Clinical Implications of Cancer Related Inflammation and Depression: A Critical Review

Background: Neuropsychiatric symptoms are problematic in cancer settings. In addition to poor quality of life, depression is associated with worsened survival. Patients who develop depression that responds to treatment have the same cancer-related survival as those patients who never had depression. Although depression in patients with cancer is common, it is often unrecognized, untreated, or at best, undertreated. There remains untapped potential for underlying cancer-related biology associated with depression to help clinicians correctly identify depressed cancer patients and orchestrate appropriate treatments to address cancer-related depression. Biologically, inflammation has been most vigorously described in its association with depression in otherwise healthy patients and to a significant extent in patients with medical illness. This association is especially relevant to patients with cancer since so many aspects of cancer induce inflammation. In addition to cancer itself, its treatments (e.g., surgery, radiation, chemotherapy, and systemic therapies) and associated factors (e.g., smoking, obesity, aging) are all associated with increased inflammation that can drive immunological changes in the brain followed by depression. This critical review investigates the relationship between depression and cancer-related inflammation. It investigates several hypotheses that support these relationships in cancer patients. Special attention is given to the data that support certain inflammatory markers specific to both cancer and depression, the neurobiological mechanisms by which inflammation can impact neurotransmitters and neurocircuits in the brain, and the data addressing interventions that reduce inflammation and depression in cancer patients, and future directions.