Biomarkers for the prediction and monitoring of the antipsychotic/antidepressant-induced hepatotoxicity: study protocol

This study is designed to address the connection between antidepressant and antipsychotic-induced hepatotoxicity with pharmacogenetic and epigenetic indicators, using a novel combined approach of CYP450 polymorphism determination and early liver injury detection via microRNA testing. The multi-centric retrospective case-control study in Slovakia involves 151 cases with signs of hepatotoxicity and 604 controls without. Participants will be tested for selected CYP450, UGT1A1 polymorphisms, and microRNAs. Anticipated findings will test if patients with specific CYP450 and UGT1A1 polymorphisms are at higher risk for drug-induced hepatotoxicity and if plasma microRNAs hsa-miR-122-5p and hsa-miR-192-5p, alone or combined, can differentiate patients with abnormal liver function. The findings could contribute to personalized treatment approach by combining genetic and epigenetic biomarkers. This study is about making treatment for mental health issues, like depression and anxiety, better and safer. Some patients respond differently to their medications, and some can have serious side effects, such as liver damage. To help with this, we are trying a new approach that uses two tests. The first test looks at certain genes to see how a person might react to medication. The second test checks for small molecules in the blood that can show if there are early signs of liver problems. We want to find out two things: Do people with certain genes have a higher risk of liver problems from their medications? Can these small molecules help us find liver issues better than regular blood tests? We will study about 755 patients from three mental health clinics in Slovakia, who have been taking their medications for at least four weeks. By identifying patients who might struggle with their medications due to their genes, we hope to catch liver problems early. This could lead to more personalized and effective treatments for everyone.本研究旨在通过细胞色素P450（CYP450）多态性检测与基于微小RNA（microRNA）的早期肝损伤检测这一全新联合方法，探讨抗抑郁药与抗精神病药诱导的肝毒性与药物基因组学及表观遗传学标志物之间的关联。本研究为在斯洛伐克开展的多中心回顾性病例对照研究，共纳入151例肝毒性阳性病例与604例健康对照。所有参与者将接受选定的CYP450、UGT1A1多态性及微小RNA检测。本研究的预期结果将验证两大科学假设：其一，携带特定CYP450与UGT1A1多态性的患者是否面临更高的药物性肝损伤风险；其二，血浆微小RNA hsa-miR-122-5p与hsa-miR-192-5p单独或联合使用时，能否有效区分肝功能异常患者。本研究成果可通过整合遗传与表观遗传学生物标志物，为个性化治疗方案的优化提供支撑。本研究致力于改善抑郁症、焦虑症等精神类疾病的临床治疗效果与用药安全性。临床中部分患者对精神药物的反应存在显著个体差异，甚至可能出现肝损伤等严重不良反应。为此，本研究采用两种检测手段的联合策略：一是检测特定基因以预判患者的药物代谢反应；二是检测血液中的小分子物质，以识别早期肝损伤迹象。本研究拟解答两个核心科学问题：一是携带特定基因的患者是否在使用精神药物后面临更高的肝损伤风险？二是上述血液小分子标志物能否比常规血液检测更精准地识别肝损伤？本研究将纳入斯洛伐克三家精神卫生诊所的约755名受试者，所有参与者均已持续服用精神药物至少四周。通过识别因遗传因素可能出现药物不耐受的患者，本研究有望实现肝损伤的早期干预，最终为全体精神疾病患者提供更具个性化且高效安全的治疗方案。