Undergoing the challenges of cancer and its treatment is an exceedingly daunting task. From a psychological standpoint, the road traveled is fraught with uncertainty, fear, frustration, and anger. On the physical side, there can be multiple bodily assaults, including surgery, chemotherapy, and radiation. Not uncommonly, these psychological and physical traumas become overwhelming and conspire to create an ever-widening sense of despair that invades virtually every aspect of one's being. Symptoms that can emerge include a profound loss of interest in usually pleasurable activities (often including social isolation), depressed mood, anxiety, impaired sleep, anorexia, fatigue, problems with memory and concentration, and, in some cases, severe desperation accompanied by suicidal ideation and even suicide attempts. This constellation of symptoms represents the syndrome of depression, and given its potentially damaging effects on quality of life, treatment adherence, and ultimately morbidity and mortality, understanding the pathophysiological pathways involved is of paramount importance for early identification, treatment, and prevention of this psychiatric disease.

Recent developments in our understanding of stress neurobiology and the contributions of the immune system to behavioral alterations have led to the recognition that the patient with cancer may be especially vulnerable to the convergence of psychological and biological forces that collude to create the substrates for depression. More specifically, data indicate that psychological stress as well as cancer and its treatment are associated with activation of innate immune responses and the release of relevant soluble proteins called cytokines, which in turn can access the brain and have powerful influences on pathways known to be involved in the pathophysiology of depression, including neuroendocrine function, neurotransmitter metabolism, synaptic plasticity, and information processing.