The possible role of the kynurenine pathway in anhedonia in adolescents
The possible role of the kynurenine pathway in anhedonia in adolescents
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DOI：
10.1007/s00702-011-0685-7
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发表时间：
2012-02-01
影响因子：
3.3
通讯作者：
Liebes, Leonard
中科院分区：
文献类型：
--
作者：
Gabbay, Vilma;Ely, Benjamin A.;Liebes, Leonard
为了解决青少年重度抑郁症（MDD）的异质性，我们调查了快感缺乏，MDD的核心症状。我们最近报道了犬尿氨酸途径（KP）的激活，这是一种中枢神经免疫途径，将色氨酸（TRP）代谢成犬尿氨酸（KYN），并将其转化为几种神经毒素，在一组高度快感缺乏的MDD青少年中。在这项研究中，我们的目的是扩展我们之前的工作，并在一组重度抑郁症青少年和一组重度抑郁症和健康对照青少年中定量测量KP活性和快感缺乏症之间的关系。36名MDD青少年（22名未服药）和20名对照纳入分析。快感缺乏症评分是根据临床医生和受试者评定的评估和半结构化的临床医生访谈得出的。血液KP代谢物，在一夜禁食后收集在AM，使用高效液相色谱法测量。KP的限速酶为吲哚胺2,3-双加氧酶（IDO），由KYN/TRP比值估计。在控制重度抑郁症严重程度的同时，使用Pearson相关检验来评估快感缺乏评分和KP测量之间的相关性。在无精神药物治疗的MDD青少年组（r = 0.42, P = 0.05）以及MDD与健康对照组（含药物治疗组：r = 0.30, P = 0.02；不含药物治疗组：r = 0.44, P = 0.004）中，IDO活性与缺乏症评分呈正相关。总之，我们的研究结果进一步支持了KP，特别是IDO在青少年重度抑郁症快感缺乏中的作用。这些结果强调了维度方法在精神疾病调查中的重要性。
To address the heterogeneous nature of adolescent major depression (MDD), we investigated anhedonia, a core symptom of MDD. We recently reported activation of the kynurenine pathway (KP), a central neuroimmunological pathway which metabolizes tryptophan (TRP) into kynurenine (KYN) en route to several neurotoxins, in a group of highly anhedonic MDD adolescents. In this study, we aimed to extend our prior work and examine the relationship between KP activity and anhedonia, measured quantitatively, in a group of MDD adolescents and in a combined group of MDD and healthy control adolescents. Thirty-six adolescents with MDD (22 medication-free) and 20 controls were included in the analysis. Anhedonia scores were generated based on clinician- and subject-rated assessments and a semi-structured clinician interview. Blood KP metabolites, collected in the AM after an overnight fast, were measured using high-performance liquid chromatography. The rate-limiting enzyme of the KP, indoleamine 2,3-dioxygenase (IDO), was estimated by the ratio of KYN/TRP. Pearson correlation tests were used to assess correlations between anhedonia scores and KP measures while controlling for MDD severity. IDO activity and anhedonia scores were positively correlated in the group psychotropic medication-free adolescents with MDD (r = 0.42, P = 0.05) and in a combined group of MDD subjects and healthy controls (including medicated patients: r = 0.30, P = 0.02; excluding medicated patients: r = 0.44, P = 0.004). In conclusions, our findings provide further support for the role for the KP, particularly IDO, in anhedonia in adolescent MDD. These results emphasize the importance of dimensional approaches in the investigation of psychiatric disorders.