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.

Figure 1

Adjusted mean inflammatory levels across medication groups and sex based on analyses of covariance (ANCOVA) adjusted for age, education, smoking status, alcohol intake, body mass index (BMI), physical activity, cardiovascular disease, diabetes, number of other chronic diseases, statins and anti-inflammatory medication; to normalize distributions C-reactive protein (CRP), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) were ln-transformed, for interpretation purposes presented means were back transformed. Abbreviations: IDS, inventory of depressive symptoms score; SNRI, serotonin–norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; TeCA, tetracyclic antidepressant. ¹Current depressive disorder and IDS ⩾25 without medication use (=reference); only significant differences from reference are shown: ^*P<0.10; ^**P<0.05.