Cytokine-Induced Depression: Current Status and Novel Targets for Depression Therapy
Current treatments of depression include psychological, pharmacological and physical approaches.
Pharmacological interventions to treat depression have previously focused on modifying dysfunctional neurotransmitter
systems. Overall, these treatments have demonstrated an ability to manage major depression but otucomes continue to be
poor in many patients, especially those with long term illness or with previous multiple relapses. This may be due to the
fact that depression is a systemic and neuroprogressive illness involving multiple biological pathways such as
immunological factors. There is substantial evidence that cytokine therapies induce depressive symptoms in clinical
populations. The model of cytokine-induced depression has provided important information relative to the risk factors and
biological pathways involved in the etiology of depressive symptoms and, most importantly, the identification and
knowledge of these factors has allowed new treatment targets to be explored. When an exogenous cytokine such as
interferon-alpha is administered, proinflammatory cytokines are activated, leading to alterations in neurotransmission and
endocrine pathways and producing neurotoxicity. Several new treatments for depression acting through pathways other
than amine neurotransmission have emerged in recent years. The regulation of the inflammatory response, the decrease in
the activity of the hypothalamic-pituitary-adrenal axis and the prevention of neurotoxicity are potential targets for new
drugs. Though these drugs are mostly at the proof-of-concept stage, some of them have already shown promising results
for the treatment of depression.
Keywords: Antidepressants, cytokines, depression, immunology, neurotoxicity, new-treatments.
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