Skip to main content

Neuropsychiatric symptoms and immune activation in patients with genital herpes

  • Uté Vollmer-Conna (a1), Marcus Chen (a2), Andrew Lloyd (a3) and Basil Donovan (a2) (a4)
<span class='bold'>Objective:</span>

Neuropsychiatric disturbances are common among patients with genital herpes simplex virus (HSV) infection. To date, no studies have examined the possible role of immune activation in the aetiology of these disturbances. The aim of this study was to examine the relationship between markers of immune activation and measures of emotional and somatic dysfunction among patients with symptomatic genital herpes.

<span class='bold'>Methods:</span>

Twenty-two patients with documented genital herpes were assessed when herpetic lesions were present and when they were not. Each assessment included a clinical examination, self-reported symptom measures as well as a blood and urine collection. Markers of immune activation [neopterin and interleukin (IL)-6] in serum and urine were quantified by enzyme-linked immunoassay. These measures were also obtained from a group of healthy control subjects.

<span class='bold'>Results:</span>

Urine, but not serum, levels of neopterin and IL-6 correlated significantly with measures of reported psychological distress and fatigue. These associations were not confined to periods of overt clinical lesions.

<span class='bold'>Conclusions:</span>

HSV-related neuropsychiatric morbidity correlates selectively with regional, but not systemic, measures of immune activation. We hypothesise that communication between the local inflammatory site in the pelvis and the brain occurs through autonomic afferent pathways.

Corresponding author
Dr Ute Vollmer-Conna, Department of Human Behaviour, School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia. Tel: +61 (02) 9385 2945; Fax: +61 (02) 9385 2944; E-mail:
Hide All
1.Cunningham AL, Mikloska Z. The Holy Grail: Immune control of human herpes simplex virus infection and disease. Herpes 2001;8(Suppl 1):6A10A.
2.Auslander BA, Biro FM, Rosenthal SL. Genital herpes in adolescents. Seminar Pediatr Infect Dis 2005;16:2430.
3.Simmons A. Clinical manifestations and treatment considerations of herpes simplex virus infection. J Infec Dis 2002;186:S71S77.
4.Parr MB, Parr EL. Intravaginal administration of herpes simplex virus type 2 to mice leads to infection of several neural and extra neural sites. J Neurovirol 2003;9:594602.
5.Duerst RJ, Morrison LA. Innate immunity to herpes simplex virus type 2. Viral Immunol 2003;16:475490.
6.Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med 1995;333:770775.
7.Carney O, Ross E, Bunker C, Ikkos G, Mindel A. A prospective study of the psychological impact on patients with a first episode of genital herpes. Genitourin Med 1994;70:4045.
8.Grreen J, Kocsis A. Psychological factors in recurrent genital herpes. Genitourin Med 1997;73:253258.
9.Werther J. Die psychogenen Dermatosen. Z Arztl Fortbild 1929;26:341346.
10.Goldmeier D, Johnson A, Jeffries Det al. Psychological aspects of recurrences of genital herpes. J Psychosom Res 1986;30:601608.
11.Mclarnon LD, Kaloupek DG. Psychological investigation of genital herpes recurrence: prospective assessment and cognitive behavioural intervention for a chronic physical disorder. Health Psychol 1988;7:231249.
12.Kemeny ME, Cohen F, ZeEgans LS, Conant MA. Psychological and immunological predictors of genital herpes recurrence. Psychosom Med 1989;51:195208.
13.Dalkvist J, Wahlin TB, Bartsch E, Forsbeck M.Herpes simplex and mood: a prospective study. Psychosom Med 1995;57:127137.
14.Cohen F, Kemeny ME, Kearney KA, Zegans LS, Neuhaos JM, Conant MA. Persistent stress as a predictor of genital herpes recurrence. Arch Intern Med 1999;159:24302434.
15.Vollmer-Conna U. Acute sickness behaviour: an immune system-to-brain communication? Psychol Med 2001;31:761767.
16.Hart B. Biological basis of the behaviour of sick animals. Neurosci Biobehav Rev 1988;12:123137.
17.Maier SF, Watkins LR. Bidirectional communication between the brain and the immune system: implications for behaviour. Anim Behav 1999;75:741751.
18.Kelley KW, Bluthe RM, Dantzer Ret al. Cytokine-induced sickness behavior. Brain Behav Immun 2003;17(Suppl 1):S112S118.
19.Vollmer-Conna U, Fazoui C, Cameron Bet al. Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans. Psychol Med 2004;34:12891297.
20.Cowan ML, Maxwell JD. Treatment of hepatitis C virus infection in intravenous drug users. Acta Neuropsychiatr 2006;18:183192.
21.Vandvik PO, Lyndersen S, Farup PG. Prevalence, comorbidity and impact of irritable bowel syndrome in Norway. Scand J Gastroenterol 2006;41:650656.
22.Vollmeer-Conna U, Lloyd A, Hickie I, Wakefield D. Chronic fatigue syndrome: an immunological perspective. Aust N Z J Psychiatry 1998;32:523527.
23.Capuron L, Hauser P, Hinze-Selch D, Miller A, Neveu PJ. Treatment of cytokine-induced depression. Brain Behav Immun 2002;16:575580.
24.Dantzer R. Somatisation: a psychoneuroimmune perspective. Psychoneuroendocrinology 2005;30:947952.
25.Fuchs D, Weiss G, Reibnegger G, Wachter H. The role of neopterin as a monitor of cellular immune activation in transplantation, inflammatory, infectious, and malignant diseases. Crit Rev Clin Lab Sci 1992;29:307341.
26.Fuchs D, Weiss G, Wachter H. Neopterin, biochemistry and clinical use as a marker for cellular immune reactions. Int Arch Allergy Immunol 1993;101:16.
27.Papanicolaou DA. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med 1998;128:127137.
28.Hickie IB, Davenport TA, Hadzi-Pavlovic Det al. Development of a simple screening tool for common mental disorders in general practice. Med J 2001;175:S10S17.
29.McNair DM, Lorr M, Droppleman LF. EdITS manual for the Profile of Mood States. San Diego: EdITS/ Educational and Industrial Testing Service, 1992.
30.Von Korff M, Ustun TB, Ormel J, Kaplan I, Simon GE. Self-report disability in an international primary care study of psychological illness. J Clin Epidemiol 1996;49:297303.
31.Kayama F, Yoshida T, Kodama Y, Matsui T, Matheson JM, Luster MI. Pro-inflammatory cytokines and interleukin 6 in the renal response to bacterial endotoxin. Cytokine 1997;9:688695.
32.Benson M, Jodal U, Aandreasson A, Karlsson A, Rydberg Svanborg C. Interleukin 6 response to urinary tract infection in childhood. Pediatr Infect Dis 1994;13:612616.
33.Fleck M, Podlech J, Weise K, Muntefering H, Falke D. Pathogenesis of HSC-1/2 induced vaginitis/vulvitis of the mouse: dependence on lesions on genetic properties of the virus and analysis of pathohistology. Arch Virol 1993;129:3551.
34.Corey L, Spear PG. Infections with herpes simplex viruses. Part 1. N Engl J Med 1986a;314:686691.
35.Corey L, Spear PG. Infections with herpes simplex viruses. Part 2. N Engl J Med 1986b;314:749757.
36.Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR. Vagal immune-to-brain communication: a visceral chemosensory pathway. Autonom Neurosci 2000;85:4959.
37.Gidron Y, Perry H, Glennie M. Does the vagus nerve inform the brain about preclinical tumours and modulate them? Lancet Oncol 2005;6:245248.
38.Craig AD. How do you feel? Interoception: the sense of the physiological condition of the body. Nature 2002;3:655666.
39.Craig AD. Interoception: the sense of physiological condition of the body. Curr Opin Neurobiol 2003;13:500505.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Acta Neuropsychiatrica
  • ISSN: 0924-2708
  • EISSN: 1601-5215
  • URL: /core/journals/acta-neuropsychiatrica
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Full text views

Total number of HTML views: 0
Total number of PDF views: 4 *
Loading metrics...

Abstract views

Total abstract views: 151 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 12th December 2017. This data will be updated every 24 hours.