Daily Stressors and Inflammation Among Family Dementia Caregivers Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Jean-Philippe Gouin, M.A. Graduate Program in Psychology The Ohio State University 2011 Dissertation Committee: Janice K. Kiecolt-Glaser, Advisor Charles F. Emery Michael W. Vasey Copyright by Jean-Philippe Gouin 2011 Abstract Acute laboratory stressors elicit elevations in circulating inflammatory biomarkers. Chronic stressors, such as family dementia caregiving, promote a state of chronic low-grade inflammation. The recurrent daily stressors associated with chronic stress may lead to repeated and sustained activation the inflammatory system. The goals of the present study were to evaluate whether greater exposure and reactivity to daily stressors fueled increased inflammation among family dementia caregivers, compared to noncaregiving controls. This cross-sectional study included 78 family dementia caregivers and 105 noncaregiving controls. A semi-structured interview, the Daily Inventory of Stressful Events, assessed the occurrence of daily stressors in the past 24 hours; self-report questionnaires evaluated mood, health, and health behaviors; a blood sample provided data on two inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6). Results showed that caregivers were more likely to experience multiple stressors in the past 24 hours than noncaregiving controls. The occurrence of multiple daily stressors was associated with greater CRP, and exposure to multiple daily stressors mediated the relationship between parental caregiving and increased CRP. Statin use moderated the relationship between daily stressors and IL-6 production; daily stressors were related to IL-6, but only among participants not using statins. Furthermore, among participants not using statins, the chronic stress of caregiving amplified IL-6, but not CRP, responses to daily stressors. The associations between daily stressors and ii inflammation remained significant even after adjusting for differences in health and health behaviors. These results indicate that the cumulative effect of daily stressors promotes sustained elevations in inflammation. Greater exposure to daily stressors among family dementia caregivers may promote the chronic low-grade inflammation and the enhanced health risk observed in this chronically-stressed population. iii To my family. iv Acknowledgments I would like to thank my advisor, Dr. Janice Kiecolt-Glaser, for her wonderful mentorship and for providing me with exciting research opportunities. I would also like to thank Dr. Charles Emery and Dr. Mike Vasey for their time and helpful feedback. A thank you also goes to Dr. Maurice Eastridge who served as the Graduate Faculty Representative on my dissertation defense. I would also like to thank my lab mate, Liisa Hantsoo, for her countless revisions of the manuscript and help throughout my graduate studies at OSU. A special thank you also goes to my friends Tammy Schuler, LaBarron Hill, Eleshia Morrison, Gizem Erdem, Molly Martinez, and Kristy Hall. They were always there to incite me to work when it was time to work and to play when it was time to play. I would also like to thank Vance for bringing joy in everyday of my life. Finally, I also wish to thank my family for their constant support. I would also like to thank the Fonds de la Recherche en Santé du Québec for its financial support throughout my doctoral studies at the Ohio State University and the NIH for its funding of the parent study (Grant # AG025732). v Vita October 21st, 1981…………………………………………….Born, Québec City, Canada 2004.................................................................B.A. Psychology, Laval University, Canada 2006 ………………………...M.Ps. Clinical Psychology, University of Montréal, Canada 2009………………………………..M.A. Clinical Psychology, The Ohio State University Publications 1. Fagundes, C.P., Murray, D., Hwang, B.S., Gouin, J.P., Thayer, J.F., Sollers, J.J., Shapiro, C., Malarkey, W., & Kiecolt-Glaser, J.K. Sympathetic and Parasympathetic Activity in Cancer-Related Fatigue: More Evidence for a Physiological Substrate in Cancer Survivors. (In Press). Psychoneuroendocrinology. 2. Gouin, JP. Chronic Stress and Immune Dysregulation. (In Press). American Journal of Lifestyle Medicine. 3. Kiecolt-Glaser, JK, Gouin, JP, Glaser, R, Malarkey, WB, Pang, N. (2011). Childhood Adversity Heightens the Impact of Later-Life Caregiving Stress on Telomere Length and Inflammation. Psychosomatic Medicine, 73(1), 16-22. 4. Gouin, J.P., & Kiecolt-Glaser, J.K. (2011). The Impact of Psychological Stress on Wound Healing: Methods and Mechanisms. Immunology and Allergy Clinics of North America,31(1), 81-93. 5. Gouin, J.P., Connors, J., Kiecolt-Glaser, J.K., Glaser, R. Malarkey, W.B., Atkinson, C., Beversdorf, D., & Quan, N. (2010). Altered Expression of Circadian Rhythm Genes Among Individuals With a History of Depression. Journal of Affective Disorders. 126 (1-2):161-166. 6. Gouin JP, Carter CS, Pournajafi-Nazarloo H, Glaser R, Malarkey W, Loving T, Stowell J, & Kiecolt-Glaser J. (In Press). Marital Behavior, Oxytocin, Vasopressin, and Wound Healing. Psychoneuroendocrinology. vi 7. Kiecolt-Glaser JK, Gouin, J.P., Hantsoo, L.V. (In Press). Close Relationships and Inflammation. Neurobehavioral Review. 8. Gouin JP, Hantsoo L, Kiecolt-Glaser JK. (2010). Stress, Negative Emotions, and Inflammation. Handbook of Social Neurosciences. Edited by J.T. Caccioppo & J. Decety. John Wiley and Sons. 9. Gouin JP, Glaser R, Loving TJ, Malarkey WB, Stowell J, Houts C, & Kiecolt- Glaser JK. (2009). Attachment avoidance predicts inflammatory responses to marital conflict. Brain, Behavior, and Immunity, 23, 898-904. 10. Gouin JP, Hantsoo L, & Kiecolt-Glaser JK. (2008). Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation, 15: 251- 259. 11. Gouin JP, Kiecolt-Glaser JK, Malarkey WB, Glaser R. (2008).The influence of anger expression on wound healing. Brain Behavior and Immunity, 22: 699-708. 12. Christian, LM, Deichert, NT, Gouin, JP, Graham, JE, Kiecolt-Glaser, JK. (2008). "Psychological influences on neuroendocrine and immune outcomes." In Handbook of Neuroscience for the Behavioral Sciences, Edited by J.T. Cacioppo & G.G. Berntson. TBD: John Wiley and Sons. 13. Achille, MA, Rosberger, Z, Robitaille, R, Lebel, S, Gouin, JP, Bultz, BD., & Chan PTK. (2006). Facilitators and obstacles to sperm banking in young men receiving gonadotoxic chemotherapy for cancer : the perspective of survivors and health care professionals. Human Reproduction, 21: 3206-3216. Fields of Study Major Field: Psychology Concentrations: Clinical Psychology Health Psychology vii Table of Contents Abstract ............................................................................................................................... ii Dedication .......................................................................................................................... iv Acknowledgments............................................................................................................... v Vita ..................................................................................................................................... vi List of Tables ..................................................................................................................... ix List of Figures .................................................................................................................... xi Chapter 1: Introduction ....................................................................................................... 1 Chapter 2: Method .......................................................................................................... 31 Chapter 3: Results ............................................................................................................. 45 Chapter 4: Discussion ....................................................................................................... 71 References ......................................................................................................................... 97 Appendix A: Tables ........................................................................................................ 133 Appendix B: Figures ....................................................................................................... 158 Appendix C: Semi-structured interviews ........................................................................ 178 Appendix C: Self-reported questionnaires ...................................................................... 185 viii List of Tables Table 1. Sociodemographic characteristics of family dementia caregivers and noncaregiving controls. ...................................................................................... ……… 131 Table 2. Self-reported health and medication use among caregivers and controls……. 132 Table 3. Caregiving status and inflammation…………………………………………. 133 Table 4. Psychosocial characteristics of family dementia caregivers and noncaregiving controls………………………………………………………………… 134 Table 5. Health behavior practices among caregivers and controls…………………… 135 Table 6. Daily stressors and inflammation……………………………………………..136 Table 7. Daily stressors, caregiving status, and inflammation……………….……..… 137 Table 8. Caregiving status by daily stress interaction and inflammation………...…… 138 Table