Abstract
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.
Highlights
Decades of research have demonstrated high rates of depression in patients with cancer across various malignancies and settings
These data suggest that non-pharmacologic interventions that reduce distress may treat both depression and inflammation, with the limited data available, the directionality of these effects remains unclear
Given the growing literature on the impact of inflammation on the brain and the many sources of inflammation in cancer patients, there is increasing interest in applying what is known about how inflammation can influence the brain and behavior to treat depression in cancer patients
Summary
Decades of research have demonstrated high rates of depression in patients with cancer across various malignancies and settings (e.g., localized or metastatic cancer, throughout survivorship). Despite the serious implications of having concurrent depressive symptoms alongside cancer and its high prevalence across cancer types, it is often not emphasized as a routine part of cancer care and remains unrecognized or inadequately treated, if addressed at all. Neurotransmitter systems and neuropathways in the Central Nervous System (CNS) that are implicated in depression are affected by inflammation induced by the presence of cancer [3]. This association is further validated because inflammation measured peripherally correlates with inflammation-induced changes in the CNS [2]. Depressive symptoms associated with inflammation do not typically respond as well to conventional psychopharmacologic therapies [6]
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