HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV)

Background: Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-alpha 2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. Materials and methods: The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-alpha 2a/RBV treatment. We used the Montgomery-Asberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times-at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. Results: Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, L-G/L-G, and S/L-G) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. Conclusions: Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression.

Automated summary

The aim of this study was to explore the associations between serotonin gene polymorphisms and tryptophan catabolite concentration during PEG-IFN-alpha 2a treatment, as well as the associations between polymorphisms within HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms. The study found that subjects with C/C genotypes of 5-HT1A and lower-expressing alleles of 5-HTTLPR had higher total depression scores and greater increase in depression scores during treatment. Associations between tryptophan concentrations and TPH-2 and 5-HTTLPR rs25531 genotypes were also observed.