Pisanu Claudia, Severino Giovanni, Minelli Alessandra, Dierssen Mara, Potier Marie-Claude, Fabbri Chiara, Serretti Alessandro, Gennarelli Massimo, Baune Bernhard T, Squassina Alessio
Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Neurosci Appl. 2024 Mar 19;3:104059. doi: 10.1016/j.nsa.2024.104059. eCollection 2024.
Treatment-resistant schizophrenia (TRS) is associated with great disability, functional impairment, and substantial socioeconomic costs. While clozapine is indicated in patients with TRS, its use is restricted to patients who have not responded to at least 2 other antipsychotics, thus implying a series of empirical trials of different drugs before receiving effective treatment. In this scenario, the identification of reliable biological markers to predict the risk for TRS before starting pharmacological treatments might significantly improve the management of TRS in its early stages. We conducted a systematic review on PubMed, Scopus and Web of Science to identify studies investigating peripheral biological markers of TRS. A total of 75 articles were included. These studies mostly investigated the association between TRS and genetic markers (n = 42, of which 16 with a genome-wide and 25 with a candidate-gene design) and protein/metabolite markers (n = 23), while only a minority of studies investigated RNA markers (n = 5), methylation levels (n = 4), gut microbiota profiles (n = 1), or more than one type of marker (n = 3). The elucidation of peripheral biomarkers of TRS is challenging due to the large heterogeneity across studies in terms of clinical definition of TRS, the relatively small sample size of many studies, as well as the lack of powered studies integrating data at a multi-omic level. Nonetheless, available studies suggest TRS to be a trait with a significant heritability and point to inflammation and cytokine imbalance as the most promising pathways involved in this complex phenotype.
难治性精神分裂症（TRS）与严重的残疾、功能障碍以及巨大的社会经济成本相关。虽然氯氮平适用于TRS患者，但其使用仅限于对至少2种其他抗精神病药物无反应的患者，这意味着在接受有效治疗之前需要进行一系列不同药物的经验性试验。在这种情况下，在开始药物治疗之前识别可靠的生物标志物以预测TRS风险可能会显著改善TRS早期阶段的管理。我们在PubMed、Scopus和Web of Science上进行了系统综述，以识别研究TRS外周生物标志物的研究。共纳入75篇文章。这些研究大多调查了TRS与遗传标志物（n = 42，其中16项采用全基因组设计，25项采用候选基因设计）和蛋白质/代谢物标志物（n = 23）之间的关联，而只有少数研究调查了RNA标志物（n = 5）、甲基化水平（n = 4）、肠道微生物群谱（n = 1）或不止一种类型的标志物（n = 3）。由于TRS临床定义的研究之间存在很大异质性、许多研究的样本量相对较小以及缺乏在多组学水平整合数据的有力研究，阐明TRS外周生物标志物具有挑战性。尽管如此，现有研究表明TRS是一种具有显著遗传性的特质，并指出炎症和细胞因子失衡是参与这种复杂表型的最有前景的途径。
