD40L (MCP-1 and sCD14 did not appear in any of the factors). Univariate regressions of each factor vs BDI-II scores yielded significance only for Factor 2 (r = 0.295; p = 0.0083 (Bonferroni-adjusted p = 0.0261). Of the Factor 2 component biomarkers, BDI-II scores correlated significantly with d-dimer and IL-6, but not CRP. Women had worse BDI-II scores (p = 0.0127). In a logistic regression with sex and Factor 2, both variables were significant (sex p = 0.0246, Factor 2 p = 0.0168). The relationship between Factor 2 and BDI was significant for men (r = 0.348 [95% CI 0.111, 0.547]; p = 0.0049), but not women (r = 0.0580 95% CI -0.488, 0.571]; p = 0.844). Viral suppression was not significant in the multivariate model. Conclusions: Some PWH with depressed mood have elevated markers of inflammation in blood. Men showed this relationship, while women did not. Together with previous findings that an inflammatory depression phenotype responds to treatment with anti-inflammatory medications, our findings suggest that treatment with anti-inflammatory medications might benefit at least a subset of depressed PWH who have a high inflammatory biomarker profile, as well as poor response to antidepressant medications alone, and that the pathophysiology of depression in men and women with HIV may differ.
AB - Background and objectives: People with HIV (PWH) often suffer from depressive symptoms which have a deleterious impact on numerous domains including antiretroviral adherence and quality of life. In the general population, a treatment-resistant phenotype of depression is associated with systemic inflammation, which is of considerable importance as it responds favorably to anti-inflammatory medications. Aging PWH experience increasing inflammation. We sought to evaluate the impact of chronic inflammation in aging PWH on depressed mood. Methods: PWH were recruited at 6 U.S. academic medical centers. Depressed mood was assessed using the Beck Depression Inventory (BDI)-II. Inflammatory biomarkers measured at the 12-year follow-up visit in blood plasma using immunoassays were neopterin, sTNFRII, d-dimer, IL-6, CRP, MCP-1, sCD14 and sCD40L. Factor analyses with oblique Equamax rotation were employed to reduce the dimensionality of the biomarkers. Results: Participants were 78 PWH, 14 (17.9%) women, 40 (51.3%) non-White, mean age 55.3 (±SD 8.29), with a nadir and current CD4 of 134 (IQR 36, 204) and 567 (316, 797), respectively. 80.5% were virally suppressed. A factor analysis of the eight inflammatory biomarkers in plasma at the 12-year follow-up visit yielded 3 Factors, with Factor 1 loading on neopterin and sTNFRII, Factor 2 loading on d-dimer, IL-6 and CRP, and Factor 3 loading on sCD40L (MCP-1 and sCD14 did not appear in any of the factors). Univariate regressions of each factor vs BDI-II scores yielded significance only for Factor 2 (r = 0.295; p = 0.0083 (Bonferroni-adjusted p = 0.0261). Of the Factor 2 component biomarkers, BDI-II scores correlated significantly with d-dimer and IL-6, but not CRP. Women had worse BDI-II scores (p = 0.0127). In a logistic regression with sex and Factor 2, both variables were significant (sex p = 0.0246, Factor 2 p = 0.0168). The relationship between Factor 2 and BDI was significant for men (r = 0.348 [95% CI 0.111, 0.547]; p = 0.0049), but not women (r = 0.0580 95% CI -0.488, 0.571]; p = 0.844). Viral suppression was not significant in the multivariate model. Conclusions: Some PWH with depressed mood have elevated markers of inflammation in blood. Men showed this relationship, while women did not. Together with previous findings that an inflammatory depression phenotype responds to treatment with anti-inflammatory medications, our findings suggest that treatment with anti-inflammatory medications might benefit at least a subset of depressed PWH who have a high inflammatory biomarker profile, as well as poor response to antidepressant medications alone, and that the pathophysiology of depression in men and women with HIV may differ.
KW - Depression
KW - HIV infection
KW - Inflammation
KW - Quality of life
KW - Sex differences
UR - http://www.scopus.com/inward/record.url?scp=85099059067&partnerID=8YFLogxK
U2 - 10.1016/j.bbih.2020.100121
DO - 10.1016/j.bbih.2020.100121
M3 - Article
AN - SCOPUS:85099059067
SN - 2666-3546
VL - 7
JO - Brain, Behavior, and Immunity - Health
JF - Brain, Behavior, and Immunity - Health
M1 - 100121
ER -