Peripheral inflammatory cytokines and immune balance in Generalised Anxiety Disorder: Case-controlled study

Brain, Behavior, and Immunity

Volumn 62, Issue , 2017, Pages 212-218

  Hou, Ruihua ^a   Garner, Matthew ^a,b   Holmes, Clive ^a   Osmond, Clive ^c   Teeling, Jessica ^b   Lau, Laurie ^a   Baldwin, David S ^a,d  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^c UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^d UNIVERSITY OF CAPE TOWN   (South Africa)

Author keywords

Anti inflammatory cytokine; Cytokine ratios; Generalised Anxiety Disorder; Inflammation; Pro inflammatory cytokine

Indexed keywords

ANXIOLYTIC AGENT; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 4; TUMOR NECROSIS FACTOR; AUTACOID;

ADULT; AGE; AGED; ALCOHOL CONSUMPTION; ANTIINFLAMMATORY ACTIVITY; ANXIETY; ANXIETY SENSITIVITY INDEX; ARTICLE; CASE CONTROL STUDY; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DEPRESSION; FEMALE; GENDER; GENERALIZED ANXIETY DISORDER; HUMAN; IMMUNITY; IMMUNOASSAY; IMMUNOMODULATION; IMMUNOPHENOTYPING; LIMIT OF DETECTION; LOGISTIC REGRESSION ANALYSIS; MAJOR CLINICAL STUDY; MALE; MINI INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; NEUROPSYCHOLOGY; PERCEIVED STRESS SCALE; PROTEIN BLOOD LEVEL; PSYCHOMETRY; SELF REPORT; SMOKING; TH1 CELL; TH2 CELL; ADOLESCENT; ANXIETY DISORDER; BLOOD; INFLAMMATION; MIDDLE AGED; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANXIETY; ANXIETY DISORDERS; CASE-CONTROL STUDIES; CROSS-SECTIONAL STUDIES; CYTOKINES; DEPRESSION; FEMALE; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; MALE; MIDDLE AGED; SELF REPORT; YOUNG ADULT;

EID: 85013031934     PISSN: 08891591     EISSN: 10902139     Source Type: Journal    
DOI: 10.1016/j.bbi.2017.01.021     Document Type: Article

References (75)

1. Ader, R., Cohen, N., Behaviorally conditioned immunosuppression. Psychosom. Med. 37 (1975), 333–340.
2. Ader, R., Cohen, N., Felten, D., Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet 345 (1995), 99–103.
3. Au, B., Smith, K.J., Gariepy, G., Schmitz, N., The longitudinal associations between C-reactive protein and depressive symptoms: evidence from the English Longitudinal Study of Ageing (ELSA). Int. J. Geriatr. Psychiatry 30 (2015), 976–984.
4. Bankier, B., Barajas, J., Martinez-Rumayor, A., Januzzi, J.L., Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients. Eur. Heart J. 29 (2008), 2212–2217.
5. Benros, M.E., Waltoft, B.L., Nordentoft, M., Ostergaard, S.D., Eaton, W.W., Krogh, J., et al. Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry 70 (2013), 812–820.
6. Berk, M., Williams, L.J., Jacka, F.N., O'Neil, A., Pasco, J.A., Moylan, S., et al. So depression is an inflammatory disease, but where does the inflammation come from?. BMC Med., 11, 2013, 200, 10.1186/1741-7015-11-200.
7. Blais, M.A., Otto, M.W., Zucker, B.G., McNally, R.J., Schmidt, N.B., Fava, M., et al. The anxiety sensitivity index: item analysis and suggestions for refinement. J. Pers. Assess. 77 (2001), 272–294.
8. Brambilla, F., Bellodi, L., Perna, G., Bertani, A., Panerai, A., Sacerdote, P., Plasma interleukin-1 beta concentrations in panic disorder. Psychiatry Res. 54 (1994), 135–142.
9. Brothers, H.M., Wilcock, D.M., Are inflammatory profiles the key to personalized Alzheimer's treatment?. Neurodegener. Dis. Manage. 3 (2013), 343–351.
10. Camacho, A., Is anxious-depression an inflammatory state?. Med. Hypotheses 81 (2013), 577–581.
11. Capuron, L., Miller, A.H., Immune system to brain signaling: neuropsychopharmacological implications. Pharmacol. Ther. 130 (2011), 226–238.
12. Cohen, S., Kamarck, T., Mermelstein, R., A global measure of perceived stress. J. Health Soc. Behav. 24 (1983), 385–396.
13. Copeland, W.E., Shanahan, L., Worthman, C., Angold, A., Costello, E.J., Generalized anxiety and C-reactive protein levels: a prospective, longitudinal analysis. Psychol. Med. 42 (2012), 2641–2650.
14. Dantzer, R., O'Connor, J.C., Freund, G.G., Johnson, R.W., Kelley, K.W., From inflammation to sickness and depression: when the immune system subjugates the brain. Nat. Rev. Neurosci. 9 (2008), 46–56.
15. de Jager, W., Bourcier, K., Rijkers, G.T., Prakken, B.J., Seyfert-Margolis, V., Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays. BMC Immunol., 10, 2009, 52, 10.1186/1471-2172-10-52.
16. Decker, D., Schondorf, M., Bidlingmaier, F., Hirner, A., von Ruecker, A.A., Surgical stress induces a shift in the type-1/type-2 T-helper cell balance, suggesting down-regulation of cell-mediated and up-regulation of antibody-mediated immunity commensurate to the trauma. Surgery 119 (1996), 316–325.
17. Demyttenaere, K., Bruffaerts, R., Posada-Villa, J., Gasquet, I., Kovess, V., Lepine, J.P., et al. Prevalence, severity and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys. JAMA 291 (2004), 2581–2590.
18. Fluitman, S., Denys, D., Vulink, N., Schutters, S., Heijnen, C., Westenberg, H., Lipopolysaccharide-induced cytokine production in obsessive-compulsive disorder and generalized social anxiety disorder. Psychiatry Res. 178 (2010), 313–316.
19. Gill, J.M., Saligan, L., Woods, S., Page, G., PTSD is associated with an excess of inflammatory immune activities. Perspec. Psychiatric Care 45 (2009), 262–277.
20. Gimeno, D., Kivimäki, M., Brunner, E.J., Elovainio, M., De Vogli, R., Steptoe, A., et al. Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study. Psychol. Med. 39 (2009), 413–423.
21. Gray, S.M., Bloch, M.H., Systematic review of proinflammatory cytokines in obsessive-compulsive disorder. Curr. Psychiatry Rep. 14 (2012), 220–228.
22. Halonen, M., Lohman, I.C., Stern, D.A., Spangenberg, A., Anderson, D., Mobley, S., et al. Th1/Th2 patterns and balance in cytokine production in the parents and infants of a large birth cohort. J Immunol. 182 (2009), 3285–3293.
23. Hoffman, D.L., Dukes, E.M., Wittchen, H.U., Human and economic burden of generalized anxiety disorder. Depression and Anxiety 25 (2008), 72–90.
24. Hoge, E.A., Brandstetter, K., Moshier, S., Pollack, M.H., Wong, K.K., Simon, N.M., Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder. Depression Anxiety 26 (2009), 447–455.
25. Hou, R., Tang, Z., Baldwin, D.S., Potential neuroimmunological targets in the treatment of anxiety disorders. Modern Trends Pharmacopsychiatry 29 (2013), 67–84.
26. Kappelmann, N., Lewis, G., Dantzer, R., Jones, P.B., Khandaker, G.M., Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol. Psychiatry, 2016, 10.1038/mp [Epub ahead of print].
27. Kemeny, M.E., An interdisciplinary research model to investigate psychosocial cofactors in disease: Application to HIV-1 pathogenesis. Brain Behav. Immun. 17 (2003), 62–72.
28. Köhler, O., Benros, M.E., Nordentoft, M., Farkouh, M.E., Iyengar, R.L., Mors, O., Krogh, J., Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71 (2014), 1381–1391.
29. Konuk, N., Tekın, I.O., Ozturk, U., Atik, L., Atasoy, N., Bektas, S., et al. Plasma levels of tumor necrosis factor-alpha and interleukin-6 in obsessive compulsive disorder. Med. Inflamm., 2007, 2007, 65704, 10.1155/2007/65704.
30. Kronfol, Z., Remick, D.G., Cytokines and the brain: implications for clinical psychiatry. Am. J. Psychiatry 157 (2000), 683–694.
31. Kubera, M., Lin, A.H., Kenis, G., Bosmans, E., van Bockstaele, D., Maes, M., Anti-Inflammatory effects of antidepressants through suppression of the interferon-gamma/interleukin-10 production ratio. J. Clin. Psychopharmacol. 21 (2001), 199–206.
32. Leonard, B.E., Myint, A., The psychoneuroimmunology of depression. Hum. Psychopharmacol. 24 (2009), 165–175.
33. Liukkonen, T., Räsänen, P., Jokelainen, J., Leinonen, M., Järvelin, M.R., Meyer-Rochow, V.B., et al. The association between anxiety and C-reactive protein (CRP) levels: results from the Northern Finland 1966 birth cohort study. Eur. Psychiatry 26 (2011), 363–369.
34. Loftis, J.M., Huckans, M., Morasco, B.J., Neuroimmune mechanisms of cytokine-induced depression: Current theories and novel treatment strategies. Neurobiol. Dis. 37 (2010), 519–533.
35. Maes, M., Evidence for an immune response in major depression: a review and hypothesis. Prog. Neuropsychopharmacol. Biol. Psychiatry 19 (1995), 11–38.
36. Maes, M., Bosmans, E., Suy, E., Vandervorst, C., De Jonckheere, C., Raus, J., Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology 24 (1990), 115–120.
37. Maes, M., Bosmans, E., Suy, E., Vandervorst, C., DeJonckheere, C., Raus, J., Depression-related disturbances in mitogen-induced lymphocyte responses and interleukin-1 beta and soluble interleukin-2 receptor production. Acta Psychiatr. Scand. 84 (1991), 379–386.
38. Maes, M., Scharpe, S., Bosmans, E., Vandewoude, M., Suy, E., Uyttenbroeck, W., et al. Disturbances in acute phase plasma proteins during melancholia: Additional evidence for the presence of an inflammatory process during that illness. Prog. Neuropsychopharmacol. Biol. Psychiatry 16 (1992), 501–515.
39. Maes, M., Stevens, W., DeClerck, L., Bridts, C., Peeters, D., Schotte, C., et al. Immune disorders in depression: higher T helper/T suppressor-cytotoxic cell ratio. Acta Psychiatr. Scand. 86 (1992), 423–431.
40. Maes, M., Song, C., Lin, A., De Jongh, R., Van Gastel, A., Kenis, G., et al. The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 10 (1998), 313–318.
41. Maes, M., Berk, M., Goehler, L., Song, C., Anderson, G., Gałecki, P., et al. Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways. BMC Med., 10, 2012, 66, 10.1186/1741-7015-10-66.
42. Maier, S.F., Bi-directional immune-brain communication: Implications for understanding stress, pain, and cognition. Brain Behav. Immun. 17 (2003), 69–85.
43. Mándi, Y., Vécsei, L., The kynurenine system and immune regulation. Neural Transm. (Vienna) 119 (2012), 197–209.
44. Marshall, G.D. Jr, Agarwal, S.K., Lloyd, C., Cohen, L., Henninger, E.M., Morris, G.J., Cytokine dysregulation associated with exam stress in healthy medical students. Brain Behav. Immun. 12 (1998), 297–307.
45. Miller, A.H., Raison, C.L., The role of inflammation in depression: from evolutionary imperative to modern treatment target. Nat. Rev. Immunol. 16 (2016), 22–34.
46. Miller, A.H., Maletic, V., Raison, C.L., Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol. Psychiatry 65 (2009), 732–741.
47. Monteleone, P., Catapano, F., Fabrazzo, M., Tortorella, A., Maj, M., Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive-compulsive disorder. Neuropsychobiology 37 (1998), 182–185.
48. Moons, W.G., Eisenberger, N.I., Taylor, S.E., Anger and fear responses to stress have different biological profiles. Brain Behav. Immun. 24 (2010), 215–219.
49. Müller, N., Schwarz, M.J., The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol. Psychiatry 12 (2007), 988–1000.
50. Müller, N., Schwarz, M.J., Immunological aspects of depressive disorders. Der Nervenarzt 78 (2007), 1261–1273.
51. Müller, N., Schwarz, M.J., The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. J. Neural Transm. Suppl. 72 (2007), 269–280.
52. Müller, N., Schwarz, M.J., Immune system and schizophrenia. Curr. Immunol. Rev. 6 (2010), 213–220.
53. Nakano, Y., Nakamura, S., Hirata, M., Harada, K., Ando, K., Tabuchi, T., et al. Immune function and lifestyle of taxi drivers in Japan. Ind. Health 36 (1998), 32–39.
54. O'Donovan, A., Hughes, B.M., Slavich, G.M., Lynch, L., Cronin, M.T., O'Farrelly, C., et al. Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships. Brain Behav. Immun. 24 (2010), 1074–1077.
55. Passos, I.C., Vasconcelos-Moreno, M.P., Costa, L.G., Kunz, M., Brietzke, E., Quevedo, J., et al. Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2 (2015), 1002–1012.
56. Pitsavos, C., Panagiotakos, D.B., Papageorgiou, C., Tsetsekou, E., Soldatos, C., Stefanadis, C., Anxiety in relation to inflammation and coagulation markers, among healthy adults: the ATTICA study. Atherosclerosis 185 (2006), 320–326.
57. Raison, C.L., Capuron, L., Miller, A.H., Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 27 (2006), 24–31.
58. Raison, C.L., Rutherford, R.E., Woolwine, B.J., Shuo, C., Schettler, P., Drake, D.F., et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 70 (2013), 31–41.
59. Scola, M.P., Thompson, S.D., Brunner, H.I., Tsoras, M.K., Witte, D., Van Dijk, M.A., et al. Interferon-gamma:interleukin 4 ratios and associated type 1 cytokine expression in juvenile rheumatoid arthritis synovial tissue. J. Rheumatol. 29 (2002), 369–378.
60. Scott, K., McGee, M.A., Schaaf, D., Baxter, J., Mental-physical comorbidity in an ethnically diverse population. Soc. Sci. Med. 66 (2008), 1165–1173.
61. Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59 (1998), 22–33.
62. Spitzer, R.L., Kroenke, K., Williams, J.B., Löwe, B., A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch. Intern. Med. 166 (2006), 1092–1097.
63. Spitzer, C., Barnow, S., Völzke, H., Wallaschofski, H., John, U., Freyberger, H.J., et al. Association of posttraumatic stress disorder with low-grade elevation of C-reactive protein: evidence from the general population. J. Psychiatr. Res. 44 (2010), 15–21.
64. Steiner, J., Bogerts, B., Sarnyai, Z., Walter, M., Gos, T., Bernstein, H.G., et al. Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: Potential role of glial NMDA receptor modulators and impaired blood-brain barrier integrity. World J. Biol. Psychiatry 13 (2012), 482–492.
65. 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 (2007), 901–912.
66. Uçeyler, N., Valenza, R., Stock, M., Schedel, R., Sprotte, G., Sommer, C., Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain. Arthritis Rheum. 54 (2006), 2656–2664.
67. van Duinen, M.A., Schruers, K.R., Griez, E.J., Maes, M., Neuroimmunological parameters in panic disorder. Acta Neuropsychiatr 16 (2004), 94–100.
68. Vieira, M.M., Ferreira, T.B., Pacheco, P.A., Barros, P.O., Almeida, C.R., Araújo-Lima, C.F., et al. Enhanced Th17 phenotype in individuals with generalized anxiety disorder. J. Neuroimmunol. 229 (2010), 212–218.
69. Vogelzangs, N., Beekman, A.T., de Jonge, P., Penninx BW (2013): Anxiety disorders and inflammation in a large adult cohort. Transl Psychiatry, 3, 2013 Apr 23, e249, 10.1038/tp.2013.27.
70. Wagner, B., Burton, A., Ainsworth, D., Interferon-gamma, interleukin-4 and interleukin-10 production by T helper cells reveals intact Th1 and regulatory TR1 cell activation and a delay of the Th2 cell response in equine neonates and foals. Vet. Res., 41, 2010, 47.
71. Wagner, E.N., Wagner, J.T., Glaus, J., Vandeleur, C.L., Castelao, E., Strippoli, M.F., et al. Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study. PLoS One, 10(4), 2015, e0123757, 10.1371/journal.pone.0123757.
72. Weizman, R., Laor, N., Wiener, Z., Wolmer, L., Bessler, H., Cytokine production in panic disorder patients. Clin. Neuropharmacol. 22 (1999), 107–109.
73. Wittchen, H.U., Jacobi, F., Rehm, J., Gustavsson, A., Svensson, M., Jönsson, B., et al. The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur. Neuropsychopharmacol. 21 (2011), 655–679.
74. Yin, Z., Siegert, S., Neure, L., Grolms, M., Liu, L., Eggens, U., et al. The elevated ratio of interferon gamma-/interleukin-4-positive T cells found in synovial fluid and synovial membrane of rheumatoid arthritis patients can be changed by interleukin-4 but not by interleukin-10 or transforming growth factor beta. Rheumatology (Oxford) 38 (1999), 1058–1067.
75. Zigmond, A.S., Snaith, R.P., The hospital anxiety and depression scale. Acta Psychiatr. Scand. 67 (1983), 361–370.