HEPATITIS

Monoaminergic neurotransmission is altered in hepatitis C virus infected patients with chronic fatigue and cognitive impairment

K Weissenborn¹, J C Ennen¹, M Bokemeyer², B Ahl¹, U Wurster¹, H Tillmann³, C Trebst¹, H Hecker⁴, G Berding⁵

¹ Department of Neurology, Medizinische Hochschule Hannover, Hannover, Germany
² Department of Neuroradiology, Medizinische Hochschule Hannover, Hannover, Germany
³ Department of Gastroenterology, Hepatology, and Endocrinology, Medizinische Hochschule Hannover, Hannover, Germany
⁴ Department of Biometrics, Medizinische Hochschule Hannover, Hannover, Germany
⁵ Department of Nuclear Medicine, Medizinische Hochschule Hannover, Hannover, Germany

Correspondence to:
Professor K Weissenborn
Neurologische Klinik, Medizinische Hochschule Hannover, 30623 Hannover, Germany; Weissenborn.Karin{at}mh-hannover.de

Background: The majority of patients with hepatitis C virus (HCV) infection suffer from disabling fatigue, cognitive dysfunction, and quality of life reduction. Meanwhile, there is increasing evidence that HCV infection can affect brain function. Recent studies have shown that fatigue and psychomotor slowing may resolve in patients with hepatitis C after treatment with ondansetron. This observation indicates alteration of serotonergic neurotransmission in HCV infected patients with chronic fatigue.

Methods: Data from 20 HCV infected patients who were referred to our clinic because of disabling fatigue and cognitive decline of unknown cause were analysed retrospectively. Patients had undergone a diagnostic programme, including clinical and psychometric examination, electroencephalogram (EEG), magnetic resonance imaging of the brain, cerebrospinal fluid analysis, and I-123-beta-CIT (2ß-carbomethoxy-3-ß-(4-[¹²³I]iodophenyl)tropane) single photon emission computerised tomography (SPECT) studies of serotonin and dopamine transporter binding capacity.

Results: All patients had pathological results on the fatigue impact scale. Two thirds of patients showed pathological attention test results. EEG, magnetic resonance imaging, and cerebrospinal fluid analysis were normal. Pathological dopamine transporter binding was present in 12/20 (60%) patients and pathological serotonin transporter binding in 8/19 (50%) patients. Patients with normal SPECT results did not significantly differ from controls with regard to psychometric test results. Interestingly, patients with both decreased serotonin and dopamine transporter binding showed significantly impaired performance in most of the tests applied. Comorbidity that could have impaired cerebral function was excluded in all patients.

Conclusion: Our findings indicate alteration of serotonergic and dopaminergic neurotransmission in HCV infected patients with chronic fatigue and cognitive impairment.

Abbreviations: BDI, Beck’s depression inventory; CSF, cerebrospinal fluid; CNS, central nervous system; DAT, dopamine transporter binding; EEG, electroencephalogram; FIS, fatigue impact scale; HADS, hospital anxiety and depression scale; HCV, hepatitis C virus; HIV, human immunodeficiency virus; I-123-beta-CIT, 2ß-carbomethoxy-3-ß-(4-[¹²³I]iodophenyl)tropane; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; SPECT, single photon emission computerised tomography; SERT, serotonin transporter binding; TAP, Testbatterie zur Aufmerksamkeitsprüfung (battery of attention tests)

Keywords: hepatitis C; chronic fatigue; cognitive dysfunction; serotonin; dopamine

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