Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Psychiatry, Jinhua Second Hospital, Jinhua, Zhejiang, China.
Psychopharmacology (Berl). 2018 Apr;235(4):1191-1198. doi: 10.1007/s00213-018-4835-6. Epub 2018 Feb 1.
It 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.
In 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.
In 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.
Of 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).
Our 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.
本研究旨在通过前瞻性、开放标签、为期 12 周的观察性试验，探究外周血脑源性神经营养因子（BDNF）水平是否可以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。
共纳入 95 例急性精神分裂症患者，同时纳入 72 例健康对照者。采用阳性和阴性症状量表（PANSS）评估症状严重程度和治疗反应，采用重复性成套神经心理状态测验（RBANS）评估认知功能。采用酶联免疫吸附法测定血浆 BDNF 水平。
在入组的 95 例患者中，68 例完成了 12 周随访。结果显示，与对照组相比，精神分裂症急性发作患者的表现明显较差（P＜0.01）。与对照组相比，患者的血浆 BDNF 水平显著降低（F=7.77，P=0.006）。患者完成研究后，PANSS 各分量表和总分均显著改善（P＜0.01）。此外，12 周奥氮平治疗可显著改善 RBANS 即刻记忆、注意力和总分（P=0.018、0.001 和 0.007）。随着临床改善，奥氮平单药治疗 12 周后患者的血浆 BDNF 水平（4.67±1.74ng/ml）也明显高于基线时（3.38±2.11ng/ml）（P＜0.01）。Spearman 相关分析显示，BDNF 水平升高与 RBANS 总分变化显著相关（r=0.28，P=0.02），但与 PANSS 总分变化不相关（r=-0.18，P=0.13）。BDNF 升高与 RBANS 注意力分量表变化显著相关（r=0.27，P=0.028）。
本研究表明，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，同时伴有血浆 BDNF 水平升高。血浆 BDNF 水平可能是急性精神分裂症认知恢复的潜在生物标志物。
