A Preliminary Study on the Relationship between Platelet Serotonin Transporter Functionality, Depression, and Fatigue in Patients with Untreated Chronic Hepatitis C

Abstract

Objective and Methods. Although the interaction between fatigue and depression in patients with chronic hepatitis C infection (HCV) has been recognized, the biological correlates of this observation have yet to be reported. We addressed this issue by examining serotonin transporter- (SERT-) driven [(14)C]-serotonin uptake rate (SUR) and serotonin content in platelets of 65 untreated HCV patients and 65 healthy control subjects (HCS). All patients completed report questionnaires for fatigue, depression, and general psychopathology. Structured interviews were conducted by a board-certified psychiatrist. Results. Whereas 36 of the patients experienced fatigue of moderate-to-severe intensity, only 16 reported symptoms of depression (BDI score > 10). Mean SUR in patients with depressive symptoms was significantly higher relative to the HCS, corresponding to a large Cohen's effect size of d = 1.45 (95% CI = 0.66-1.83). Patients who rated their fatigue to have a marked impact on mood and activity displayed a moderate relationship between the BDI score and SUR (n = 18, r = 0.563, P = 0.015), which becomes stronger after controlling for age, gender, and thrombocytopenia (r part = 0.710, P = 0.003). In the univariate analysis, high fatigue interference score, thrombocytopenia, and high SUR were all significant predictors of depression. Conclusions. High SERT activity could be implicated in the expression of depressive symptoms especially in a subgroup of HCV patients who are feeling fatigue as markedly distressing.

Figure 1

Interference of fatigue with mood and activity in patients categorized in mild, moderate, and severe fatigue intensity groups. Note: mean fatigue interference score = arithmetic mean of BFI items 4–9; the dotted line indicates the cutoff for moderate-to-severe interference score.

Figure 2

Relationship between BDI and BFI intensity scale (a) or BFI interference scale (b) in patients with chronic hepatitis C. Note. BDI: Beck Depression Inventory; BFI: Brief Fatigue Inventory; BFI intensity score = mean of three items (fatigue at present, at its usual level, and at its worst); ● previous IFN-α treatment; ○ treatment-naïve.

Figure 3

Relationship between blood platelet count and 5HT uptake rate in platelets of male and female patients with chronic hepatitis C. Note: 5HT uptake rate is expressed in pMol/10⁹ plts.×5 min and platelet count in ×10⁹ plts./L blood.

Figure 4

Relationship between the BDI total score and platelet 5HT uptake rate in patients with differed degrees of fatigue interference with mood and activity. Note: the dotted line indicates the cutoff for classification of BDI scores into depressed and nondepressed.