The International Journal of Neuropsychopharmacology

Special Section

Introduction to the Special Section

The depressogenic effects of cytokines: implications for the psychological and organic aetiology and treatment of depression

Michael Maes c1a1
a1 Department of Psychiatry, University Hospital of Maastricht, Maastricht, The Netherlands


This Special Section of the International Journal of Neuropsychopharmacology presents papers which review the current status of the relationship between the inflammatory response system (IRS) and major ‘endogenous’ and ‘organic’ (due to a medical condition) depression. Studies published over the last 11 years and reviewed in this Special Section begin to test the necessary conditions which are needed to accept the hypothesis that an activation of the IRS is involved in the pathophysiology and aetiology of ‘endogenous’ and ‘organic’ depression. This hypothesis suggests that some types of ‘endogenous’ and ‘organic’ depression may be related to IRS activation, such as an increased production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β), IL-6, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN)-γ. These cytokines are stress-sensitive, may cause depression, they have specific effects on brain systems involved in the pathogenesis of major depression, such as the serotonergic system and the hypothalamic–pituitary–adrenal (HPA) axis, and their production may be suppressed by antidepressants. Future research should examine whether anti-inflammatory drugs are effective in the treatment of depression and whether naturally occurring variants of the ‘IRS’ genes confer susceptibility to the development of the depressive phenotype through altered function of the respective gene products.

(Received June 10 2002)
(Reviewed June 11 2002)
(Revised August 8 2002)
(Accepted August 11 2002)

c1 Address for correspondence: Dr M. Maes, Professor of Psychiatry, Department of Psychiatry, University Hospital of Maastricht, Postbus 5800, 6202 AZ Maastricht, The Netherlands. Tel.: (The Netherlands): 0031-43-3781025 E-mail: Fax: (The Netherlands): 0031-43-3781026 Fax: (Belgium): 0032-89-723531 Website: http://