- Email: [email protected]
The impact of somatopsychic factors on the incidence, therapy, and outcome of cancer
Accepted Manuscript The Impact of Somatopsychic Factors on the Incidence, Therapy, and Outcome of Cancer Ying Wang, Daiming Fan PII:
S2452-3100(17)30087-2
DOI:
10.1016/j.coisb.2017.04.013
Reference:
COISB 55
To appear in:
Current Opinion in Systems Biology
Received Date: 12 October 2016 Revised Date:
21 April 2017
Accepted Date: 21 April 2017
Please cite this article as: Wang Y, Fan D, The Impact of Somatopsychic Factors on the Incidence, Therapy, and Outcome of Cancer, Current Opinion in Systems Biology (2017), doi: 10.1016/ j.coisb.2017.04.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title Page The Impact of SomatopsychicFactors on the Incidence, Therapy, and Outcome of Cancer
3 Ying Wang1, Daiming Fan2
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Science and Technology, Luoyang, China, 471003
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710032
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The First Affiliated Hospital and College of Clinical Medicine of Henan University of
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Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China,
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Correspondence author: Daiming Fan2,
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Military Medical University, Xi'an, China, 710032 Email: [email protected]
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Xijing Hospital of Digestive Diseases, Fourth
12 Abstract
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Although not fully proven yet, in a way, cancer isseen as a disorder correlated with
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somatopsychic factors such as worry and depression. Previous epidemiological and
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experimental studies have revealed the potentially causative roles of psychological disorders
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in tumor development. According to some studies, psychological stress can undermine
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immune function through multiple biological and behavioral pathways, which may be one of
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the causes for carcinogenesis. The findings that malignant cells express antigens that can be
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recognized by immune cells and that immune effector mechanisms are tumoricidal has
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increased our understanding of the relationship between immune function and the biology of
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cancer. Integrative treatment methods, including yoga, massage, music, and mindfulness-
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based therapy have been found to be helpful in cancer therapy partly because they can reduce
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stress and improve mood.
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Graphical abstract
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Highlights
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Psychological disorders may be potential causative factors in tumor development.
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Psychological stress can undermine immune function through multiple biological and
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behavioral pathways to some extent.
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In a way, immune dysfunction is correlated with the biology of cancer.
Cancer is partly seen as a somatopsychic disorder.
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Funding
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This work was supported by the National Natural Science Foundation of China (No.
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81301763,2013; No. 81572849, 2015)
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ACCEPTED MANUSCRIPT Introduction
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The harmonious state of the body, mind, and soul has always been considered to be the
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cornerstone of holistic health,from the west to the east and from ancient to modern times.
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Traditional Chinese medicine proposes that chronic mood extremes, such as joy, grief,
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depression, fear, anger, and anxiety, are very harmful to health; moreover, prolonged and
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severe depression and anger play important roles in malignant tumorigenesis. Galen, the
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physician to Roman emperors who contributed to our early understanding of medicine and
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anatomy, wrote about the adverse effect of sorrow on health in his famous paper titled “On
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the Avoidance of Sorrow.” Herein, we reviewed the effect of psychological disorders on the
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development of cancer, illustrating thatcancer is partly seen as asomatopsychic disorder.
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Integrative treatment methods, including yoga, massage, music, and mindfulness-based
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therapy, have been found to be helpful in cancer therapy because they can reduce stress and
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improve mood.
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14 Main text of review
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Psychological disorders: potential risk factors for cancer
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Epidemiological and experimental studies have revealed the potentially causative roles of
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psychological disorders on tumor development. For example, depressed attitude [1] and social
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isolation [2] are two psychosocial factors that are associated with the incidence of cancer [3].
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Some evidence from animal studies is consistent with these findings. Hilakivi-Clarke et al.
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administered clomipramine to neonatal rats to mimic a state resembling human endogenous
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depression and observed an elevated incidence of mammary tumors and a shortened lifespan
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[4]. The relationship between negative emotions and tumorigenesis has been studied and
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debated for decades. In a 1990 review [5], Friedman stated that although there was little solid
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evidence [6, 7] to support the hypothesis that emotional factors such as depression and stress
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predispose individuals to cancer [8, 9], 36% of respondents to the 1987 National Health
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Interview Survey believed that stress increases a person's chances of developing cancer.
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However, different views have also emerged; for example, Schwarz posited in 1996 that
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ACCEPTED MANUSCRIPT stress and depression do not cause cancer [10]. Jones SM et al surveyed 594 long-term (5–
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10 years post-diagnosis) survivors of cancer (breast, prostate, colorectal, lung, melanoma) in a
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cross-sectional study to find that worry about cancer was related to worse functioning (odds
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ratio (OR) range 1.40 to 1.46, all p's < .01), indicating that worry about cancer was associated
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with negative, but not positive, effects of cancer[11].
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Although not proven in every study, accumulating evidence suggests that mental states are
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risk factors for the development, progression, and prognosis of cancer.In particular,
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depression, anxiety, and anger are among the predictors of patient lifespan, quality of life ,
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etc., for a variety of tumors, including lung [12-16], ovary [17], head and neck [18, 19], breast
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[20-23], colorectum[24], pancreas [25], and cancer.
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Among the psychological disorders, depression is the most studied with respect to cancer. In
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1957, the Minnesota Multiphasic Personality Inventory was used to measure depression in a
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baseline examination of 2,020 middle-aged employed men, and it was found to be associated
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(P < 0.001) with a twofold increase in the risk of death fromcancerduring 17 years of follow-
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up [1]. Similarly, Whitlock and Siskind studied 39 men and 90 women over the age of 40 who
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were cancer-free at the time they were diagnosed with depression [33]. Five men and one
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woman died of cancer during the 2–4-year follow-up; for the men, this was significantly
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higher than expected [26]. Friedman reported in 1994 that, after follow-up for up to 19 years,
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923 patients diagnosed with some form of depression showed a slightly elevated risk of
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cancercompared with other members of a 143,574-person cohort (standardized morbidity
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ratio 1.21, 95% confidence interval [CI] 0.95–1.53) [27]. Pinquart and Duberstein analyzed
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the results of 105 samples derived from 76 prospective studies and concluded that depression
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and high levels of depressive symptoms predicted mortality [28]. Mausbach and Irwin
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performed a retrospective analysis of administrative data on 5,055 patients with an ICD-9
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diagnosis ofcancer from a single large healthcare system, and they found that depressed
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patients were significantly more likely to be hospitalized overnight and to be readmitted to a
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hospital for a 30-day stay than non-depressed patients with cancer[29].
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ACCEPTED MANUSCRIPT Evidence from human studies has shown a correlation between depression and lung cancer
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incidence. For example, in one study, 22 of 134 (16%) lungcancerpatients had symptoms of a
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major depressive illness at the time of first presentation. This prevalence was higher than that
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found in patients with nonmalignant chest conditions or in controls without serious disease
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[16]. Moreover, Linkins and Comstock performed a 12-year follow-up of residents of
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Washington County, Maryland, and found that depressed mood was related to the
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development of all cancers, but only among persons who reported smoking at least 15
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cigarettes per day [30].
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A study of the effect of depression on adherence to adjuvant endocrine therapy in women
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with breast cancer found that depression was significantly associated with nonadherence to
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therapy (Cohen's d = 0.35, 95% CI 0.19–0.52)[31]. Desai et al. reported in 1999 that a
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positive history of majordepressionwas associated with an increased likelihood of late-stage
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diagnosis with breastcancer(odds ratio = 9.81, P = 0.039) [32]. A meta-analysis performed by
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Satin et al. suggested that depression predicts mortality, but not disease progression, in cancer
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patients, although the association had a low level of significance[33]. In contrast, in 1994,
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McGee et al. reported that a meta-analysisof available studies indicated a small and
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marginally significant association betweendepressionand the development ofcancer; however,
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the practical significance of this association for the prevention ofcancerwas negligible [34].
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Overall, negative emotions are correlated with an elevated prevalence, worse response to
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therapy, and worse prognosis of cancer. Furthermore, depression has been found to be
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associated with head and neck cancer [35].
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Although some studies have failed to find a causative relationship between emotions and the
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development of cancer, psychotherapy has been found to affect the course of cancer in
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depressed patients [36]. Management of depression in patients with cancer can enhance their
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ability to adapt to the disease and tolerate the treatments [37] andimprove their quality of life
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[38, 39]. Failure to diagnose or reluctance to treatdepression in patients withcanceris a
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common error among physicians, and it can increase patient morbidity and mortality [40].
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ACCEPTED MANUSCRIPT Do psychological disorders play thecausative roles in attenuating immune function?
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It remains controversial whether psychological disorders could attenuate immune function.
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Some studies have shown that psychological stress may undermine immune function [41,
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42]through multiple biological and behavioral pathways [43]. For example, depression can
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reduce cell-mediated immunity and increase inflammatory processes [44], and, conversely,
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some viral diseases can affect the brain, resulting in mood disorders or cognitive impairment
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[45]. A variety of evidence has shown that long-lasting negative emotions, such as depression,
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anxiety, and loss of interest and pleasure, collectively termed major depressive disorder, can
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disturb the metabolism of catecholamines and other neurotransmitters, which in turn promotes
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the pathogenesis of neuropsychiatric symptoms [46]. Moreover, evidence has also shown that
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major depression can either activate (e.g., increase macrophage activity and levels of acute-
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phase proteins) or inhibit (e.g., suppress natural killer cell activity) the immune system [47,
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48]. In 2005, Reiche et al. [49] posited that consecutive steps of the immune response are
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either inhibited or enhanced by previous or parallel stress states, depending on the type and
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intensity of the stressor and on the animal species, strain, sex, or age. However, the stressors
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and depression both correlated not only with downregulated cytotoxic T cell [50] and natural
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killer cell activities, resulting in compromised antitumor immune surveillance [51, 52], but
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also with events that modulate the development and accumulation of somatic mutations and
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genomic instability in the tumor [53-55].
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The central nervous system can regulate immune function through a number of mediators,
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including neurotransmitters, neuropeptides, and hormones. Acute episodes of major
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depression are accompanied by immune dysfunction, such as monocytosis and increased
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blood levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α). Additionally,
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patients in a depressive state were found to have a markedly elevated density of quinolinic
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acid-positive cells in the subgenual anterior cingulate cortex (P = 0.003) and the anterior
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midcingulate cortex (P = 0.015) compared with control subjects [56].
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The hypothalamic–pituitary–adrenal gland axis (HPA axis) is the main system controlling an
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individual’s response to stress. Under normal physiological conditions, the HPA axis is self-
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ACCEPTED MANUSCRIPT regulated through negative feedback mechanisms. Thus, ligand binding to glucocorticoid
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receptors in the hypothalamus and the pituitary inhibits HPA axis activity and reduces
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glucocorticoid secretion from the adrenal cortex. Psychoneuroimmunological studies have
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investigated the relationship between the psychological and physiological features
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ofcancerrisk and progression. Persistent activation of the HPA axis during the chronic stress
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response and depression is thought to undermine the immune response and promote the
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development and progression of some types ofcancer[49].Abnormal HPA axis activation may
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be related to an increased release of proinflammatory cytokines from stimulated lymphocytes
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in the periphery and the brain. Dysregulation of HPA axis activation could result in immune
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deviation, and, conversely, immune activation could induce HPA axis disturbances [57][48].
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Animal models have shown that exposure of C57BL/6 mice to chronic unpredictable stress
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for eight weeks resulted in increased adrenal gland weight and an overactive HPA axis,
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resulting in increased levels of serum corticosterone [58]. Exogenous glucocorticoids can
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inhibit endotoxin-induced fever in animal models [59], and experiments performed
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byElenkov et al. also showed that exogenous glucocorticoids suppressed inflammation, IL-12
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production by antigen-presenting cells, and proinflammatory cytokine expression [60]. With
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regard to the mechanisms by which depression affects inflammation, Myint et al. found an
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increased kynurenine to tryptophan ratio and a decreased concentration of neuroprotective
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kynurenic acid in depressed patients compared to that in control subjects [61]. Gabbay et al.
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reported similar findings [62]. However, this notion has been challenged in recent years by
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Hughes et al. [63] and Maesand Rief[64]. Moreover, the finding that patients with severe
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depressive disorders have hypercortisolemia and hypercatecholaminemiaalso supports the
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possibility that depressive disorders could affect cellular immunity[65]. Finally, the median
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concentration of thyroid-stimulating hormone receptor antibodies was significantly higher in
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a cohort of depressed women than in the control subjects (P < 0.001), indicating that these
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antibodies might be biomarkers ofimmune dysfunctionin depression [66].
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Is immune dysfunction correlated withthe pathogenesis of cancer?
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immune functions are comparatively normal when they are diagnosed with cancer. However,
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there are alsofindings suggesting that malignant cells express antigens that can be recognized
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by immune cells and that immune effector mechanisms are tumoricidal, which has increased
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our understanding of the relationship between immune function and the biology of cancer
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[67].
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Two types of cellular immune responses are of clinical significance: one is antigen-specific
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immunity, which is mediated by T cells that recognize tumor-associated peptide antigens
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bound to surface HLA class I or class II molecules, and the second is antigen-nonspecific
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immunity, which is mediated by natural killer cells that are activated by a failure to recognize
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self HLA class I molecules [68]. Evasion of the immune system is one of the hallmarks of
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cancer because tumor cells have developed a variety of cellular and molecular mechanisms to
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avoid antitumor immune responses [69]. Moreover, immunodeficiency is associated with a
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higher risk of malignancy [70] due to the lack of a cellular antitumor immune response [68,
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71].
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A variety of tumors have been shown to be associated with immune dysfunction. For example,
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Poch et al. found that serum levels of IL-2 were reduced and levels of TNF-α, transforming
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growth factor-β1, IL-10, and other cytokines were significantly elevated in patients with
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pancreatic cancer, providing evidence for a systemicimmune dysfunction characterized by a
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shift toward a T-helper type 2 cytokine profile [72]. Campbell et al. reported that the
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percentage of CD4+ and CD8+ cells producing type 1 (IL-2, IFN-γ, and TNF-α) and type 2
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(IL-4) cytokines was significantly lower in patients with breast cancer than in healthy women,
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indicating a generalimmune dysfunctionin these patients [73].
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A number of studies have investigated the molecular mechanisms by which immune
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dysfunction occurs in cancer. Patients with renal cell carcinoma showed dysregulation of
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CD8+ T cells and miR-29b and miR-198 microRNAs that were associated with dysfunctional
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immunity [74]. Kudo-Saito identified follistatin-like 1, a soluble protein secreted by snail
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family zinc finger 1-expressingcancercells, as a key determinant of bone metastasis that acts
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ACCEPTED MANUSCRIPT by inducing a systemic state of immune dysfunction[75]. Furthermore, targeting follistatin-
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like 1 prevented bone metastasis and the consequent immune dysfunction[76]. Increase in
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myeloid-derived suppressor cells is associated with cancer immunosuppression and
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angiogenesis. Tissue inhibitor of metalloproteinase-2 may function as a negative regulator of
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myeloid-derived suppressor cells, which has implications for immunotherapeutic and/or
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antiangiogenic treatment of non-small cell lung cancer [77].
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Immune dysfunction predisposes patients to the development of cancer, and tumor cells
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develop multiple cellular and molecular mechanisms to avoid antitumor immune responses.
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Experimental evidence has shown that continuous administration of vascular endothelial
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growth factor, a factor produced by most solid tumors, compromises the functional
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maturation of dendritic cells, decreases T to B cell ratios in peripheral lymphoid organs, and
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induces rapid and dramatic thymic atrophy in tumor-bearing animals [73]. The mechanisms
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by which tumors induce T cell dysfunction may include increased production of immature
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myeloid cells [78].
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Somatopsychic treatment of cancer
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Integrative treatment methods, including yoga [79], massage [80], music [81], and
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mindfulness-based therapy [82] have been found to be helpful in cancer therapy because they
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can reduce stress and improve mood, which illustrates, at some level, the impact of
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somatopsychic factors on the homeostasis of patients with cancer. The use of yoga
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therapy has been shown to improve the physical and psychosocial quality of life (QoL) for
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breast cancerpatients with a range of benefits relevant to radiation therapy[83]. A study
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performed by Carson JWet al showed that women who participated in the yoga program
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showed significantly greater improvements relative to the control condition in hot-flash
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frequency, severity, and total scores and levels of joint pain, fatigue, sleep disturbance,
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symptom-related bother, and vigor;this suggests a promising support for the beneficial effects
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of a comprehensive yoga program for hot flashes and other menopausal symptoms in
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earlystage breast cancer survivors[84].Likewise, music interventions may have beneficial
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effects on anxiety, pain[85, 86], fatigue, and QoL in people with cancer[87]; moreover,
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Jasemi M et al. found the positive effects of music therapy on decreasing levels of depression
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and anxiety in patients with cancer[88], and
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cancer care can be improved by offering music-based resources/services because music can
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be a lifeline and support biopsychosocial and spiritual well-being[89].
O'Callaghan CC et al. also reported that
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5 Conclusion
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Although not fully confirmed yet, i.e., some studies showed that there were no evidence of a
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correlation between psychological disorders such as depression, anxiety, and anger and the
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prevalence of certain tumors, a variety of evidence, from animal models and human studies,
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supports the involvement of psychological factors in the development and progression of
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cancer. There are several potential reasons for this discrepancy. First, the intensity and
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duration of mood disorders in animal models are easily controlled by modulating the
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frequency and intensity of the stimuli. Second, the methodology in animals and human studies
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are quite different. In human studies, questionnaires are the most common method of
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obtaining baseline and end-point psychological data, and the results may be affected by the
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patient’s somatopsychic state at the time of responding to the questions. In animal models,
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statistical parameters are set to ensure objective collection and quantitative analysis of the
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data. Finally, the different methods of evaluation of human studies will affect the conclusions;
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hence, it is important to set clear, unified, and feasible evaluation standards to allow
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comparisons of the results of human studies.
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In a way, cancer is currently seen as a somatopsychic disorder. Integrative treatment methods,
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includingyoga [79], massage [80], music [81], and mindfulness-based therapy [82] have been
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found to be helpful in cancer therapy because they can reduce stress and improve mood. Of
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course, future studies are needed to verify these benefits.
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Acknowledgements
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We thank Prof. Luonan Chen for his wise, generous and intellectual advice and writing
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instructions.
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[1] Shekelle RB, Jr RW, Ostfeld AM, Garron DC, Bieliauskas LA, Liu SC, et al. Psychological depression and 17-year risk of death from cancer. Psychosomatic Medicine. 1981;43:117-25. [2] Reynolds P, Kaplan GA. Social connections and risk for cancer: prospective evidence from the Alameda County Study. Behavioral Medicine. 1990;16:101-10. [3] Mathé G. Depression, stressful events and the risk of cancer. Biomedecine & Pharmacotherapy. 1996;50:1-2. [4] Hilakivi-Clarke L, Wright A, Lippman ME. DMBA-induced mammary tumor growth in rats exhibiting increased or decreased ability to cope with stress due to early postnatal handling or antidepressant treatment. Physiology & Behavior. 1993;54:229-36. [5] Friedman GD. Depression, worry, and the incidence of cancer. American Journal of Public Health. 1990;80:1396-7. [6] Fox BH. Depressive symptoms and risk of cancer. Jama the Journal of the American Medical Association. 1989;262:1231-. [7] PhD BHF. Current Theory of Psychogenic Effects on Cancer Incidence and Prognosis. Journal of Psychosocial Oncology. 1983;1:17-31. [8] Pelletier KR. Mind as healer, mind as slayer : a holistic approach to preventing stress disorders: Dell; 1977. [9] Mcquade W, Aikman A. Stress: What it is, what it can do to your health, how to fight back. 1974. [10] Schwarz R. [Stress and depression are not causes of cancer]. Strahlentherapie Und Onkologie. 1996;172:632-3. *[11] Jones SM, Ziebell R, Walker R, Nekhlyudov L, Rabin BA, Nutt S, et al. Association of worry about cancer to benefit finding and functioning in long-term cancer survivors. Supportive Care in Cancer. 2016:1-6. 594 long-term survivors of cancer in a cross-sectional study was performed, indicating that worry about cancer was related to worse functioning, negative, but not positive, effects of cancer. [12] Schellekens MPJ, Hurk DGMVD, Prins JB, Molema J, Drift MAVD, Speckens AEM. The suitability of the Hospital Anxiety and Depression Scale, Distress Thermometer and other instruments to screen for psychiatric disorders in both lung cancer patients and their partners. Journal of Affective Disorders. 2016;203:176–83. [13] Yan SR, Fen Gu RN, Li-li Hou RN, Yin-qing Hu RN. Self‐reported depression among patients with non‐small cell lung cancer. Thoracic Cancer. 2014;6:334-7. *[14] RN SCMO, RN ERP. Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer. European Journal of Cancer Care. 2016. A sample of 178 patients with advanced lung cancer completed a demographic questionnaire, and authors reported a significant negative impact on quality of life for depression and lung cancer symptom cluster.
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Cancer. Asian Pacific Journal of Cancer Prevention Apjcp. 2016;17. This descriptive study involved a correlation method with 98 women living in KermanshahIran with breast cancer, The findings revealed that not only is depression high, but also there is a negative significant relationship betweendepression and the quality of life, with predictive potential. [23] Mcfarland DC, Andreotti C, Harris K, Mandeli J, Tiersten A, Holland J. Early Childhood Adversity and its Associations With Anxiety, Depression, and Distress in Women With Breast Cancer. Psychosomatics. 2015;57:174-84. *[24] Foster C, Haviland J, Winter J, Grimmett C, Chivers SK, Batehup L, et al. Pre-Surgery Depression and Confidence to Manage Problems Predict Recovery Trajectories of Health and Wellbeing in the First Two Years following Colorectal Cancer: Results from the CREW Cohort Study. Plos One. 2016;11. 872 adults receiving curative intent surgery during November 2010 to March 2012. Questionnaires at baseline, 3, 9, 15, 24 months post-surgery assessed QoL, health status, wellbeing, confidence to manage illness-related problems, social support, co-morbidities, socio-demographic, clinical and treatment characteristics. Groupbased trajectory analyses identified distincttrajectories and predictors for QoL, health status and wellbeing. It was found that higher pre-surgery depressionand lower self-efficacy were significantly associated with poorer trajectories for all three outcomes after adjusting for other important predictors including disease characteristics, stoma, anxiety and social support. *[25] Olson SH, Xu Y, Herzog K, Saldia A, Defilippis EM, Li P, et al. Weight Loss, Diabetes, Fatigue, and Depression Preceding Pancreatic Cancer. Pancreas. 2015;230:82-5. Using information from personal interviews with 510 cases and 463 controls, we obtained adjusted odds ratios for weightloss, long-term and new-onset diabetes, fatigue, and depression before diagnosis. Authors found that fatigue and depression are also potential precursors of diagnosis of pancreatic Cancer. [26] Whitlock FA, Siskind M. Depression and cancer: a follow-up study. Psychological Medicine. 1979;9:747-52. [27] Friedman GD. Psychiatrically-diagnosed depression and subsequent cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 1994;3:11-3. [28] Pinquart M, Duberstein PR. Depression and cancer mortality: a meta-analysis. Psychological Medicine. 2010;40:1797-810. [29] Mausbach BT, Irwin SA. Depression and healthcare service utilization in patients with cancer. Psycho-Oncology. 2016. [30] Linkins RW, Comstock GW. Depressed mood and development of cancer. American Journal of Epidemiology. 1990;132:962-72. *[31] Mausbach BT, Schwab RB, Irwin SA. Depression as a predictor of adherence to adjuvant endocrine therapy (AET) in women with breast cancer: a systematic review and meta-analysis. Breast Cancer Research & Treatment. 2015;152:239-46. The purpose of this meta-analysis was to analyze the available evidence concerning the effects of depression on non-adherence toadjuvant endocrine therapy (AET) in women with breast cancer. The results suggested that AET adherence may be lower among women with greater depressive symptoms, and this effect may be exacerbated in
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[50] Moynihan JA. Mechanisms of stress-induced modulation of immunity. Brain Behavior & Immunity. 2003;17 Suppl 1:11-6. [51] Leonard BE, Song C. Stress and the immune system in the etiology of anxiety and depression. Pharmacology Biochemistry & Behavior. 1996;54:299-303. [52] Schleifer SJ, Keller SE, Meyerson AT, Raskin MJ, Davis KL, Stein M. Lymphocyte function in major depressive disorder. Archives of General Psychiatry. 1984;41:484-6. [53] Li GY, Yao KT, Glaser R. Sister chromatid exchange and nasopharyngeal carcinoma. International Journal of Cancer. 1989;43:613-8. [54] Glaser R, Thorn BE, Tarr KL, Kiecolt-Glaser JK, D'Ambrosio SM. Effects of stress on methyltransferase synthesis: an important DNA repair enzyme. Health Psychology Official Journal of the Division of Health Psychology American Psychological Association. 1985;4:403-12. [55] Forlenza MJ, Baum A. Psychosocial influences on cancer progression: alternative cellular and molecular mechanisms. Current Opinion in Psychiatry. 2000;13:639-45. [56] Steiner J, Walter M, Gos T, Guillemin GJ, Bernstein HG, Schwabedissen LMZ, et al. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission? Journal of Neuroinflammation. 2011;8:92. [57] Carroll BJ, Curtis GC, Mendels J. Cerebrospinal fluid and plasma free cortisol concentrations in depression. Psychological Medicine. 1976;6:235-44. *[58] Monteiro S, Roque S, De S-CD, Sousa N, Correia-Neves M, Cerqueira JJ. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice. Frontiers in Psychiatry. 2015;6:6. In this study, authors showed that by extending the unpredictable stress (CUS) protocol to 8 weeks was possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight, and an overactive hypothalamicpituitary-adrenal axis with increased levels of serum corticosterone. [59] Coelho MM, Souza GE, Pelá IR. Endotoxin-induced fever is modulated by endogenous glucocorticoids in rats. American Journal of Physiology. 1992;263:423-7. [60] Elenkov IJ, Papanicolaou DA, Wilder RL, Chrousos GP. Modulatory effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: clinical implications. Proceedings of the Association of American Physicians. 1996;108:37481. [61] Myint AM, Leonard BE, Steinbusch HW, Kim YK. Th1, Th2, and Th3 cytokine alterations in major depression - Journal of Affective Disorders. Journal of Affective Disorders. 2005;88:167-73. [62] Gabbay V, Klein RG, Katz Y, Mendoza S, Guttman LE, Alonso CM, et al. The possible role of the kynurenine pathway in adolescent depression with melancholic features. Journal of Child Psychology & Psychiatry. 2010;51:935–43. [63] Hughes MM, Carballedo A, Mcloughlin DM, Amico F, Harkin A, Frodl T, et al. Tryptophan depletion in depressed patients occurs independent of kynurenine pathway activation. Brain Behavior & Immunity. 2012;26:979-87. [64] Maes M, Rief W. Diagnostic classifications in depression and somatization should include biomarkers, such as disorders in the tryptophan catabolite (TRYCAT) pathway.
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Psychiatry Research. 2012;196:243-9. [65] Hickie I, Bennett B, Wakefield D, Mitchell P, Hickie C, Silove D, et al. Biochemical correlates of in vivo cell-mediated immune dysfunction in patients with depression: A preliminary report. International Journal of Immunopharmacology. 1995;17:685-90. *[66] Fam J, Rush AJ, Burt T, Chan ES, Siddiqui FJ, Assam PN, et al. Thyroid Autoimmune Antibodies and Major Depressive Disorder in Women. Annals of the Academy of Medicine Singapore. 2015;44:284-9. In this study, authors found that median TSH receptor antibody concentration was significantly higher in the depressed than control group (P <0.001). Area under the ROC curve was 0.80. Higher TSH receptor antibody titres were associated with greater depression severity scores. [67] Appelbaum JW. The role of the immune system in the pathogenesis of cancer. Seminars in Oncology Nursing. 1992;8:51-62. [68] Waller EK. Cellular immunotherapy and cancer. Seminars in Oncology. 2004;31:87-90. [69] Ohm JE, Carbone DP. Immune dysfunction in cancer patients. Oncology. 2002;16:11-8. *[70] Gangemi S, Allegra A, Musolino C. Lymphoproliferative disease and cancer among patients with common variable immunodeficiency. Leukemia Research. 2015;11:389-96. This review discusses the latest insights into the links between common variable immunodeficiency (CVI) and malignancies. Although Ig therapy greatly reduces the number of infections and enhances survival, it does not appear to address the development of cancer, especially lymphoma. [71] Hadden JW. Immunodeficiency and cancer: prospects for correction. International Immunopharmacology. 2003;3:1061-71. [72] Poch B, Lotspeich E, Ramadani M, Gansauge S, Beger HG, Gansauge F. Systemic immune dysfunction in pancreatic cancer patients. Langenbeck S Archives of Surgery. 2007;392:353-8. [73] Campbell MJ, Scott J, Maecker HT, Park JW, Esserman LJ. Immune dysfunction and micrometastases in women with breast cancer. Breast Cancer Research & Treatment. 2005;91:163-71. [74] Gigante M, Pontrelli P, Herr W, Gigante M, D’Avenia M, Zaza G, et al. miR-29b and miR-198 overexpression in CD8 + T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction. Journal of Translational Medicine. 2016;14:1-13. [75] Kudosaito C. FSTL1 promotes bone metastasis by causing immune dysfunction. Oncoimmunology. 2013;2:1091-6. [76] Kudosaito C, Fuwa T, Murakami K, Kawakami Y. Targeting FSTL1 prevents tumor bone metastasis and consequent immune dysfunction. Cancer Research. 2013;73:6185-93. [77] Guedez L, Jensen-Taubman S, Bourboulia D, Kwityn CJ, Wei B, Caterina J, et al. TIMP2 targets tumor-associated myeloid suppressor cells with effects in cancer immune dysfunction and angiogenesis. Journal of Immunotherapy. 2012;35:502-12. [78] Gabrilovich DI, Velders MP, Sotomayor EM, Kast WM. Mechanism of immune dysfunction in cancer mediated by immature Gr-1+ myeloid cells. Journal of Immunology. 2001;166:5398-406. [79] Bower JE, Woolery A, Sternlieb B, Garet D. Yoga for cancer patients and survivors.
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Cancer Control Journal of the Moffitt Cancer Center. 2005;12:165-71. [80] Wilkinson S, Barnes K, Storey L. Massage for symptom relief in patients with cancer: systematic review. Journal of Advanced Nursing. 2008;63:430-9. [81] Rykov MH. Experiencing Music Therapy Cancer Support. Journal of Health Psychology. 2008;13:190-200. [82] Ba JES, Rgn CH. Mindfulness-Based Stress Reduction as supportive therapy in cancer care: systematic review. Journal of Advanced Nursing. 2005;52:315–27. *[83] Galliford M, Robinson S, Bridge P, Carmichael M. Salute to the sun: a new dawn in yoga therapy for breast cancer. Journal of Medical Radiation Sciences. 2017. A search of peer reviewed journal articles published between January 2009 and July 2014 was conducted. The most reported psychosocial benefits of yoga therapy were anxiety, emotional and social functioning, stress, depression and global QoL. [84] Carson JW, Carson KM, Porter LS, Keefe FJ, Seewaldt VL. Yoga of Awareness program for menopausal symptoms in breast cancer survivors: results from a randomized trial. Supportive Care in Cancer. 2009;17:1301-9. [85] Priyadharshini K, Shoba N. Effect of Music Therapy on Pain and Anxiety Levels of Cancer Patients: A Pilot Study. Indian Journal of Palliative Care. 2016;22:307. [86] Gao J, Chen S, Lin S, Han H. Effect of music therapy on pain behaviors in rats with bone cancer pain. Journal of Buon Official Journal of the Balkan Union of Oncology. 2016;21:466. [87] Bradt J, Dileo C, Grocke D, Magill L. Music interventions for improving psychological and physical outcomes in cancer patients. Cochrane Database of Systematic Reviews. 2011;66:CD006911. [88] Jasemi M, Aazami S, Zabihi RE. The Effects of Music Therapy on Anxiety and Depression of Cancer Patients. Indian Journal of Palliative Care. 2016;22:455-8. *[89] O'Callaghan CC, Mcdermott F, Reid P, Michael N, Hudson P, Zalcberg JR, et al. Music's Relevance for People Affected by Cancer: A Meta-Ethnography and Implications for Music Therapists. 2016:thw013. In this article, authors concluded that cancer care can be improved through offering musicbased resources/services, which give cancer patients and carers opportunities to extend music usage for personal support and, for carers, to support patients.
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S2452-3100(17)30087-2
DOI:
10.1016/j.coisb.2017.04.013
Reference:
COISB 55
To appear in:
Current Opinion in Systems Biology
Received Date: 12 October 2016 Revised Date:
21 April 2017
Accepted Date: 21 April 2017
Please cite this article as: Wang Y, Fan D, The Impact of Somatopsychic Factors on the Incidence, Therapy, and Outcome of Cancer, Current Opinion in Systems Biology (2017), doi: 10.1016/ j.coisb.2017.04.013. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Title Page The Impact of SomatopsychicFactors on the Incidence, Therapy, and Outcome of Cancer
3 Ying Wang1, Daiming Fan2
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Science and Technology, Luoyang, China, 471003
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710032
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The First Affiliated Hospital and College of Clinical Medicine of Henan University of
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Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China,
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Correspondence author: Daiming Fan2,
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Military Medical University, Xi'an, China, 710032 Email: [email protected]
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Xijing Hospital of Digestive Diseases, Fourth
12 Abstract
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Although not fully proven yet, in a way, cancer isseen as a disorder correlated with
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somatopsychic factors such as worry and depression. Previous epidemiological and
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experimental studies have revealed the potentially causative roles of psychological disorders
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in tumor development. According to some studies, psychological stress can undermine
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immune function through multiple biological and behavioral pathways, which may be one of
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the causes for carcinogenesis. The findings that malignant cells express antigens that can be
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recognized by immune cells and that immune effector mechanisms are tumoricidal has
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increased our understanding of the relationship between immune function and the biology of
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cancer. Integrative treatment methods, including yoga, massage, music, and mindfulness-
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based therapy have been found to be helpful in cancer therapy partly because they can reduce
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stress and improve mood.
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Graphical abstract
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Highlights
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Psychological disorders may be potential causative factors in tumor development.
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Psychological stress can undermine immune function through multiple biological and
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behavioral pathways to some extent.
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In a way, immune dysfunction is correlated with the biology of cancer.
Cancer is partly seen as a somatopsychic disorder.
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Funding
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This work was supported by the National Natural Science Foundation of China (No.
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81301763,2013; No. 81572849, 2015)
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ACCEPTED MANUSCRIPT Introduction
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The harmonious state of the body, mind, and soul has always been considered to be the
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cornerstone of holistic health,from the west to the east and from ancient to modern times.
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Traditional Chinese medicine proposes that chronic mood extremes, such as joy, grief,
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depression, fear, anger, and anxiety, are very harmful to health; moreover, prolonged and
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severe depression and anger play important roles in malignant tumorigenesis. Galen, the
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physician to Roman emperors who contributed to our early understanding of medicine and
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anatomy, wrote about the adverse effect of sorrow on health in his famous paper titled “On
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the Avoidance of Sorrow.” Herein, we reviewed the effect of psychological disorders on the
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development of cancer, illustrating thatcancer is partly seen as asomatopsychic disorder.
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Integrative treatment methods, including yoga, massage, music, and mindfulness-based
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therapy, have been found to be helpful in cancer therapy because they can reduce stress and
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improve mood.
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14 Main text of review
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Psychological disorders: potential risk factors for cancer
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Epidemiological and experimental studies have revealed the potentially causative roles of
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psychological disorders on tumor development. For example, depressed attitude [1] and social
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isolation [2] are two psychosocial factors that are associated with the incidence of cancer [3].
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Some evidence from animal studies is consistent with these findings. Hilakivi-Clarke et al.
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administered clomipramine to neonatal rats to mimic a state resembling human endogenous
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depression and observed an elevated incidence of mammary tumors and a shortened lifespan
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[4]. The relationship between negative emotions and tumorigenesis has been studied and
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debated for decades. In a 1990 review [5], Friedman stated that although there was little solid
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evidence [6, 7] to support the hypothesis that emotional factors such as depression and stress
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predispose individuals to cancer [8, 9], 36% of respondents to the 1987 National Health
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Interview Survey believed that stress increases a person's chances of developing cancer.
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However, different views have also emerged; for example, Schwarz posited in 1996 that
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ACCEPTED MANUSCRIPT stress and depression do not cause cancer [10]. Jones SM et al surveyed 594 long-term (5–
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10 years post-diagnosis) survivors of cancer (breast, prostate, colorectal, lung, melanoma) in a
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cross-sectional study to find that worry about cancer was related to worse functioning (odds
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ratio (OR) range 1.40 to 1.46, all p's < .01), indicating that worry about cancer was associated
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with negative, but not positive, effects of cancer[11].
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Although not proven in every study, accumulating evidence suggests that mental states are
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risk factors for the development, progression, and prognosis of cancer.In particular,
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depression, anxiety, and anger are among the predictors of patient lifespan, quality of life ,
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etc., for a variety of tumors, including lung [12-16], ovary [17], head and neck [18, 19], breast
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[20-23], colorectum[24], pancreas [25], and cancer.
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Among the psychological disorders, depression is the most studied with respect to cancer. In
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1957, the Minnesota Multiphasic Personality Inventory was used to measure depression in a
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baseline examination of 2,020 middle-aged employed men, and it was found to be associated
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(P < 0.001) with a twofold increase in the risk of death fromcancerduring 17 years of follow-
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up [1]. Similarly, Whitlock and Siskind studied 39 men and 90 women over the age of 40 who
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were cancer-free at the time they were diagnosed with depression [33]. Five men and one
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woman died of cancer during the 2–4-year follow-up; for the men, this was significantly
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higher than expected [26]. Friedman reported in 1994 that, after follow-up for up to 19 years,
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923 patients diagnosed with some form of depression showed a slightly elevated risk of
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cancercompared with other members of a 143,574-person cohort (standardized morbidity
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ratio 1.21, 95% confidence interval [CI] 0.95–1.53) [27]. Pinquart and Duberstein analyzed
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the results of 105 samples derived from 76 prospective studies and concluded that depression
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and high levels of depressive symptoms predicted mortality [28]. Mausbach and Irwin
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performed a retrospective analysis of administrative data on 5,055 patients with an ICD-9
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diagnosis ofcancer from a single large healthcare system, and they found that depressed
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patients were significantly more likely to be hospitalized overnight and to be readmitted to a
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hospital for a 30-day stay than non-depressed patients with cancer[29].
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incidence. For example, in one study, 22 of 134 (16%) lungcancerpatients had symptoms of a
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major depressive illness at the time of first presentation. This prevalence was higher than that
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found in patients with nonmalignant chest conditions or in controls without serious disease
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[16]. Moreover, Linkins and Comstock performed a 12-year follow-up of residents of
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Washington County, Maryland, and found that depressed mood was related to the
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development of all cancers, but only among persons who reported smoking at least 15
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cigarettes per day [30].
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A study of the effect of depression on adherence to adjuvant endocrine therapy in women
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with breast cancer found that depression was significantly associated with nonadherence to
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therapy (Cohen's d = 0.35, 95% CI 0.19–0.52)[31]. Desai et al. reported in 1999 that a
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positive history of majordepressionwas associated with an increased likelihood of late-stage
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diagnosis with breastcancer(odds ratio = 9.81, P = 0.039) [32]. A meta-analysis performed by
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Satin et al. suggested that depression predicts mortality, but not disease progression, in cancer
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patients, although the association had a low level of significance[33]. In contrast, in 1994,
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McGee et al. reported that a meta-analysisof available studies indicated a small and
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marginally significant association betweendepressionand the development ofcancer; however,
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the practical significance of this association for the prevention ofcancerwas negligible [34].
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Overall, negative emotions are correlated with an elevated prevalence, worse response to
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therapy, and worse prognosis of cancer. Furthermore, depression has been found to be
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associated with head and neck cancer [35].
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Although some studies have failed to find a causative relationship between emotions and the
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development of cancer, psychotherapy has been found to affect the course of cancer in
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depressed patients [36]. Management of depression in patients with cancer can enhance their
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ability to adapt to the disease and tolerate the treatments [37] andimprove their quality of life
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[38, 39]. Failure to diagnose or reluctance to treatdepression in patients withcanceris a
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common error among physicians, and it can increase patient morbidity and mortality [40].
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ACCEPTED MANUSCRIPT Do psychological disorders play thecausative roles in attenuating immune function?
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It remains controversial whether psychological disorders could attenuate immune function.
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Some studies have shown that psychological stress may undermine immune function [41,
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42]through multiple biological and behavioral pathways [43]. For example, depression can
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reduce cell-mediated immunity and increase inflammatory processes [44], and, conversely,
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some viral diseases can affect the brain, resulting in mood disorders or cognitive impairment
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[45]. A variety of evidence has shown that long-lasting negative emotions, such as depression,
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anxiety, and loss of interest and pleasure, collectively termed major depressive disorder, can
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disturb the metabolism of catecholamines and other neurotransmitters, which in turn promotes
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the pathogenesis of neuropsychiatric symptoms [46]. Moreover, evidence has also shown that
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major depression can either activate (e.g., increase macrophage activity and levels of acute-
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phase proteins) or inhibit (e.g., suppress natural killer cell activity) the immune system [47,
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48]. In 2005, Reiche et al. [49] posited that consecutive steps of the immune response are
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either inhibited or enhanced by previous or parallel stress states, depending on the type and
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intensity of the stressor and on the animal species, strain, sex, or age. However, the stressors
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and depression both correlated not only with downregulated cytotoxic T cell [50] and natural
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killer cell activities, resulting in compromised antitumor immune surveillance [51, 52], but
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also with events that modulate the development and accumulation of somatic mutations and
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genomic instability in the tumor [53-55].
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The central nervous system can regulate immune function through a number of mediators,
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including neurotransmitters, neuropeptides, and hormones. Acute episodes of major
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depression are accompanied by immune dysfunction, such as monocytosis and increased
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blood levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α). Additionally,
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patients in a depressive state were found to have a markedly elevated density of quinolinic
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acid-positive cells in the subgenual anterior cingulate cortex (P = 0.003) and the anterior
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midcingulate cortex (P = 0.015) compared with control subjects [56].
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The hypothalamic–pituitary–adrenal gland axis (HPA axis) is the main system controlling an
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individual’s response to stress. Under normal physiological conditions, the HPA axis is self-
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ACCEPTED MANUSCRIPT regulated through negative feedback mechanisms. Thus, ligand binding to glucocorticoid
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receptors in the hypothalamus and the pituitary inhibits HPA axis activity and reduces
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glucocorticoid secretion from the adrenal cortex. Psychoneuroimmunological studies have
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investigated the relationship between the psychological and physiological features
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ofcancerrisk and progression. Persistent activation of the HPA axis during the chronic stress
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response and depression is thought to undermine the immune response and promote the
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development and progression of some types ofcancer[49].Abnormal HPA axis activation may
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be related to an increased release of proinflammatory cytokines from stimulated lymphocytes
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in the periphery and the brain. Dysregulation of HPA axis activation could result in immune
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deviation, and, conversely, immune activation could induce HPA axis disturbances [57][48].
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Animal models have shown that exposure of C57BL/6 mice to chronic unpredictable stress
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for eight weeks resulted in increased adrenal gland weight and an overactive HPA axis,
13
resulting in increased levels of serum corticosterone [58]. Exogenous glucocorticoids can
14
inhibit endotoxin-induced fever in animal models [59], and experiments performed
15
byElenkov et al. also showed that exogenous glucocorticoids suppressed inflammation, IL-12
16
production by antigen-presenting cells, and proinflammatory cytokine expression [60]. With
17
regard to the mechanisms by which depression affects inflammation, Myint et al. found an
18
increased kynurenine to tryptophan ratio and a decreased concentration of neuroprotective
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kynurenic acid in depressed patients compared to that in control subjects [61]. Gabbay et al.
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reported similar findings [62]. However, this notion has been challenged in recent years by
21
Hughes et al. [63] and Maesand Rief[64]. Moreover, the finding that patients with severe
22
depressive disorders have hypercortisolemia and hypercatecholaminemiaalso supports the
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possibility that depressive disorders could affect cellular immunity[65]. Finally, the median
24
concentration of thyroid-stimulating hormone receptor antibodies was significantly higher in
25
a cohort of depressed women than in the control subjects (P < 0.001), indicating that these
26
antibodies might be biomarkers ofimmune dysfunctionin depression [66].
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Is immune dysfunction correlated withthe pathogenesis of cancer?
ACCEPTED MANUSCRIPT It is known that for most cancer patients, especially those with early stage diseases, their
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immune functions are comparatively normal when they are diagnosed with cancer. However,
3
there are alsofindings suggesting that malignant cells express antigens that can be recognized
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by immune cells and that immune effector mechanisms are tumoricidal, which has increased
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our understanding of the relationship between immune function and the biology of cancer
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[67].
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Two types of cellular immune responses are of clinical significance: one is antigen-specific
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immunity, which is mediated by T cells that recognize tumor-associated peptide antigens
9
bound to surface HLA class I or class II molecules, and the second is antigen-nonspecific
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immunity, which is mediated by natural killer cells that are activated by a failure to recognize
11
self HLA class I molecules [68]. Evasion of the immune system is one of the hallmarks of
12
cancer because tumor cells have developed a variety of cellular and molecular mechanisms to
13
avoid antitumor immune responses [69]. Moreover, immunodeficiency is associated with a
14
higher risk of malignancy [70] due to the lack of a cellular antitumor immune response [68,
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71].
16
A variety of tumors have been shown to be associated with immune dysfunction. For example,
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Poch et al. found that serum levels of IL-2 were reduced and levels of TNF-α, transforming
18
growth factor-β1, IL-10, and other cytokines were significantly elevated in patients with
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pancreatic cancer, providing evidence for a systemicimmune dysfunction characterized by a
20
shift toward a T-helper type 2 cytokine profile [72]. Campbell et al. reported that the
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percentage of CD4+ and CD8+ cells producing type 1 (IL-2, IFN-γ, and TNF-α) and type 2
22
(IL-4) cytokines was significantly lower in patients with breast cancer than in healthy women,
23
indicating a generalimmune dysfunctionin these patients [73].
24
A number of studies have investigated the molecular mechanisms by which immune
25
dysfunction occurs in cancer. Patients with renal cell carcinoma showed dysregulation of
26
CD8+ T cells and miR-29b and miR-198 microRNAs that were associated with dysfunctional
27
immunity [74]. Kudo-Saito identified follistatin-like 1, a soluble protein secreted by snail
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family zinc finger 1-expressingcancercells, as a key determinant of bone metastasis that acts
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ACCEPTED MANUSCRIPT by inducing a systemic state of immune dysfunction[75]. Furthermore, targeting follistatin-
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like 1 prevented bone metastasis and the consequent immune dysfunction[76]. Increase in
3
myeloid-derived suppressor cells is associated with cancer immunosuppression and
4
angiogenesis. Tissue inhibitor of metalloproteinase-2 may function as a negative regulator of
5
myeloid-derived suppressor cells, which has implications for immunotherapeutic and/or
6
antiangiogenic treatment of non-small cell lung cancer [77].
7
Immune dysfunction predisposes patients to the development of cancer, and tumor cells
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develop multiple cellular and molecular mechanisms to avoid antitumor immune responses.
9
Experimental evidence has shown that continuous administration of vascular endothelial
10
growth factor, a factor produced by most solid tumors, compromises the functional
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maturation of dendritic cells, decreases T to B cell ratios in peripheral lymphoid organs, and
12
induces rapid and dramatic thymic atrophy in tumor-bearing animals [73]. The mechanisms
13
by which tumors induce T cell dysfunction may include increased production of immature
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myeloid cells [78].
15
Somatopsychic treatment of cancer
16
Integrative treatment methods, including yoga [79], massage [80], music [81], and
17
mindfulness-based therapy [82] have been found to be helpful in cancer therapy because they
18
can reduce stress and improve mood, which illustrates, at some level, the impact of
19
somatopsychic factors on the homeostasis of patients with cancer. The use of yoga
20
therapy has been shown to improve the physical and psychosocial quality of life (QoL) for
21
breast cancerpatients with a range of benefits relevant to radiation therapy[83]. A study
22
performed by Carson JWet al showed that women who participated in the yoga program
23
showed significantly greater improvements relative to the control condition in hot-flash
24
frequency, severity, and total scores and levels of joint pain, fatigue, sleep disturbance,
25
symptom-related bother, and vigor;this suggests a promising support for the beneficial effects
26
of a comprehensive yoga program for hot flashes and other menopausal symptoms in
27
earlystage breast cancer survivors[84].Likewise, music interventions may have beneficial
28
effects on anxiety, pain[85, 86], fatigue, and QoL in people with cancer[87]; moreover,
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ACCEPTED MANUSCRIPT 1
Jasemi M et al. found the positive effects of music therapy on decreasing levels of depression
2
and anxiety in patients with cancer[88], and
3
cancer care can be improved by offering music-based resources/services because music can
4
be a lifeline and support biopsychosocial and spiritual well-being[89].
O'Callaghan CC et al. also reported that
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5 Conclusion
7
Although not fully confirmed yet, i.e., some studies showed that there were no evidence of a
8
correlation between psychological disorders such as depression, anxiety, and anger and the
9
prevalence of certain tumors, a variety of evidence, from animal models and human studies,
10
supports the involvement of psychological factors in the development and progression of
11
cancer. There are several potential reasons for this discrepancy. First, the intensity and
12
duration of mood disorders in animal models are easily controlled by modulating the
13
frequency and intensity of the stimuli. Second, the methodology in animals and human studies
14
are quite different. In human studies, questionnaires are the most common method of
15
obtaining baseline and end-point psychological data, and the results may be affected by the
16
patient’s somatopsychic state at the time of responding to the questions. In animal models,
17
statistical parameters are set to ensure objective collection and quantitative analysis of the
18
data. Finally, the different methods of evaluation of human studies will affect the conclusions;
19
hence, it is important to set clear, unified, and feasible evaluation standards to allow
20
comparisons of the results of human studies.
21
In a way, cancer is currently seen as a somatopsychic disorder. Integrative treatment methods,
22
includingyoga [79], massage [80], music [81], and mindfulness-based therapy [82] have been
23
found to be helpful in cancer therapy because they can reduce stress and improve mood. Of
24
course, future studies are needed to verify these benefits.
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Acknowledgements
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We thank Prof. Luonan Chen for his wise, generous and intellectual advice and writing
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instructions.
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[1] Shekelle RB, Jr RW, Ostfeld AM, Garron DC, Bieliauskas LA, Liu SC, et al. Psychological depression and 17-year risk of death from cancer. Psychosomatic Medicine. 1981;43:117-25. [2] Reynolds P, Kaplan GA. Social connections and risk for cancer: prospective evidence from the Alameda County Study. Behavioral Medicine. 1990;16:101-10. [3] Mathé G. Depression, stressful events and the risk of cancer. Biomedecine & Pharmacotherapy. 1996;50:1-2. [4] Hilakivi-Clarke L, Wright A, Lippman ME. DMBA-induced mammary tumor growth in rats exhibiting increased or decreased ability to cope with stress due to early postnatal handling or antidepressant treatment. Physiology & Behavior. 1993;54:229-36. [5] Friedman GD. Depression, worry, and the incidence of cancer. American Journal of Public Health. 1990;80:1396-7. [6] Fox BH. Depressive symptoms and risk of cancer. Jama the Journal of the American Medical Association. 1989;262:1231-. [7] PhD BHF. Current Theory of Psychogenic Effects on Cancer Incidence and Prognosis. Journal of Psychosocial Oncology. 1983;1:17-31. [8] Pelletier KR. Mind as healer, mind as slayer : a holistic approach to preventing stress disorders: Dell; 1977. [9] Mcquade W, Aikman A. Stress: What it is, what it can do to your health, how to fight back. 1974. [10] Schwarz R. [Stress and depression are not causes of cancer]. Strahlentherapie Und Onkologie. 1996;172:632-3. *[11] Jones SM, Ziebell R, Walker R, Nekhlyudov L, Rabin BA, Nutt S, et al. Association of worry about cancer to benefit finding and functioning in long-term cancer survivors. Supportive Care in Cancer. 2016:1-6. 594 long-term survivors of cancer in a cross-sectional study was performed, indicating that worry about cancer was related to worse functioning, negative, but not positive, effects of cancer. [12] Schellekens MPJ, Hurk DGMVD, Prins JB, Molema J, Drift MAVD, Speckens AEM. The suitability of the Hospital Anxiety and Depression Scale, Distress Thermometer and other instruments to screen for psychiatric disorders in both lung cancer patients and their partners. Journal of Affective Disorders. 2016;203:176–83. [13] Yan SR, Fen Gu RN, Li-li Hou RN, Yin-qing Hu RN. Self‐reported depression among patients with non‐small cell lung cancer. Thoracic Cancer. 2014;6:334-7. *[14] RN SCMO, RN ERP. Effects of symptom clusters and depression on the quality of life in patients with advanced lung cancer. European Journal of Cancer Care. 2016. A sample of 178 patients with advanced lung cancer completed a demographic questionnaire, and authors reported a significant negative impact on quality of life for depression and lung cancer symptom cluster.
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Cancer Control Journal of the Moffitt Cancer Center. 2005;12:165-71. [80] Wilkinson S, Barnes K, Storey L. Massage for symptom relief in patients with cancer: systematic review. Journal of Advanced Nursing. 2008;63:430-9. [81] Rykov MH. Experiencing Music Therapy Cancer Support. Journal of Health Psychology. 2008;13:190-200. [82] Ba JES, Rgn CH. Mindfulness-Based Stress Reduction as supportive therapy in cancer care: systematic review. Journal of Advanced Nursing. 2005;52:315–27. *[83] Galliford M, Robinson S, Bridge P, Carmichael M. Salute to the sun: a new dawn in yoga therapy for breast cancer. Journal of Medical Radiation Sciences. 2017. A search of peer reviewed journal articles published between January 2009 and July 2014 was conducted. The most reported psychosocial benefits of yoga therapy were anxiety, emotional and social functioning, stress, depression and global QoL. [84] Carson JW, Carson KM, Porter LS, Keefe FJ, Seewaldt VL. Yoga of Awareness program for menopausal symptoms in breast cancer survivors: results from a randomized trial. Supportive Care in Cancer. 2009;17:1301-9. [85] Priyadharshini K, Shoba N. Effect of Music Therapy on Pain and Anxiety Levels of Cancer Patients: A Pilot Study. Indian Journal of Palliative Care. 2016;22:307. [86] Gao J, Chen S, Lin S, Han H. Effect of music therapy on pain behaviors in rats with bone cancer pain. Journal of Buon Official Journal of the Balkan Union of Oncology. 2016;21:466. [87] Bradt J, Dileo C, Grocke D, Magill L. Music interventions for improving psychological and physical outcomes in cancer patients. Cochrane Database of Systematic Reviews. 2011;66:CD006911. [88] Jasemi M, Aazami S, Zabihi RE. The Effects of Music Therapy on Anxiety and Depression of Cancer Patients. Indian Journal of Palliative Care. 2016;22:455-8. *[89] O'Callaghan CC, Mcdermott F, Reid P, Michael N, Hudson P, Zalcberg JR, et al. Music's Relevance for People Affected by Cancer: A Meta-Ethnography and Implications for Music Therapists. 2016:thw013. In this article, authors concluded that cancer care can be improved through offering musicbased resources/services, which give cancer patients and carers opportunities to extend music usage for personal support and, for carers, to support patients.
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