Stress:  Research Article

Psychoimmunology Menu

Psychological and Immunological Predictors of Genital Herpes Recurrence

CITATION:  Kemeny, M.E., Cohen, F., Zegans, L.S., and Conant, M.A.(1989) Psychological and Immunological Predictors of Genital Herpes Recurrence.  Psychosomatic Medicine 51:195-208.

ABSTRACT:  The relationships among stressful life experience, mood, helper-inducer (CD4+) and suppressor-cytotoxic (CD8+) T cells and genital herpes simplex virus (HSV) recurrence were investigated prospectively in 36 patients with recurrent HSV. The following factors were measured monthly for six months: stressful life experience (including current acute and ongoing stressors, residual effects of previous stressors, and anticipation of future stressors), negative mood, health behaviors, other possible HSV triggers, HSV recurrences, and the proportion of CD4+ and CD8+ cells (in half the sample). Results averaging monthly scores over the six-month study period indicated that: 1) subjects with high levels of stressful experience had a lower proportion of both CD4+ and CD8+ cells, 2) subjects with high levels of depressive mood, anxiety, or hostility had a lower proportion of CD8+ cells, and 3) subjects with high levels of depressive mood who did not report many symptoms of other infections had a higher rate of
HSV recurrence. A model is proposed linking depressive mood, CD8+ cells, and HSV recurrence.


1. Elliott GR, Eisdorfer C (eds): Stress and Human Health. New York, Springer, 1982

2. Weiner H: Psychobiology and Human Disease. New York, Elsevier, 1977

3. Hinkle LE, Jr The effect of exposure to culture change, social change, and changes in interpersonal relationships on health. In Dohrenwend BS, Dohrenwend BP (eds), Stressful Life Events. Their Nature and Effects. New York, Wiley, 1974, 9-44.

4 (ackson GG, Dowling HF, Anderson TO, Riff L, Saporta J, Turck M: Susceptibility and immunity to common upper respiratory viral infections—The common cold. Ann Intern Med 53:719-738,1960

5. Meyer RJ, Haggerty RJ: Streptococcal infections in families. Pediatrics 29:539-549,1962

6. Boyce VVT, Jensen EW, Cassel JC. Collier AM, Smith AH, Ramey CT: Influence of life events and family routines on childhood respiratory tract illness. Pediatrics 60:609-615, 1977

7. McClelland DC, Alexander C, Marks E: The need for power, stress, immune function, and illness among male prisoners. J Abnorm Psychol 91:61-70,1982

8. Coe CL, Rosenberg LT, Levine S: Immunological consequences of maternal separation in infant primates.Paper presented at the First International Workshop on Neuroimmunology, Bethosda, MD, 1984

9. Shavit Y. Terman GW, Martin FC, Lewis JW, Licbeskind JC, Gale RP: Stress, opioid peptides, the immune system, and cancer. J Immunol 135(Suppl):834-837,1985

10. Glaser R, Rice J, Speicher CE, Stout JC. Kiecolt-Glaser JK: Stress depresses interferon production by leukocytes concomitant with a decrease in natural killer cell activity. Behav Neurosci 100:675-678, 1986

11. Kiecolt-Glaser JK, Garner W, Speicher C, Penn GM, Holliday J, Glaser R: Psychosocial modifiers of immunocompetence in medical students. Psychosom Med 46:7-14, 1984

12. Kiocolt-Glaser JK. Glaser R. Williger D, Stout JC, Messick G, Sheppard S, Ricker D, Romisher SC, Briner W, Bonnell G, Donnerberg R: Psychosocial enhancement of immunocompetence in a geriatric population. Health Psychol 4:25-41, 1985

13. Schleifer S, Keller S. Camerino M, Thorton J, Stein M: Suppression of lymphocyte stimulation following bereavement. JAMA 250:374-377. 1983

14. Kiecolt-Glaser JK, Glaser R: Behavioral influences on immune function: Evidence for the interplay between stress and health. In Field T, McCabe P, Schneiderman N (eds), Stress and Coping, Vol 2. 206 Psychosomatic Medicine 51:195-208 (1989)

15. Palmblad J: Stress and immunologic competence—Studies in man. In Ader R (ed), Psychoneuroimmunology. New York, Academic Press, 1981, 229-257

16. Stein M, Keller SE, Schleifer SJ: Stress and immunomodulation- The role of depression and neuroendocrine function. J Immunol 135:827-833, 1985

17. Ader R, Cohen N: Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus. Science 215:1534-1536,1982

18. Rogers MP, Dubey D, Reich P: The influence of the psyche and the brain on immunity and susceptibility: A critical review. Psychosom Med 38:447-451, 1979

19. Hill TJ: Herpes simplex virus latency. In Roizman B (ed), The Herpesviruses, Vol 3, New York, Plenum Press, 1985, 175-240

20. Klein R: Pathogenic mechanisms of recurrent herpes simplex virus infections. Brief review. Arch Virol 51:1-13, 1976

21. Blyth W, Hill T: Establishment, maintenance, and control of herpes simplex virus (HSV) latency. In Rouse B, Lopez C (eds), Immunobiology of Herpes Simplex Virus Infection. Boca Raton, FL, CRC Press, 1985. 9-32

22. Sheridan J, Donnerberg A, Aurelian L, Elpern D: Immunity to herpes simplex virus type 2. IV. Impaired lymphokine production during recrudescence correlates with an imbalance in T lymphocyte subsets. J Immunol 129:326-331, 1982

23. Shillitoe E), Wilton JMA, Lehner T: Sequential cell mediated immune responses to herpes simplex virus after recurrent herpetic infection in humans. Infect Immun 18:130-137, 1977

24. Lopez C, Kirkpatrick D, Read S, Fitzgerald P, Pitt J, Pahwa S, Ching C, Smithwick E: Correlation between low natural killing of fibroblasts infected with herpes simplex virus type 1 and susceptibility to herpes virus infections. J Infect Dis 147:1030-1035, 1983

25. Rouse BT: Cell-mediated immune mechanisms. In Rouse B, Lopez C (eds), Immunobiology of Herpes Simplex Virus Infection. Boca Raton, FL, CRC Press, 1985, 107-120

26. Russell AS, Kaiser J, Lao V: Cell mediated immunity to herpes simplex in man. IV. The correlation of lymphocyte stimulation and inhibition of leukocyte migration. J Immunol Methods 9:273,1976

27. Guinan ME, MacCalman J, Kern ER, Overall JC, Spruance SL: The course of untreated recurrent genital herpes simplex infection in 27 women. N Engl J Med 304:759-763,1981

28. Taylor BJ: The psychological and behavioral effects of genital herpes on women. Dissertation Abstracts International, 39/03:2529B, 1978

29. Watson DB: The relationship of genital herpes and life stress as moderated by locus of control and social support. Unpublished manuscript. University of Southern California, Long Beach, 1984

30. Silver PS, Auerbach SM, Vishniavsky N, Kaplowitz LG: Psychological factors in recurrent genital herpes infection: Stress, coping style, social support, emotional dysfunction, and symptom recurrence. ) Psychosom Res 30:163-171. 1986

31. Vanderplate C, Kerrick G: Stress reduction treatment of severe recurrent genital herpes virus. Unpublished manuscript, 1985

32. Schmidt DD, Zyzanski S, Ellner J, Kumar ML. Arno J: Stress as a precipitating factor in subjects with recurrent herpes labialis. J Fam Pract 20:359-366, 1985

33. Cohen F: Personality, stress, and the development of physical illness. In Stone GC, Cohen F, Adler NE & Associates (eds), Health Psychology: A Handbook. San Francisco, Jossey-Bass, 1979, 77-111.

34. Goldmeier D, Johnson A: Does psychiatric illness affect the recurrence rate of genital herpes? Br J Vener Dis 54:40-43, 1982

35. Katcher A, Honori A, Brightman V, Luborsky L, Ship I: Prediction of the incidence of recurrent herpes labialis and systemic illness from psychological measurements. J Dent Res 52:49-58, 1973

36. Friedman E, Katcher A. Brightman V: Incidence of recurrent herpes labialis and upper respiratory infection: A prospective study of the influence of biologic, social and psychologic predictors. Oral Surg 43:873-878, 1977

37. Luborsky L, Mintz J, Brightman V, Katcher A: Herpes simplex virus and moods: A longitudinal study. J Psychosom Res 20: 543-548, 1976

38. Glaser R, Kiecolt-Glaser JK, Speicher CE, Holliday JE: Stress, loneliness, and herpesvirus latency. J Behav Med 8:249-260, 1985

39. Koff WC, Dunegan MA: Neuroendocrine hormones suppress macrophage-mediated lysis of herpes simplex virus-infected cells. J Immunol 136:705-709,1986

40. Targan S, Britvan L, Dorcy F: Activation of human NKCA by moderate exercise: Increased frequency of NK cells with enhanced capability of effector-target lytic interactions. Clin Exp Immunol 45352-360, 1981

41. Bistrian BR, Blackburn GL, Serimshaw NS: Cellular immunity in semistarved states in hospitalized adults Am J Clin Nutr 28:1148-1155, 1975

42. Lazarus RS, Folkman S: Stress, Appraisal and Coping. New York, Springer, 1984

43. Cohen F: Stress and bodily disease. Psychiat Clinics North Am 4(2):269-286,1981

44. Sarason IG, Johnson JH, Siegel SM: Assessing the impact of life changes: The Social Support Questionnaire. J Consult Clin Psychol 46:932-946, 1978

45. Sarason IG, Levine HM, Sarason BR: Assessing the impact of life changes. In Millon T, Green C, Meagher R (eds), Handbook of Clinical Health Psychology. New York, Plenum, 1982, 377-399

46. DeLongis A, Coyne JC, Dakoff G, Folkman S, Lazarus RS: Relationship of daily hassles, uplifts, and major life events to health status. Health Psychol 1:119-136, 1982

47. Zegans LS: The Anticipated Life Stress Scale, 1974

48. McNair DM, Lorr N, Droppleman LF: Profile of Mood States. San Diego, Educational and Industrial Testing Service, 1971

49. Parkerson G, Gehlbach S, Wagner E, James S, Clapp N, Muhlbaier L: The Duke-UNC Health Profile: An adult health status instrument for primary care. Med Care 19:806-828, 1981

50. Schleifer S, Keller S, Siris SG, David KL, Stein M: Depression and immunity. Arch Gen Psychiatry 42:129-133, 1985

51. Watson D, Clark LA: Negative affectivity: The disposition to experience aversive emotional states. Psychol Bull 96:465-490,1984

52. Bierman SM: Recurrent genital herpes simplex infection. A trivial disorder. Arch Dermatol 121:513-517, 1985

53. American Social Health Association: Help membership HSV survey research project results. The Helper 3:1-5, 1981

54. Kemeny ME: Psychological and immunological predictors of genital herpes recurrence. Unpublished doctoral dissertation, University of California, San Francisco, 1985