Journal Mobile Options
Table of Contents
Vol. 82, No. 5, 2013
Issue release date: August 2013
Psychother Psychosom 2013;82:332-340

A Biopsychosocial Model of Interferon-Alpha-Induced Depression in Patients with Chronic Hepatitis C Infection

Baranyi A. · Meinitzer A. · Stepan A. · Putz-Bankuti C. · Breitenecker R.J. · Stauber R. · Kapfhammer H.-P. · Rothenhäusler H.-B.
aDepartment of Psychiatry, bClinical Institute of Medical and Chemical Laboratory Diagnostics and cDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, and dDepartment of Innovation Management and Entrepreneurship, Alpen-Adria Universität Klagenfurt, Klagenfurt, Austria

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Background: The aim of this prospective study was to gain a more comprehensive picture of the biopsychosocial effects of interferon-α (IFN-α) treatment of patients with chronic hepatitis C (HCV). The predictors of depressive development and changes in health-related quality of life, life satisfaction and cognitive ability were measured with the inclusion of the social context. Furthermore, the effects of IFN-α treatment on indoleamine 2,3-dioxygenase, the level of tryptophan supply in the brain, the development of neurotoxic kynurenine metabolites and the thyroid glands were investigated. Therefore, for the first time the conditions for the development of depressive episodes in HCV patients treated with IFN-α were examined over the entire period of treatment as well as 3 months later, applying a holistic biopsychosocial model. Method: Psychiatric and biological assessments were carried out at 6 different times: before, during (at 1, 3, 6 and 9 months) and after the end of IFN-α treatment. Results: During IFN-α treatment 22 (53.7%) of 41 patients fulfilled the criteria for a treatment-related depressive disorder at least once during treatment. Contributing factors are tryptophan depletion (tryptophan to competing amino acids quotient), increased neurotoxic challenge (kynurenine to kynurenic acid quotient), less social support, female gender, preexisting psychiatric vulnerability, means of transmission, low financial security, impaired sexual satisfaction, small circle of friends, impaired physical role, strong body pain, low general health and vitality, reduced social functioning, impaired mental health and impaired emotional role. Conclusions: The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies.

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Crone C, Gabriel GM: Comprehensive review of hepatitis C for psychiatrists: risks, screening, diagnosis, treatment, and interferon-based therapy complications. J Psychiatr Pract 2003;9:93-110.
  2. Dinwiddie SH, Shicker L, Newman T: Prevalence of hepatitis C among psychiatric patients in the public sector. Am J Psychiatry 2003;160:172-174.
  3. Udina M, Castellvi P, Moreno-Espana J, Navines R, Valdes M, Forns X, Langohr K, Sola R, Vieta E, Martin-Santos R: Interferon-induced depression in chronic hepatitis C: a systematic review and meta-analysis. J Clin Psychiatry 2012;73:1128-1138.
  4. Grassi L, Satriano J, Serra A, Biancosino B, Zotos S, Sighinolfi L, Ghinelli F: Emotional stress, psychosocial variables and coping associated with hepatitis C virus and human immunodeficiency virus infections in intravenous drug users. Psychother Psychosom 2002;71:342-349.
  5. Patten SB, Barbui C: Drug-induced depression: a systematic review to inform clinical practice. Psychother Psychosom 2004;73:207-215.
  6. Bonaccorso S, Marino V, Biondi M, Grimaldi F, Ippoliti F, Maes M: Depression induced by treatment with interferon-alpha in patients affected by hepatitis C virus. J Affect Disord 2002;72:237-241.
  7. Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Verkerk R, Meltzer H, Maes M: Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to interferon-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol 2002;22:86-90.
  8. Raison CL, Borisov AS, Broadwell SD, Capuron L, Woolwine BJ, Jacobson IM, Nemeroff CB, Miller AH: Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry 2005;66:41-48.
  9. Wichers MC, Koek GH, Robaeys G, Verkerk R, Scharpe S, Maes M: IDO and interferon-alpha-induced depressive symptoms: a shift in hypothesis from tryptophan depletion to neurotoxicity. Mol Psychiatry 2005;10:538-544.
  10. Wichers M, Maes M: The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. Int J Neuropsychopharmacol 2002;5:375-388.
  11. McHutchison JG, Ware JE Jr, Bayliss MS, Pianko S, Albrecht JK, Cort S, Yang I, Neary MP, Hepatitis Interventional Therapy Group: The effects of interferon alpha-2b in combination with ribavirin on health related quality of life and work productivity. J Hepatol 2001;34:140-147.
  12. Fava GA, Freyberger HJ, Bech P, Christodoulou G, Sensky T, Theorell T, Wise TN: Diagnostic criteria for use in psychosomatic research. Psychother Psychosom 1995;63:1-8.
  13. Fava GA, Mangelli L, Ruini C: Assessment of psychological distress in the setting of medical disease. Psychother Psychosom 2001;70:171-175.
  14. Fava GA, Ruini C, Tomba E, Wise TN: The biopsychosocial factor. Psychother Psychosom 2012;81:1-4.
  15. Tomba E, Bech P: Clinimetrics and clinical psychometrics: macro- and micro-analysis. Psychother Psychosom 2012;81:333-343.
  16. Herve C, Beyne P, Jamault H, Delacoux E: Determination of tryptophan and its kynurenine pathway metabolites in human serum by high-performance liquid chromatography with simultaneous ultraviolet and fluorimetric detection. J Chromatogr B Biomed Appl 1996;675:157-161.
  17. Schwarz EL, Roberts WL, Pasquali M: Analysis of plasma amino acids by HPLC with photodiode array and fluorescence detection. Clin Chim Acta 2005;354:83-90.
  18. Lehfeld H, Erzigkeit H: The SKT - a short cognitive performance test for assessing deficits of memory and attention. Int Psychogeriatr 1997;9(suppl 1):115-121.
  19. Ware JE, Snow KK, Kosinski M, Gandek B: SF-36 Health Survey. Manual and Interpretation Guide. Boston, Health Institute, New England Medical Center, 2008.
  20. Stewart AL, Hays RD, Ware JE: The MOS short-form general health survey. Reliability and validity in a patient population. Med Care 1988;26:724-735.
  21. Fahrenberg J, Myrtek M, Schuhmacher J: Fragebogen zur Lebenszufriedenheit (FLZ) Handanweisung. Göttingen, Hogrefe, 2000.
  22. Sherbourne CD, Stewart AL: The MOS social support survey. Soc Sci Med 1991;32:705-714.
  23. Hamilton M: Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278-296.
  24. Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J: An inventory for measuring depression. Arch Gen Psychiatry 1961;4:561-571.
  25. Stein MD, Solomon DA, Herman DS, Anderson BJ, Miller I: Depression severity and drug injection HIV risk behaviors. Am J Psychiatry 2003;160:1659-1662.
  26. Malaguarnera M, Laurino A, Di Fazio I, Pistone G, Castorina M, Guccione N, Rampello L: Neuropsychiatric effects and type of IFN-alpha in chronic hepatitis C. J Interferon Cytokine Res 2001;21:273-278.
  27. Dieperink E, Willenbring M, Ho SB: Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: a review. Am J Psychiatry 2000;157:867-876.
  28. O'Connor JC, Lawson MA, Andre C, Briley EM, Szegedi SS, Lestage J, Castanon N, Herkenham M, Dantzer R, Kelley KW: Induction of IDO by bacille Calmette-Guérin is responsible for development of murine depressive-like behavior. J Immunol 2009;182:3202-3212.
  29. Schaefer M, Winterer J, Sarkar R, Uebelhack R, Franke L, Heinz A, Friebe A: Three cases of successful tryptophan add-on or monotherapy of hepatitis C and IFN-alpha-associated mood disorders. Psychosomatics 2008;49:442-446.
  30. Raison CL, Dantzer R, Kelley KW, Lawson MA, Woolwine BJ, Vogt G, Spivey JR, Saito K, Miller AH: 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.
  31. Wilson MP, Castillo EM, Batey AM, Sapyta J, Aronson S: Hepatitis C and depressive symptoms: psychological and social factors matter more than liver injury. Int J Psychiatry Med 2010;40:199-215.
  32. Marcellin P, Lau GK, Zeuzem S, Heathcote EJ, Pockros PJ, Reddy KR, Piratvisuth T, Farci P, Chow WC, Jia JD, Paik W, Wintfeld N, Pluck N: Comparing the safety, tolerability and quality of life in patients with chronic hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a. Liver Int 2008;28:477-485.
  33. Dan AA, Martin LM, Crone C, Ong JP, Farmer DW, Wise T, Robbins SC, Younossi ZM: Depression, anemia and health-related quality of life in chronic hepatitis C. J Hepatol 2006;44:491-498.
  34. McAndrews MP, Farcnik K, Carlen P, Damyanovich A, Mrkonjic M, Jones S, Heathcote EJ: Prevalence and significance of neurocognitive dysfunction in hepatitis C in the absence of correlated risk factors. Hepatology 2005;41:801-808.
  35. Reichenberg A, Gorman JM, Dieterich DT: Interferon-induced depression and cognitive impairment in hepatitis C virus patients: a 72 week prospective study. AIDS 2005;19(suppl 3):S174-S178.
  36. Wobrock T, Mihm U, Lohr C, Hofmann WP, Sarrazin C, Zeuzem S, Falkai P: Cognition in hepatitis C patients treated with pegylated interferon. World J Biol Psychiatry 2009;10:819-826.
  37. Evon DM, Ramcharran D, Belle SH, Terrault NA, Fontana RJ, Fried MW, Virahep-C Study Group: Prospective analysis of depression during peginterferon and ribavirin therapy of chronic hepatitis C: results of the Virahep-C study. Am J Gastroenterol 2009;104:2949-2958.
  38. Capuron L, Ravaud A, Miller AH, Dantzer R: Baseline mood and psychosocial characteristics of patients developing depressive symptoms during interleukin-2 and/or interferon-alpha cancer therapy. Brain Behav Immunol 2004;18:205-213.

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50