School of Medicine, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, Centre for Neuroimaging Sciences, De Crespigny Park, London, SE5 8AF, United Kingdom.
CNS Drugs. 2020 Dec;34(12):1229-1251. doi: 10.1007/s40263-020-00765-x. Epub 2020 Sep 25.
Converging lines of evidence suggest that activation of microglia (innate immune cells in the central nervous system [CNS]) is present in a subset of patients with schizophrenia. The extent to which antipsychotic drug treatment contributes to or combats this effect remains unclear. To address this question, we reviewed the literature for evidence that antipsychotic exposure influences brain microglia as indexed by in vivo neuroimaging and post-mortem studies in patients with schizophrenia and experimental animal models. We found no clear evidence from clinical studies for an effect of antipsychotics on either translocator protein (TSPO) radioligand binding (an in vivo neuroimaging measure of putative gliosis) or markers of brain microglia in post-mortem studies. In experimental animals, where drug and illness effects may be differentiated, we also found no clear evidence for consistent effects of antipsychotic drugs on TSPO radioligand binding. By contrast, we found evidence that chronic antipsychotic exposure may influence central microglia density and morphology. However, these effects were dependent on the dose and duration of drug exposure and whether an immune stimulus was present or not. In the latter case, antipsychotics were generally reported to suppress expression of inflammatory cytokines and inducible inflammatory enzymes such as cyclooxygenase and microglia activation. No clear conclusions could be drawn with regard to any effect of antipsychotics on brain microglia from current clinical data. There is evidence to suggest that antipsychotic drugs influence brain microglia in experimental animals, including possible anti-inflammatory actions. However, we lack detailed information on how these drugs influence brain microglia function at the molecular level. The clinical relevance of the animal data with regard to beneficial treatment effects and detrimental side effects of antipsychotic drugs also remains unknown, and further studies are warranted.
越来越多的证据表明，小胶质细胞（中枢神经系统中的先天免疫细胞）的激活存在于一部分精神分裂症患者中。抗精神病药物治疗对这种效应的促进或对抗作用程度尚不清楚。为了解决这个问题，我们查阅了文献，以寻找抗精神病药物暴露是否会影响精神分裂症患者的活体神经影像学和尸检研究以及实验动物模型中小胶质细胞的证据。我们没有从临床研究中发现抗精神病药物对转位蛋白（TSPO）放射性配体结合（一种潜在神经胶质增生的活体神经影像学测量）或尸检研究中小胶质细胞标志物有影响的明确证据。在实验动物中，药物和疾病的作用可能会有所不同，我们也没有发现抗精神病药物对 TSPO 放射性配体结合有一致影响的明确证据。相比之下，我们发现有证据表明，慢性抗精神病药物暴露可能会影响中枢小胶质细胞密度和形态。然而，这些影响取决于药物暴露的剂量和时间以及是否存在免疫刺激。在后一种情况下，抗精神病药物通常被报道会抑制炎症细胞因子和诱导性炎症酶（如环氧化酶）的表达，以及小胶质细胞的激活。从目前的临床数据来看，我们无法得出任何关于抗精神病药物对大脑小胶质细胞有影响的明确结论。有证据表明，抗精神病药物会影响实验动物的大脑小胶质细胞，包括可能具有抗炎作用。然而，我们缺乏关于这些药物如何在分子水平上影响大脑小胶质细胞功能的详细信息。关于抗精神病药物的治疗益处和不良反应的动物数据的临床相关性也尚不清楚，需要进一步的研究。
