title: Biological mechanisms of depression following treatment with interferon for chronic hepatitis C: A critical systematic review.
abstract: A significant subset of patients infected by the hepatitis C virus (HCV) develops a major depressive episode (MDE) during Interferon-alpha (IFN-α) based immunotherapy. We performed a systematic review of studies which examined biological mechanisms contributing to the onset of a MDE during IFN-α-based immunotherapy for HCV.
  
  
  
  Major electronic databases were searched from inception up until 15th February 2016 for peer-reviewed prospective studies that had enrolled HCV infected patients who received IFN-α treatment. A diagnosis of MDE had to be established by means of a standardized diagnostic interview at baseline and endpoint.
  
  
  
  Eight unique references met inclusion criteria. A total of 826 participants with HCV (37.3% females, mean age 46.7 years) were included in this systematic review. The overall MDE incidence rate was 34.8%, with follow-up ranging between 4 and 48 weeks. The methodological quality varied across selected studies. It was observed that Interleukin-6, salivary cortisol, arachidonic acid / eicosapentaenoicacid plus docosahexaenoic acid ratio, and genetic polymorphisms may present variations which are linked to a predisposition to INF-α-induced depression.
  
  
  
  A meta-analysis could not be performed due to the diverse biological mechanisms investigated and the lack of replicated evidence.
  
  
  
  This systematic review indicates that several potential mechanisms may be implicated in the onset of a MDE following IFN-α-based immunotherapy for chronic HCV. However, replicated evidence is lacking and therefore the mechanisms involved in IFN-α-induced depression in humans remain unclear.
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Myrela O
authors.initials: MO
authors.lastname: Machado
authors.affiliation: Department of Psychiatry and psychology, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM and Department of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Oriolo
authors.affiliation: Department of Mental Health ULSS 10 "Veneto Orientale", Venice, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortolato
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: IMPACT Strategic Research Centre, Deakin University, School of Medicine and Barwon Health, Geelong, VIC, Australia; Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Department of Psychiatry, Faculty of Medicine, State University of Londrina, Londrina, Brazil; Department of Psychiatry, Medical University Plovdiv, Plovdiv, Bulgaria; Revitalis, Waalre, The Netherlands.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
authors.affiliation: Department of Neuroscience, University of Padova, Padova, Italy; Mental Health Department, Local Health Unit ULSS 17, Monselice, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
authors.forename: Iria
authors.initials: I
authors.lastname: Grande
authors.affiliation: Department of Psychiatry and psychology, Institute of Neuroscience, Hospital Clinic, IDIBAPS, CIBERSAM and Department of Medicine, University of Barcelona, Barcelona, Catalonia, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
authors.affiliation: Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Vieta
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Neuroscience, University of Padova, Padova, Italy; Mental Health Department, Local Health Unit ULSS 17, Monselice, Padova, Italy. Electronic address: andrefc7@terra.com.br.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003863:Depression / Q000097:blood / Q000139:chemically induced* / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D000998:Antiviral Agents; C508600:IL6 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6
keywords: Depression; Hepatitis C; Inflammation; Interferon-alpha; Psychoneuroimmunology