附加美金刚可能改善中老年双相情感障碍 II 型患者的认知功能并减轻炎症。

Add-on memantine may improve cognitive functions and attenuate inflammation in middle- to old-aged bipolar II disorder patients.

机构信息

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Yanjiao Furen Hospital, Hebei, China.

Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

出版信息

J Affect Disord. 2021 Jan 15;279:229-238. doi: 10.1016/j.jad.2020.10.003. Epub 2020 Oct 6.

DOI:10.1016/j.jad.2020.10.003

PMID:33069121

Abstract

OBJECTIVES

Chronic inflammation and neuroprogression underlie bipolar disorder (BP) and associated cognitive deficits. Memantine (MM) exerts neuroprotective effects by reducing neuroinflammation. Therefore, we investigated whether add-on low-dose MM (5 mg/day) in BP-II patients may improve cognition and inflammation.

METHODS

We combined two 12-week randomized, double-blind, placebo-controlled studies (NCT01188148 and NCT03039842) for analysis. Each participant was allocated to the MM or placebo group. Symptom severity, neuropsychological tests, and the cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were evaluated at baseline and endpoint. A subgroup analysis of middle- to old-aged BP-II patients was also performed.

RESULTS

We recruited 155 BP-II patients (23 of which were middle- to old-aged) for the MM group and 170 patients (20 of which were middle- to old-aged) for the placebo group. Add-on MM did not result in significant improvements in cognitive functions in all BP-II patients, but a group difference in TNF-α levels was found in the MM group (P=0.04). Specifically, in middle- to old-aged BP-II patients, there was a significant time and group interaction effect on omission T-scores, hit reaction time T-scores, and hit reaction time standard error T-scores on continuous performance tests (CPTs) in the MM group (P=0.007, 0.02, and 0.01, respectively), and a decrease in plasma TNF-α levels (P=0.04).

LIMITATIONS

The sample size of middle- to old-aged BP-II patients were limited.

CONCLUSION

Add-on MM may attenuate inflammation in BP-II and improve cognition in middle- to old-aged BP-II patients.

摘要

目的

慢性炎症和神经进展是双相障碍（BP）及其相关认知缺陷的基础。美金刚（MM）通过减少神经炎症发挥神经保护作用。因此，我们研究了 BP-II 患者中添加低剂量 MM（5mg/天）是否可以改善认知和炎症。

方法

我们对两项为期 12 周的随机、双盲、安慰剂对照研究（NCT01188148 和 NCT03039842）进行了合并分析。每位参与者均被分配到 MM 或安慰剂组。在基线和终点时评估症状严重程度、神经心理学测试以及细胞因子血浆水平[肿瘤坏死因子-α（TNF-α）、C 反应蛋白（CRP）、白细胞介素-8（IL-8）、转化生长因子-β1（TGF-β1）和脑源性神经营养因子（BDNF）]。还对中年至老年 BP-II 患者进行了亚组分析。

结果

我们招募了 155 名 BP-II 患者（其中 23 名为中年至老年）进入 MM 组，170 名患者（其中 20 名为中年至老年）进入安慰剂组。在所有 BP-II 患者中，添加 MM 并未显著改善认知功能，但在 MM 组中发现 TNF-α 水平存在组间差异（P=0.04）。具体而言，在中年至老年 BP-II 患者中，在 MM 组中，连续操作测试（CPTs）中的遗漏 T 评分、命中反应时间 T 评分和命中反应时间标准误差 T 评分出现显著的时间和组间交互作用效应（P=0.007、0.02 和 0.01），并且血浆 TNF-α 水平下降（P=0.04）。