TY - JOUR
T1 - Sex differences in the association of baseline c-reactive protein (CRP) and acute-phase treatment outcomes in major depressive disorder
T2 - Findings from the EMBARC study
AU - Jha, Manish K.
AU - Minhajuddin, Abu
AU - Chin-Fatt, Cherise
AU - Greer, Tracy L.
AU - Carmody, Thomas J.
AU - Trivedi, Madhukar H.
N1 - Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6
Y1 - 2019/6
N2 - Peripheral inflammation is associated with poor response to antidepressant treatments. However, whether sex differentially affects this association remains unknown. Participants of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) with baseline plasma samples were included in this study (n = 220; male n = 75, female n = 145). Depression severity [Hamilton Rating Scale for Depression 17-item (HAMD-17)] was measured at baseline and weeks- 1, 2, 3, 4, 6, and 8. Plasma c-reactive protein (CRP) was measured with commercially-available ELISA kits at baseline, week-1, and week-8. Sex difference in prediction of baseline-to-week-8 HAMD-17 change by baseline CRP was tested with sex-by-baseline-CRP-by-time interaction in mixed model analysis. Additionally, changes in CRP from baseline-to-week-8 CRP and its association with HAMD-17 changes over that period were also evaluated. Covariates included body mass index, site, smoking status, and age. There was a significant sex difference in association of baseline-to-week-8 HAMD-17 reduction with baseline CRP (p = 0.033). Higher baseline CRP was associated with lower baseline-to-week-8 HAMD-17 reduction in females (p < 0.0001) but not in males (p = 0.632). Additionally, CRP was significantly reduced (p = 0.041, effect size = 0.254) from baseline-to-week-8, but there were no sex differences in this reduction (p = 0.249). Baseline-to-week-8 changes in HAMD-17 and CRP were not significantly associated either overall (p = 0.348) or based on sex (p = 0.370). In a large study of depressed outpatients, we replicated previous findings that elevated baseline CRP levels are associated with worse antidepressant treatment outcomes. However, this effect was limited only to females. These findings emphasize the importance of studying sex differences in biological mechanisms linking inflammation and depression.
AB - Peripheral inflammation is associated with poor response to antidepressant treatments. However, whether sex differentially affects this association remains unknown. Participants of Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) with baseline plasma samples were included in this study (n = 220; male n = 75, female n = 145). Depression severity [Hamilton Rating Scale for Depression 17-item (HAMD-17)] was measured at baseline and weeks- 1, 2, 3, 4, 6, and 8. Plasma c-reactive protein (CRP) was measured with commercially-available ELISA kits at baseline, week-1, and week-8. Sex difference in prediction of baseline-to-week-8 HAMD-17 change by baseline CRP was tested with sex-by-baseline-CRP-by-time interaction in mixed model analysis. Additionally, changes in CRP from baseline-to-week-8 CRP and its association with HAMD-17 changes over that period were also evaluated. Covariates included body mass index, site, smoking status, and age. There was a significant sex difference in association of baseline-to-week-8 HAMD-17 reduction with baseline CRP (p = 0.033). Higher baseline CRP was associated with lower baseline-to-week-8 HAMD-17 reduction in females (p < 0.0001) but not in males (p = 0.632). Additionally, CRP was significantly reduced (p = 0.041, effect size = 0.254) from baseline-to-week-8, but there were no sex differences in this reduction (p = 0.249). Baseline-to-week-8 changes in HAMD-17 and CRP were not significantly associated either overall (p = 0.348) or based on sex (p = 0.370). In a large study of depressed outpatients, we replicated previous findings that elevated baseline CRP levels are associated with worse antidepressant treatment outcomes. However, this effect was limited only to females. These findings emphasize the importance of studying sex differences in biological mechanisms linking inflammation and depression.
KW - Antidepressant response
KW - C-reactive protein
KW - Depression
KW - Inflammation
KW - Major depressive disorder
KW - Sex differences
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U2 - 10.1016/j.jpsychires.2019.03.013
DO - 10.1016/j.jpsychires.2019.03.013
M3 - Article
C2 - 30959227
AN - SCOPUS:85064195667
SN - 0022-3956
VL - 113
SP - 165
EP - 171
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -