Open Access, Peer-reviewed
pISSN 1015-4817
eISSN 2289-0963
    J Korean Neuropsychiatr Assoc. 2015 Nov;54(4):506-514. Korean.
    Published online Nov 30, 2015.
    https://doi.org/10.4306/jknpa.2015.54.4.506
    Copyright © 2015 Korean Neuropsychiatric Association
    Original Article

    A Study on the Anxiety of the Chronic Viral Hepatitis Patients Receiving Pegylated Interferon Therapy

    Ji-Hyun Kim, MD,1 Hee-Yeon Choi, MD,1 Tae-Hun Kim, MD, PhD,2 and Soo In Kim, MD, PhD1
      • 1Department of Psychiatry, School of Medicine, Ewha Womans University, Seoul, Korea.
      • 2Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul, Korea.
    • Address for correspondence: Soo In Kim, MD, PhD. Department of Psychiatry, School of Medicine, Ewha Womans University, 1071 Anyangcheon-ro, Yangcheon-gu, Seoul 07985, Korea. Tel +82-2-2650-2821, Fax +82-2-2650-5164, Email: 72sooik@ewha.ac.kr
    Received September 01, 2015; Revised September 14, 2015; Accepted September 22, 2015.

    Abstract

    Objectives

    The aim of this study was to clarify anxiety symptoms associated with the pegylated interferon (PEG-IFN) treatment and to determine which factors are associated with these anxiety symptoms.

    Methods

    The subjects were 30 patients with hepatitis B and C viral infections who were waiting to receive PEG-IFN treatment. For assessment of depressive and anxiety symptoms, the Beck Depression Inventory and the State-Trait Anxiety Inventory were used. Patients were examined before treatment and then prospectively during the 2 weeks, 4 weeks and 1 years of therapy. We analyzed the changes in anxiety and depression symptoms, and applied multiple regression analysis to identify factors that significantly affect the anxiety symptoms.

    Results

    Compared to pre-treatment baseline, anxiety symptoms increased 2 weeks after treatment, and gradually decreased 4 weeks, and 1 year after treatment. And, we analyzed the sub-factors of depressive symptoms that affect the anxiety symptoms. After 2 weeks of treatment, cognitive-affective factors and hypochondriasis factors of depressive symptoms had an effect on anxiety symptoms. Furthermore after 4 weeks of treatment, the cognitive-affective factors had an effect on anxiety symptoms.

    Conclusion

    In this study, we found a significant increase in anxiety symptoms after PEG-IFN treatment, and cognitive-affective depressive factors significantly affect anxiety symptoms.

    Keywords
    Hepatitis B; Hepatitis C; Anxiety; Peginterferon alfa-2

    Figures

    Fig. 1
    Total (A) and subscale (B and C) score of the STAI by visit. *: p<0.05, **: p<0.001. STAI : State-Trait Anxeity Inventory, SAI : State Anxiety Inventory, TAI : Trait Anxiety Inventory.

    Fig. 2
    Total (A) and subscale (B-E) score of the BDI by visit. BDI : Beck Depression Inventory.

    Tables

    Table 1
    Sociodemographic characteristics and clinical conditions of patients (n=30)

    Table 2
    Associations of anxiety symptoms with depressive symptoms factors by stepwise regression analyses

    Table 3
    Associations of anxiety symptoms with depressive symptoms by univariate linear regression analyses

    Notes

    Conflicts of Interest:The authors have no financial conflicts of interest.

    References

      1. Bissinger AL, Fehrle C, Werner CR, Lauer UM, Malek NP, Berg CP. Epidemiology and genotyping of patients with chronic hepatitis B: genotype shifting observed in patients from central Europe. Pol J Microbiol 2015;64:15–21.
      1. Croagh CM, Desmond PV, Bell SJ. Genotypes and viral variants in chronic hepatitis B: a review of epidemiology and clinical relevance. World J Hepatol 2015;7:289–303.
      1. Zdilar D, Franco-Bronson K, Buchler N, Locala JA, Younossi ZM. Hepatitis C, interferon alfa, and depression. Hepatology 2000;31:1207–1211.
      1. Renault PF, Hoofnagle JH, Park Y, Mullen KD, Peters M, Jones DB, et al. Psychiatric complications of long-term interferon alfa therapy. Arch Intern Med 1987;147:1577–1580.
      1. Dieperink E, Ho SB, Thuras P, Willenbring ML. A prospective study of neuropsychiatric symptoms associated with interferon-alpha-2b and ribavirin therapy for patients with chronic hepatitis C. Psychosomatics 2003;44:104–112.
      1. Reddy KR, Wright TL, Pockros PJ, Shiffman M, Everson G, Reindollar R, et al. Efficacy and safety of pegylated (40-kd) interferon alpha-2a compared with interferon alpha-2a in noncirrhotic patients with chronic hepatitis C. Hepatology 2001;33:433–438.
      1. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958–965.
      1. Gohier B, Goeb JL, Rannou-Dubas K, Fouchard I, Calès P, Garré JB. Hepatitis C, alpha interferon, anxiety and depression disorders: a prospective study of 71 patients. World J Biol Psychiatry 2003;4:115–118.
      1. Navinés R, Castellví P, Moreno-España J, Gimenez D, Udina M, Cañizares S, et al. Depressive and anxiety disorders in chronic hepatitis C patients: reliability and validity of the Patient Health Questionnaire. J Affect Disord 2012;138:343–351.
      1. Lotrich FE, Rabinovitz M, Gironda P, Pollock BG. Depression following pegylated interferon-alpha: characteristics and vulnerability. J Psychosom Res 2007;63:131–135.
      1. Martín-Santos R, Díez-Quevedo C, Castellví P, Navinés R, Miquel M, Masnou H, et al. De novo depression and anxiety disorders and influence on adherence during peginterferon-alpha-2a and ribavirin treatment in patients with hepatitis C. Aliment Pharmacol Ther 2008;27:257–265.
      1. Kessler RC, DuPont RL, Berglund P, Wittchen HU. Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys. Am J Psychiatry 1999;156:1915–1923.
      1. King PD, Wilkes JD, Diaz-Arias AA. Hepatitis C virus infection in non-Hodgkin's lymphoma. Clin Lab Haematol 1998;20:107–110.
      1. Middeldorp CM, Cath DC, Van Dyck R, Boomsma DI. The co-morbidity of anxiety and depression in the perspective of genetic epidemiology. A review of twin and family studies. Psychol Med 2005;35:611–624.
      1. Demirkan A, Penninx BW, Hek K, Wray NR, Amin N, Aulchenko YS, et al. Genetic risk profiles for depression and anxiety in adult and elderly cohorts. Mol Psychiatry 2011;16:773–783.
      1. Anisman H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci 2009;34:4–20.
      1. Bayat N, Alishiri GH, Salimzadeh A, Izadi M, Saleh DK, Lankarani MM, et al. Symptoms of anxiety and depression: a comparison among patients with different chronic conditions. J Res Med Sci 2011;16:1441–1447.
      1. Katon W, Lin EH, Kroenke K. The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen Hosp Psychiatry 2007;29:147–155.
      1. McLaughlin TP, Khandker RK, Kruzikas DT, Tummala R. Overlap of anxiety and depression in a managed care population: prevalence and association with resource utilization. J Clin Psychiatry 2006;67:1187–1193.
      1. Marciniak MD, Lage MJ, Dunayevich E, Russell JM, Bowman L, Landbloom RP, et al. The cost of treating anxiety: the medical and demographic correlates that impact total medical costs. Depress Anxiety 2005;21:178–184.
      1. Sareen J, Jacobi F, Cox BJ, Belik SL, Clara I, Stein MB. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med 2006;166:2109–2116.
      1. Stein MB, Roy-Byrne PP, Craske MG, Bystritsky A, Sullivan G, Pyne JM, et al. Functional impact and health utility of anxiety disorders in primary care outpatients. Med Care 2005;43:1164–1170.
      1. Spielberger CD, Gorsuch RL. In: Manual for the State-trait anxiety inventory (form Y) ("self-evaluation questionnaire"). Palo Alto: Consulting Psychologists Press; 1983.
      1. Kim JT. In: Relationship between trait anxiety and sociality [dissertation]. Seoul: College of Medicine, Korea University; 1978.
      1. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561–571.
      1. Lee MK, Lee YH, Park SH, Son CH, Jung YJ, Hong SG, et al. A Standardization study of Beck Depression Inventory 1-Korean version (K-BDI). Korean J Psychopathol 1995;4:77–95.
      1. Yang HJ. In: Factor analysis of the beck depression inventory in anxiety disorder [dissertation]. Seoul: College of Medicine, Hanyang University; 2011.
      1. Bonaccorso S, Puzella A, Marino V, Pasquini M, Biondi M, Artini M, et al. Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. Psychiatry Res 2001;105:45–55.
      1. Mahajan S, Avasthi A, Grover S, Chawla YK. Role of baseline depressive symptoms in the development of depressive episode in patients receiving antiviral therapy for hepatitis C infection. J Psychosom Res 2014;77:109–115.
      1. Boscarino JA, Lu M, Moorman AC, Gordon SC, Rupp LB, Spradling PR, et al. Predictors of poor mental and physical health status among patients with chronic hepatitis C infection: the Chronic Hepatitis Cohort Study (CHeCS). Hepatology 2015;61:802–811.
      1. Loftis JM, Patterson AL, Wilhelm CJ, McNett H, Morasco BJ, Huckans M, et al. Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study. J Psychosom Res 2013;74:57–63.
      1. Ning K, Ye N, Leong HW. On preprocessing and antisymmetry in de novo peptide sequencing: improving efficiency and accuracy. J Bioinform Comput Biol 2008;6:467–492.
      1. O'Donovan A, Hughes BM, Slavich GM, Lynch L, Cronin MT, O'Farrelly C, et al. Clinical anxiety, cortisol and interleukin-6: evidence for specificity in emotion-biology relationships. Brain Behav Immun 2010;24:1074–1077.
      1. Udina M, Navinés R, Capuron L, Martín-Santos R. Serotonin and interleukin-6: the role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms. Psychoneuroendocrinology 2013;38:1830–1831.
      1. Dantzer R. Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 2001;15:7–24.
      1. Sakić B, Szechtman H, Braciak T, Richards C, Gauldie J, Denburg JA. Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6. Brain Res Bull 1997;44:155–165.
      1. Späth-Schwalbe E, Hansen K, Schmidt F, Schrezenmeier H, Marshall L, Burger K, et al. Acute effects of recombinant human interleukin-6 on endocrine and central nervous sleep functions in healthy men. J Clin Endocrinol Metab 1998;83:1573–1579.
      1. Connor TJ, Song C, Leonard BE, Merali Z, Anisman H. An assessment of the effects of central interleukin-1beta, -2, -6, and tumor necrosis factor-alpha administration on some behavioural, neurochemical, endocrine and immune parameters in the rat. Neuroscience 1998;84:923–933.
      1. Licinio J, Kling MA, Hauser P. Cytokines and brain function: relevance to interferon-alpha-induced mood and cognitive changes. Semin Oncol 1998;25 1 Suppl 1:30–38.
      1. Kim H, Chen L, Lim G, Sung B, Wang S, McCabe MF, et al. Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression. J Clin Invest 2012;122:2940–2954.
      1. Morikawa O, Sakai N, Obara H, Saito N. Effects of interferon-alpha, interferon-gamma and cAMP on the transcriptional regulation of the serotonin transporter. Eur J Pharmacol 1998;349:317–324.
      1. Kamata M, Higuchi H, Yoshimoto M, Yoshida K, Shimizu T. Effect of single intracerebroventricular injection of alpha-interferon on monoamine concentrations in the rat brain. Eur Neuropsychopharmacol 2000;10:129–132.
      1. Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, et al. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry 2010;15:393–403.
      1. Pergamin-Hight L, Bakermans-Kranenburg MJ, van Ijzendoorn MH, Bar-Haim Y. Variations in the promoter region of the serotonin transporter gene and biased attention for emotional information: a meta-analysis. Biol Psychiatry 2012;71:373–379.
      1. De La Garza R 2nd, Asnis GM, Pedrosa E, Stearns C, Migdal AL, Reinus JF, et al. Recombinant human interferon-alpha does not alter reward behavior, or neuroimmune and neuroendocrine activation in rats. Prog Neuropsychopharmacol Biol Psychiatry 2005;29:781–792.
      1. Udina M, Castellví P, Moreno-España J, Navinés R, Valdés M, Forns X, et al. Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry 2012;73:1128–1138.
      1. Carrión JA, Gonzalez-Colominas E, García-Retortillo M, Cañete N, Cirera I, Coll S, et al. A multidisciplinary support programme increases the efficiency of pegylated interferon alfa-2a and ribavirin in hepatitis C. J Hepatol 2013;59:926–933.
      1. Neri S, Bertino G, Petralia A, Giancarlo C, Rizzotto A, Calvagno GS, et al. A multidisciplinary therapeutic approach for reducing the risk of psychiatric side effects in patients with chronic hepatitis C treated with pegylated interferon α and ribavirin. J Clin Gastroenterol 2010;44:e210–e217.
    MeSH Terms
    Anxiety*
    Depression
    Hepatitis B
    Hepatitis C
    Hepatitis*
    Humans
    Hypochondriasis
    Interferons*
    Prospective Studies
    Metrics
    Share
    Figures
    slide
    slide

    1 / 2

    Tables
    slide
    slide
    slide

    1 / 3

    PERMALINK