TY - JOUR
T1 - Multi-modal analysis of inflammation as a potential mediator of depressive symptoms in young people with HIV
T2 - The GOLD Depression Study
AU - Mudra Rakshasa-Loots, Arish
AU - Naidoo, Shalena
AU - Hamana, Thandi
AU - Fanqa, Busiswa
AU - van Wyhe, Kaylee S.
AU - Lindani, Filicity
AU - van der Kouwe, Andre J. W.
AU - Glashoff, Richard
AU - Kruger, Sharon
AU - Robertson, Frances
AU - Cox, Simon R.
AU - Meintjes, Ernesta M.
AU - Laughton, Barbara
N1 - Funding Information:
This work was supported by funding from the Wellcome Trust (Grant Number 218493/ Z/19/Z) and the Harold Hyam Wingate Foundation (Medical Research Travel Grant) awarded to AMRL. Neuroimaging and infrastructure for this study was supported by NIH Grant R01HD099846 for the GOLD cohort (co-principal investigators: AvdK, EM, and BL). Blood biomarker analysis was supported by seed funding from the SAMRC/SU Extramural Unit on the Genomics of Brain Disorders awarded to AMRL. SRC was supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (221890/Z/20/Z). There was no additional external funding received for this study.
Publisher Copyright:
© 2024 Public Library of Science. All rights reserved.
PY - 2024/2/22
Y1 - 2024/2/22
N2 - People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (β = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, β = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, β = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1β, β = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression.
AB - People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (β = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, β = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, β = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1β, β = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression.
U2 - 10.1371/journal.pone.0298787
DO - 10.1371/journal.pone.0298787
M3 - Article
SN - 1932-6203
VL - 19
SP - 1
EP - 21
JO - PLoS ONE
JF - PLoS ONE
IS - 2
M1 - e0298787
ER -