心境稳定的双相障碍患者血清中成熟脑源性神经营养因子 (BDNF)及其前体 proBDNF 水平异常：两项独立队列研究。
Abnormality in serum levels of mature brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in mood-stabilized patients with bipolar disorder: a study of two independent cohorts.
机构信息
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg SE-416 85, Sweden.
Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg SE-416 85, Sweden.
出版信息
J Affect Disord. 2014 May;160:1-9. doi: 10.1016/j.jad.2014.01.009. Epub 2014 Feb 24.
BACKGROUND
Early detection and diagnosis of bipolar disorder can be difficult. Tools are needed to help clinicians detect bipolar disorder earlier, which would ameliorate the prognosis.
METHODS
ELISA kits that distinguish between mature brain derived neurotrophic factor (BDNF) and proBDNF, we compared serum levels of mature BDNF, proBDNF, and matrix metalloproteinase-9 (MMP-9) in two independent cohorts (Sahlgrenska cohort and Karolinska cohort) of mood-stabilized bipolar patients and healthy controls. The total sample size in both cohorts consisted of 263 (48+215) bipolar patients and 155 (43+112) healthy controls.
RESULTS
Levels of mature BDNF and the ratio mature BDNF/proBDNF were significantly higher in patients than in controls. Serum levels of proBDNF were significantly lower in patients compared to controls. Serum levels of MMP-9 did not differ between the groups but MMP-9 correlated positively and significantly with mature BDNF. Mature BDNF, proBDNF, the ratio of mature BDNF/proBDNF and interactions with MMP-9 explained the diagnostic dichotomy in both cohorts with high significance, using multivariate logistic ANCOVA (gender, age, and BMI were covaried out). The model explained 41% of the diagnostic variance in the Sahlgrenska cohort (p<0.0001) and 15% in the Karolinska cohort (p<0.0001). In both cohorts, the equations provided good power for diagnostic classification. The diagnostic sensitivity was 89% in the Sahlgrenska and 74% in the Karolinska cohort, and specificity 77% and 64%, respectively.
LIMITATION
The study is cross-sectional with no longitudinal follow up. The cohorts are relatively small with no medication-free patients. There are no "ill patient controls".
CONCLUSION
Abnormalities in the conversion of proBDNF to mature BDNF may be associated with pathogenesis of bipolar disorder. Clinical use of these biomarkers may provide opportunities for earlier detection and correct treatment.
背景
双相障碍的早期检测和诊断可能较为困难。需要有工具来帮助临床医生更早地发现双相障碍，从而改善预后。
方法
我们比较了两个独立的心境稳定的双相障碍患者和健康对照者队列（Sahlgrenska 队列和 Karolinska 队列）的血清成熟脑源性神经营养因子（BDNF）和前脑源性神经营养因子（proBDNF）的 ELISA 试剂盒，检测成熟 BDNF、proBDNF 和基质金属蛋白酶-9（MMP-9）的水平。两个队列的总样本量包括 263 名（48+215）双相障碍患者和 155 名（43+112）健康对照者。
结果
患者的成熟 BDNF 水平和成熟 BDNF/proBDNF 比值明显高于对照组。与对照组相比，患者的 proBDNF 水平明显较低。两组之间 MMP-9 水平无差异，但 MMP-9 与成熟 BDNF 呈显著正相关。使用多变量逻辑协方差分析（共变量为性别、年龄和 BMI），成熟 BDNF、proBDNF、成熟 BDNF/proBDNF 比值以及与 MMP-9 的相互作用可以很好地解释两个队列的诊断二分法，具有高度显著性（p<0.0001）。该模型解释了 Sahlgrenska 队列中 41%的诊断差异（p<0.0001），解释了 Karolinska 队列中 15%的诊断差异（p<0.0001）。在两个队列中，该方程都提供了很好的诊断分类能力。Sahlgrenska 队列的诊断敏感性为 89%，Karolinska 队列的诊断敏感性为 74%，特异性分别为 77%和 64%。
局限性
该研究为横断面研究，没有纵向随访。队列相对较小，没有无药物治疗的患者。没有“患病对照者”。
结论
proBDNF 向成熟 BDNF 转化的异常可能与双相障碍的发病机制有关。这些生物标志物的临床应用可能为早期发现和正确治疗提供机会。
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