Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all ...aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients.
Behavioral symptoms are a common adverse effect of breast cancer diagnosis and treatment and include disturbances in energy, sleep, mood, and cognition. These symptoms cause serious disruption in ...patients' quality of life and may persist for years after treatment. Patients need accurate information about the occurrence of these adverse effects as well as assistance with symptom management. This review considers four of the most common behavioral sequelae of breast cancer, namely fatigue, sleep disturbance, depression, and cognitive impairment. Research on the prevalence, mechanisms, and treatment of each symptom is described, concluding with recommendations for future studies.
Highlights • 26 randomized controlled trials of Tai Chi, Qigong, yoga, and meditation reviewed. • Trials showed consistent reductions in genomic markers of inflammation. • Mixed effects on ...circulating and cellular inflammatory markers.
Highlight ► This review examines the current state of the evidence linking inflammation and cancer-related fatigue, and considers neural mechanisms and risk factors.
•The aggregated effect size of early adversity on CRP is very small, z = .07.•The aggregated effect size of early adversity on IL-6 is very small, z = .17.•More studies looking at TNF-α are ...needed.•More studies using in vitro assays of immune cells are needed.
This study provides a comprehensive review of the published research on the association between early life adversity and markers of inflammation in children and adolescents. We conducted a systematic review of the published literature on the association between early life adversity and markers of inflammation in pediatric populations. To date, 27 studies have been published in this area representing a wide range of global populations and diverse methods of which nearly half were prospective, longitudinal studies. Of these 27, only 12 studies shared an inflammatory outcome with 4 or more other studies; 9 for CRP, and 6 for IL-6. The association between early life adversity and both CRP, z = .07 .04, .10, and IL-6, z = .17 −.07, .42, were small and only significant for CRP although comparable in magnitude to the effects observed in adult samples. Descriptively, the association between early life adversity and CRP appeared to be stronger in studies conducted in infants and adolescents compared with middle childhood. There was minimal evidence of publication bias for studies measuring CRP, but evidence of publication bias for studies using IL-6. Eight studies have looked at the association between early life adversity and stimulated inflammatory cytokines in vitro, and both the methods and results of these studies were mixed; the majority observed exaggerated production of inflammatory cytokines despite mixed methodological approaches that make comparisons across studies difficult. In summary, the evidence supporting an association between early life adversity and inflammation in pediatric samples is limited so far by the number of studies and their heterogeneous methodological approaches. More research that is grounded in a developmental framework and informed by the complexity of the innate immune system is needed in this area.
•Physical trauma, disrupted caregiving, & unpredictability have unique developmental implications.•RSD may be a useful animal analog for childhood adversity involving physical trauma.•Maternal ...separation may be useful for understanding disrupted caregiving.•CVS may be useful for understanding living in an unpredictable developmental environment.•Infancy and pubertal may be sensitive periods for childhood adversity exposure.
Childhood adversity has been repeatedly and robustly linked to physical and mental illness across the lifespan. Yet, the biological pathways through which this occurs remain unclear. Functioning of the inflammatory arm of the immune system and the hypothalamic-pituitary-adrenal (HPA)-axis are both hypothesized pathways through which childhood adversity leads to disease. This review provides a novel developmental framework for examining the role of adversity type and timing in inflammatory and HPA-axis functioning. In particular, we identify elements of childhood adversity that are salient to the developing organism: physical threat, disrupted caregiving, and unpredictable environmental conditions. We propose that existing, well-characterized animal models may be useful in differentiating the effects of these adversity elements and review both the animal and human literature that supports these ideas. To support these hypotheses, we also provide a detailed description of the development and structure of both the HPA-axis and the inflammatory arm of the immune system, as well as recent methodological advances in their measurement. Recommendations for future basic, developmental, translational, and clinical research are discussed.
•Exogenously-induced inflammation leads to expression of 3 features of depression.•They are neural reactivity to negative stimuli, reward processing, somatic symptoms.•Little evidence for the role of ...inflammation in cognitive control was observed.•Effects of inflammation on behavior depend on the timing and dose of the stimulus.
A wealth of evidence has implicated inflammation in the development of depression. Yet, the heterogeneous nature of depression has impeded efforts to understand, prevent, and treat the disease. The purpose of this integrative review is to summarize the connections between inflammation and established core features of depression that exhibit more homogeneity than the syndrome itself: exaggerated reactivity to negative information, altered reward processing, decreased cognitive control, and somatic syndrome. For each core feature, we first provide a brief overview of its relevance to depression and neurobiological underpinnings, and then review evidence investigating a potential role of inflammation. We focus primarily on findings from experimental paradigms of exogenously-induced inflammation. We conclude that inflammation likely plays a role in exaggerated reactivity to negative information, altered reward reactivity, and somatic symptoms. There is less evidence supporting an effect of inflammation on cognitive control as assessed by standard neuropsychological measures. Finally, we discuss implications for future research and recommendationsfor how to test the role of inflammation in the pathogenesis of heterogeneous psychiatric disorders.
Fatigue, depression, and sleep disturbance are common adverse effects of cancer treatment and frequently co-occur. However, the possibility that inflammatory processes may underlie this constellation ...of symptoms has not been examined.
Women (N = 103) who had recently finished primary treatment (ie, surgery, radiation, chemotherapy) for early-stage breast cancer completed self-report scales and provided blood samples for determination of plasma levels of inflammatory markers: soluble tumor necrosis factor (TNF) receptor II (sTNF-RII), interleukin-1 receptor antagonist, and C-reactive protein.
Symptoms were elevated at the end of treatment; greater than 60% of participants reported clinically significant problems with fatigue and sleep, and 25% reported elevated depressive symptoms. Women treated with chemotherapy endorsed higher levels of all symptoms and also had higher plasma levels of sTNF-RII than women who did not receive chemotherapy (all P < .05). Fatigue was positively associated with sTNF-RII, particularly in the chemotherapy-treated group (P < .05). Depressive symptoms and sleep problems were correlated with fatigue but not with inflammatory markers.
This study confirms high rates of behavioral symptoms in breast cancer survivors, particularly those treated with chemotherapy, and indicates a role for TNF-α signaling as a contributor to postchemotherapy fatigue. Results also suggest that fatigue, sleep disturbance, and depression may stem from distinct biologic processes in post-treatment survivors, with inflammatory signaling contributing relatively specifically to fatigue.
A growing body of evidence indicates that patients with cancer who receive cytotoxic treatments (such as chemotherapy or radiotherapy) have an increased risk of accelerated physical and cognitive ...ageing. Furthermore, accelerated biological ageing is a suspected driving force behind many of these observed effects. In this Review, we describe the mechanisms of biological ageing and how they apply to patients with cancer. We highlight the important role of specific behavioural factors, namely stress, sleep and lifestyle-related factors such as physical activity, weight management, diet and substance use, in the accelerated ageing of patients with cancer and cancer survivors. We also present a framework of how modifiable behaviours could operate to either increase the risk of accelerated ageing, provide protection, or promote resilience at both the biological level and in terms of patient-reported outcomes.
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