title: Serotonin and interleukin-6: the role of genetic polymorphisms in IFN-induced neuropsychiatric symptoms.
abstract: BACKGROUND
  Cytokines and serotonin neurotransmission may play an important role on the development of psychopathological symptoms during interferon (IFN) treatment. The aim of the present study was to investigate the association between IFN-induced depression, anxiety and fatigue and functional genetic variants at the interleukin-6 gene (IL-6) and serotonin transporter gene (SERT).
  
  
  METHODS
  385 consecutive Caucasian outpatients with chronic hepatitis C initiating treatment with IFN-alpha and ribavirin were included. All patients were interviewed at baseline using the Structured Clinical Interview for DSM-IV (SCID-I) and those with a current major depressive disorder or anxiety disorder before starting treatment were excluded. Depression and anxiety were assessed at baseline during the treatment (at 4, 12, 24 and 48 weeks) using the Hospital Anxiety and Depression Scale and fatigue was evaluated using a visual analogue scale. The 5-HTTLPR region of SERT gene and the functional polymorphism located at the promoter region of IL-6 gene (rs1800795) were genotyped.
  
  
  RESULTS
  Genotypic distribution was in the Hardy-Weinberg equilibrium for SERT (p=0.41) and for IL-6 (p=0.72) polymorphisms. At baseline we found only a significant effect of IL-6 polymorphism on fatigue symptoms. During antiviral treatment we reported that subjects with CC genotype (IL-6) presented significantly lower changes from baseline in IFN-induced depression (p=0.005) and IFN-induced anxiety (p=0.004). We did not find statistically significant differences on depression (p=0.21) or anxiety (p=0.15) between SS/SL and LL genotypes of SERT.
  
  
  CONCLUSIONS
  Genetic variations in the IL-6 gene increase the risk of IFN-induced depression and anxiety. The IL-6 polymorphism was associated with fatigue rates in patients with chronic hepatitis C before treatment. Our study confirms the role of inflammatory mechanisms in IFN-induced psychopathological symptoms.
authors.affiliation: Department of Psychiatry, Hospital Clínic, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Catalonia, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Udina
authors.forename: José
authors.initials: J
authors.lastname: Moreno-España
authors.forename: Ricard
authors.initials: R
authors.lastname: Navinés
authors.forename: Dolors
authors.initials: D
authors.lastname: Giménez
authors.forename: Klaus
authors.initials: K
authors.lastname: Langohr
authors.forename: Mònica
authors.initials: M
authors.lastname: Gratacòs
authors.forename: Lucile
authors.initials: L
authors.lastname: Capuron
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.forename: Ricard
authors.initials: R
authors.lastname: Solà
authors.forename: Rocío
authors.initials: R
authors.lastname: Martín-Santos
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000627:therapeutic use; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001007:Anxiety / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D015331:Cohort Studies; D003863:Depression / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D004359:Drug Therapy, Combination; D005221:Fatigue / Q000139:chemically induced* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015850:Interleukin-6 / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D017354:Point Mutation; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology; D044465:White People
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000998:Antiviral Agents; C508600:IL6 protein, human; D016898:Interferon-alpha; D015850:Interleukin-6; D011994:Recombinant Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: 5-HTTLPR; Anxiety; Depression; Fatigue; Genetic; Hepatitis C; IL-6; Interferon alpha; Rs1800795; SERT