Psychoneuroimmunology of Depression

Michael Irwin
Department of Psychiatry
University of California, San Diego
San Diego VA Medical Center
San Diego, California 92161.



1. Andreoli A, Keller SE, Rabaeus M, Zaugg L, Garrone G, Taban C. Immunity, major depression, and panic disorder comorbidity. Biol Psychiatry 1992;31:896–908.

2. Belluardo N, Mudo G, Cella S, Bindoni M. Effect of cerebral hemisphere decortication on the cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse. Brain Res 1990;524: 297–302.

3. Bernton E, Meltzer M, Holaday JW. Suppression of macrophage activation and T-lymphocyte function in hypoprolactinemic mice. Science 1988;239:401–404.

4. Brown R, Li Z, Vriend CY, et al. Suppression of splenic macrophage interleukin-1 secretion following intracerebroventricular injection of interleukin-1b: evidence for pituitary–adrenal and sympathetic control. Cell Immunol 1991;132:84–93.

5. Bryant HU, Roudebush RE. Suppressive effects of morphine pellet implants on in vivo parameters of immune function. J Pharm Exp Ther 1990;255(2):410–414.

6. Carr DJJ, Gebhardt BM, Paul D. Alpha adrenergic and Mu-2 opioid receptors are involved in morphine-induced suppression of splenocyte natural killer activity. J Pharm Exp Ther 1993;264(3): 1179–1186.

7. Clodi M, Svoboda T, Kotzmann H, et al. Effect of elevated serum prolactin concentrations on cytokine production and natural killer cell activity. Neuroendocrinology 1992;56:775–779.

8. Coe CL, Rosenberg LT, Levine S. Immunological consequences of psychological disturbance and maternal loss in infancy. In: Rovee-Collier C, Lipsitt LP, eds. Advances in infancy research. Norwood, OH: Ablex Publishing; 1985:98–136.

9. Cohen S, Tyrrell DA, Smith AP. Psychological stress and susceptibility to the common cold. New Engl J Med 1991;325(9):606–656.

10. Cohen S, Williamson G. Stress and infectious disease in humans. Psychol Bull 1991;109(1):5–24.

11. Cross RJ, Bryson JS, Roszman TL. Immunologic disparity in the hypopituitary dwarf mouse. J Immunol 1992;148(5):1347–1352.

12. Cross RJ, Roszman TL. Central catecholamine depletion impairs in vivo immunity but not in vitro lymphocyte activation. J Neuroimmunol 1988;19:33–45.

13. Cunnick JE, Lysle DT, Kucinski BJ, Rabin BS. Evidence that shock-induced immune suppression is mediated by adrenal hormones and peripheral b-adrenergic receptors. Pharmacol Biochem Behav 1990;36:645–651.

14. Cupps TR, Fauci AS. Corticosteroid-mediated immunoregulation in man. Immunol Rev 1982;65:133–155.

15. Darko D, Irwin M, Risch SC, Gillin JC. Plasma beta-endorphin and natural killer cell activity in patients with major depression. Psychiatry Res 1992;43:111–119.

16. Darko DF, Gillin JC, Risch SC, et al. Mitogen-stimulated lymphocyte proliferation and pituitary hormones in major depression. Biol Psychiatry 1989;26:145–155.

17. Darko DF, Wilson NW, Gillin JC, Golshan S. A critical appraisal of mitogen-induced lymphocyte proliferation in depressed patients. Am J Psychiatry 1991;148(3):337–344.

18. Evans DL, Folds JD, Petitto JM, et al. Circulating natural killer cell phenotypes in men and women with major depression. Arch Gen Psychiatry 1992;49:388–395.

19. Farrar WL, Hill JM, Harel-Bellan A, Vinocour M. The immunological brain. Immunol Rev 1987;100:361–377.

20. Fawzy FI, Kemeny ME, Fawzy NW, et al. A structured psychiatric intervention for cancer patients. II. Changes over time in immunological measures. Arch Gen Psychiatry 1990;47(8):729–735.

21. Felten DL, Felten SY, Bellinger DL, et al. Noradrenergic sympathetic neural interactions with the immune system: structure and function. Immunol Rev 1987;100:225–260.

22. Fiatarone MA, Morley JE, Bloom ET, Benton D, Solomon GF, Makinodan T. The effects of exercise on natural killer cell activity in young and old subjects. J Gerontol 1989;44:M37–M45.

23. Fischler B, Bocken R, DeWaele M, Thielemans K. Major depressive disorder, endogenicity and natural killer cell numbers and activity. Int J Neurosci 1990;51:357–358.

24. Flores CM, Hernandez MC, Hargreaves KM, Bayer BM. Restraint stress-induced elevations in plasma corticosterone and b-endorphin are not accompanied by alterations in immune function. J Neuroimmunol 1990;28:219–225.

25. Fox BH. Depressive symptoms and risk of cancer. JAMA 1989;262:1231–1231.

26. Glaser R, Kennedy S, Lafuse WP, et al. Psychological stressinduced modulation of interleukin-2 receptor gene expression and interleukin-2 production in peripheral blood leukocytes. Arch Gen Psychiatry 1990;47:707–712.

27. Glaser R, Kiecolt-Glaser JK, Bonneau RH, Malarkey W, Kennedy S, Hughes J. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom Med 1992;54:22–29.

28. Hartmann DP, Holaday JW, Bernton EW. Inhibition of lymphocyte proliferation by antibodies to prolactin. FASEB J 1989;3:2194–2202.

29. Heijnen CJ, Kavelaars AK, Ballieux RE. b-Endorphin: cytokine and neuropeptide. Immunol Rev 1991;119:41–63.

30. Hellstrand K, Hermodsson S. Role of serotonin in the regulation of human natural killer cell cytotoxicity. J Immunol 1987;139(3):869–875.

31. Herbert TB, Cohen S. Depression and immunity: a meta-analytic review. Psychosom Med 1993;55:364–379.

32. Hickie I, Hickie C, Lloyd A, Silove D, Wakefield D. Impaired in vivo immune responses in patients with melancholia. Br J Psychiatry 1993;162:751–757.

33. Irwin M. Brain corticotropin releasing hormone and interleukin-1b induced suppression of specific antibody production. Endocrinology 1993;133:1352–1360.

34. Irwin M, Brown M, Patterson T, Hauger R, Mascovich A, Grant I. Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress. FASEB J 1991;5:3100–3107.

35. Irwin M, Caldwell C, Smith TL, Brown S, Schuckit MA, Gillin JC. Major depressive disorder, alcoholism, and reduced natural killer cell cytotoxicity: role of severity of depressive symptoms and alcohol consumption. Arch Gen Psychiatry 1990;47:713–719.

36. Irwin M, Hauger RL, Jones L, Provencio M, Britton KT. Sympathetic nervous system mediates central corticotropin-releasing factor induced suppression of natural killer cytotoxicity. J Pharmacol Exp Ther 1990;255(1):101–107.

37. Irwin M, Lacher U, Caldwell C. Depression and reduced natural killer cytotoxicity: a longitudinal study of depressed patients and control subjects. Psychol Med 1992;22:1045–1050.

38. Irwin M, Patterson T, Smith TL, et al. Reduction of immune function in life stress and depression. Biol Psychiatry 1990;270:22–30.

39. Irwin M, Smith TL, Gillin JC. Electroencephalographic sleep and natural killer activity in depressed patients and control subjects. Psychosom Med 1992;54:10–21.

40. Irwin M, Smith TL, Gillin JC. Reduced natural killer cytotoxicity in depressed patients. Life Sci 1987;41:2127–2133.

41. Irwin MR, Vale W, Rivier C. Central corticotropin releasing factor mediates the suppressive effect of stress on natural killer cytotoxicity. Endocrinology 1990;126(6):2837–2844.

42. Jain R, Zwickler D, Hollander CS, et al. Corticotropin-releasing factor modulates the immune response to stress in the rat. Endocrinology 1991;128:1329–1336.

43. Johnson HM, Downs MO, Pontzer CH, Blalock JE. Neuroendocrine peptide hormone regulation of immunity. Neuroimmunoendocrinol Chem Immunol [Basel] 1992;2:49–83.

44. Kang DH, Davidson RJ, Coe CL, Wheeler RE, Tamarken AJ. Frontal brain asymmetry and immune function. Behav Neurosci 1991;105(6):860–869.

45. Karalis K, Sano H, Redwine J, Listwak S, Wilder RL, Chrousos GP. Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo. Science 1991;254:421–423.

46. Keller SE, Schleifer SJ, Liotta AS, Bond RN, Farhoody N, Stein M. Stress-induced alterations of immunity in hypophysectomized rats. Proc Natl Acad Sci USA 1988;85:9297–9301.

47. Kiecolt-Glaser JK, Dura JR, Speicher CE, Trask OJ, Glaser R. Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom Med 1991;53:345–362.

48. Kronfol Z, House JD. Depression, hypothalamic–pituitary adrenocortical activity and lymphocyte function. Psychopharmacol Bull 1985;21:476–478.

49. Kronfol Z, Hover JD, Silva J, et al. Depression, urinary free cortisol excretion, and lymphocyte function. Br J Psychiatry 1986;148: 70–73.

50. Kronfol Z, Nair M, Goodson J, Goel K, Haskett R, Schwartz S. Natural killer cell activity in depressive illness: a preliminary report. Biol Psychiatry 1989;26:753–756.

51. Krueger JM, Karnovsky ML. Sleep and the immune response. Ann NY Acad Sci 1987;496:510–516.

52. Laudenslager M, Capitanio JP, Reite M. Possible effects of early separation experiences on subsequent immune function in adult macaque monkeys. Am J Psychiatry 1985;142(7):862–864.

53. Lowy MT, Reder AT, Gormley GJ, Meltzer HY. Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: relationship to the dexamethasone suppression test. Biol Psychiatry 1988; 24:619–630.

54. Maes M, Bosmans E, Suy E, Minner B, Raus J. Impaired lymphocyte stimulation by mitogens in severely depressed patients a complex interface with HPA axis hyperfunction, noradrenergic activity and the ageing process. Br J Psychiatry 1989;155:793–798.

55. Maes M, Bosmans E, Suy E, Vandervorst C, deJonckheere C, Raus J. Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1b and soluble interleukin-2 receptor production. Acta Psychiatr Scand 1991;84:379–386.

56. Maier SF, Laudenslager ML. Inescapable shock, shock controllability, and mitogen stimulated lymphocyte proliferation. Brain Behav Immun 1988;2:87–91.

57. Miller AH, Asnis GM, Lackner C, Halbreich U, Norin AJ. Depression, natural killer cell activity, and cortisol secretion. Biol Psychiatry 1991;29:878–886.

58. Moldofsky H, Lue FA, Davidson JR, Gorczynski R. Effects of sleep deprivation on human immune function. FASEB J 1989;3:1972–1977.

59. Munck A, Guyre PM, Holbrook NJ. Physiological functions of glucocorticoids in stress and their relation to pharmacologic actions. Endocrine Rev 1984;5:25–44.

60. Murray DR, Irwin M, Rearden CA, Ziegler M, Motulsky H, Maisel AS. Sympathetic and immune interactions during dynamic exercise: mediation via a b2-adrenergic dependent mechanism. Circulation 1992;86:203–213.

61. Nair MPN, Schwartz SA, Wu K, Kronfol Z. Effect of neuropeptide Y on natural killer activity of normal human lymphocytes. Brain Behav Immun 1993;7:70–78.

62. Nerozzi D, Santoni A, Bersani G, et al. Reduced natural killer cell activity in major depression: neuroendocrine implications. Psychoneuroendocrinology 1989;14:295–302.

63. Palmblad J, Petrini B, Wasserman J, Akerstedt T. Lymphocyte and granulocyte reactions during sleep deprivation. Psychosom Med 1979;41(4):273–278.

64. Saperstein A, Brand H, Audhya T, et al. Interleukin 1b mediates stress-induced immunosuppression via corticotropin-releasing factor. Endocrinology 1992;30(1):152–158.

65. Schleifer SJ, Keller SE, Bond RN, Cohen J, Stein M. Major depressive disorder and immunity: role of age, sex, severity, and hospitalization. Arch Gen Psychiatry 1989;46:81–87.

66. Schleifer SJ, Keller SE, Meyerson AT, Raskin MJ, Davis KL, Stein M. Depression and immunity: lymphocyte function in ambulatory depressed patients, hospitalized schizophrenic patients, and patients hospitalized for herniotheraphy. Arch Gen Psychiatry 1985;42: 129–133.

67. Schleifer S, Keller SE, Meyerson AT, Raskin MD, Davis KL, Stein M. Lymphocyte function in major depressive disorder. Arch Gen Psychiatry 1984;41:484–486.

68. Sibinga NES, Goldstein A. Opioid peptides and opioid receptors in cells of the immune system. Ann Rev Immunol 1988;6:219–249.

69. Singh VK. Stimulatory effect of corticotropin-releasing neurohormone on human lymphocyte proliferation and interleukin-2 receptor expression. J Neuroimmunol 1989;23:257–262.

70. Spiegel D, Bloom J, Kraemer HC, Gottheil E. The beneficial effect of psychosocial treatment on survival of metastatic breast cancer patients: a randomized prospective outcome study. Lancet 1989;10/14:888–891.

71. Stein M, Miller AH, Trestman RL. Depression, the immune system, and health and illness. Arch Gen Psychiatry 1991;48:171–177.

72. Sternberg EM, Young WS III, Calogero AE, et al. A central nervous system defect in biosynthesis of corticotropin-releasing hormone is associated with susceptibility to streptococcal cell wall-induced arthritis in Lewis rats. Proc Natl Acad Sci USA 1989;86:4771–4775.

73. Sundar SK, Cierpial MA, Kilts C, Ritchie JC, Weiss JM. Brain IL-1-induced immunosuppression occurs through activation of both pituitary-adrenal axis and sympathetic nervous system by corticotropin-releasing factor. J Neurosci 1990;10(11):3701–3706.

74. Weber RJ, Pert A. The periaqueductal gray matter mediates opiate-induced immunosuppression. Science 1989;245:188–190.

75. Webster EL, Tracey DE, Jutila MA, Wolfe SAJr, DeSouza EB. Corticotropin-releasing factor receptors in mouse spleen: identification of receptor-bearing cells as resident macrophages. Endocrinology 1990;127:440–452.

76. Weisse CS. Depression and immunocompetence: a review of the literature. Psychol Bull 1992;111(3):475–489.

77. Wodarz N, Rupprecht R, Kornhuber J, et al. Normal lymphocyte responsiveness to lectins but impaired sensitivity to in vitro glucocorticoids in major depression. J Affect Disord 1991;22:241–248.

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published 2000