Elsevier

Cancer Treatment Reviews

Volume 52, January 2017, Pages 58-70
Cancer Treatment Reviews

Hot Topic
Depression in cancer: The many biobehavioral pathways driving tumor progression

https://doi.org/10.1016/j.ctrv.2016.11.004Get rights and content

Highlights

  • Depression is highly prevalent among individuals with cancer.

  • Co-morbid depression may lead to a worse prognosis among cancer patients.

  • Evidence instantiates the role of inflammation and oxidative and nitrosative stress in the pathophysiology both of cancer and depression.

  • Psychosocial stressors in cancer promote inflammation, a dysregulation of the hypothalamic-pituitary-adrenal axis and reduced immunosurveilence.

  • Behavioral strategies may target biological mechanisms relevant to tumor progression and depressive clinical manifestations.

Abstract

Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote: (1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic–pituitaryadrenal axis. Consequently, the prompt recognition of depression among patients with cancer who may benefit of treatment strategies targeting depressive symptoms, cognitive dysfunction, fatigue and sleep disturbances, is a public health priority. Moreover, behavioral strategies aiming at reducing psychological distress and depressive symptoms, including addressing unhealthy diet and life-style choices, as well as physical inactivity and sleep dysfunction, may represent important strategies not only to treat depression, but also to improve wider cancer-related outcomes. Herein, we provide a comprehensive review of the intertwined biobehavioral pathways linking depression to cancer progression. In addition, the clinical implications of these findings are critically reviewed.

Introduction

Major Depressive Disorder (MDD) is more common among individuals affected by cancer as compared to the general population. While the average rate of MDD is 3.3% in the general population, the prevalence of MDD among individuals with cancer is approximately 12.5%, which is up to four-times the rate reported in population-based samples [1]. Evidence indicates that co-morbid depression may be associated with a worse prognosis and increased mortality rate in cancer populations [2]. In fact, depression is an independent predictor of more frequent and longer hospitalizations, diminished quality of life and decreased compliance to treatments [3]. Meta-analytic evidence indicates that depression triples the risk for non-adherence to medications in women with breast cancer [4]. Moreover, demotivation may promote maladaptive depressive coping styles with a detrimental effect on survival [5] as well as a possible increase in suicidality [6]. Notwithstanding depression is under-recognized in populations with cancer, limited evidence provides support for the routine screening of distress in cancer populations [7]. Importantly, the treatment of depression has been associated with increased survival in women with metastatic cancer [8]. Furthermore, interventions aiming at improving depression management, education and behavioral activation (i.e. emphasizing pleasant event scheduling and overcoming avoidance behaviors), along with the use of antidepressant treatments when appropriate, have been recognized as effective in reducing depressive burden in individuals with cancer [9].

Notwithstanding the burgeoning and stressful potential associated with a diagnosis of cancer, the large prevalence of depression among individuals with cancer is likely to not be entirely explained by the effects of psychological distress. In recent years, advances in the neurobiology of depression and in the physiopathology of cancer have led to the identification of some shared bio-behavioral mechanisms [10], [11], [12], [13], [14]. This field has witnessed an ever increasing accumulation of emerging findings, which deserve a critical review.

Therefore, this comprehensive narrative review aims to: (1) explore epidemiological links between depression and cancer progression; (2) summarize biological mechanisms relevant for the development and recurrence of depressive episodes as well as for cancer progression, with potential mutual reciprocal interactions; and (3) describe behavioral interventions that may target mechanistic pathways relevant to both depression and cancer progression.

Section snippets

Search strategy

A comprehensive search for peer-reviewed articles published in English was performed in the PubMed/Medline database including the following search terms: “Major Depressive Disorder”, “cancer”, “tumor”, “inflammation”, “oxidative and nitrosative stress”, “HPA axis”, “diet”, “microbiota”, “physical exercise”, “sleep dysfunction” up until February 15th, 2016. Bibliographies from selected articles were reviewed to identify additional original reports aligned with our objectives.

Epidemiological links between depression and cancer

Most studies report that the prevalence of depression in oncological populations range from 15% to 30%, with variations attributable to different screening tools and diagnostic criteria across studies [15]. These heterogeneous results are in part explainable by the fact that only a limited number of studies have assessed the prevalence of depression in cancer samples by means of a validated structured diagnostic interview according to criteria established in the Diagnostic and Statistical

The role of stress and inflammation

Tumorigenesis and cancer progression are characterized by the acquisition of six biological attributes, representing the “hallmarks of cancer” namely (1) resisting cell death; (2) sustaining proliferative signaling; (3) evading growth suppressors; (4) inducing angiogenesis (5) resisting cell death; and (6) activating invasion and metastasis [31]. Continued oxidative stress can propitiate chronic inflammation, which may influence cancer progression. Hence, oxidative stress can activate

Effects of psychological treatments on depression in patients with cancer

Recent results support the hypothesis that a variety of psychological interventions may be effective in promoting resilience to stress and reinforcing social support, including standard cognitive behavioral therapy and mindfulness-based therapy, but also multimodal approaches including psychoeducational interventions, anticipatory guidance and measures of psychosocial support [148]. As recently reviewed elsewhere extensively [1], the majority of RCTs were performed on subjects suffering from

Concluding remarks

Individual suffering from cancer are at high risk of experiencing major depressive episodes throughout the trajectory of the disease, although this risk appears to be specially prominent within the first year of diagnosis. Recent advances in the understanding of the neurobiological underpinnings of depression indicate that high levels of psychosocial stress and low social support may significantly contribute to the development of depressive symptoms in cancer populations, not only by increasing

Conflicts of interest

The authors declare no conflicts of interest.

Acknowledgments

AFC is supported by a research fellowship award from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; Brazil). CAK is the recipient of a postdoctoral fellowship award from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES; Brazil).

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