Brain-derived neurotrophic factor as a biomarker for cognitive recovery in acute schizophrenia: 12-week results from a prospective longitudinal study
Brain-derived neurotrophic factor as a biomarker for cognitive recovery in acute schizophrenia: 12-week results from a prospective longitudinal study
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脑源性神经营养因子作为急性精神分裂症认知恢复的生物标志物：前瞻性纵向研究的 12 周结果
DOI：
10.1007/s00213-018-4835-6
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发表时间：
2018-04-01
影响因子：
3.4
通讯作者：
Zhang, Chen
中科院分区：
文献类型：
--
作者：
Zhang, Yi;Fang, Xinyu;Zhang, Chen
理由人们普遍认为，认知功能受损是精神分裂症的核心特征。有证据表明脑源性神经营养因子(BDNF)在认知功能中的作用。目的：本研究采用前瞻性、开放式、为期12周的观察试验，探讨外周脑源性神经营养因子是否可作为奥氮平改善精神分裂症患者认知功能的潜在生物标志物。我们还招募了72名健康人作为对照组。采用阳性与阴性症状量表(PANSS)评定症状严重程度及治疗反应。认知功能评定采用可重复使用的神经心理状态评定量表(RBANS)。结果95例患者中，68例完成了为期12周的随访。结果表明，精神分裂症急性加重期患者的心理健康水平明显低于正常对照组(P<0.05， <； <0.01)。脑源性神经营养因子水平明显低于对照组(F= 7.77，P= 0.006)。当患者完成这项研究时，观察到每个PANSS子分数和总分数都有显著的改善(Ps， <； ，0.01)。此外，奥氮平治疗12周后，RBAN的即刻记忆力、注意力和总分均有显著改善(P分别为 0.018、0.001和0.007)。随着临床症状的改善，奥氮平治疗12周后血浆脑源性神经营养因子水平(4.67 ± 1.74 ng/ml)也明显高于治疗前(3.38 ± 2.11 ng/ml)(P<； 0.01)。Spearman相关分析显示，脑源性神经营养因子水平的升高与 总分的变化显著相关(r= 0.2 8，P=0.0 2)，而与PANSS总分的变化无关(r= − 0.18，P= 0.13)。脑源性神经营养因子的增加与脑源性神经营养因子水平的变化显著相关(r= 0.27，P= 0.028)。结论奥氮平可改善急性精神分裂症患者的精神症状和认知功能障碍，尤其是注意力和即刻记忆功能障碍，同时伴有血浆脑源性神经营养因子水平的升高。血浆脑源性神经营养因子水平可能是急性精神分裂症认知功能恢复的潜在生物标志物。
RationaleIt is generally accepted that impaired cognitive function is a core feature of schizophrenia. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in cognitive function. Olanzapine was reported to yield cognitive improvement in patients with schizophrenia.ObjectivesIn this study, we performed a prospective, open-label, 12-week observation trial to investigate whether peripheral BDNF may represent a potential biomarker for the effect of cognitive improvement induced by olanzapine in patients with schizophrenia.MethodsIn total, 95 patients with acute schizophrenia were enrolled in the study. We also recruited 72 healthy individuals for a control group. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate symptom severity and treatment response. Cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma BDNF levels were measured with an enzyme-linked immunosorbent assay.ResultsOf the 95 patients consented into the study, 68 completed the 12-week follow up. Our results showed that schizophrenia patients with acute exacerbation had significantly poorer performance than that of the controls (Ps < 0.01). A significantly decreased plasma level of BDNF in patients was observed compared with the controls (F= 7.77,P= 0.006). A significant improvement in each PANSS subscore and total score was observed when the patients completed this study (Ps < 0.01). Additionally, 12-week olanzapine treatment exhibited significant improvements in RBANS immediate memory, attention, and total scores (P= 0.018, 0.001, and 0.007, respectively). Along with the clinical improvement, plasma BDNF levels after 12-week olanzapine monotherapy (4.67 ± 1.74 ng/ml) were also significantly increased compared with those at baseline (3.38 ± 2.11 ng/ml) (P< 0.01). Spearman’s correlation analysis showed that the increase in plasma levels of BDNF is significantly correlated with the change in the RBANS total scores (r= 0.28,P= 0.02) but not with the change in the PANSS total scores (r= − 0.18,P= 0.13). There is a significant correlation of BDNF increase with the change of RBANS attention subscore (r= 0.27,P= 0.028).ConclusionsOur findings suggest that olanzapine improves psychiatric symptoms and cognitive dysfunction, particularly attention and immediate memory, in patients with acute schizophrenia, in parallel with increased plasma BDNF levels. Plasma BDNF levels may be a potential biomarker for cognitive recovery in acute schizophrenia.