Elsevier

Psychoneuroendocrinology

Volume 36, Issue 8, September 2011, Pages 1137-1147
Psychoneuroendocrinology

Sympathetic and parasympathetic activity in cancer-related fatigue: More evidence for a physiological substrate in cancer survivors

https://doi.org/10.1016/j.psyneuen.2011.02.005Get rights and content

Summary

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. This study evaluated relationships between fatigue and both sympathetic and parasympathetic nervous system activity in breast cancer survivors. Norepinephrine and heart rate variability (HRV) were evaluated at rest, as well as during and after a standardized laboratory speech and mental arithmetic stressor. The participants, 109 women who had completed treatment for stage 0–IIIA breast cancer within the past two years, were at least two months post surgery, radiation or chemotherapy, whichever occurred last. Women who reported more fatigue had significantly higher norepinephrine and lower HRV before and after the stressor than their less fatigued counterparts. Fatigue was not related to treatment or disease variables including treatment type, cancer stage, time since diagnosis, and time since treatment. Importantly, the relationship between HRV and cancer-related fatigue was sizeable. Based on research that has demonstrated characteristic age-related HRV decrements, our findings suggest a 20-year difference between fatigued and non-fatigued cancer survivors, raising the possibility that fatigue may signify accelerated aging. Furthermore, lower HRV and elevated norepinephrine have been associated with a number of adverse health outcomes; accordingly, fatigue may also signal the need for increased vigilance to other health threats.

Section snippets

Participants

The study data were drawn from the baseline sample of a clinical trial addressing the potential benefits of yoga for breast cancer survivors, and participants were recruited through breast cancer clinics and media announcements. Women could not participate in our study if they were currently practicing yoga, took yoga classes within the last 6 months, or practiced yoga for more than 3 months over their lifetime. Eligible women had completed treatment for stage 0–IIIA breast cancer within the

Results

Table 1 reports descriptive information for the 109 participants.

Fatigued and nonfatigued participants did not differ by treatment type, cancer stage, time since diagnosis, time since last treatment, age, activity level, Her2 receptor status, progesterone receptor status, estrogen receptor status, tamoxifan/aromatase use, or albumin and hemoglobin levels. The 6 participants who had any Charlson-rated comorbidities were divided equally between the fatigued and nonfatigued groups. As would be

Discussion

Cancer-related fatigue is a notable clinical problem that can affect cancer survivors many years beyond treatment, and thus a better understanding of the factors that contribute to its development and maintenance is important. Women who reported more fatigue had significantly higher norepinephrine and lower HRV before and after the stressor than women who reported less fatigue, providing evidence that fatigue is associated with a maladaptive autonomic profile characterized by higher sympathetic

Role of the funding sources

Work on this paper was supported in part by NIH grants R01CA126857, R01 CA131029, NCRR Grant UL1RR025755, which funds the Clinical Research Center, the Ohio State Comprehensive Cancer Center Core Grant CA16058, and an American Cancer Society Postdoctoral Fellowship Grant PF-11-007-01-CPPB awarded to the first author.

Conflict of interest

The authors have no financial interests or relationships that pose potential conflicts of interest with this article.

Acknowledgements

We appreciate the helpful assistance of Heather Preston, Cathie Atkinson, and Lindsay Madaras.

References (60)

  • G. Prue et al.

    Cancer-related fatigue: a critical appraisal

    European Journal of Cancer

    (2006)
  • K.D. Stein et al.

    Further validation of the multidimensional fatigue symptom inventory-short form

    Journal of Pain and Symptom Management

    (2004)
  • P. Stein et al.

    Heart rate variability: a measure of cardiac autonomic tone

    American Heart Journal

    (1994)
  • R. Straub et al.

    Sympathetic neurotransmitters in joint inflammation

    Rheumatic Disease Clinics of North America

    (2005)
  • L.M. Tak et al.

    As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders

    Biological Psychology

    (2009)
  • J. Thayer et al.

    The role of vagal function in the risk for cardiovascular disease and mortality

    Biological Psychology

    (2007)
  • M. Vlcek et al.

    Heart rate variability and catecholamines during hypoglycemia and orthostasis

    Autonomic Neuroscience

    (2008)
  • M. Altemus et al.

    Responses to laboratory psychosocial stress in postpartum women

    Psychosomatic Medicine

    (2001)
  • M.R. Basco et al.

    Outcome measures of depression

  • G. Berntson et al.

    Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications

    Psychophysiology

    (1993)
  • G.G. Berntson et al.

    Autonomic space and psychophysiological response

    Psychophysiology

    (1994)
  • A. Bierhaus et al.

    A mechanism converting psychosocial stress into mononuclear cell activation

    Proceedings of the National Academy of Sciences of the United States of America

    (2003)
  • J. Bower

    Behavioral symptoms in patients with breast cancer and survivors

    Journal of Clinical Oncology

    (2008)
  • J.E. Bower et al.

    Altered cortisol response to psychologic stress in breast cancer survivors with persistent fatigue

    Psychosomatic Medicine

    (2005)
  • J.E. Bower et al.

    Fatigue and proinflammatory cytokine activity in breast cancer survivors

    Psychosomatic Medicine

    (2002)
  • J.E. Bower et al.

    Fatigue in long-term breast carcinoma survivors: a longitudinal investigation

    Cancer

    (2006)
  • J.E. Bower et al.

    Fatigue in long-term breast carcinoma survivors: a longitudinal investigation

    Cancer

    (2006)
  • J.E. Bower et al.

    Fatigue in breast cancer survivors: occurrence, correlates, and impact on quality of life

    Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology

    (2000)
  • R. Brook et al.

    Autonomic imbalance, hypertension, and cardiovascular risk

    American Journal of Hypertension

    (2000)
  • C.S. Cleeland et al.

    Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism? A cytokine-immunologic model of cancer symptoms

    Cancer

    (2003)
  • Cited by (122)

    • Fatigue after neurosurgery in patients with a brain tumor: The role of autonomic dysregulation and disturbed sleep

      2022, Journal of Psychosomatic Research
      Citation Excerpt :

      Brain tumors may result in excess fatigue as a result of an overall loss of homeostasis because they may directly interfere with neural networks and neuroendocrine processes involved in energy regulation [13,15–17]. Studies in breast cancer survivors indicate that measures of reduced parasympathetic nervous system activity are related to higher levels of fatigue [11,21]. In addition, sleep is essential for optimal energy regulation and may therefore play an independent role in cancer-related fatigue.

    • Physical and psychological impact of surgery on the operating surgeon

      2024, International Journal of Gynecological Cancer
    View all citing articles on Scopus
    View full text