Faster speed of onset of the depressive episode is associated with lower cytokine serum levels (IL-2, -4, -6, -10, TNF-α and IFN-γ) in patients with major depression.

INTRODUCTION: Cytokines might play a key role in the pathophysiology of major depressive disorder (MDD). The speed of onset of depressive episodes has been discussed as an important clinical parameter in MDD. The aim of this study was to investigate a potential influence of the speed of onset of the depressive episode on cytokine serum levels. METHOD: Serum level of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) granulocyte and monocyte colony stimulating factor (GM-CSF) were measured in a total of 92 patients with MDD that did not respond to at least one previous antidepressant treatment. Patients were retrospectively divided in two groups: Faster (≤4 weeks) and slower (>4 weeks) onset of the depressive episode defined as the time passing from the first depressive symptoms to a full-blown depressive episode by using information from a clinical interview. RESULTS: We found significantly lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with a faster onset compared to patients with a slower onset of the depressive episodes. Furthermore, lower cytokine serum levels of IL-2, IL-8, IL-10 and IFN-γ were found in patients with a shorter duration (less than 6 months) compared to a longer duration (6-24 months) of the current depressive episode. This effect on cytokines was independent from the effect of the speed of onset of the depressive episode. CONCLUSIONS: Patients with faster onset of the depressive episode might represent a biological subtype of MDD with lower serum levels of IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ.

Cytokine serum levels remain unchanged during lithium augmentation of antidepressants in major depression.

Lithium augmentation (LA) of antidepressants is a first-line therapy in treatment-resistant depression. Immunomodulatory effects of lithium have been described. The cytokine hypothesis of depression postulates that cytokines play a key role in the pathophysiology of depression. Concordantly, it has been shown that proinflammatory cytokine serum levels decrease during antidepressant treatment. The aim of this study was to investigate changes in cytokine serum levels during LA. Serum concentrations of the cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor alpha, interferon-gamma, granulocyte and monocyte colony stimulating factor were measured in a total of 95 acutely depressed patients before and after four weeks of LA. Changes in cytokine levels were corrected for the confounding factors severity of depression, treatment response, lithium serum level, gender, age and body mass index in a linear mixed-model analysis. We did not find a significant change in any of the measured cytokine serum levels during LA (p > 0.05). In conclusion, our study does not support the role of cytokine serum levels as a state marker in treatment of depression with LA.