Department of Psychiatry and Mental Health Institute of the Second Xiangya Hospital, Central South University; Chinese National Clinical Research Center on Mental Disorders, Chinese National Technology Institute on Mental Disorders, Hunan Key Laboratory of Psychiatry and Mental Health, Changsha, Hunan, China; Department of Psychiatry, Guangzhou First People's Hospital, the Second Affiliated Hospital, South China University of Technology, Guangzhou, Guangdong, China.
GuangzhouBaiyun Psychiatric Hospital, Guangzhou, Guangdong, China.
Schizophr Res. 2019 Oct;212:92-98. doi: 10.1016/j.schres.2019.08.005. Epub 2019 Aug 12.
Cognitive deficits of schizophrenia are predictors of poor function, but antipsychotic medication has limited efficacy for cognitive deficits. These deficits in learning and memory may result from activity of pro-inflammatory cytokines, which microglia produce. The microglia inhibitor minocycline might arrest this cytokine damage to the hippocampus and reverse the cognitive deficits of schizophrenia.
A double-blind, placebo-controlled study involved 75 patients with schizophrenia who randomly received low dose (100 mg/day) or high dose minocycline (200 mg/day) or placebo added to risperidone. MATRICS Consensus Cognitive Battery (MCCB) was used to assess the cognitive functioning, and serum levels of Interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) were assessed.
Minocycline group was significantly superior to minocycline or placebo group not only for the improvements in cognitive tests' scores as well (P < 0.05), but for IL-1β and IL-6 serum levels reduction (P < 0.01). The amelioration of cognitive deficits with minocycline correlated not only with the remission of negative symptoms, but also with the reduction in serum levels of IL-1β and IL-6.
Minocycline adjunctive treatment was effective in improving cognitive deficits of patients with schizophrenia. The beneficial effect of minocycline may be related to reducing pro-inflammatory cytokines through microglia inhibition.
精神分裂症的认知缺陷是功能不良的预测因子,但抗精神病药物对认知缺陷的疗效有限。这种学习和记忆缺陷可能是由小胶质细胞产生的促炎细胞因子的活性引起的。小胶质细胞抑制剂米诺环素可能阻止这种细胞因子对海马体的损害,并逆转精神分裂症的认知缺陷。
一项双盲、安慰剂对照的研究纳入了 75 名精神分裂症患者,他们随机接受低剂量(100mg/天)或高剂量米诺环素(200mg/天)或安慰剂联合利培酮治疗。使用 MATRICS 共识认知电池(MCCB)评估认知功能,评估血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平。
米诺环素组不仅在认知测试评分的改善方面明显优于米诺环素或安慰剂组(P<0.05),而且在 IL-1β 和 IL-6 血清水平的降低方面也明显优于米诺环素或安慰剂组(P<0.01)。米诺环素改善认知缺陷不仅与阴性症状的缓解相关,还与 IL-1β 和 IL-6 血清水平的降低相关。
米诺环素辅助治疗可有效改善精神分裂症患者的认知缺陷。米诺环素的有益作用可能与通过抑制小胶质细胞减少促炎细胞因子有关。