Serum Serotonin Levels are Associated with Antiviral Therapy Outcomes in Patients with Chronic Hepatitis C

Abstract

The role of serotonin in contributing to viral clearance has not been investigated in patients with chronic hepatitis C (HCV). In this prospective study we collected blood samples from 39 patients prior to and during antiviral therapy. Participants completed mood rating scales to monitor psychiatric symptoms, and serum serotonin and tryptophan levels were measured. Significant differences in serotonin levels were found between patients who achieved sustained viral responses (SVRs) and those who did not. Regression analysis revealed that serotonin was the only variable with a statistically significant relationship with antiviral therapy outcomes, even after controlling for other variables known to be associated with outcomes. Baseline serum serotonin levels, in combination with other variables such as degree of liver fibrosis, may be clinically useful for identifying patients in whom HCV can be cleared by antiviral therapy. Additional clinical predictors that could forecast treatment success are needed so that interventions to improve SVR rates, and reduce side effects, can be developed.

Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: A 16-week prospective study

“…Consistent with our previous report [16], we found that in the total sample of patients, serotonin levels were significantly lower after 16 weeks of antiviral therapy, as compared to baseline (week 0) ( t =6.16, df =30, p <.0001). The Low and High Somatic groups did not show significant between-group differences in serotonin levels at week 16.…”

“…IFN stimulates indolamine 2,3-dioxygenase (IDO) which leads to a peripheral depletion of tryptophan [15]. Patients on IFN therapy have altered serum levels of tryptophan (a serotonin precursor) and serotonin [16,17], and some of these changes in the serotonergic system are associated with increased depressive symptoms [18,19], as well as with alterations in specific cytokine levels [20]. However, more recent reports including our own findings do not support consistent correlations between IFN-induced depression and serotonin or tryptophan levels [16,21–24].…”

“…Patients on IFN therapy have altered serum levels of tryptophan (a serotonin precursor) and serotonin [16,17], and some of these changes in the serotonergic system are associated with increased depressive symptoms [18,19], as well as with alterations in specific cytokine levels [20]. However, more recent reports including our own findings do not support consistent correlations between IFN-induced depression and serotonin or tryptophan levels [16,21–24]. Given that both pro-inflammatory cytokines (e.g., interferons) and HCV are associated with an upregulation of indolamine 2,3 dioxygenase (an enzyme which converts tryptophan into kynurenine) [25], further research is needed to determine more sensitive markers of serotonin metabolism which could be used to predict or influence IFN-induced depression in patients with HCV.…”

5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

“…The rats had at least 5 days to recover before 25B-NBOMe was administered. The effects of 6-OHDA and 5,7-DHT were confirmed by measuring catecholamine and serotonin levels in brain tissue using high-performance liquid chromatography (Loftis et al, 2010).…”

Immunological dynamics associated with rapid virological response during the early phase of type I interferon therapy in patients with chronic hepatitis C

“…Additionally, when we analyzed the diverse cytokine responses, only the levels of IL-17A, IP-10, and FGF among a total of 11 cytokines were significantly associated with RVR in a viral genotype-dependent manner (Table 2 and Fig 1). Baseline levels of several cellular factors such as TSLP [38] and serotonin [39], were also poorly correlated with early virological outcomes upon treatment. Lower IL-17A, FGF, and VEGF levels were differentially measured in the plasma of RVR patients than in that of the non-RVR group when infected with genotype 1.…”