Imaging cerebral tryptophan metabolism in brain tumor-associated depression.
Imaging cerebral tryptophan metabolism in brain tumor-associated depression.
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DOI：
10.1186/s13550-015-0136-9
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发表时间：
2015-12
期刊：
影响因子：
3.2
通讯作者：
Juhász C
中科院分区：
文献类型：
--
作者：
Bosnyák E;Kamson DO;Behen ME;Barger GR;Mittal S;Juhász C
脑肿瘤患者的抑郁与生活质量受损和生存期缩短有关。色氨酸对血清素和犬尿氨酸代谢产物的代谢改变可能在肿瘤相关抑郁症中起作用。我们最近对脑肿瘤患者的α [11C]甲基- l-色氨酸(AMT)-PET的研究表明，不仅在肿瘤肿块中，而且在正常的对侧大脑中也存在色氨酸代谢异常。在目前的研究中，我们探讨了色氨酸在这些大脑区域的代谢是否与抑郁症有关。21例脑肿瘤患者（平均年龄：57岁）（10例脑膜瘤，8例胶质瘤，3例脑转移）接受了AMT-PET扫描。MRI和AMT- pet图像共同注册，AMT动力学参数，包括分布体积（VD '，净色氨酸运输的估计）和K（单向摄取，与色氨酸代谢有关），在肿瘤肿块和未受影响的皮质和皮质下区域的对侧测量。抑郁评分（基于贝克抑郁量表ii [BDI-II]）与肿瘤大小、分级、类型和AMT-PET变量相关。BDI-II平均评分为12±10（范围：2-33）；在7名患者（33%）中确定了临床抑郁水平。在整个组（Spearman’s rho = 0.63, p = 0.004）和18个原发性脑肿瘤亚组（r = 0.68, p = 0.004）中，高BDI-II评分与高丘脑AMT K值相关性最强。抑郁亚组前额叶和纹状体VD值高于非抑郁组（p < 0.05）；当中度/重度抑郁症患者与无/轻度抑郁症患者相比，组间差异更加明显（额叶：p = 0.005；纹状体：p < 0.001）。肿瘤大小、分级和肿瘤类型与抑郁评分无关。PET检测的丘脑、纹状体和额叶皮层色氨酸转运和代谢异常与脑肿瘤患者的抑郁有关。这些变化可能表明血清素和犬尿氨酸途径之间的不平衡，并可作为脑肿瘤相关抑郁的分子成像标志物。本文的在线版本（doi:10.1186/s13550-015-0136-9）包含补充材料，可供授权用户使用。
Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumor-associated depression. Our recent studies with alpha[11C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression. Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD’, an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables. The mean BDI-II score was 12 ± 10 (range: 2–33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman’s rho = 0.63, p = 0.004) and in the subgroup of 18 primary brain tumors (r = 0.68, p = 0.004). Frontal and striatal VD’ values were higher in the depressed subgroup than in non-depressed patients (p < 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p = 0.005; striatal: p < 0.001). Tumor size, grade, and tumor type were not related to depression scores. Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of brain tumor-associated depression. ClinicalTrials.gov NCT02367469 The online version of this article (doi:10.1186/s13550-015-0136-9) contains supplementary material, which is available to authorized users.