Biomarkers for Suicidality

自杀的生物标志物

• 批准号: 10216982
• 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/10216982
• 关键词: Anxiety; 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; Drug usage; 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; Light; Major Depressive Disorder; Manuals; Maps; Measurement; Mental disorders; Molecular; Moods; Nature; Pathway Analysis; Pathway interactions; Patient Self-Report; Peripheral; Persons; Pharmacogenomics; Post-Traumatic Stress Disorders; Psyche structure; Psychiatric Diagnosis; Psychiatry; 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; candidate marker; clinical application; clinical biomarkers; clinical practice; cohort; comorbidity; completed suicide; design; drug candidate; drug repurposing; functional genomics; gender difference; ideation; impression; male; patient stratification; personalized approach; personalized predictions; potential biomarker; precision medicine; 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秒就有一人自杀身亡。有一个精神科医生 紊乱会增加风险。个人自我报告或对医疗保健的临床印象 专业人士并不总是可靠的。制定和验证定量和客观的 预测和预防自杀(构思、企图、完成)的方法迫在眉睫 需要的。我们小组最近的工作已经确定了血液基因表达生物标记物 使用纵向受试者内设计跟踪自杀行为，并在自杀中进行验证 完成者，并在独立的队列中测试他们评估状态的能力(自杀倾向 意念)，以及预测特质(未来因自杀住院)的能力。这些研究 是在患有精神障碍的男性中进行的(Le-Nule escu等人。分子 《精神病学》2013年，尼库列斯库等人。分子精神病学2015)和患有 精神障碍(Levey等人)分子精神病学2016)。这些研究指出 一些相似之处以及重要的性别差异。一个根本问题 有待回答：是寻求更通用的跨性别预测指标 和跨诊断，或寻求更个性化的预测性别和 诊断将更有成效，最终转化为临床实践？我们 我试图用最近的一系列研究来回答这个根本问题 (尼库列斯库等人)分子精神病学2017)，并希望扩展和巩固这一点 在这项拨款申请中提出的工作。首先，我们将巩固血液检测结果 自杀的基因表达生物标记物在自然界中更普遍，起作用 不同性别和不同的精神疾病诊断，并在独立的预测 一群人。第二，更个性化的发现和测试方法，按性别和 将进行精神诊断。我们将比较个性化的结果 通用方法的方法，以确定哪种方法识别得更好 独立队列中的预测者。第三，顶级生物标志物也将用于 了解所涉及的生物途径，以及与其他疾病的共病 AS在药物基因组学和重新调整药物用途方面产生了线索。这项工作将允许我们 建立概括性、歧视性和潜在的个性化 生物标志物和生物标志物小组，对开发这一领域具有高度相关性 作为精准医学，具有充分的临床适用性。鉴于自杀是一种潜在的 作为可预防的死亡原因，我们这样的努力的必要性怎么强调都不为过。