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Brain Imaging and Behavior

, Volume 7, Issue 4, pp 511–523 | Cite as

The association between pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints following adjuvant chemotherapy for breast cancer

  • K. L. Pomykala
  • P. A. Ganz
  • J. E. Bower
  • L. Kwan
  • S. A. Castellon
  • S. Mallam
  • I. Cheng
  • R. Ahn
  • E. C. Breen
  • M. R. Irwin
  • D. H. S. SilvermanEmail author
SI: Neuroimaging Studies of Cancer and Cancer Treatment

Abstract

To examine relationships following adjuvant chemotherapy between circulating pro-inflammatory cytokines, regional cerebral metabolism, and cognitive complaints in early stage breast cancer patients. 33 breast cancer patients who had completed initial treatment (surgery, ± radiation, 23 chemotherapy, 10 no chemotherapy) obtained resting (18)F-FDG PET/CT brain imaging at baseline and 1 year later. Pro-inflammatory cytokine markers (IL-1ra, sTNF-RII, CRP, and IL-6) and cognitive complaints were also assessed at both time points. At baseline, consistent correlations were seen between the left medial frontal and right inferior lateral anterior temporal cortices and inflammatory markers within the chemotherapy group, and not in the no chemotherapy group. After 1 year, correlations persisted in the medial frontal cortex and the temporal cortex, the latter shifting superiorly. Both of these regional correlations demonstrated the highest levels of significance when looking across the 1 year time frame (IL-1ra: peak voxel p < 0.0005; cluster size p < 0.0005, p = 0.001 after correction (medial prefrontal), p < 0.0005; cluster size p = 0.001, p = 0.029 corr. (anterior temporal), sTNF-RII: p < 0.0005; cluster size p = 0.001, p = 0.040 corr. (medial prefrontal)). Positive correlations were also seen within the chemotherapy group between baseline memory complaints and the medial frontal (p < 0.0005; cluster size p < 0.0005, p < 0.0005 corr.) and anterior temporal (p < 0.0005; cluster size p < 0.0005, p = 0.002 corr.) cortices at baseline and 1 year later. Metabolism in the medial prefrontal cortex and anterior temporal cortex was found to correlate with both memory complaints and cytokine marker levels in chemotherapy patients.

Keywords

Positron emission tomography Brain imaging Breast cancer Cognitive complaints Chemotherapy Pro-inflammatory cytokines 

Notes

Acknowledgments

Supported by grant NIH/NCI R01 CA 109650 and the Breast Cancer Research Foundation (PAG); R01-AG034588; R01-AG026364; R01 CA160245-01; R01-CA119159; R01 HL095799; R01 DA032922-01; P30-AG028748 to MRI; and UCLA CTSI UL1TR000124, the Cousins Center for Psychoneuroimmunology (MRI).

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. ACS (2011). Cancer Facts & Figures 2011. GA, USA.Google Scholar
  2. Ahles, T. A., & Saykin, A. J. (2007). Candidate mechanisms for chemotherapy-induced cognitive changes. [Research support, N.I.H., extramural review]. Nature Reviews. Cancer, 7(3), 192–201. doi: 10.1038/nrc2073.PubMedCentralPubMedCrossRefGoogle Scholar
  3. Ahles, T. A., Saykin, A. J., Furstenberg, C. T., Cole, B., Mott, L. A., Skalla, K., et al. (2002). Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. [Comparative Study Research Support, U.S. Gov’t, P.H.S.]. Journal of Clinical Oncology, 20(2), 485–493.PubMedCrossRefGoogle Scholar
  4. Ahles, T. A., Saykin, A. J., McDonald, B. C., Li, Y., Furstenberg, C. T., Hanscom, B. S., et al. (2010). Longitudinal assessment of cognitive changes associated with adjuvant treatment for breast cancer: impact of age and cognitive reserve. [Clinical Trial Research Support, N.I.H., extramural]. Journal of Clinical Oncology, 28(29), 4434–4440. doi: 10.1200/JCO.2009.27.0827.PubMedCrossRefGoogle Scholar
  5. Alexander, S., Minton, O., Andrews, P., & Stone, P. (2009). A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome. [Research Support, Non-U.S. Gov’t]. European Journal of Cancer, 45(3), 384–392. doi: 10.1016/j.ejca.2008.09.010.PubMedCentralPubMedCrossRefGoogle Scholar
  6. Argyriou, A., Assimakopoulous, K., Iconomou, G., Giannakopoulou, F., & Kalofonos, H. (2011). Either called “Chemobrain” or “Chemofog” the long-term chemotherapy-induced cognitive decline in cancer survivors is real. Journal of Pain and Symptom Management, 41(1), 126–139.CrossRefGoogle Scholar
  7. Barber, R. (2011). Inflammatory signaling in Alzheimer disease and depression. [Review]. Cleveland Clinic Journal of Medicine, 78(Suppl 1), S47–S49. doi: 10.3949/ccjm.78.s1.08.PubMedCrossRefGoogle Scholar
  8. Biglia, N., Bounous, V. E., Malabaila, A., Palmisano, D., Torta, D. M., D’Alonzo, M., et al. (2012). Objective and self-reported cognitive dysfunction in breast cancer women treated with chemotherapy: a prospective study. European Journal of Cancer Care (England), 21(4), 485–492. doi: 10.1111/j.1365-2354.2011.01320.x.CrossRefGoogle Scholar
  9. Bower, J. E., Ganz, P. A., Aziz, N., & Fahey, J. L. (2002). Fatigue and proinflammatory cytokine activity in breast cancer survivors. Psychosomatic Medicine, 64(4), 604–611.PubMedGoogle Scholar
  10. Bower, J. E., Ganz, P. A., Aziz, N., Olmstead, R., Irwin, M. R., & Cole, S. W. (2007). Inflammatory responses to psychological stress in fatigued breast cancer survivors: relationship to glucocorticoids. [Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Brain, Behavior, and Immunity, 21(3), 251–258. doi: 10.1016/j.bbi.2006.08.001.PubMedCrossRefGoogle Scholar
  11. Bower, J. E., Ganz, P. A., Tao, M. L., Hu, W., Belin, T. R., Sepah, S., et al. (2009). Inflammatory biomarkers and fatigue during radiation therapy for breast and prostate cancer. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Clinical Cancer Research, 15(17), 5534–5540. doi: 10.1158/1078-0432.CCR-08-2584.PubMedCentralPubMedCrossRefGoogle Scholar
  12. Bower, J. E., Ganz, P. A., Irwin, M. R., Kwan, L., Breen, E. C., & Cole, S. W. (2011). Inflammation and behavioral symptoms after breast cancer treatment: do fatigue, depression, and sleep disturbance share a common underlying mechanism? [Research Support, N.I.H., Extramural]. Journal of Clinical Oncology, 29(26), 3517–3522. doi: 10.1200/JCO.2011.36.1154.PubMedCrossRefGoogle Scholar
  13. Bower, J. E., Ganz, P. A., Irwin, M. R., Castellon, S., Arevalo, J., & Cole, S. W. (2013). Cytokine genetic variations and fatigue among patients with breast cancer. Journal of Clinical Oncology. doi: 10.1200/JCO.2012.46.2143.PubMedGoogle Scholar
  14. Brezden, C. B., Phillips, K. A., Abdolell, M., Bunston, T., & Tannock, I. F. (2000). Cognitive function in breast cancer patients receiving adjuvant chemotherapy. [Research Support, Non-U.S. Gov’t]. Journal of Clinical Oncology, 18(14), 2695–2701.PubMedGoogle Scholar
  15. Castellon, S. A., Ganz, P. A., Bower, J. E., Petersen, L., Abraham, L., & Greendale, G. A. (2004). Neurocognitive performance in breast cancer survivors exposed to adjuvant chemotherapy and tamoxifen. [Clinical Trial Comparative Study Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.]. Journal of Clinical and Experimental Neuropsychology, 26(7), 955–969. doi: 10.1080/13803390490510905.PubMedCrossRefGoogle Scholar
  16. Chelune, G., Heaton, R., & Lehman, R. (1986). Neuropsychological and personality correlates of patients’ complaints of disability. R.E.T. Gerald Goldstein. Advances in Clinical Neuropsychology, 3, 95–126.CrossRefGoogle Scholar
  17. Collado-Hidalgo, A., Bower, J. E., Ganz, P. A., Cole, S. W., & Irwin, M. R. (2006). Inflammatory biomarkers for persistent fatigue in breast cancer survivors. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Clinical Cancer Research, 12(9), 2759–2766. doi: 10.1158/1078-0432.CCR-05-2398.PubMedCrossRefGoogle Scholar
  18. Collins, B., Mackenzie, J., Stewart, A., Bielajew, C., & Verma, S. (2009). Cognitive effects of chemotherapy in post-menopausal breast cancer patients 1 year after treatment. [Research Support, Non-U.S. Gov’t]. Psycho-Oncology, 18(2), 134–143. doi: 10.1002/pon.1379.PubMedCrossRefGoogle Scholar
  19. Correa, D. D., & Ahles, T. A. (2008). Neurocognitive changes in cancer survivors. [Review]. Cancer Journal, 14(6), 396–400. doi: 10.1097/PPO.0b013e31818d8769.CrossRefGoogle Scholar
  20. Deprez, S., Amant, F., Yigit, R., Porke, K., Verhoeven, J., Van den Stock, J., et al. (2011). Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. [Research Support, Non-U.S. Gov’t]. Human Brain Mapping, 32(3), 480–493. doi: 10.1002/hbm.21033.PubMedCrossRefGoogle Scholar
  21. Deprez, S., Amant, F., Smeets, A., Peeters, R., Leemans, A., Van Hecke, W., et al. (2012). Longitudinal assessment of chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning. [Research Support, Non-U.S. Gov’t]. Journal of Clinical Oncology, 30(3), 274–281. doi: 10.1200/JCO.2011.36.8571.PubMedCrossRefGoogle Scholar
  22. Dietrich, J., Monje, M., Wefel, J., & Meyers, C. (2008). Clinical patterns and biological correlates of cognitive dysfunction associated with cancer therapy. [Research Support, Non-U.S. Gov’t Review]. The Oncologist, 13(12), 1285–1295. doi: 10.1634/theoncologist.2008-0130.PubMedCrossRefGoogle Scholar
  23. Eisenberger, N. I., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R. (2009). An fMRI study of cytokine-induced depressed mood and social pain: the role of sex differences. [Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. NeuroImage, 47(3), 881–890. doi: 10.1016/j.neuroimage.2009.04.040.PubMedCentralPubMedCrossRefGoogle Scholar
  24. Ferguson, R. J., McDonald, B. C., Saykin, A. J., & Ahles, T. A. (2007). Brain structure and function differences in monozygotic twins: possible effects of breast cancer chemotherapy. [Case Reports Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Twin Study]. Journal of Clinical Oncology, 25(25), 3866–3870. doi: 10.1200/JCO.2007.10.8639.PubMedCentralPubMedCrossRefGoogle Scholar
  25. Friston, K., Ashburner, J., Kiebel, S., Nichols, T., & Penny, W. (2007). Statistical parametric mapping: The analysis of functional brain images. Burlington: Academic.Google Scholar
  26. Fritz-French, C., & Tyor, W. (2012). Interferon-alpha (IFNalpha) neurotoxicity. [Review]. Cytokine & Growth Factor Reviews, 23(1–2), 7–14. doi: 10.1016/j.cytogfr.2012.01.001.CrossRefGoogle Scholar
  27. Ganz, P. A., Bower, J. E., Kwan, L., Castellon, S. A., Silverman, D. H., Geist, C., et al. (2012). Does tumor necrosis factor-alpha (TNF-alpha) play a role in post-chemotherapy cerebral dysfunction? Brain, Behavior, and Immunity. doi: 10.1016/j.bbi.2012.07.015.Google Scholar
  28. Ganz, P., Kwan, L., Castellon, S. A., Oppenheim, A., Bower, J. E., Silverman, D., et al. (2013). Cognitive complaints after breast cancer treatments: Is there a relationship to neuropsychological test performance? Journal of the National Cancer Institute.Google Scholar
  29. Hannestad, J., Subramanyam, K., Dellagioia, N., Planeta-Wilson, B., Weinzimmer, D., Pittman, B., et al. (2012). Glucose metabolism in the insula and cingulate is affected by systemic inflammation in humans. [Randomized Controlled Trial Research Support, N.I.H., Extramural]. Journal of Nuclear Medicine, 53(4), 601–607. doi: 10.2967/jnumed.111.097014.PubMedCentralPubMedCrossRefGoogle Scholar
  30. Jansen, C. E., Cooper, B. A., Dodd, M. J., & Miaskowski, C. A. (2011). A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Supportive Care in Cancer, 19(10), 1647–1656. doi: 10.1007/s00520-010-0997-4.PubMedCrossRefGoogle Scholar
  31. Kesler, S., Janelsins, M., Koovakkattu, D., Palesh, O., Mustian, K., Morrow, G., et al. (2012). Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain, Behavior, and Immunity. doi: 10.1016/j.bbi.2012.05.017.PubMedCentralPubMedGoogle Scholar
  32. Kuo, H. K., Yen, C. J., Chang, C. H., Kuo, C. K., Chen, J. H., & Sorond, F. (2005). Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. [Meta-Analysis Review]. Lancet Neurology, 4(6), 371–380. doi: 10.1016/S1474-4422(05)70099-5.PubMedCrossRefGoogle Scholar
  33. Lee, B. N., Dantzer, R., Langley, K. E., Bennett, G. J., Dougherty, P. M., Dunn, A. J., et al. (2004). A cytokine-based neuroimmunologic mechanism of cancer-related symptoms. [Research Support, Non-U.S. Gov’t Review]. Neuroimmunomodulation, 11(5), 279–292. doi: 10.1159/000079408.PubMedCrossRefGoogle Scholar
  34. Marsland, A. L., Petersen, K. L., Sathanoori, R., Muldoon, M. F., Neumann, S. A., Ryan, C., et al. (2006). Interleukin-6 covaries inversely with cognitive performance among middle-aged community volunteers. [Research Support, N.I.H., Extramural]. Psychosomatic Medicine, 68(6), 895–903. doi: 10.1097/01.psy.0000238451.22174.92.PubMedCrossRefGoogle Scholar
  35. McDonald, B. C., Conroy, S. K., Ahles, T. A., West, J. D., & Saykin, A. J. (2010). Gray matter reduction associated with systemic chemotherapy for breast cancer: a prospective MRI study. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Breast Cancer Research and Treatment, 123(3), 819–828. doi: 10.1007/s10549-010-1088-4.PubMedCentralPubMedCrossRefGoogle Scholar
  36. McDonald, B. C., Conroy, S. K., Ahles, T. A., West, J. D., & Saykin, A. J. (2012). Alterations in brain activation during working memory processing associated with breast cancer and treatment: a prospective functional magnetic resonance imaging study. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Journal of Clinical Oncology, 30(20), 2500–2508. doi: 10.1200/JCO.2011.38.5674.PubMedCrossRefGoogle Scholar
  37. Myers, J. S. (2010). The possible role of cytokines in chemotherapy-induced cognitive deficits. Advances in Experimental Medicine and Biology, 678, 119–123.PubMedCrossRefGoogle Scholar
  38. O’Bryant, S. E., Xiao, G., Barber, R., Reisch, J., Doody, R., Fairchild, T., et al. (2010). A serum protein-based algorithm for the detection of Alzheimer disease. [Research Support, N.I.H., Extramural]. Archives of Neurology, 67(9), 1077–1081. doi: 10.1001/archneurol.2010.215.PubMedCentralPubMedCrossRefGoogle Scholar
  39. Orre, I. J., Murison, R., Dahl, A. A., Ueland, T., Aukrust, P., & Fossa, S. D. (2009). Levels of circulating interleukin-1 receptor antagonist and C-reactive protein in long-term survivors of testicular cancer with chronic cancer-related fatigue. [Research Support, Non-U.S. Gov’t]. Brain, Behavior, and Immunity, 23(6), 868–874. doi: 10.1016/j.bbi.2009.04.003.PubMedCrossRefGoogle Scholar
  40. Pusztai, L., Mendoza, T. R., Reuben, J. M., Martinez, M. M., Willey, J. S., Lara, J., et al. (2004). Changes in plasma levels of inflammatory cytokines in response to paclitaxel chemotherapy. [Clinical Trial Comparative Study Controlled Clinical Trial Research Support, Non-U.S. Gov’t]. Cytokine, 25(3), 94–102.PubMedCrossRefGoogle Scholar
  41. Rourke, S. B., Halman, M. H., & Bassel, C. (1999). Neuropsychiatric correlates of memory-metamemory dissociations in HIV-infection. [Comparative Study Research Support, Non-U.S. Gov’t]. Journal of Clinical and Experimental Neuropsychology, 21(6), 757–768. doi: 10.1076/jcen.21.6.757.852.PubMedCrossRefGoogle Scholar
  42. Schagen, S. B., van Dam, F. S., Muller, M. J., Boogerd, W., Lindeboom, J., & Bruning, P. F. (1999). Cognitive deficits after postoperative adjuvant chemotherapy for breast carcinoma. [Clinical Trial Controlled Clinical Trial Research Support, Non-U.S. Gov’t]. Cancer, 85(3), 640–650.PubMedCrossRefGoogle Scholar
  43. Silverman, D. H., Dy, C. J., Castellon, S. A., Lai, J., Pio, B. S., Abraham, L., et al. (2007). Altered frontocortical, cerebellar, and basal ganglia activity in adjuvant-treated breast cancer survivors 5–10 years after chemotherapy. [Research Support, Non-U.S. Gov’t]. Breast Cancer Research and Treatment, 103(3), 303–311. doi: 10.1007/s10549-006-9380-z.PubMedCrossRefGoogle Scholar
  44. Silverman, D. H., Geist, C. L., Kenna, H. A., Williams, K., Wroolie, T., Powers, B., et al. (2011). Differences in regional brain metabolism associated with specific formulations of hormone therapy in postmenopausal women at risk for AD. [Randomized Controlled Trial Research Support, N.I.H., Extramural]. Psychoneuroendocrinology, 36(4), 502–513. doi: 10.1016/j.psyneuen.2010.08.002.PubMedCentralPubMedCrossRefGoogle Scholar
  45. Talairach, J., & Tournoux, P. (1988). Co-planar stereotaxic atlas of the human brain (3-Dimensional proportional system: An approach to cerebral imaging). New York: Thieme.Google Scholar
  46. Tchen, N., Juffs, H. G., Downie, F. P., Yi, Q. L., Hu, H., Chemerynsky, I., et al. (2003). Cognitive function, fatigue, and menopausal symptoms in women receiving adjuvant chemotherapy for breast cancer. [Comparative Study Research Support, Non-U.S. Gov’t]. Journal of Clinical Oncology, 21(22), 4175–4183. doi: 10.1200/JCO.2003.01.119.PubMedCrossRefGoogle Scholar
  47. Teunissen, C. E., van Boxtel, M. P., Bosma, H., Bosmans, E., Delanghe, J., De Bruijn, C., et al. (2003). Inflammation markers in relation to cognition in a healthy aging population. Journal of Neuroimmunology, 134(1–2), 142–150.PubMedCrossRefGoogle Scholar
  48. Tilvis, R. S., Kahonen-Vare, M. H., Jolkkonen, J., Valvanne, J., Pitkala, K. H., & Strandberg, T. E. (2004). Predictors of cognitive decline and mortality of aged people over a 10-year period. [Research Support, Non-U.S. Gov’t]. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 59(3), 268–274.PubMedCrossRefGoogle Scholar
  49. Torres, M. A., Pace, T. W., Liu, T., Felger, J. C., Mister, D., Doho, G. H., et al. (2013). Predictors of depression in breast cancer patients treated with radiation: role of prior chemotherapy and nuclear factor kappa B. Cancer. doi: 10.1002/cncr.28003.Google Scholar
  50. van Dam, F. S., Schagen, S. B., Muller, M. J., Boogerd, W., vd Wall, E., Droogleever Fortuyn, M. E., et al. (1998). Impairment of cognitive function in women receiving adjuvant treatment for high-risk breast cancer: high-dose versus standard-dose chemotherapy. [Clinical Trial Randomized Controlled Trial]. Journal of the National Cancer Institute, 90(3), 210–218.PubMedCrossRefGoogle Scholar
  51. Wang, X. S., Shi, Q., Williams, L. A., Mao, L., Cleeland, C. S., Komaki, R. R., et al. (2010). Inflammatory cytokines are associated with the development of symptom burden in patients with NSCLC undergoing concurrent chemoradiation therapy. [Research Support, N.I.H., Extramural]. Brain, Behavior, and Immunity, 24(6), 968–974. doi: 10.1016/j.bbi.2010.03.009.PubMedCentralPubMedCrossRefGoogle Scholar
  52. Wang, X. S., Williams, L. A., Krishnan, S., Liao, Z., Liu, P., Mao, L., et al. (2012). Serum sTNF-R1, IL-6, and the development of fatigue in patients with gastrointestinal cancer undergoing chemoradiation therapy. [Research Support, N.I.H., Extramural]. Brain, Behavior, and Immunity, 26(5), 699–705. doi: 10.1016/j.bbi.2011.12.007.PubMedCentralPubMedCrossRefGoogle Scholar
  53. Wefel, J. S., & Schagen, S. B. (2012). Chemotherapy-related cognitive dysfunction. [Review]. Current Neurology and Neuroscience Reports, 12(3), 267–275. doi: 10.1007/s11910-012-0264-9.PubMedCrossRefGoogle Scholar
  54. Wefel, J. S., Kayl, A. E., & Meyers, C. A. (2004). Neuropsychological dysfunction associated with cancer and cancer therapies: a conceptual review of an emerging target. [Review]. British Journal of Cancer, 90(9), 1691–1696. doi: 10.1038/sj.bjc.6601772.PubMedCentralPubMedGoogle Scholar
  55. Wefel, J. S., Witgert, M. E., & Meyers, C. A. (2008). Neuropsychological sequelae of non-central nervous system cancer and cancer therapy. [Review]. Neuropsychology Review, 18(2), 121–131. doi: 10.1007/s11065-008-9058-x.PubMedCrossRefGoogle Scholar
  56. Wefel, J. S., Saleeba, A. K., Buzdar, A. U., & Meyers, C. A. (2010). Acute and late onset cognitive dysfunction associated with chemotherapy in women with breast cancer. [Clinical Trial, Phase III Randomized Controlled Trial]. Cancer, 116(14), 3348–3356. doi: 10.1002/cncr.25098.PubMedCrossRefGoogle Scholar
  57. WHO (2012). Cancer fact sheet No. 297. http://www.who.int/mediacentre/factsheets/fs297/en/.

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • K. L. Pomykala
    • 1
  • P. A. Ganz
    • 2
    • 3
    • 4
  • J. E. Bower
    • 4
    • 5
    • 6
  • L. Kwan
    • 4
  • S. A. Castellon
    • 7
    • 8
  • S. Mallam
    • 1
  • I. Cheng
    • 1
  • R. Ahn
    • 1
  • E. C. Breen
    • 6
    • 8
  • M. R. Irwin
    • 5
    • 6
    • 8
  • D. H. S. Silverman
    • 1
    Email author
  1. 1.Department of Molecular and Medical PharmacologyDavid Geffen School of Medicine at UCLALos AngelesUSA
  2. 2.Department of Health Policy & ManagementUCLA Fielding School of Public HealthLos AngelesUSA
  3. 3.Department of MedicineDavid Geffen School of Medicine at UCLALos AngelesUSA
  4. 4.Division of Cancer Prevention and Control ResearchJonsson Comprehensive Cancer Center at UCLALos AngelesUSA
  5. 5.Department of PsychologyUniversity of CaliforniaLos AngelesUSA
  6. 6.Cousins Center of PsychoneuroimmunologySemel Institute for NeuroscienceLos AngelesUSA
  7. 7.VA Greater Los Angeles Health Care SystemLos AngelesUSA
  8. 8.Department of Psychiatry and Biobehavioral SciencesDavid Geffen School of Medicine at UCLALos AngelesUSA

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