Questions raised by the cytokine hypothesis of depression

The cytokine hypothesis of depression raises a certain number of questions. These questions include: the inability of the theory to account for the classical (Freudian) psychodynamics of depression; the role of sensitization in cytokine-induced depression; the compatibility of some of the effects of cytokines (on sleep, on cognition, on the HPA) with the hypothesis; the possibility of occurrence of depression in the absence of an increase in circulating cytokines; the nature of the relationships between cytokines, stress, and depression; the compatibility of the effects of cytokines on brain monoamines with the current monoamine hypothesis of depression; the inability of antidepressants to fully abrogate the brain effects of individual cytokines in animal experiments. Based on these limitations of the theory, it is proposed to define a new clinical entity designated as "the cytokine-associated depressive syndrome."