Bannink Marjolein, Fekkes Durk, Van Gool Arthur R, Kruit Wim H J, Sleijfer Stefan, van der Holt Bronno, Eggermont Alexander M M, Stoter Gerrit, Hengeveld Michiel W
Department of Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
Neuropsychobiology. 2007;55(3-4):225-31. doi: 10.1159/000108382. Epub 2007 Sep 17.
Interferon-alpha (IFN-alpha) treatment is often associated with psychiatric side effects and has been found to lower the amount of tryptophan (TRP) available to the brain. The alterations in tryptophan metabolism might underlie the psychiatric side effects during treatment with IFN-alpha.
In this study, 43 oncology patients treated with IFN-alpha were included. In order to study de novo depressions, depressed patients at baseline were excluded. Psychiatric evaluation comprising clinical judgment combined with a structured psychiatric interview and observer-based and self-report rating scales was performed at baseline and at 4 weeks, 8 weeks and 6 months after the start of treatment with IFN-alpha, and in the case of emerging psychopathology. Blood samples were drawn at the same evaluation times and assessed for concentrations of TRP, large neutral amino acids, kynurenine, 5-hydroxyindole acetic acid, neopterin and biopterin.
During treatment with IFN-alpha, several alterations in laboratory parameters occurred that were consistent with an increased degradation of peripheral TRP. Psychometric ratings revealed hardly any psychiatric changes. No consistent associations were found between changes in the laboratory assessments determined and the diverse psychiatric measures.
In this study, IFN-alpha was found to alter TRP metabolism without inducing psychiatric side effects. Therefore, a possible relationship between TRP metabolism and depression was not substantiated by this study.
α干扰素(IFN-α)治疗常伴有精神方面的副作用,且已发现其会降低大脑可利用的色氨酸(TRP)量。色氨酸代谢的改变可能是IFN-α治疗期间精神副作用的潜在原因。
本研究纳入了43例接受IFN-α治疗的肿瘤患者。为研究新发抑郁症,排除了基线时的抑郁患者。在基线时、IFN-α治疗开始后的4周、8周和6个月以及出现精神病理学症状时,进行了包括临床判断、结构化精神访谈以及基于观察者和自我报告的评定量表的精神评估。在相同的评估时间采集血样,检测TRP、大分子中性氨基酸、犬尿氨酸、5-羟吲哚乙酸、新蝶呤和生物蝶呤的浓度。
在IFN-α治疗期间,实验室参数出现了一些变化,这些变化与外周TRP降解增加一致。心理测量评定几乎未显示出任何精神方面的改变。在实验室检测结果的变化与各种精神测量指标之间未发现一致的关联。
在本研究中,发现IFN-α可改变TRP代谢,但未诱发精神副作用。因此,本研究未证实TRP代谢与抑郁症之间可能存在的关系。