Kauer-Sant'Anna Marcia, Kapczinski Flávio, Andreazza Ana C, Bond David J, Lam Raymond W, Young L Trevor, Yatham Lakshmi N
Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Int J Neuropsychopharmacol. 2009 May;12(4):447-58. doi: 10.1017/S1461145708009310. Epub 2008 Sep 4.
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.
双相 I 型障碍（BD）的长期预后比之前认为的更差，存在持续性认知障碍和功能衰退。可能构成这些变化基础的神经生物学机制仍不清楚。脑源性神经营养因子（BDNF）水平和细胞因子的变化是潜在因素。本研究的目的是检查 BD 患者疾病早期和晚期的细胞因子和 BDNF 水平及其关系。我们测量了总共 60 例双相 I 型障碍患者的血清 BDNF、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）水平，并将疾病早期患者的这些水平与晚期患者的进行比较，还将两组患者与 60 名匹配的健康对照进行比较。BDNF 仅在双相情感障碍晚期患者中降低。此外，BDNF 水平与病程呈负相关。相比之下，与对照组相比，BD 早期所有白细胞介素和 TNF-α 均升高。虽然在 BD 晚期 TNF-α 和 IL-6 仍显著高于对照组，但 IL-10 并非如此。当比较疾病早期和晚期患者的水平时，与早期相比，BD 晚期的 BDNF 和 IL-6 显著降低。相反，TNF-α 在晚期显著升高。疾病晚期炎症防御功能的失效可能导致 BDNF 降低和细胞因子持续升高；因此，这些可能有潜力作为 BD 疾病进展的标志物。
