Grant Number:	1R01CA131029-01 Interpret this number
Primary Investigator:	Kiecolt-Glaser, Janice
Organization:	Ohio State University
Project Title:	Fatigue, Depression, and Inflammation in Cancer Survivors: a Prospective Study
Fiscal Year:	2008

DESCRIPTION (provided by applicant): Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long-term survivors. Persistent fatigue in survivors may be related in part to overactivation of the inflammatory network; the immune activation that is secondary to the tissue destruction and associated inflammation from many cancer therapies may leave patients vulnerable to the behavioral consequences of proinflammatory cytokines, including fatigue. What is more, a cancer diagnosis and cancer treatments can be quite stressful, and stress and depression can directly enhance the production of proinflammatory cytokines. Fatigue has been well-studied in breast cancer survivors, but far less is known about fatigue in other cancer survivor populations. Furthermore, although several lines of evidence suggest that inflammation plays a significant role in cancer-related fatigue, the data are limited, and longitudinal data in survivors are almost nonexistent. Moreover, the extent to which the incidence and prevalence of fatigue among cancer survivors differs from comparable adults without a cancer history remains an important question; similarly, whether there are differences in inflammation between cancer survivors and adults without a cancer history is unknown. This project provides the opportunity to examine mechanistic connections among fatigue, depression, NF-B activation, health behaviors, and proinflammatory cytokines both cross-sectionally and longitudinally, with initial data on each of these key dimensions collected before cancer treatment, as well as 6 months, 18 months, and 30 months after completion of primary treatment. Subjects will be stage I-IIIA breast cancer survivors, stage I- IIIC colon cancer survivors, and men and women who had a benign diagnosis following an initial abnormal test for breast or colon cancer. The proposed project would provide the first prospective study of inflammation, depression, and fatigue from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group. Specific Aims: (1) To assess the association between inflammation and fatigue cross-sectionally at each of the time points, as well as the extent to which higher levels of inflammatory markers at baseline predict subsequent fatigue; to evaluate these relationships in breast and colon cancer patients, as well as noncancer controls, and to compare the magnitude of both cross-sectional and longitudinal associations across the three groups. (2) To evaluate relationships between past or current syndromal depression and/or depressive symptoms with inflammatory markers, NF-B activation, and fatigue, as well as their association with subsequent inflammation and fatigue. (3) To appraise the relative impact of health-related behaviors (sleep, pain, physical activity, n-6:n-3 dietary fatty acids, central adiposity, and chronic health conditions) as correlates and predictors of syndromal depression and depressive symptoms, inflammatory markers, and fatigue. Fatigue is the most common post-treatment problem among cancer survivors, affecting a third or more of long- term survivors. Several lines of evidence suggest that immune system activation plays a significant role in cancer-related fatigue; however, the data are limited and longitudinal data as well as data comparing survivors to noncancer controls are almost nonexistent. The proposed project would provide the first prospective study of inflammation, depression, fatigue, and health-related behaviors from pretreatment through survivorship in two groups of cancer survivors, as well as a noncancer comparison group.




Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship.
Authors: Madison A.A. , Andridge R. , Kantaras A.H. , Renna M.E. , Bennett J.M. , Alfano C.M. , Povoski S.P. , Agnese D.M. , Lustberg M. , Wesolowski R. , et al. .
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EPub date: 2023-09-04 00:00:00.0.
PMID: 37686689
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Depression and anxiety in colorectal cancer patients: Ties to pain, fatigue, and inflammation.
Authors: Renna M.E. , Shrout M.R. , Madison A.A. , Alfano C.M. , Povoski S.P. , Lipari A.M. , Carson W.E. , Malarkey W.B. , Kiecolt-Glaser J.K. .
Source: Psycho-oncology, 2022-06-25 00:00:00.0; , .
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PMID: 35751505
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The gut connection: Intestinal permeability as a pathway from breast cancer survivors' relationship satisfaction to inflammation across treatment.
Authors: Shrout M.R. , Madison A.A. , Renna M.E. , Alfano C.M. , Povoski S.P. , Lipari A.M. , Agnese D.M. , Carson W.E. , Malarkey W.B. , Bailey M.T. , et al. .
Source: Brain, Behavior, And Immunity, 2022 Feb; 100, p. 145-154.
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Frequent Interpersonal Stress and Inflammatory Reactivity Predict Depressive-Symptom Increases: Two Tests of the Social-Signal-Transduction Theory of Depression.
Authors: Madison A.A. , Andridge R. , Shrout M.R. , Renna M.E. , Bennett J.M. , Jaremka L.M. , Fagundes C.P. , Belury M.A. , Malarkey W.B. , Kiecolt-Glaser J.K. .
Source: Psychological Science, 2022 01; 33(1), p. 152-164.
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Distress Trajectories in Black and White Breast Cancer Survivors: From Diagnosis to Survivorship.
Authors: Madison A.A. , Peng J. , Shrout M.R. , Renna M.E. , Alfano C.M. , Povoski S.P. , Lipari A.M. , Agnese D.M. , Carson W.E. , Malarkey W.B. , et al. .
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Fluctuations in depression and anxiety predict dysregulated leptin among obese breast cancer survivors.
Authors: Renna M.E. , Shrout M.R. , Madison A.A. , Jaremka L.M. , Alfano C.M. , Povoski S.P. , Agnese D.M. , Carson W.E. , Kiecolt-Glaser J.K. .
Source: Journal Of Cancer Survivorship : Research And Practice, 2021-01-06 00:00:00.0; , .
EPub date: 2021-01-06 00:00:00.0.
PMID: 33409856
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Childhood abuse histories predict steeper inflammatory trajectories across time.
Authors: Renna M.E. , Peng J. , Shrout M.R. , Madison A.A. , Andridge R. , Alfano C.M. , Povoski S.P. , Lipari A.M. , Malarkey W.B. , Kiecolt-Glaser J.K. .
Source: Brain, Behavior, And Immunity, 2021 Jan; 91, p. 541-545.
EPub date: 2020-11-07 00:00:00.0.
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Endotoxemia coupled with heightened inflammation predicts future depressive symptoms.
Authors: Madison A.A. , Andridge R. , Padin A.C. , Wilson S. , Bailey M.T. , Alfano C.M. , Povoski S.P. , Lipari A.M. , Agnese D.M. , Carson W.E. , et al. .
Source: Psychoneuroendocrinology, 2020 Dec; 122, p. 104864.
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Within-person changes in cancer-related distress predict breast cancer survivors' inflammation across treatment.
Authors: Renna M.E. , Shrout M.R. , Madison A.A. , Alfano C.M. , Povoski S.P. , Lipari A.M. , Agnese D.M. , Carson W.E. , Kiecolt-Glaser J.K. .
Source: Psychoneuroendocrinology, 2020 Nov; 121, p. 104866.
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Stress Reactivity: What Pushes Us Higher, Faster, and Longer - and Why It Matters.
Authors: Kiecolt-Glaser J.K. , Renna M.E. , Shrout M.R. , Madison A.A. .
Source: Current Directions In Psychological Science, 2020-10-01 00:00:00.0; 29(5), p. 492-498.
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Relationship satisfaction predicts lower stress and inflammation in breast cancer survivors: A longitudinal study of within-person and between-person effects.
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Source: Psychoneuroendocrinology, 2020 Aug; 118, p. 104708.
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Cognitive problems of breast cancer survivors on proton pump inhibitors.
Authors: Madison A.A. , Woody A. , Bailey B. , Lustberg M.B. , Ramaswamy B. , Wesolowski R. , Williams N. , Reinbolt R. , VanDeusen J.B. , Sardesai S. , et al. .
Source: Journal Of Cancer Survivorship : Research And Practice, 2020 Apr; 14(2), p. 226-234.
EPub date: 2020-01-13 00:00:00.0.
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Inflammatory Cytokines and Comorbidity Development in Breast Cancer Survivors Versus Noncancer Controls: Evidence for Accelerated Aging?
Authors: Alfano C.M. , Peng J. , Andridge R.R. , Lindgren M.E. , Povoski S.P. , Lipari A.M. , Agnese D.M. , Farrar W.B. , Yee L.D. , Carson W.E. , et al. .
Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2017-01-10 00:00:00.0; 35(2), p. 149-156.
EPub date: 2016-11-28 00:00:00.0.
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Daily stressors, past depression, and metabolic responses to high-fat meals: a novel path to obesity.
Authors: Kiecolt-Glaser J.K. , Habash D.L. , Fagundes C.P. , Andridge R. , Peng J. , Malarkey W.B. , Belury M.A. .
Source: Biological Psychiatry, 2015-04-01 00:00:00.0; 77(7), p. 653-60.
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Cognitive problems among breast cancer survivors: loneliness enhances risk.
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Source: Psycho-oncology, 2014 Dec; 23(12), p. 1356-64.
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Omega-3 fatty acids and stress-induced immune dysregulation: implications for wound healing.
Authors: Kiecolt-Glaser J.K. , Glaser R. , Christian L.M. .
Source: Military Medicine, 2014 Nov; 179(11 Suppl), p. 129-33.
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Attachment anxiety is related to Epstein-Barr virus latency.
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Source: Brain, Behavior, And Immunity, 2014 Oct; 41, p. 232-8.
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Source: Health Psychology : Official Journal Of The Division Of Health Psychology, American Psychological Association, 2014 Sep; 33(9), p. 948-57.
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Attachment style and respiratory sinus arrhythmia predict post-treatment quality of life in breast cancer survivors.
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Yoga's impact on inflammation, mood, and fatigue in breast cancer survivors: a randomized controlled trial.
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Telomere length: a marker of disease susceptibility?
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Beta-blockers may reduce intrusive thoughts in newly diagnosed cancer patients.
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Depressive symptoms enhance stress-induced inflammatory responses.
Authors: Fagundes C.P. , Glaser R. , Hwang B.S. , Malarkey W.B. , Kiecolt-Glaser J.K. .
Source: Brain, Behavior, And Immunity, 2013 Jul; 31, p. 172-6.
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Loneliness promotes inflammation during acute stress.
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Source: Psychological Science, 2013-07-01 00:00:00.0; 24(7), p. 1089-97.
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Synergistic relationships among stress, depression, and troubled relationships: insights from psychoneuroimmunology.
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Source: Depression And Anxiety, 2013 Apr; 30(4), p. 288-96.
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Childhood adversity and herpesvirus latency in breast cancer survivors.
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Source: Health Psychology : Official Journal Of The Division Of Health Psychology, American Psychological Association, 2013 Mar; 32(3), p. 337-44.
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Long lasting effects of smoking: breast cancer survivors' inflammatory responses to acute stress differ by smoking history.
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Source: Psychoneuroendocrinology, 2013 Feb; 38(2), p. 179-87.
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Stressful early life experiences and immune dysregulation across the lifespan.
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Authors: Gouin J.P. , Kiecolt-Glaser J.K. .
Source: Critical Care Nursing Clinics Of North America, 2012 Jun; 24(2), p. 201-13.
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Fatigue, inflammation, and ¿-3 and ¿-6 fatty acid intake among breast cancer survivors.
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Source: Journal Of Clinical Oncology : Official Journal Of The American Society Of Clinical Oncology, 2012-04-20 00:00:00.0; 30(12), p. 1280-7.
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Fatigue and herpesvirus latency in women newly diagnosed with breast cancer.
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Social support and socioeconomic status interact to predict Epstein-Barr virus latency in women awaiting diagnosis or newly diagnosed with breast cancer.
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Relationships and Inflammation across the Lifespan: Social Developmental Pathways to Disease.
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Sympathetic and parasympathetic activity in cancer-related fatigue: more evidence for a physiological substrate in cancer survivors.
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PMID: 21094925
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Close relationships, inflammation, and health.
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Psychological stress, telomeres, and telomerase.
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Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
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Psychoneuroimmunology: Psychology's Gateway to the Biomedical Future.
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Source: Perspectives On Psychological Science : A Journal Of The Association For Psychological Science, 2009 Jul; 4(4), p. 367-9.
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Arm/hand swelling and perceived functioning among breast cancer survivors 12 years post-diagnosis: CALGB 79804.
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