Pandurangi Ananda K, Buckley Peter F
Virginia Commonwealth University, Richmond, VA, USA.
School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Curr Top Behav Neurosci. 2020;44:227-244. doi: 10.1007/7854_2019_91.
In recent years, there is a new optimism in schizophrenia therapeutics with the emergence of immunomodulation as a potential treatment approach. Current evidence points to various immunological abnormalities in schizophrenia, including cell-mediated processes, acute phase proteins, cytokines, and intracellular mediators. Trait- and state-related immune dysfunction appears to exist, and a strong case can therefore be made for immunomodulation therapies in the prevention, treatment, and/or moderating the course of schizophrenia.Immunomodulation approaches include use of nonsteroidal anti-inflammatory agents to stop or moderate an over-activated inflammatory process, anti-oxidants, nutrients, vitamins, herbal products, and other neuroprotection agents that inhibit pro-inflammatory processes, optimal use of antipsychotic drugs (APDs) that may have anti-inflammatory actions or in certain cases such as clozapine may enhance blunted inflammatory responses, and biological agents to antagonize specific immune mediators such as the cytokines. A combination of two or more of the above approaches is also worthy of consideration.In this chapter, the available data for each of the above approaches is reviewed and discussed. Strengths and limitations of current studies are identified, and suggestions are made for future studies. For example, identifying patients with high levels of specific biomarkers such as C-Reactive Protein, IL-6, IFN-γ, TNF-α, and genetic polymorphisms of cytokines, and match them with clinical subgroups such as prodromal, first episode psychosis, chronic psychosis, and negative symptoms with the aim of developing targeted treatment approaches and more personalized medicine. Meanwhile, since the science and trial data are not advanced enough to make definitive recommendations, clinicians should stay up to date with the literature, obtain detailed immunological histories, and review the risk-benefit ratio of adding available immune modulating agents to standard therapies, to provide optimal and state-of-the-art care to patients.
近年来，随着免疫调节作为一种潜在治疗方法的出现，精神分裂症治疗领域出现了新的乐观情绪。目前的证据表明，精神分裂症存在各种免疫异常，包括细胞介导过程、急性期蛋白、细胞因子和细胞内介质。特质相关和状态相关的免疫功能障碍似乎都存在，因此有充分的理由采用免疫调节疗法来预防、治疗和/或缓和精神分裂症的病程。免疫调节方法包括使用非甾体抗炎药来阻止或缓和过度激活的炎症过程、抗氧化剂、营养素、维生素、草药产品以及其他抑制促炎过程的神经保护剂，优化使用可能具有抗炎作用的抗精神病药物（APD），或者在某些情况下，如氯氮平，可能增强减弱的炎症反应，以及使用生物制剂来拮抗特定的免疫介质，如细胞因子。上述两种或更多方法的联合使用也值得考虑。
在本章中，将对上述每种方法的现有数据进行综述和讨论。确定当前研究的优势和局限性，并对未来研究提出建议。例如，识别具有高水平特定生物标志物（如C反应蛋白、白细胞介素-6、干扰素-γ、肿瘤坏死因子-α）以及细胞因子基因多态性的患者，并将他们与临床亚组（如前驱期、首发精神病、慢性精神病和阴性症状）相匹配，以开发有针对性的治疗方法和更个性化的药物。同时，由于科学和试验数据还不够先进，无法给出明确的建议，临床医生应及时了解文献，获取详细的免疫病史，并评估在标准治疗中添加现有免疫调节药物的风险效益比，以便为患者提供最佳和最先进的护理。
