Recovery from major depressive disorder episode after non-pharmacological treatment is associated with normalized cytokine levels

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Several lines of evidence show that the immune system is implicated in the pathophysiology of major depressive disorder (MDD) and that treatment with antidepressants affects cytokine and C-reactive protein (CRP) levels. Few studies have investigated immune markers during non-pharmacological treatment. In this follow-up study, we investigated whether CRP and elevated plasma cytokine levels observed before treatment of an acute episode of MDD are normalized during non-pharmacological treatment.


We obtained clinical assessments and blood for CRP and cytokine analysis from 50 unmedicated MDD patients, and cytokine levels from healthy controls. The patients received ‘therapy as usual’ for 12 weeks, and the assessments were then repeated. Of the 43 completers, 29 patients did not receive medication.


In the patients receiving treatment without antidepressants, the depressive symptoms and the plasma levels of eight cytokines (interleukin (IL)-1Ra, IL-5,-6,-8,-10, G-CSF, IFN-γ, and TNF-α) were significantly reduced (P = 0.002–0.048). The cytokine levels were no longer different from the controls. The plasma CRP level did not change.


Cytokine plasma levels normalized during recovery from an acute depressive episode in MDD without antidepressant treatment. These findings may have implications for the understanding of the role of the immune system in depression and recovery from depression.

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