Functional Polymorphism in the Interleukin 6 (IL6) Gene with Respect to Depression Induced in the Course of Interferon-α and Ribavirin Treatment in Chronic Hepatitis Patients.

Dorota Frydecka,Krzysztof Małyszczak,Tomasz Pawłowski,Dariusz Pawlak

doi:10.1007/s00005-016-0441-7

Abstract

Interleukin (IL)-6 is a multifactorial cytokine known to be increased in patients with chronic hepatitis C (CHC) and to be predictive of depression incidence. The aim of the study was to explore the association between IL6 gene C-174G polymorphism and depressive symptom severity in the longitudinal study design following the course of pegylated interferon/ribavirin treatment in CHC patients. In our study, we included 62 CHC subjects. They were assessed using present state examination, Beck Depression Inventory (BDI) and Montgomery Åsberg Depression Rating Scale (MADRS) at weeks 0, 3, 5, 9, 13, 24 and 24 weeks after the end of treatment. The risk of depression was associated with higher baseline MADRS score and BDI score. Interestingly, when stratified by IL6 C-174G polymorphism, higher baseline depressive symptom severity measured by MADRS and BDI predicted higher risk of depression in the course of antiviral treatment only in high IL-6 producers—G allele carriers (patients with GG and CG genotypes) (p = 0.004, p = 0.00008, respectively). There is interaction between severity of baseline depressive symptoms at the beginning of antiviral therapy and IL6 gene C-174G polymorphism leading to increased risk for the development of depressive episode in CHC patients in the course of antiviral treatment.

Highlights

Interferon (IFN)-a is the main pharmacological treatment for chronic hepatitis C virus (HCV) infection, because of its potent antiviral, antiproliferation and immunomodulatory properties (Lamers et al 2012); at the same time IFN-a is known to induce several neuropsychiatric side effects, including anorexia, fatigue, lethargy, loss of interest, lack of concentration, irritability, cognitive decline, emotional lability and social withdrawal (Cattie et al 2014)
The depressive symptoms were diminished 24 weeks after the end of the treatment as assessed by Montgomery Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) (5.37 ± 6.35 and 4.75 ± 7.76, respectively; p \ 0.0001) reaching the level of depression assessed at the beginning of treatment by MADRS and BDI (p = 0.25 and p = 0.11, respectively; Fig. 1)
After stratifying patients according to the IL-6 gene (IL6) gene C-174 gene polymorphism genotypes, we have shown that higher baseline depressive symptom severity measured by MADRS and BDI predicted higher risk of depression in the course of antiviral treatment in G only allele carriers (p = 0.004, p = 0.00008, respectively; Table 4)

Summary

Introduction

Interferon (IFN)-a is the main pharmacological treatment for chronic hepatitis C virus (HCV) infection, because of its potent antiviral, antiproliferation and immunomodulatory properties (Lamers et al 2012); at the same time IFN-a is known to induce several neuropsychiatric side effects, including anorexia, fatigue, lethargy, loss of interest, lack of concentration, irritability, cognitive decline, emotional lability and social withdrawal (Cattie et al 2014). Depression is a common side effect and in some rare cases may be associated with deliberate self-harm or suicide attempts. Identification of risk factors that lead to depression may help to recognize patients at risk who may benefit from additional psychological support (Smith et al 2011).

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