Cytokines, “Depression Due to A General Medical Condition,” and Antidepressant Drugs

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Activation of the immune system during various medical conditions produces neural, neuroendocrine, and behavioral effects. The psychological and physiological effects of immune activation resemble many characteristics of depression. The essential features of depression are depressed mood and loss of interest or pleasure in all, or almost all activities (anhedonia). Several associated symptoms are also present, including, appetite disturbance, change in body weight, sleep disturbance, psychomotor disturbance, fatigue, loss of energy, and difficulty in thinking or concentrating (DSM-IV, 1994). Depression is also characterized by specific alterations in the functioning of neurochemical and neuroendocrine systems, including monoaminergic systems and the hypothalamic-pituitary-adrenal (HPA) axis (Brown, Steinberg, & van Praag, 1994; Holsboer, 1995). Most of these psychological and neuroendocrine symptoms appear both in humans and animals during diseases that involve immune activation. Based on these findings, and on several additional lines of evidence that will be presented below, we have recently argued that immune activation is involved in the etiology and symptomatology of depression associated with various medical conditions (Yirmiya, 1997).