Baseline Immune Activation as a Risk Factor for the Onset of Depression During Interferon-Alpha Treatment

Background Major depression has been associated cross-sectionally with increased cell-mediated immune activation but causality has been difficult to establish. This study prospectively investigated the hypothesis that baseline level of immune activation predicts the development of depression during interferon-alpha (IFN-α) treatment. Methods Sixteen hepatitis C patients without psychiatric disorder underwent IFN-α treatment. Proinflammatory and anti-inflammatory cytokines were determined before starting treatment. Presence of a major depressive disorder (MDD) was assessed at baseline and several times during treatment. Results Baseline soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were significantly increased in the five subjects that developed MDD during treatment compared with those that did not, with standardized effect sizes of 1.08, 1.16, and 1.25, respectively, controlling for marijuana use, cigarette smoking, and baseline level of depressive symptoms. Conclusions Results suggest that increased immune activation, rather than an epiphenomenon, is a causal risk factor for the development of MDD.