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多氯联苯与抑郁症:德国HELPcB监测项目中一条与多巴胺相关的神经化学通路的横断面和纵向研究

Polychlorinated biphenyls and depression: cross-sectional and longitudinal investigation of a dopamine-related Neurochemical path in the German HELPcB surveillance program.

作者信息

Gaum Petra Maria, Gube Monika, Schettgen Thomas, Putschögl Franziska Maria, Kraus Thomas, Fimm Bruno, Lang Jessica

机构信息

Institute for Occupational Medicine, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.

Health Office of the city and area of Aachen, Trierer Straße 1, 52070, Aachen, Germany.

出版信息

Environ Health. 2017 Oct 10;16(1):106. doi: 10.1186/s12940-017-0316-3.

Abstract

BACKGROUND

Exposure to polychlorinated biphenyls (PCBs) is associated with depressive symptomatology. A cause of depressive symptoms is a disturbance in the neurotransmitter system of dopamine (DA). Animal as well as human studies report that PCBs can influence the DA system. This study examined whether PCB-related depressive symptoms are affected by DA metabolites in humans with high PCB body burden.

METHODS

This study is part of the German HELPcB surveillance program (Health Effects in high Level exposure to PCB) for occupationally exposed workers and their relatives. Data was collected from 178 participants on two measurement time points (t1 and t2) with a one-year time lag in between the two time points. PCBs were analyzed in plasma via human biomonitoring and a validated questionnaire was used to identify existence and severity of depressive symptoms. As a surrogate for DA, we measured its metabolites homovanillic acid (HVA) and vanillylmandelic acid (VMA) in urine. Mediation analyses were performed to test whether the association between PCB exposure and severity of depressive symptoms is mediated by urinary concentration of DA metabolites HVA and VMA. The mediation was tested with the SPSS macro MEDIATE.

RESULTS

We found a significant mediation over time for lower-chlorinated, higher-chlorinated and dioxin-like PCBs. The positive association between PCB exposure with severity of depressive symptoms was mediated by the main DA metabolite HVA. At t1 a higher exposure with PCBs was associated with lower concentration in urinary HVA. A reduced HVA concentration at t1 was correlated with increased depressive symptoms severity at t2. No meditations were found for VMA.

CONCLUSIONS

This work indicates that the association of PCB exposure and an increase of depressive symptoms after one year is mediated by the DA metabolite HVA as a surrogate for DA. These are first steps towards finding an explanation for an underlying neurochemical pathomechanism of PCB-related depressive symptomatology.

摘要

背景

接触多氯联苯(PCBs)与抑郁症状有关。抑郁症状的一个原因是多巴胺(DA)神经递质系统紊乱。动物和人类研究均报告称,多氯联苯会影响多巴胺系统。本研究调查了体内多氯联苯负荷较高的人群中,与多氯联苯相关的抑郁症状是否受多巴胺代谢物的影响。

方法

本研究是德国针对职业暴露工人及其亲属的HELPcB监测项目(高剂量多氯联苯暴露对健康的影响)的一部分。在两个测量时间点(t1和t2)收集了178名参与者的数据,两个时间点之间相隔一年。通过人体生物监测分析血浆中的多氯联苯,并使用经过验证的问卷来确定抑郁症状的存在和严重程度。作为多巴胺的替代指标,我们测量了尿液中其代谢物高香草酸(HVA)和香草扁桃酸(VMA)。进行中介分析以检验多氯联苯暴露与抑郁症状严重程度之间的关联是否由多巴胺代谢物HVA和VMA的尿液浓度介导。使用SPSS宏MEDIATE对中介作用进行检验。

结果

我们发现,低氯、高氯和类二噁英多氯联苯随时间存在显著的中介作用。多氯联苯暴露与抑郁症状严重程度之间的正相关由主要多巴胺代谢物HVA介导。在t1时,多氯联苯暴露量较高与尿液中HVA浓度较低相关。t1时HVA浓度降低与t2时抑郁症状严重程度增加相关。未发现VMA有中介作用。

结论

这项研究表明,多氯联苯暴露与一年后抑郁症状增加之间的关联是由作为多巴胺替代指标的多巴胺代谢物HVA介导的。这些是朝着解释多氯联苯相关抑郁症状潜在神经化学发病机制迈出的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b464/5635510/733ec0b70e83/12940_2017_316_Fig1_HTML.jpg

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