Insomnia, Fatigue, and Depression: Theoretical and Clinical Implications of a Self-reinforcing Feedback Loop in Cancer.

Introduction: Insomnia is emerging as a modifiable major risk factor for mental and physical problems, including cancer, and it may contribute to cancer-related fatigue and depression. Since both fatigue and depression may favor insomnia as well, we may hypothesize a self-reinforcing feedback loop among these factors in cancer. Methods: With the aim of discussing this hypothesis, PubMed, PsycINFO, and Embase electronic databases were searched for literature published according to the PRISMA method with several combinations of terms such as "insomnia" and "cancer" and "fatigue" and "depression". On this basis, we conducted a narrative review about theoretical aspects of insomnia in the context of cancer and about its role in cancer-related fatigue and depression. Results: Twenty-one papers were selected according to inclusion/exclusion criteria. Insomnia is frequent in cancer, and it is associated with cancer-related comorbid conditions such as emotional distress, depressive symptoms, and cancer-related fatigue. The hyperactivation of stress and inflammatory systems, which sustain insomnia, may contribute to cancer-related depression and fatigue. A deleterious feedback loop may be created, and it may perpetuate not only insomnia but also these cancer-related comorbid conditions. Conclusion: Although the understanding of the causal relationship between insomnia/ depression/fatigue in individuals with cancer is limited, we may hypothesize that these symptoms can exacerbate and maintain each other. When insomnia is established in cancer, it may lead to a vicious cycle with fatigue and depression and may contribute to adverse cancer outcomes. Interventions targeting insomnia could provide a promising approach not only for insomnia but also for cancer-related symptoms among cancer patients.