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9b - From inflammation to sickness and depression: the cytokine connection

from Section 2 - Cancer Symptom Mechanisms and Models: Clinical and Basic Science

Published online by Cambridge University Press:  05 August 2011

By
Robert Dantzer  and
Keith W. Kelley
Edited by
Charles S. Cleeland ,
Michael J. Fisch  and
Adrian J. Dunn
Robert Dantzer
Affiliation:
University of Illinois
Keith W. Kelley
Affiliation:
University of Illinois
Charles S. Cleeland
Affiliation:
University of Texas, M. D. Anderson Cancer Center
Michael J. Fisch
Affiliation:
University of Texas, M. D. Anderson Cancer Center
Adrian J. Dunn
Affiliation:
University of Hawaii, Manoa
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Summary

The possibility that inflammation plays a major role in the symptoms of sickness and depression experienced by cancer patients was initially proposed by a group of investigators led by Charles Cleeland, one of the editors of this book. The authors' reasoning was based on analogies. Laboratory animals injected with proinflammatory cytokines, or with cytokine inducers such as lipopolysaccharide, develop striking signs of sickness characterized by pain, wasting, cognitive impairment, anxiety, and fatigue. The same symptoms are observed in many patients with cancer and are exacerbated during inflammation-inducing cancer treatments, such as chemotherapy and radiotherapy. In addition, cancer patients subjected to long-term immunotherapy with interferon (IFN)-α and/or interleukin (IL)-2 for the treatment of metastatic kidney cancer or metastatic melanoma rapidly develop symptoms of sickness that can culminate in true depressive disorders. Since Cleeland's seminal paper was published, many studies have confirmed that nonspecific symptoms such as fatigue, even in long-term cancer survivors, are associated with inflammatory biomarkers and cannot be explained away solely as psychological difficulties related to coping with a diagnosis of cancer or living with the disease. A recent review paper confirmed the plausibility of the relationship between inflammation and the behavioral comorbidities experienced by patients with cancer and pointed to the pivotal role of neuroendocrine-immune mechanisms in this relationship.

The objective of this chapter is to discuss the neuroimmune mechanisms that are likely to be responsible for the development of symptoms of sickness and depression in patients with cancer.

Type
Chapter
Information
Cancer Symptom Science
Measurement, Mechanisms, and Management
 , pp. 95 - 109
Publisher: Cambridge University Press
Print publication year: 2010

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References

Cleeland, CS, Bennett, GJ, Dantzer, R, et al. Are the symptoms of cancer and cancer treatment due to a shared biologic mechanism?Cancer 97(11):2919–2925, 2003.CrossRefGoogle ScholarPubMed
Miller, AH, Ancoli-Israel, S, Bower, JE, Capuron, L, Irwin, MR. Neuroendocrine-immune mechanisms of behavioral comorbidities in patients with cancer. J Clin Oncol 26(6):971–982, 2008.CrossRefGoogle Scholar
Miller, NE, Gottesman, KS, Holmes, JE. Effects of chemostimulation of brain and of bacterial endotoxins on eating and drinking. Science 136(3513):327–328, 1962.CrossRefGoogle ScholarPubMed
Smith, EM, Harbour-McMenamin, D, Blalock, JE. Lymphocyte production of endorphins and endorphin-mediated immunoregulatory activity. J Immunol 135(2 Suppl):779s–782s, 1985.Google ScholarPubMed
Besedovsky, HO, del Rey, AE, Sorkin, E. Immune-neuroendocrine interactions. J Immunol 135(2 Suppl):750s–754s, 1985.Google ScholarPubMed
Besedovsky, HO, del Rey, A. Physiology of psychoneuroimmunology: a personal view. Brain Behav Immun 21(1):34–44, 2007.CrossRefGoogle ScholarPubMed
Wan, W, Janz, L, Vriend, CY, Sorensen, CM, Greenberg, AH, Nance, DM. Differential induction of c-Fos immunoreactivity in hypothalamus and brain stem nuclei following central and peripheral administration of endotoxin. Brain Res Bull 32(6):581–587, 1993.CrossRefGoogle Scholar
Wan, W, Wetmore, L, Sorensen, CM, Greenberg, AH, Nance, DM. Neural and biochemical mediators of endotoxin and stress-induced c-fos expression in the rat brain. Brain Res Bull 34(1):7–14, 1994.CrossRefGoogle ScholarPubMed
Watkins, LR, Wiertelak, EP, Goehler, , et al. Neurocircuitry of illness-induced hyperalgesia. Brain Res 639(2):283–299, 1994.CrossRefGoogle ScholarPubMed
Bluthé, RM, Walter, V, Parnet, P, et al. Lipopolysaccharide induces sickness behaviour in rats by a vagal mediated mechanism. C R Acad Sci III 317(6):499–503, 1994.Google ScholarPubMed
Bluthé, RM, Michaud, B, Kelley, KW, Dantzer, R. Vagotomy attenuates behavioural effects of interleukin-1 injected peripherally but not centrally. Neuroreport 7(9):1485–1488, 1996.CrossRefGoogle Scholar
Bluthé, RM, Michaud, B, Kelley, KW, Dantzer, R. Vagotomy blocks behavioural effects of interleukin-1 injected via the intraperitoneal route but not via other systemic routes. Neuroreport 7(15–17):2823–2827, 1996.CrossRefGoogle Scholar
Layé, S, Bluthé, RM, Kent, S, et al. Subdiaphragmatic vagotomy blocks induction of IL-1 beta mRNA in mice brain in response to peripheral LPS. Am J Physiol 268(5 Pt 2):R1327–R1331, 1995.Google ScholarPubMed
Romeo, HE, Tio, DL, Rahman, SU, Chiappelli, F, Taylor, AN. The glossopharyngeal nerve as a novel pathway in immune-to-brain communication: relevance to neuroimmune surveillance of the oral cavity. J Neuroimmunol 115(1–2):91–100, 2001.CrossRefGoogle ScholarPubMed
Romeo, HE, Tio, DL, Taylor, AN. Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation. J Neuroimmunol 136(1–2):104–111, 2003.CrossRefGoogle ScholarPubMed
Luheshi, GN, Bluthé, RM, Rushforth, D, et al. Vagotomy attenuates the behavioural but not the pyrogenic effects of interleukin-1 in rats. Auton Neurosci 85(1–3):127–132, 2000.CrossRefGoogle Scholar
Marvel, FA, Chen, CC, Badr, N, Gaykema, RP, Goehler, . Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei. Brain Behav Immun 18(2):123–134, 2004.CrossRefGoogle ScholarPubMed
Saper, CB, Breder, CD. The neurologic basis of fever. N Engl J Med 330(26):1880–1886, 1994.Google ScholarPubMed
Dantzer, R, Kelley, KW. Twenty years of research on cytokine-induced sickness behavior. Brain Behav Immun 21(2):153–160, 2007.CrossRefGoogle ScholarPubMed
Konsman, JP, Parnet, P, Dantzer, R. Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25(3):154–159, 2002.CrossRefGoogle ScholarPubMed
Konsman, JP, Dantzer, R. How the immune and nervous systems interact during disease-associated anorexia. Nutrition 17(7–8):664–668, 2001.CrossRefGoogle ScholarPubMed
Konsman, JP, Vigues, S, Mackerlova, L, Bristow, A, Blomqvist, A. Rat brain vascular distribution of interleukin-1 type-1 receptor immunoreactivity: relationship to patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli. J Comp Neurol 472(1):113–129, 2004.CrossRefGoogle ScholarPubMed
Konsman, JP, Veeneman, J, Combe, C, Poole, S, Luheshi, GN, Dantzer, R. Central nervous action of interleukin-1 mediates activation of limbic structures and behavioural depression in response to peripheral administration of bacterial lipopolysaccharide. Eur J Neurosci 28(12):2499–2510, 2008.CrossRefGoogle ScholarPubMed
Blatteis, CM, Li, S, Li, Z, Feleder, C, Perlik, V. Cytokines, PGE2 and endotoxic fever: a re-assessment. Prostaglandins Other Lipid Mediat 76(1–4):1–18, 2005.CrossRefGoogle ScholarPubMed
Blatteis, CM. The onset of fever: new insights into its mechanism. Prog Brain Res 162:3–14, 2007.CrossRefGoogle ScholarPubMed
Dantzer, R, Konsman, JP, Bluthé, RM, Kelley, KW. Neural and humoral pathways of communication from the immune system to the brain: parallel or convergent?Auton Neurosci 85(1–3):60–65, 2000.CrossRefGoogle ScholarPubMed
Dunn, AJ, Swiergiel, AH. The role of cytokines in infection-related behavior. Ann N Y Acad Sci 840:577–585, 1998.CrossRefGoogle ScholarPubMed
Bluthé, RM, Layé, S, Michaud, B, Combe, C, Dantzer, R, Parnet, P. Role of interleukin-1beta and tumour necrosis factor-alpha in lipopolysaccharide-induced sickness behaviour: a study with interleukin-1 type I receptor-deficient mice. Eur J Neurosci 12(12):4447–4456, 2000.Google ScholarPubMed
Avitsur, R, Yirmiya, R. Cytokines inhibit sexual behavior in female rats: I. Synergistic effects of tumor necrosis factor alpha and interleukin-1. Brain Behav Immun 13(1):14–32, 1999.CrossRefGoogle ScholarPubMed
Yirmiya, R. Endotoxin produces a depressive-like episode in rats. Brain Res 711(1–2):163–174, 1996.CrossRefGoogle ScholarPubMed
Borowski, T, Kokkinidis, L, Merali, Z, Anisman, H. Lipopolysaccharide, central in vivo biogenic amine variations, and anhedonia. Neuroreport 9(17):3797–3802, 1998.CrossRefGoogle ScholarPubMed
Smith, RS. The macrophage theory of depression. Med Hypotheses 35(4):298–306, 1991.CrossRefGoogle Scholar
Maes, M. A review on the acute phase response in major depression. Rev Neurosci 4(4):407–416, 1993.CrossRefGoogle ScholarPubMed
Maes, M, Smith, R, Scharpé, S. The monocyte-T-lymphocyte hypothesis of major depression. Psychoneuroendocrinology 20(2):111–116, 1995.CrossRefGoogle ScholarPubMed
Maes, M. Major depression and activation of the inflammatory response system. Adv Exp Med Biol 461:25–46, 1999.CrossRefGoogle ScholarPubMed
Yirmiya, R, Weidenfeld, J, Pollak, Y, et al. Cytokines, “depression due to a general medical condition,” and antidepressant drugs. Adv Exp Med Biol 461:283–316, 1999.CrossRefGoogle Scholar
Dantzer, R, Wollman, E, Vitkovic, L, Yirmiya, R. Cytokines and depression: fortuitous or causative association?Mol Psychiatry 4(4):328–332, 1999.CrossRefGoogle ScholarPubMed
Dunn, AJ, Swiergiel, AH. Effects of interleukin-1 and endotoxin in the forced swim and tail suspension tests in mice. Pharmacol Biochem Behav 81(3):688–693, 2005.CrossRefGoogle ScholarPubMed
Simen, BB, Duman, CH, Simen, AA, Duman, RS. TNFalpha signaling in depression and anxiety: behavioral consequences of individual receptor targeting. Biol Psychiatry 59(9):775–785, 2006.CrossRefGoogle ScholarPubMed
Goshen, I, Kreisel, T, Ben-Menachem-Zidon, O, et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 13(7):717–728, 2008.CrossRefGoogle ScholarPubMed
Koo, JW, Duman, RS. IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci U S A 105(2):751–756, 2008.CrossRefGoogle ScholarPubMed
Capuron, L, Gumnick, JF, Musselman, DL, et al. Neurobehavioral effects of interferon-alpha in cancer patients: phenomenology and paroxetine responsiveness of symptom dimensions. Neuropsychopharmacology 26(5):643–652, 2002.CrossRefGoogle ScholarPubMed
Kent, S, Bluthé, RM, Dantzer, R, et al. Different receptor mechanisms mediate the pyrogenic and behavioral effects of interleukin 1. Proc Natl Acad Sci U S A 89(19):9117–9120, 1992.CrossRefGoogle ScholarPubMed
Hart, BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 12(2):123–137, 1988.CrossRefGoogle ScholarPubMed
Aubert, A, Goodall, G, Dantzer, R. Compared effects of cold ambient temperature and cytokines on macronutrient intake in rats. Physiol Behav 57(5):869–873, 1995.CrossRefGoogle ScholarPubMed
Aubert, A, Goodall, G, Dantzer, R, Gheusi, G. Differential effects of lipopolysaccharide on pup retrieving and nest building in lactating mice. Brain Behav Immun 11(2):107–118, 1997.CrossRefGoogle ScholarPubMed
Aubert, A, Dantzer, R. The taste of sickness: lipopolysaccharide-induced finickiness in rats. Physiol Behav 84(3):437–444, 2005.CrossRefGoogle ScholarPubMed
Werner, ER, Werner-Felmayer, G, Fuchs, D, Hausen, A, Reibnegger, G, Wachter, H. Parallel induction of tetrahydrobiopterin biosynthesis and indoleamine 2,3-dioxygenase activity in human cells and cell lines by interferon-gamma. Biochem J 262(3):861–866, 1989.CrossRefGoogle ScholarPubMed
Mellor, AL, Munn, DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4(10):762–774, 2004.CrossRefGoogle ScholarPubMed
Fuchs, D, Möller, AA, Reibnegger, G, Stöckle, E, Werner, ER, Wachter, H. Decreased serum tryptophan in patients with HIV-1 infection correlates with increased serum neopterin and with neurologic/psychiatric symptoms. J Acquir Immune Defic Syndr 3(9):873–876, 1990.Google ScholarPubMed
Widner, B, Sepp, N, Kowald, E, Kind, S, Schmuth, M, Fuchs, D. Degradation of tryptophan in patients with systemic lupus erythematosus. Adv Exp Med Biol 467:571–577, 1999.CrossRefGoogle ScholarPubMed
Huang, A, Fuchs, D, Widner, B, Glover, C, Henderson, DC, Allen-Mersh, TG. Serum tryptophan decrease correlates with immune activation and impaired quality of life in colorectal cancer. Br J Cancer 86(11):1691–1696, 2002.CrossRefGoogle ScholarPubMed
Wirleitner, B, Rudzite, V, Neurauter, G, et al. Immune activation and degradation of tryptophan in coronary heart disease. Eur J Clin Invest 33(7):550–554, 2003.CrossRefGoogle ScholarPubMed
Capuron, L, Ravaud, A, Neveu, PJ, Miller, AH, Maes, M, Dantzer, R. Association between decreased serum tryptophan concentrations and depressive symptoms in cancer patients undergoing cytokine therapy. Mol Psychiatry 7(5):468–473, 2002.CrossRefGoogle ScholarPubMed
Swardfager, W, Herrmann, N, Dowlati, Y, et al. Indoleamine 2,3-dioxygenase activation and depressive symptoms in patients with coronary artery disease. Psychoneuroendocrinology 34(10):1560–1566, 2009.CrossRefGoogle ScholarPubMed
Wurtman, RJ. Food consumption, neurotransmitter synthesis, and human behaviour. Experientia Suppl 44:356–369, 1983.CrossRefGoogle ScholarPubMed
Mendelsohn, D, Riedel, WJ, Sambeth, A. Effects of acute tryptophan depletion on memory, attention and executive functions: a systematic review. Neurosci Biobehav Rev 33(6):926–952, 2009.CrossRefGoogle ScholarPubMed
Frenois, F, Moreau, M, O'Connor, J, et al. Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior. Psychoneuroendocrinology 32(5):516–531, 2007.CrossRefGoogle ScholarPubMed
Moreau, M, André, C, O'Connor, JC, et al. Inoculation of Bacillus Calmette-Guerin to mice induces an acute episode of sickness behavior followed by chronic depressive-like behavior. Brain Behav Immun 22(7):1087–1095, 2008.CrossRefGoogle ScholarPubMed
O'Connor, JC, Lawson, MA, André, C, et al. Induction of IDO by bacille Calmette-Guerin is responsible for development of murine depressive-like behavior. J Immunol 182(5):3202–3212, 2009.CrossRefGoogle ScholarPubMed
O'Connor, JC, Lawson, MA, André, C, et al. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 14(5):511–522, 2009.CrossRefGoogle ScholarPubMed
Henry, CJ, Huang, Y, Wynne, A, et al. Minocycline attenuates lipopolysaccharide (LPS)-induced neuroinflammation, sickness behavior, and anhedonia. J Neuroinflammation 5:15, 2008.CrossRefGoogle ScholarPubMed
O'Connor, JC, André, C, Wang, Y, et al. Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci 29(13):4200–4209, 2009.CrossRefGoogle ScholarPubMed
Ball, HJ, Yuasa, HJ, Austin, CJ, Weiser, S, Hunt, NH. Indoleamine 2,3-dioxygenase-2; a new enzyme in the kynurenine pathway. Int J Biochem Cell Biol 41(3):467–471, 2009.CrossRefGoogle ScholarPubMed
Kanai, M, Nakamura, T, Funakoshi, H. Identification and characterization of novel variants of the tryptophan 2,3-dioxygenase gene: differential regulation in the mouse nervous system during development. Neurosci Res 64(1):111–117, 2009.CrossRefGoogle ScholarPubMed
Moreau, M, Lestage, J, Verrier, D, et al. Bacille Calmette-Guerin inoculation induces chronic activation of peripheral and brain indoleamine 2,3-dioxygenase in mice. J Infect Dis 192(3):537–544, 2005.CrossRefGoogle ScholarPubMed
Dunn, AJ, Wang, J, Ando, T. Effects of cytokines on cerebral neurotransmission: comparison with the effects of stress. Adv Exp Med Biol 461:117–127, 1999.CrossRefGoogle ScholarPubMed
Godbout, JP, Moreau, M, Lestage, J, et al. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology 33(10):2341–2351, 2008.CrossRefGoogle ScholarPubMed
Barneoud, P, Rivet, JM, Vitiello, S, Moal, M, Neveu, PJ. Brain norepinephrine levels after BCG stimulation of the immune system. Immunol Lett 18(3):201–204, 1988.CrossRefGoogle ScholarPubMed
Mössner, R, Heils, A, Stöber, G, Okladnova, O, Daniel, S, Lesch, KP. Enhancement of serotonin transporter function by tumor necrosis factor alpha but not by interleukin-6. Neurochem Int 33(3):251–254, 1998.CrossRefGoogle Scholar
Tsao, CW, Lin, YS, Chen, CC, Bai, CH, Wu, SR. Cytokines and serotonin transporter in patients with major depression. Prog Neuropsychopharmacol Biol Psychiatry 30(5):899–905, 2006.CrossRefGoogle ScholarPubMed
Zhu, CB, Blakely, RD, Hewlett, WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacology 31(10):2121–2131, 2006.Google ScholarPubMed
Katafuchi, T, Kondo, T, Take, S, Yoshimura, M. Brain cytokines and the 5-HT system during poly I: C-induced fatigue. Ann N Y Acad Sci 1088:230–237, 2006.CrossRefGoogle ScholarPubMed
Lestage, J, Verrier, D, Palin, K, Dantzer, R. The enzyme indoleamine 2,3-dioxygenase is induced in the mouse brain in response to peripheral administration of lipopolysaccharide and superantigen. Brain Behav Immun 16(5):596–601, 2002.CrossRefGoogle ScholarPubMed
Fukui, S, Schwarcz, R, Rapoport, SI, Takada, Y, Smith, QR. Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J Neurochem 56(6):2007–2017, 1991.CrossRefGoogle ScholarPubMed
Schwarcz, R. The kynurenine pathway of tryptophan degradation as a drug target. Curr Opin Pharmacol 4(1):12–17, 2004.CrossRefGoogle ScholarPubMed
Müller, N, Schwarz, MJ. A psychoneuroimmunological perspective to Emil Kraepelins dichotomy: schizophrenia and major depression as inflammatory CNS disorders. Eur Arch Psychiatry Clin Neurosci 258(Suppl 2):97–106, 2008.CrossRefGoogle ScholarPubMed
Guillemin, GJ, Cullen, KM, Lim, CK, et al. Characterization of the kynurenine pathway in human neurons. J Neurosci 27(47):12884–12892, 2007.CrossRefGoogle ScholarPubMed
Gabbay, V, Liebes, L, Katz, Y, et al. The kynurenine pathway in adolescent depression: preliminary findings from a proton MR spectroscopy study. Prog Neuropsychopharmacol Biol Psychiatry 34(1):37–44, 2010.CrossRefGoogle ScholarPubMed
Wichers, MC, Koek, GH, Robaeys, G, Verkerk, R, Scharpé, S, Maes, M. IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry 10(6):538–544, 2005.CrossRefGoogle ScholarPubMed
Raison, CL, Dantzer, R, Kelley, KW, et al. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry:e-pub ahead of print, 2009.Google ScholarPubMed
Valentine, AD, Meyers, CA, Kling, MA, Richelson, E, Hauser, P. Mood and cognitive side effects of interferon-alpha therapy. Semin Oncol 25(1 Suppl 1):39–47, 1998.Google ScholarPubMed
Capuron, L, Ravaud, A. Prediction of the depressive effects of interferon alfa therapy by the patient's initial affective state. N Engl J Med 340(17):1370, 1999.CrossRefGoogle ScholarPubMed
Capuron, L, Ravaud, A, Miller, AH, Dantzer, R. Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy. Brain Behav Immun 18(3):205–213, 2004.CrossRefGoogle ScholarPubMed
Capuron, L, Raison, CL, Musselman, DL, Lawson, DH, Nemeroff, CB, Miller, AH. Association of exaggerated HPA axis response to the initial injection of interferon-alpha with development of depression during interferon-alpha therapy. Am J Psychiatry 160(7):1342–1345, 2003.CrossRefGoogle ScholarPubMed
Miller, AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun 23(2):149–158, 2009.CrossRefGoogle Scholar
Bull, SJ, Huezo-Diaz, P, Binder, EB, et al. Functional polymorphisms in the interleukin-6 and serotonin transporter genes, and depression and fatigue induced by interferon-alpha and ribavirin treatment. Mol Psychiatry 14(12):1095–1104, 2009.CrossRefGoogle ScholarPubMed
Danese, A, Moffitt, TE, Pariante, CM, Ambler, A, Poulton, R, Caspi, A. Elevated inflammation levels in depressed adults with a history of childhood maltreatment. Arch Gen Psychiatry 65(4):409–415, 2008.CrossRefGoogle ScholarPubMed
Miller, GE, Chen, E, Fok, AK, et al. Low early-life social class leaves a biological residue manifested by decreased glucocorticoid and increased proinflammatory signaling. Proc Natl Acad Sci U S A 106(34):14716–14721, 2009.CrossRefGoogle Scholar
Capuron, L, Pagnoni, G, Demetrashvili, MF, et al. Basal ganglia hypermetabolism and symptoms of fatigue during interferon-alpha therapy. Neuropsychopharmacology 32(11):2384–2392, 2007.CrossRefGoogle ScholarPubMed
Capuron, L, Pagnoni, G, Demetrashvili, M, et al. Anterior cingulate activation and error processing during interferon-alpha treatment. Biol Psychiatry 58:190–196, 2005.CrossRefGoogle ScholarPubMed
Brydon, L, Harrison, NA, Walker, C, Steptoe, A, Critchley, HD. Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans. Biol Psychiatry 63(11):1022–1029, 2008.CrossRefGoogle ScholarPubMed
Harrison, NA, Brydon, L, Walker, C, et al. Neural origins of human sickness in interoceptive responses to inflammation. Biol Psychiatry 66(5):415–422, 2009.CrossRefGoogle ScholarPubMed
Harrison, NA, Brydon, L, Walker, C, Gray, MA, Steptoe, A, Critchley, HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry 66(5):407–414, 2009.CrossRefGoogle ScholarPubMed
O'Connor, MF, Irwin, MR, Wellisch, DK. When grief heats up: pro-inflammatory cytokines predict regional brain activation. Neuroimage 47(3):891–896, 2009.CrossRefGoogle ScholarPubMed
Irwin, MR, Miller, AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun 21(4):374–383, 2007.CrossRefGoogle ScholarPubMed
Thornton, LM, Andersen, BL, Schuler, TA, Carson, WE. A psychological intervention reduces inflammatory markers by alleviating depressive symptoms: secondary analysis of a randomized controlled trial. Psychosom Med 71(7):715–724, 2009.CrossRefGoogle ScholarPubMed
Stewart, JC, Rand, KL, Muldoon, MF, Kamarck, TW. A prospective evaluation of the directionality of the depression-inflammation relationship. Brain Behav Immun 23(7):936–944, 2009.CrossRefGoogle ScholarPubMed
Miller, GE, Rohleder, N, Stetler, C, Kirschbaum, C. Clinical depression and regulation of the inflammatory response during acute stress. Psychosom Med 67(5):679–687, 2005.CrossRefGoogle ScholarPubMed
Miller, GE, Freedland, KE, Carney, RM. Depressive symptoms and the regulation of proinflammatory cytokine expression in patients with coronary heart disease. J Psychosom Res 59(4):231–236, 2005.CrossRefGoogle ScholarPubMed
Rohleder, N, Miller, GE. Acute deviations from long-term trait depressive symptoms predict systemic inflammatory activity. Brain Behav Immun 22(5):709–716, 2008.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, JK, Gouin, JP, Hantsoo, L. Close relationships, inflammation, and health. Neurosci Biobehav Rev: e-pub ahead of print, 2009.Google Scholar
Segerstrom, SC, Kemeny, ME. Worried to death? Stress, worry, and immune dysregulation in health and HIV. In: Plotnikoff, NP, Faith, RE, Murgo, AJ, Good, RA, eds. Cytokines: Stress and Immunity. Boca Raton FL: CRC Press, 2007:17–28.Google Scholar
Brydon, L, Walker, C, Wawrzyniak, AJ, Chart, H, Steptoe, A. Dispositional optimism and stress-induced changes in immunity and negative mood. Brain Behav Immun 23(6):810–816, 2009.CrossRefGoogle ScholarPubMed
Steptoe, A, Hamer, M, Chida, Y. The effects of acute psychological stress on circulating inflammatory factors in humans: a review and meta-analysis. Brain Behav Immun 21(7):901–912, 2007.CrossRefGoogle ScholarPubMed
Anisman, H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci 34(1):4–20, 2009.Google ScholarPubMed
del Rey, A, Roggero, E, Randolf, A, et al. IL-1 resets glucose homeostasis at central levels. Proc Natl Acad Sci U S A 103(43):16039–16044, 2006.CrossRefGoogle ScholarPubMed
McIntyre, RS, Soczynska, JK, Konarski, JZ, et al. Should depressive syndromes be reclassified as “Metabolic Syndrome Type II”?Ann Clin Psychiatry 19(4):257–264, 2007.CrossRefGoogle ScholarPubMed

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