摘要

管理精神疾病的外延转录组血液生物标志物

作者(年代):黛娜韦斯曼

重度抑郁症和双相情感障碍是世界范围内导致残疾的主要原因，但仍有许多人未被诊断、误诊或治疗无效。诊断依赖于症状的临床评估，目前还没有可用的分子诊断测试。识别和验证血液生物标志物可以提供更准确和客观的诊断手段。遗传和表观遗传事件涉及精神病学病因学，其中RNA编辑修饰与炎症和神经精神疾病有关。腺苷-肌苷RNA编辑是一种生理细胞过程，在健康和疾病中通过调节突触水平的蛋白质功能来翻译环境线索。RNA编辑是导致蛋白质功能多样性的转录后过程。这些标记形成了基因组和环境之间的分子界面。特别令人感兴趣的是发生在染色体15q25.3上的磷酸二酯酶8A基因上的RNA编辑修饰，该基因组区域经常与重度抑郁症的早期发病有关。ALCEDIAG ? ?s的EDITDIAG测试通过RNA编辑修饰在血液中识别不同病理状况的患者的特异性签名，例如在16周内接受干扰素和利巴韦林治疗的丙型肝炎感染患者队列。 This treatment is well known to trigger depression in 50% of patients. RNA editing modifications were measured each two weeks as well as clinical evaluations of depression (MINI). An algorithm was identified which allows to discriminate patients with depression from others with a high specificity and sensitivity; a cohort of depressed patients (n=163) was compared to controls (n=69). A specific RNA editing signature was identified in depressed patients. The test shows that RNA editing related blood biomarkers allow to stratify patients, characterizes psychiatric conditions and follows up the disease/treatment modifications along time. This test paves the way for a better management of psychiatric patients. Recent Publications 1. Weissmann D, Underwood M, Salvetat N, Cavarec L and Vincent L (2016) Region specific alterations of A-to-I RNA editin of serotonin 2c receptor in cortex of suicides with major depression. Translational Psychiatry 6(8):e878. 2. Van Der Laan S, Salvetat N, Weissmann D and Molina F (2017) Emerging RNA editing biomarkers will foster drug development. Drug Discovery Today 22(7):1056-1063. 3. Cavarec L, Vincent L, Le Borgne C, Plusquellec C and Ollivier N (2013) In Vitro screening for drug-induced depression and/or suicidal adverse effects: a new toxicogenomic assay based on CE-SSCP analysis of HTR2C mRNA editing in SHSY5Y cells. Neurotox Res. 23(1):49-62. 4. Cambon K, Dos-Santos Coura R, Groc L, Carbon A and Weissmann D (2010) Aggressive behavior during social interaction in mice is controlled by the modulation of tyrosine hydroxylase expression in the prefrontal cortex. Neuroscience 171(3):840-51.