A Functional Serotonin Transporter Gene Polymorphism and Depressive Effects Associated With Interferon- α Treatment

• Published in: Psychosomatics (Washington, D.C.) Vol. 51; no. 2; pp. 137 - 148
• Main Authors: Pierucci-Lagha, Amira, Ph.D, Covault, Jonathan, M.D., Ph.D, Bonkovsky, Herbert L., M.D, Feinn, Richard, Ph.D, Abreu, Christine, M.S, Sterling, Richard K., M.D, Fontana, Robert J., M.D, Kranzler, Henry R., M.D
• Format: Journal Article
• Language: English
• Published: Arlington, VA Elsevier Inc 01.03.2010; American Psychiatric Publishing
• Subjects: Alleles; Antiviral Agents - adverse effects; Biological and medical sciences; Depressive Disorder - chemically induced; Depressive Disorder - ethnology; Depressive Disorder - genetics; Drug toxicity and drugs side effects treatment; Ethnicity - statistics & numerical data; Female; Gene Frequency; Genotype; Hepatitis C - drug therapy; Humans; Interferon-alpha - therapeutic use; Internal Medicine; Male; Medical sciences; Middle Aged; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Polymorphism, Genetic - genetics; Prevalence; Psychiatry; Serotonin Plasma Membrane Transport Proteins - genetics; United States - epidemiology; United States; North America; America; Mood disorder; Social environment; Human; Alpha interferon; Toxicity; Multicenter study; Mental health; Pharmacotherapy; Hepatic disease; Depression; Genetic determinism; Infection; Symptomatology; Treatment; Follow up study; Viral disease; Risk factor; Genetics; Digestive diseases; Antiviral; Evolution; Public health; Viral hepatitis C; Polymorphism
• ISSN: 0033-3182; 1545-7206
• DOI: 10.1016/S0033-3182(10)70674-5

Background Interferon-alpha (IFN- α ) 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- α -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- α -induced depressive symptoms in 1,015 patients with chronic hepatitis C (CHC) receiving pegylated IFN- α 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- α -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- α therapy for CHC in a population-specific manner.