LINGO3和POU3F1去甲基化介导童年期虐待影响青少年自伤行为易感性的作用机制：队列研究

既往研究表明童年期虐待与青少年自伤行为相关，但两者的因果关系及有关生物学机制需进一步阐明。基于前期研究，我们假设LINGO3和POU3F1去甲基化可介导童年期虐待影响青少年自伤行为易感性。本研究拟首先利用前期收集的样本验证外周血淋巴细胞中LINGO3和POU3F1去甲基化与青少年自伤行为的关联；然后利用课题组建立的青少年队列分析童年期虐待与唾液中LINGO3和POU3F1去甲基化的相关性；随访队列研究对象三年，推断童年期虐待与青少年自伤行为的因果关系并分析LINGO3和POU3F1去甲基化的中介作用。同时，运用动物实验探讨童年期不同照顾水平和母婴分离暴露对青春期大鼠情绪行为、海马和额叶皮层神经细胞生长及LINGO3和POU3F1去甲基化的影响。研究结果将可明确童年期虐待和青少年自伤行为的因果关系及LINGO3和POU3F1去甲基化的中介作用，为预防、诊断和治疗青少年自伤行为提供科学依据。

Previous studies suggested that childhood abuse was associated with non-suicidal self-injury susceptibility among adolescents, however the causal association of childhood abuse with non-suicidal self-injury and the related biological mechanism need to be further studied. Based on our previous studies, we hypothesized that demethylation of LINGO3 and POU3F1 could mediate the impact of childhood abuse on non-suicidal self-injury susceptibility. In this project, we will firstly use pre-collected samples to verify the association of LINGO3 and POU3F1 demethylation in peripheral blood lymphocytes with non-suicidal self-injury, then we will use the baseline of our adolescent cohort to analyze the association between childhood abuse and demethylation of LINGO3 and POU3F1 in saliva, and will follow up the cohort participants for three years to infer the causal association of childhood abuse with non-suicidal self-injury among adolescents, and to investigate the mediated effect of LONGO3 and POU3F1 demethylation. We will also use animal experiments to investigate the impact of different childhood care levels or mother-infant separation exposure on adolescent rats' emotional behaviors, hippocampal and frontal cortical nerve cell growth, and demethylation of LINGO3 and POU3F1. Our findings will clarify the association of childhood abuse with non-suicidal self-injury among adolescents, and the mediated effects of LINGO3 and POU3F1 demethylation, which could provide scientific evidence for the prevention, diagnosis and treatment of non-suicidal self-injury among adolescents.