Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-07-07T13:46:02.957Z Has data issue: false hasContentIssue false
  • English
  • Français

Cognitive impairment in patients with chronic hepatitis treated with interferon alpha (IFNα): results from a prospective study

Published online by Cambridge University Press:  16 April 2020

Klaus Lieb ,
Marc A. Engelbrecht ,
Oliver Gut ,
Bernd L. Fiebich ,
Joachim Bauer ,
Gesa Janssen  and
Martin Schaefer
Klaus Lieb
Affiliation:
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, 79104Freiburg, Germany
Marc A. Engelbrecht
Affiliation:
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, 79104Freiburg, Germany
Oliver Gut
Affiliation:
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, 79104Freiburg, Germany
Bernd L. Fiebich
Affiliation:
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Hauptstr. 5, 79104Freiburg, Germany
Joachim Bauer
Affiliation:
Department of Psychosomatics, University of Freiburg Medical School, Hauptstr. 8, 79104Freiburg, Germany
Gesa Janssen
Affiliation:
Department of Psychiatry, Charité-University Medicine Berlin, Campus Charité Mitte, Schumannstr. 20/21, 10117Berlin, Germany
Martin Schaefer*
Affiliation:
Department of Psychiatry, Charité-University Medicine Berlin, Campus Charité Mitte, Schumannstr. 20/21, 10117Berlin, Germany
*
*Corresponding author. Tel.: +49 30 450 517011; fax: +49 30 450 517922. E-mail address: [email protected]
Get access

Abstract

Background.

Treatment with low-dose interferon alpha (IFN-α) is often associated with neuropsychiatric side effects. In addition to depression and anxiety, IFN-α associated cognitive impairment significantly affects patient’s mental health and quality of life.

Aims of the study.

To measure possible effects of low-dose IFN-α on cognitive functioning and its relationship to the development of depression and anxiety.

Method.

We prospectively followed 38 patients with a chronic hepatitis B or C by neuropsychological tests and psychiatric self-rating scales during 12 weeks of low-dose treatment with IFN-α.

Results.

Before IFN-α treatment, neuropsychological tests as well as self-ratings in the Beck’s Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS) and the Self-Report Symptom Inventory 90 Items-Revised (SCL-90-R) were within the normal range. Following 12 weeks of treatment with IFN-α resulted in a slight, but significant increase in depression scores. Neuropsychological assessment after 12 weeks of IFN-α treatment showed a significant decrease of the immediate recall in the Auditory-Verbal Learning Test (AVLT) and a significant reduction of words recited in the Controlled Oral Word Association Test (COWA). Cognitive impairment did not significantly correlate with depressive symptoms or anxiety.

Conclusion.

Our results indicate that even low-dose IFN-α induces cognitive impairment independent from depressive symptoms, which might be related to functional disturbances in the prefrontal cortex and the hippocampus. We suggest close monitoring of cognitive function during IFN-α treatment of chronic hepatitis.

Keywords

InterferonCytokineCognitionDepressionAnxiety
Type
Original articles
Information
European Psychiatry , Volume 21 , Issue 3 , April 2006 , pp. 204 - 210
Copyright
Copyright © European Psychiatric Association 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Beck, A.T., Ward, C.H., Mendelson, M., Mock, J., Erbaugh, J.An inventory for measuring depression. Arch. Gen. Psychiatry 1961;4:561–571.CrossRefGoogle ScholarPubMed
Benton, A.L.Neuropsychological assessment. Annu. Rev. Psychol 1994;45:1–23.CrossRefGoogle ScholarPubMed
Capuron, L., Neurauter, G., Musselman, D.L., Lawson, D.H., Nemeroff, C.B., Fuchs, D., et al.Interferon-alpha-induced changes in tryptophan metabolism. Relationship to depression and paroxetine treatment. Biol. Psychiatry 2003;54:906–914.CrossRefGoogle ScholarPubMed
Carpiniello, B., Orru, M.G., Baita, A., Pariante, C.M., Farci, G.Mania induced by withdrawal of treatment with interferon alfa. Arch. Gen. Psychiatry 1998;55:88–89.CrossRefGoogle ScholarPubMed
Chao, C.C., Hu, S.Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures. Dev. Neurosci 1994;16:172–179.CrossRefGoogle ScholarPubMed
Chao, C.C., Hu, S., Ehrlich, L., Peterson, P.K.Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-d-aspartate receptors. Brain Behav. Immun 1995;9:355–365.CrossRefGoogle ScholarPubMed
Dieperink, E., Willenbring, M., Ho, S.B.Neuropsychiatric symptoms associated with hepatitis C and interferon alpha: a review. Am. J. Psychiatry 2000;157:867–876.CrossRefGoogle ScholarPubMed
Fattovich, G., Giustina, G., Favarato, S., Ruol, A.A survey of adverse events in 11,241 patients with chronic viral hepatitis treated with alfa interferon. J. Hepatol 1996;24:38–47.CrossRefGoogle ScholarPubMed
Franke, G.SCL-90-R: Die Symptom-Checkliste von derogatis—Deutsche Version. 1st ed., Goettingen GmbH: Beltz Test; 2002.Google Scholar
Goldman-Rakic, P.S. In: Circuity of the Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory. 1987. p. 75–81.Google Scholar
Haria, M., Benfield, P.Interferon-alpha-2a. A review of its pharmacological properties and therapeutic use in the management of viral hepatitis. Drugs 1995;50:873–896.CrossRefGoogle ScholarPubMed
Hauser, P., Khosla, J., Aurora, H., Laurin, J., Kling, M.A., Hill, J., et al.A prospective study of the incidence and open-label treatment of interferon-induced major depressive disorder in patients with hepatitis C. Mol. Psychiatry 2002;7:942–947.CrossRefGoogle ScholarPubMed
Herrmann, C.International experiences with the Hospital Anxiety and Depression Scale—a review of validation data and clinical results. J. Psychosom. Res 1997;42:17–41.CrossRefGoogle ScholarPubMed
Heubrock, D.The Auditory Verbal Learning Test (AVLT) in clinical and experimental neuropsychology: administration, evaluation and research findings. Z. Differentielle Diagn. Psychol 1992;13:161–174.Google Scholar
Hu, S., Sheng, W.S., Ehrlich, L.C., Peterson, P.K., Chao, C.C.Cytokine effects on glutamate uptake by human astrocytes. Neuroimmunomodulation 2000;7:153–159.CrossRefGoogle ScholarPubMed
Hunt, C.M., Dominitz, J.A., Bute, B.P., Waters, B., Blasi, U., Williams, D.M.Effect of interferon-alpha treatment of chronic hepatitis C on health-related quality of life. Dig. Dis. Sci 1997;42:2482–2486.CrossRefGoogle ScholarPubMed
Janssen, H.L., Brouwer, J.T., Van der Mast, R.C., Schalm, S.W.Suicide associated with alfa-interferon therapy for chronic viral hepatitis. J. Hepatol 1994;21:241–243.CrossRefGoogle ScholarPubMed
Juengling, F.D., Ebert, D., Gut, O., Engelbrecht, M.A., Rasenack, J., Nitzsche, E.U., et al.Prefrontal cortical hypometabolism during low-dose interferon alpha treatment. Psychopharmacology (Berlin) 2000;152:383–389.CrossRefGoogle ScholarPubMed
Katafuchi, T., Take, S., Hori, T.Roles of cytokines in the neural-immune interactions: modulation of NMDA responses by IFN-alpha. Neurobiology (Bp.) 1995;3:319–327.Google ScholarPubMed
Kirkwood, J.M., Bender, C., Agarwala, S., Tarhini, A., Shipe-Spotloe, J., Smelko, B., et al.Mechanisms and management of toxicities associated with high-dose interferon alfa-2b therapy. J. Clin. Oncol 2002;20:3703–3718.CrossRefGoogle ScholarPubMed
Kizilbash, A.H., Vanderploeg, R.D., Curtiss, G.The effects of depression and anxiety on memory performance. Arch. Clin. Neuropsychol 2002;17:57–67.CrossRefGoogle ScholarPubMed
Malaguarnera, M., Di, F.I., Restuccia, S., Pistone, G., Ferlito, L., Rampello, L.Interferon alpha-induced depression in chronic hepatitis C patients: comparison between different types of interferon alpha. Neuropsychobiology 1998;37:93–97.CrossRefGoogle ScholarPubMed
Malik, U.R., Makower, D.F., Wadler, S.Interferon-mediated fatigue. Cancer 2001;92:1664–1668.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
McDonald, E.M., Mann, A.H., Thomas, H.C.Interferons as mediators of psychiatric morbidity. An investigation in a trial of recombinant alpha-interferon in hepatitis-B carriers. Lancet 1987;2:1175–1178.CrossRefGoogle Scholar
Mendoza-Fernandez, V., Andrew, R.D., Barajas-Lopez, C.Interferon-alpha inhibits long-term potentiation and unmasks a long-term depression in the rat hippocampus. Brain Res 2000;885:14–24.CrossRefGoogle ScholarPubMed
Meyers, C.A., Obbens, E.A., Scheibel, R.S., Moser, R.P.Neurotoxicity of intraventricularly administered alpha-interferon for leptomeningeal disease. Cancer 1991;68:88–92.3.0.CO;2-5>CrossRefGoogle ScholarPubMed
Meyers, C.A., Scheibel, R.S., Forman, A.D.Persistent neurotoxicity of systemically administered interferon-alpha. Neurology 1991;41:672–676.CrossRefGoogle ScholarPubMed
Miyaoka, H., Otsubo, T., Kamijima, K., Ishii, M., Onuki, M., Mitamura, K.Depression from interferon therapy in patients with hepatitis C. Am. J. Psychiatry 1999;156:1120.Google ScholarPubMed
Nozaki, O., Takagi, C., Takaoka, K., Takata, T., Yoshida, M.Psychiatric manifestations accompanying interferon therapy for patients with chronic hepatitis C: an overview of cases in Japan. Psychiatry Clin. Neurosci 1997;51:175–180.CrossRefGoogle ScholarPubMed
Okanoue, T., Sakamoto, S., Itoh, Y., Minami, M., Yasui, K., Sakamoto, M., et al.Side effects of high-dose interferon therapy for chronic hepatitis C. J. Hepatol 1996;25:283–291.CrossRefGoogle ScholarPubMed
Oswald, W.D., Roth, E.Der Zahlen-Verbindungs-Test (ZVT) Handanweisung. 2nd ed., Goettingen, Toronto, Zuerich: Verlag für Psychologie; 1994.Google Scholar
Pavol, M.A., Meyers, C.A., Rexer, J.L., Valentine, A.D., Mattis, P.J., Talpaz, M.Pattern of neurobehavioral deficits associated with interferon alfa therapy for leukemia. Neurology 1995;45:947–950.CrossRefGoogle ScholarPubMed
Prior, T.I., Chue, P.S.Psychotic depression occurring after stopping interferon-alpha. J. Clin. Psychopharmacol 1999;19:385–386.CrossRefGoogle ScholarPubMed
Renault, P.F., Hoofnagle, J.H.Side effects of alpha interferon. Semin. Liver Dis 1989;9:273–277.CrossRefGoogle ScholarPubMed
Renault, P.F., Hoofnagle, J.H., Park, Y., Mullen, K.D., Peters, M., Jones, D.B., et al.Psychiatric complications of long-term interferon alfa therapy. Arch. Intern. Med 1987;147:1577–1580.CrossRefGoogle ScholarPubMed
Rifflet, H., Vuillemin, E., Oberti, F., Duverger, P., Laine, P., Garre, J.B., et al.Suicidal impulses in patients with chronic viral hepatitis C during or after therapy with interferon alpha. Gastroenterol. Clin. Biol 1998;22:353–357.Google ScholarPubMed
Scalori, A., Apale, P., Panizzuti, F., Mascoli, N., Pioltelli, P., Pozzi, M., et al.Depression during interferon therapy for chronic viral hepatitis: early identification of patients at risk by means of a computerized test. Eur. J. Gastroenterol. Hepatol 2000;12:505–509.CrossRefGoogle ScholarPubMed
Schaefer, M., Boetsch, T., Laakmann, G.Psychosis in a methadone-substituted patient during interferon-alpha treatment of hepatitis C. Addiction 2000;95:1101–1104.Google Scholar
Schaefer, M., Engelbrecht, M.A., Gut, O., Fiebich, B.L., Bauer, J., Schmidt, F., et al.Interferon alpha (IFNalpha) and psychiatric syndromes: a review. Prog Neuropsychopharmacol. Biol. Psychiatry 2002;26:731–746.CrossRefGoogle ScholarPubMed
Schaefer, M., Schmidt, F., Horn, M., Schmid-Wendtner, M.H., Volkenandt, M.Depression during treatment with interferon alpha. Psychosomatics 2004;45:176.CrossRefGoogle ScholarPubMed
Shad, J.A., McHutchison, J.G.Current and future therapies of hepatitis C. Clin. Liver Dis 2001;5:335–359.CrossRefGoogle ScholarPubMed
Squire, L.R.Memory systems. C. R. Acad. Sci. III 1998;321:153–156.CrossRefGoogle ScholarPubMed
Squire, L.R., Zola, S.M.Episodic memory, semantic memory, and amnesia. Hippocampus 1998;8:205–211.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Strite, D., Valentine, A.D., Meyers, C.A.Manic episodes in two patients treated with interferon alpha. J. Neuropsychiatry Clin. Neurosci 1997;9:273–276.Google ScholarPubMed
Trask, P.C., Esper, P., Riba, M., Redman, B.Psychiatric side effects of interferon therapy: prevalence, proposed mechanisms, and future directions. J. Clin. Oncol 2000;18:2316–2326.CrossRefGoogle ScholarPubMed
Tulving, E., Markowitsch, H.J.Episodic and declarative memory: role of the hippocampus. Hippocampus 1998;8:198–204.3.0.CO;2-G>CrossRefGoogle ScholarPubMed
Valentine, A.D., Meyers, C.A.Successful treatment of interferon-alpha-induced mood disorder with nortriptyline. Psychosomatics 1995;36:418–419.CrossRefGoogle ScholarPubMed
Valentine, A.D., Meyers, C.A., Kling, M.A., Richelson, E., Hauser, P.Mood and cognitive side effects of interferon-alpha therapy. Semin. Oncol 1998;25:39–47.Google ScholarPubMed
Vargha-Khadem, F., Gadian, D.G., Watkins, K.E., Connelly, A., Van Paesschen, W., Mishkin, M.Differential effects of early hippocampal pathology on episodic and semantic memory. Science 1997;277:376–380.CrossRefGoogle ScholarPubMed
Wichers, M.C., Maes, M.The role of indoleamine 2,3-dioxygenase (IDO) in the pathophysiology of interferon-alpha-induced depression. J. Psychiatry Neurosci 2004;29:11–17.Google ScholarPubMed
Zdilar, D., Franco-Bronson, K., Buchler, N., Locala, J.A., Younossi, Z.M.Hepatitis C, interferon alfa, and depression. Hepatology 2000;31:1207–1211.CrossRefGoogle ScholarPubMed
Zigmond, A.S., Snaith, R.P.The Hospital Anxiety and Depression Scale. Acta Psychiatr. Scand 1983;67:361–370.CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.