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Gastroenterology. 2007 Apr;132(4):1279-86. Epub 2007 Feb 25.

Serotonin-1A receptor gene HTR1A variation predicts interferon-induced depression in chronic hepatitis C.

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  • 1Medizinische Klinik und Poliklinik II, Department of Gastroenterology and Hepatology, University of Würzburg, Würzburg, Germany.



Interferon-induced depression is a major complication in antiviral therapy of chronic hepatitis C. Little is known about underlying mechanisms and reliable predictive factors associated with cytokine-induced depressive symptoms.


In a cohort of 139 hepatitis C-infected outpatients treated with interferon alfa-2b, we investigated the impact of functional gene variants of the cerebral serotonin (5-HT) signalling pathway previously implicated in depression risk. Depression was monitored using the Hospital Anxiety and Depression Scale (HADS). All patients were genotyped for functional variations in the 5-HT(1A) receptor (HTR1A), 5-HT transporter (SLC6A4, 5-HTT), and tryptophan hydoxylase-2 (TPH2).


Homozygosity for the HTR1A-1019G variant significantly increased both incidence and severity of interferon-induced depression. Maximum increases in HADS depression scores during antiviral therapy correlated with HTR1A variation (P = .011). Clinically relevant depression was significantly associated with the HTR1A-1019G genotype (P = .017; OR, 2.95). 5-HTT and TPH2 variations did not contribute significantly to the prediction of interferon-induced depression by HTR1A (sensitivity, 35.9%; specificity, 84.0%).


Our findings suggest an impact of allelic variation in 5-HT(1A) receptor expression on the development of interferon alfa-induced depression during antiviral treatment of chronic hepatitis C. Prediction models of interferon-induced depressive symptoms based on HTR1A variation offer a perspective for an antidepressant selective serotonin reuptake inhibitor prophylaxis in patients genetically at risk for interferon-induced depression.

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