A psychoneuroimmunological review on cytokines involved in antidepressant treatment response

Objectives: The literature exploring the role that cytokine functioning plays in the pathogenesis and treatment of depressive illness is reviewed. The review focuses on the influence of antidepressants on cytokines, and on how treatment response might be affected by genetic variants of cytokines.

Method: The authors systematically reviewed the scientific literature on the subject over the last 20 years, searching PubMed, PsychInfo, and Cochrane databases.

Results: Antidepressants modulate cytokine functioning, and these mechanisms appear to directly influence treatment outcome in depression. Antidepressants appear to normalize serum levels of major inflammatory cytokines, including interleukin (IL)-1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Antidepressants are postulated to modulate cytokine functioning through their effects on intracellular cyclic adenosyl monophosphate (cAMP), serotonin metabolism, the hypothalamo-pituitary-adrenocortical (HPA) axis or through a direct action on neurogenesis. Preliminary research shows that cytokine genotypes and functioning may be able to help predict antidepressant treatment response.

Conclusions: Current literature demonstrates an association between antidepressant action and cytokine functioning in major depression. Improved understanding of the specific pharmacologic and pharmacogenetic mechanisms is needed. Such knowledge may serve to enhance our understanding of depression, leading to promising new directions in the pathology, nosology, and treatment of depression.