Asymmetric Dimethylarginine Responses During Interferon-α–Induced Depression in Patients With Chronic Hepatitis C Infection

OBJECTIVE: The aim of this study was to examine the association of depressive symptoms with asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Patients with chronic hepatitis C infection were examined during interferon-α (IFN-α) treatment, which is often associated with treatment-induced depression. The associations between IFN-α-induced depressive symptoms with ADMA and SDMA levels were prospectively investigated until 3 months after treatment. METHODS: Psychiatric and biological assessments were obtained at six different time points: before, during (at 1, 3, 6, and 9 months), and after the end of IFN-α treatment. RESULTS: During IFN-α treatment, 22 (53.7%) patients fulfilled the criteria for a treatment-related depressive disorder at least once during treatment. The increase in ADMA levels from baseline (depression group: 0.63 [0.08] μM, no depression group: 0.69 [0.08] μM) in response to IFN-α treatment was considerably higher in patients with IFN-α treatment-induced depressive episodes compared with patients without treatment-induced depressive episodes (3 months after the start of treatment: depression group: 0.72 [0.08] μM, no depression group: 0.72 [0.11] μM; ADMA: repeated-measure design analysis of variance [time × depression]: F(5,151) = 2.446, p = .036). The increase in SDMA was not associated with treatment-induced depression. CONCLUSIONS: Depression in response to IFN-α treatment is associated with elevated ADMA levels. These findings are relevant to nitric oxide-related biological pathways linking depression to increased cardiovascular disease risk. Future studies are needed to clarify the role of serotonin in these pathways and may lead to preventative treatment strategies.