Cytokines, Depression, and Psychoneuroimmunology

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Cytokines such as interferon (IFN)-alpha may cause dopamine depletion and affect the pathways of monoamine metabolism. Their alterations may result in behavioral changes including depression, psychomotor slowing, and fatigue (Miller, 2009).

How can cytokines affect the psychological conditions?

Studies have found that cytokine treatments such as interferon (IFN)-alpha may influence regional brain activities with lower cerebrospinal fluid levels of the dopamine metabolite and homovanillic acid (Miller, 2009). The cytokines may stimulate the neural circuits such as the dorsal anterior cingulate cortex related to anxiety and other behavioral alterations.

In the cytokine-associated psychiatric disorders, serotonin metabolism is important. Serotonin reuptake inhibitors have been used for IFN-alpha-induced depression (Miller, 2009). IFN-alpha may alter the metabolic enzymes such as indoleamine-2,3-dioxygenase (IDO).

In addition, other cytokine signaling pathways may be influenced including the pathways of p38 mitogen activated protein kinase (MAPKs) (Miller, 2009). Such changes may affect the production and reuptake of serotonin.

In summary, cytokine alterations may affect the pathways in the brain and behaviors by influencing the balance in behavioral and immune responses. Further studies in psychoneuroimmunology (PNI) about these pathways may contribute to personalized medicine of the relevant disorders.


Miller AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun. 2009 Feb;23(2):149-58. doi: 10.1016/j.bbi.2008.08.006.

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