Association of depressive disorders, depression characteristics and antidepressant medication with inflammation

Abstract

Growing evidence suggests that immune dysregulation may be involved in depressive disorders, but the exact nature of this association is still unknown and may be restricted to specific subgroups. This study examines the association between depressive disorders, depression characteristics and antidepressant medication with inflammation in a large cohort of controls and depressed persons, taking possible sex differences and important confounding factors into account. Persons (18–65 years) with a current (N=1132) or remitted (N=789) depressive disorder according to DSM-IV criteria and healthy controls (N=494) were selected from the Netherlands Study of Depression and Anxiety. Assessments included clinical characteristics (severity, duration and age of onset), use of antidepressant medication and inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)). After adjustment for sociodemographics, currently depressed men, but not women, had higher levels of CRP (1.33 versus 0.92 mg l−1, P<0.001, Cohen's d=0.32) and IL-6 (0.88 versus 0.72 pg ml−1, P=0.01, Cohen's d=0.23) than non-depressed peers. Associations reduced after considering lifestyle and disease indicators — especially body mass index — but remained significant for CRP. After full adjustment, highest inflammation levels were found in depressed men with an older age of depression onset (CRP, TNF-α). Furthermore, inflammation was increased in men using serotonin–norepinephrine reuptake inhibitors (CRP, IL-6) and in men and women using tri- or tetracyclic antidepressants (CRP), but decreased among men using selective serotonin reuptake inhibitors (IL-6). In conclusion, elevated inflammation was confirmed in depressed men, especially those with a late-onset depression. Specific antidepressants may differ in their effects on inflammation.

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress

“…Although some studies have demonstrated that antidepressants decrease inflammatory cytokines (38,39), others report either no effect (31,40,41) or even increased levels (42,43). This discrepancy is likely due to a number of factors, including the class of antidepressant used for treatment or the heterogeneity of the patient population (44). In our studies, we only included treatment-resistant patients that typically exhibit greater proinflammatory profiles (45), which may contribute to decreased treatment efficacy and increased relapse.…”

A review of peripheral biomarkers in major depression: The potential of inflammatory and oxidative stress biomarkers

“…In a recent metaanalysis on longitudinal studies by Valkanova et al (2013) it was also established that raised CRP levels were associated with an increased risk of subsequent depression. However, these findings are not uniform and in subgroup analyses, elevated CRP was associated with atypical depression (Hickman et al, 2013), somatic symptoms (Duivis et al, 2013), depressed men with an older age of depression onset (Vogelzangs et al, 2012), depressed men in general (Elovainio et al, 2009, Ford and Erlinger, 2004, Liukkonen et al, 2011, depressed patients with a greater history of childhood adversity (Miller and Cole, 2012), and cumulative depressive episodes (Copeland et al, 2012).…”

The Role of Immune System in Depression Disorder

“…Additionally, rise of inflammatory markers such as CRP, IL-6, and TNF-α, have been reported in a cross-sectional study assessing 2415 participants [26]. Maes et al have accomplished a cross-sectional survey showing a positive correlation between levels of inflammatory markers (TNF-α and IL-1) and the extent of depressive episodes [27].…”