A functional serotonin transporter gene polymorphism and depressive effects associated with interferon-alpha treatment

Psychosomatics. Mar-Apr 2010;51(2):137-48. doi: 10.1176/appi.psy.51.2.137.


Background: Interferon-alpha (IFN-alpha) treatment frequently induces depression, potentially leading to early dose reductions or a shorter duration of treatment, which can adversely affect outcomes, including quality of life.

Objective: Defining relevant risk factors for IFN-alpha-induced depression is essential in order to identify prophylactic treatment strategies.

Method: The authors examined whether a functional polymorphism (5-HTTLPR) in the gene encoding the serotonin transporter moderates IFN-alpha-induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN-alpha and ribavirin. Depressive symptoms were assessed at baseline, 12 weeks, and 20 weeks of treatment.

Results: Depression symptoms increased during antiviral treatment; 5-HTTLPR genotype moderated IFN-alpha-induced depression symptoms in both non-Hispanic Caucasians and Hispanic patients, although the opposite risk allele was associated with depression in the two populations.

Conclusion: 5-HTTLPR may moderate risk for the development of depressive symptoms during IFN-alpha therapy for CHC in a population-specific manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antiviral Agents / adverse effects*
  • Depressive Disorder / chemically induced*
  • Depressive Disorder / ethnology
  • Depressive Disorder / genetics*
  • Ethnicity / statistics & numerical data
  • Female
  • Gene Frequency
  • Genotype
  • Hepatitis C / drug therapy*
  • Humans
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Prevalence
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • United States / epidemiology


  • Antiviral Agents
  • Interferon-alpha
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins

Grant support