Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder
Brain-derived neurotrophic factor and inflammatory markers in patients with early- vs. late-stage bipolar disorder
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DOI：
10.1017/s1461145708009310
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发表时间：
2009-05-01
影响因子：
4.8
通讯作者：
Yatham, Lakshmi N.
中科院分区：
文献类型：
--
作者：
Kauer-Sant'Anna, Marcia;Kapczinski, Flavio;Yatham, Lakshmi N.
双相I型障碍(BD)的长期预后比之前认为的更差，并伴有持续性的认知障碍和功能下降。可能支撑这些变化的神经生物学基础仍不清楚。脑源性神经营养因子(BDNF)水平和细胞因子的变化是潜在的候选因素。本研究的目的是检测BD患者在疾病早期和晚期的细胞因子和BDNF水平及其相互关系。我们测定了60例BD I患者的血清BDNF、TNF-α、IL-6和IL-10水平，比较了疾病早期和疾病晚期患者的水平，并与60例匹配的健康对照组进行了比较。脑源性神经营养因子仅在双相障碍晚期降低。此外，脑源性神经营养因子水平与病程呈负相关。相反，在BD的早期阶段，与对照组相比，所有白介素类和肿瘤坏死因子-α都升高了。在BD晚期，肿瘤坏死因子-α和IL-6继续显著高于对照组，而IL-10则无明显变化。当比较疾病早期和晚期患者的水平时，BD晚期患者的BDNF和IL-6水平明显低于早期患者。相反，肿瘤坏死因子-α在发病后期显著升高。在疾病的晚期，炎症防御的失败可能是BDNF减少和细胞因子持续升高的原因；因此，这些可能成为BD疾病进展的标志。
Bipolar I disorder (BD) has a poorer longer-term outcome than previously thought, with persistent cognitive impairment and functional decline. The neurobiological underpinnings that might underlie these changes remain unknown. Changes in brain-derived neurotrophic factor (BDNF) levels and cytokines are potential candidates. The aim of this study was to examine both cytokine and BDNF levels and their relationship in BD patients in the early and late stages of the disorder. We measured serum BDNF, TNF-alpha, IL-6 and IL-10 levels in a total of 60 patients with BD I and we compared those in early stages of illness with those in late stages of illness and also compared both groups with 60 matched healthy controls. BDNF was decreased only in those patients in the late stage of bipolar disorder. Moreover, BDNF levels were negatively correlated with length of illness. In contrast, all interleukins and TNF-alpha were increased in the early stages of BD, compared to controls. While TNF-alpha and IL-6 continued to be significantly higher than controls at late stages of BD, IL-10 did not. When levels were compared between patients at early and late stages of illness, there was a significant decrease in BDNF and IL-6 in the later stage of BD compared to the early stage. Inversely, TNF-alpha showed a significant increase at the later stage. Failure of inflammatory defences in the late stage of the disorder may account for reduction in BDNF and continued elevations in cytokines; thus these may have the potential to serve as markers of illness progression in BD.