A pilot resting-state functional connectivity study of the kynurenine pathway in adolescents with depression and healthy controls
A pilot resting-state functional connectivity study of the kynurenine pathway in adolescents with depression and healthy controls
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DOI：
10.1016/j.jad.2017.11.040
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发表时间：
2018-02-01
影响因子：
6.6
通讯作者：
Gabbay, Vilma
中科院分区：
文献类型：
--
作者：
DeWitt, Samuel J.;Bradley, Kailyn A.;Gabbay, Vilma
背景资料：神经免疫学犬尿氨酸途径（KP）已被假设在抑郁/快感缺乏症状和相关CNS紊乱中发挥作用。吲哚胺2，3-双加氧酶（IDO）是导致神经营养[犬尿烯酸（KA）]和神经毒性[喹啉酸（QUIN）]分支的限速酶。在这个试点中，我们试图研究血液KP神经毒性/营养措施和快感缺乏/抑郁相关网络的青少年与抑郁症（MDD）和健康controls.Methods：主题是14精神药物治疗自由的青少年与MDD和7 HC，年龄12-19岁。所有人都接受了静息状态功能性磁共振成像（fMRI）扫描。生成体素映射，指示4个双侧种子[（背侧前扣带皮层（dACC）、膝周ACC（pgACC）、膝下ACC（sgACC）和丘脑核（NAc）]和其余脑区域之间的相关强度。fMRI分析是家庭明智的错误纠正。KP代谢产物采用液相色谱-串联质谱法测定。结果：右前扣带回和右楔前叶之间的连接与KA水平呈正相关。同一个集群与IDO活性呈负相关。在一个更自由的聚类阈值的探索性分析显示，KA/QUIN比率与pgACC和右内侧前额叶皮层之间的连接呈正相关。最后，pgACC和左颞下回之间的连接与QUIN levels.Limitations呈正相关：调查结果是初步的，由于样本量小。结论：这项试点研究是第一份报告，在抑郁的青少年表现出的KP和快感缺失/抑郁相关的大脑网络之间的关联。该试验为金伯利进程在MDD中的假定作用提供了证据。
Background: The neuroimmunological kynurenine pathway (KP) has been hypothesized to play a role in depressive/ anhedonic symptoms and related CNS disturbances. Indoleamine 2,3-dioxygenase (IDO) is the rate limiting enzyme which leads to neurotrophic [kynurenic acid (KA)] and neurotoxic [Quinolinic acid (QUIN)] branches. In this pilot, we sought to examine associations between blood KP neuro-toxic/trophic measures and anhedonia/depression associated networks in youth with major depression (MDD) and healthy controls (HC).Methods: Subjects were 14 psychotropic-medication free adolescents with MDD and 7 HC, ages 12-19 yo. All underwent resting-state functional magnetic resonance imagining (fMRI) scans. Voxel-wise maps were generated indicating correlation strengths among 4 bilateral seeds [(dorsal anterior cingulate cortex (dACC), perigenual ACC (pgACC), subgenual ACC (sgACC) and nucleus accumbens (NAc)] and remaining brain regions. FMRI analyses were family-wise error corrected. KP metabolites were measured using liquid chromatography-tandem mass spectrometry.Results: Connectivity between the right dACC and the right precuneus was positively correlated with KA levels. This same cluster demonstrated an inverse correlation with IDO activity. Exploratory analysis at a more liberal clustering threshold showed the KA/QUIN ratio was positively correlated with connectivity between the pgACC and the right medial prefrontal cortex. Lastly, connectivity between the pgACC and the left inferior temporal gyrus was positively correlated with QUIN levels.Limitations: Findings are preliminary due to the small sample size.Conclusions: This pilot study is the first report in depressed adolescents demonstrating associations between the KP and anhedonia/depression-associated brain networks. This pilot adds evidence to the putative role of the KP in MDD.