Biomarkers for Suicidality

自杀的生物标志物

• 批准号: 10629215
• 负责人: Alexander B Niculescu
• 金额: $ 39.38万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-02 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10629215
• 关键词: Acceleration; Alcoholism; Anxiety Disorders; Applications Grants; Area; Autopsy; Bioinformatics; Biological; Biological Markers; Biology; Biopsy; Bipolar Disorder; Blood; Blood specimen; Brain; Candidate Disease Gene; Cause of Death; Clinical; Computerized Medical Record; Coroner; County; Data; Databases; Diagnosis; Diagnostic; Disease; Enrollment; Ensure; Feeling suicidal; Female; Future; Gender; Gene Expression; Gene Expression Profile; Gene Expression Profiling; Gene Proteins; Genes; Genetic; Genomic approach; Goals; Health Professional; Hospitalization; Human; IL6 gene; Impairment; Individual; Inpatients; Interview; Major Depressive Disorder; Manuals; Maps; Measurement; Mental disorders; Molecular; Mood Disorders; Nature; Pathway Analysis; Pathway interactions; Patient Self-Report; Peripheral; Persons; Pharmaceutical Preparations; Pharmacogenomics; Post-Traumatic Stress Disorders; Productivity; Psychiatric Diagnosis; Psychiatry; Psychoses; Publishing; Reproducibility; Research; Risk; Role; Schizoaffective Disorders; Schizophrenia; Series; Severities; Site; Specificity; Study Subject; Subgroup; Suicide; Suicide prevention; Symptoms; Testing; Therapeutic; Thinking; Tissues; Translations; Validation; Visit; Work; biomarker panel; biomarker validation; candidate identification; candidate marker; clinical application; clinical biomarkers; clinical practice; cohort; comorbidity; design; drug candidate; drug repurposing; functional genomics; gender difference; ideation; impression; male; patient stratification; personalized approach; personalized predictions; potential biomarker; pragmatic implementation; precision medicine; psychiatric comorbidity; suicidal; targeted biomarker; trait; translational approach; treatment response

One person dies by suicide every 40 seconds worldwide. Having a psychiatric disorder increases risk. Self-report of an individual or clinical impression of a healthcare professional are not always reliable. Developing and validating quantitative and objective ways for predicting and preventing suicidality (ideation, attempts, completions) is urgently needed. Recent work by our group has identified blood gene expression biomarkers that track suicidality using longitudinal within-subject designs, validated them in suicide completers, and tested them in independent cohorts for ability to assess state (suicidal ideation), and ability to predict trait (future hospitalizations for suicidality). These studies were conducted in males with psychiatric disorders (Le-Niculescu et al. Molecular Psychiatry 2013, Niculescu et al. Molecular Psychiatry 2015) and in females with psychiatric disorders (Levey et al. Molecular Psychiatry 2016). The studies pointed to some similarities as well as to important gender differences. A fundamental question remains to be answered: is a quest for more universal predictors that work across genders and are trans-diagnostic, or a quest for more personalized predictors by gender and diagnosis going to be more productive, for ultimate translation to clinical practice? We endeavored to answer this fundamental question with a recent series of studies (Niculescu et al. Molecular Psychiatry 2017), and would like to extend and solidify that with the work proposed in this grant application. First, we will solidify findings for blood gene expression biomarkers for suicidality that are more universal in nature, working across genders and various psychiatric diagnoses, and are predictive in independent cohorts. Second, a more personalized discovery and testing approach, by gender and psychiatric diagnosis, will be undertaken. We will compare the results of the personalized approach to the universal approach, to determine which approach identifies better predictors in independent cohorts. Third, the top biomarkers will also be used to understand the biological pathways involved, co-morbidity with other disorders, as well as generate leads on pharmacogenomics and repurposed drugs. This work will permit us to establish generalizability, discriminatory power, and potential personalization of biomarkers and panels of biomarkers, of high relevance to developing this area towards full clinical applicability as precision medicine. Given the fact that suicide is a potentially preventable cause of death, the need for efforts such as ours cannot be overstated.

全世界每40秒就有一人自杀。去看精神病医生 紊乱会增加风险。个人或医疗保健临床印象的自我报告 专业人士并不总是可靠的。开发和验证定量和客观 预测和预防自杀（意念，企图，完成）的方法是迫切的 needed.我们小组最近的工作已经确定了血液基因表达生物标志物， 使用纵向受试者内设计跟踪自杀倾向，并在自杀中验证 完成者，并在独立队列中测试他们评估状态（自杀）的能力 意念）和预测特质的能力（未来因自杀而住院）。这些研究 在患有精神障碍的男性中进行（Le-Niculescu et al. Psychiatry 2013，Niculescu et al. Molecular Psychiatry 2015）和患有 精神疾病（Levey et al. Molecular Psychiatry 2016）。研究指出， 一些相似之处以及重要的性别差异。一根本性的问题 仍然有待回答：是一个寻求更普遍的预测，跨性别的工作 并且是跨诊断的，或者是对性别的更个性化的预测的追求， 诊断将更有成效，最终转化为临床实践？我们 为了回答这个基本问题，最近的一系列研究 （Niculescu et al. Molecular Psychiatry 2017），并希望扩展和巩固这一点 在这项资助申请中提出的工作。首先，我们将巩固血液的发现 自杀倾向的基因表达生物标志物在自然界中更普遍， 跨性别和各种精神病诊断，并预测独立的 同伙第二，一种更加个性化的发现和测试方法， 将进行精神病诊断。我们将比较个性化的结果 的方法，以确定哪种方法更好地识别 独立队列中的预测因子。第三，顶级生物标志物也将用于 了解所涉及的生物学途径，与其他疾病的共病，以及 在药物基因组学和再利用药物方面产生了线索。这项工作将使我们 建立普遍性，区分力，和潜在的个性化， 生物标志物和生物标志物组，与开发该领域具有高度相关性， 作为精准医疗的完全临床适用性。鉴于自杀是一种潜在的 由于可预防的死亡原因，我们作出努力的必要性怎么强调都不为过。