Abstract
BackgroundControversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. Scarce data about anxiety and its relationships with cytokines are available in pregnant women. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression.MethodsWomen exhibiting severe depression (SD) and severe anxiety (SA) during the 3rd trimester of pregnancy (n = 139) and control subjects exhibiting neither depression nor anxiety (n = 40) were assessed through the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Serum cytokines were measured by a multiplex bead-based assay. Correlation tests were used to analyze the data and comparisons between groups were performed. A general linear model of analysis of variance was constructed using the group as a dependent variable, interleukin concentrations as independent variables, and HDRS/HARS scores and gestational weeks as covariables.ResultsThe highest levels of Th1- (IL-6, TNF-α, IL-2, IFN-γ), Th17- (IL-17A, IL-22), and Th2- (IL-9, IL-10, and IL-13) related cytokines were observed in women with SD + SA. The SA group showed higher concentrations of Th1- (IL-6, TNF-α, IL-2, IFN-γ) and Th2- (IL-4, and IL-10) related cytokines than the controls. Positive correlations were found between HDRS and IL-2, IL-6, and TNF-α in the SA group (p < 0.03), and between HDRS and Th1- (IL-2, IL-6, TNF-α), Th2- (IL-9, IL-10, IL-13) and Th17- (IL-17A) cytokines (p < 0.05) in the SD + SA group. After controlling the correlation analysis by gestational weeks, the correlations that remained significant were: HDRS and IL-2, IL-6, IL-9, and IL-17A in the SD + SA group (p < 0.03). HARS scores correlated with IL-17A in the SA group and with IL-17A, IL-17F, and IL-2 in the SD + SA group (p < 0.02). The linear model of analysis of variance showed that HDRS and HARS scores influenced cytokine concentrations; only IL-6 and TNF-α could be explained by the group.ConclusionsWe found that the cytokine profiles differ when comparing pregnant subjects exhibiting SA with comorbid SD against those showing only SA without depression.
Highlights
Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects
Higher concentrations of (Th17)-related cytokines (IL-17A, IL-17F, IL-21, IL-22) were found in the severe anxiety (SA) + severe depression (SD) group, when compared to the values displayed by the SA group, or between the IL-17A and IL-17F concentrations and those observed in the CTRL group
Our data show that patients exhibiting severe anxiety and comorbid depression display significant increases in serum proinflammatory and anti-inflammatory-related cytokines that correlated with the intensity of depressive symptoms measured by Hamilton Depression Rating Scale (HDRS)
Summary
Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression. Depression during pregnancy is an important topic, both for understanding the pathophysiology of the disease and determining adequate treatment. Pregnant women experience more stressful events than non-pregnant women [10, 11], and frequently report tiredness or fatigue (87.2–96.5%) [12], symptoms commonly associated with depression and anxiety [13]. Pregnant subjects with antenatal depression have a higher rate of preeclampsia and preterm birth associated with poor fetal and infant outcomes (motor and mental development) [10, 14]
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