J Korean Neuropsychiatr Assoc.  2015 Nov;54(4):506-514. 10.4306/jknpa.2015.54.4.506.

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

• Kim JH
• Choi HY
• Kim TH
• Kim SI

• KMID: 2149333
• DOI: http://doi.org/10.4306/jknpa.2015.54.4.506

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.

Keyword

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

MeSH Terms

Anxiety*
Depression
Hepatitis B
Hepatitis C
Hepatitis*
Humans
Hypochondriasis
Interferons*
Prospective Studies
Interferons

Figure

• 

  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.

Reference

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.

2. 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.

3. Zdilar D, Franco-Bronson K, Buchler N, Locala JA, Younossi ZM. Hepatitis C, interferon alfa, and depression. Hepatology. 2000; 31:1207–1211.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. Lotrich FE, Rabinovitz M, Gironda P, Pollock BG. Depression following pegylated interferon-alpha: characteristics and vulnerability. J Psychosom Res. 2007; 63:131–135.

11. 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.

12. 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.

13. King PD, Wilkes JD, Diaz-Arias AA. Hepatitis C virus infection in non-Hodgkin's lymphoma. Clin Lab Haematol. 1998; 20:107–110.

14. 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.

15. 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.

16. Anisman H. Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci. 2009; 34:4–20.

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

22. 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.

23. Spielberger CD, Gorsuch RL. Manual for the State-trait anxiety inventory (form Y) ("self-evaluation questionnaire"). Palo Alto: Consulting Psychologists Press;1983.

24. Kim JT. Relationship between trait anxiety and sociality [dissertation]. Seoul: College of Medicine, Korea University;1978.

25. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4:561–571.

26. 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.

27. Yang HJ. Factor analysis of the beck depression inventory in anxiety disorder [dissertation]. Seoul: College of Medicine, Hanyang University;2011.

28. 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.

29. 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.

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. Dantzer R. Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun. 2001; 15:7–24.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. 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.

46. 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.

47. 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.

48. 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.