Biomarkers for Suicidality

自杀的生物标志物

基本信息

批准号：
10425292
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
项目类别：
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/10425292
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 pragmatic implementation precision medicine psychiatric comorbidity targeted biomarker trait translational approach treatment response

项目摘要

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.

全球每 40 秒就有一人死于自杀。患有精神病紊乱会增加风险。个人或临床医疗印象的自我报告专业并不总是可靠的。制定和验证定量和目标预测和预防自杀的方法（意念、尝试、完成）迫在眉睫需要。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追踪自杀倾向，并在自杀中验证它们完成者，并在独立队列中测试他们评估状态（自杀倾向）的能力意念）和预测特质的能力（未来因自杀而住院）。这些研究是在患有精神疾病的男性中进行的（Le-Niculescu 等人，分子生物学）精神病学 2013，Niculescu 等人。分子精神病学 2015）和女性精神疾病（Levey 等人，分子精神病学 2016）。研究指出一些相似之处以及重要的性别差异。一个基本问题仍有待回答：寻求更通用、跨性别的预测变量并且是跨诊断的，或者是根据性别和性别来寻求更个性化的预测因子诊断是否会更有成效，最终转化为临床实践？我们试图通过最近的一系列研究来回答这个基本问题（Niculescu 等人，分子精神病学 2017），并希望扩展和巩固这一点与本拨款申请中提议的工作。首先，我们将巩固血液研究结果自杀倾向的基因表达生物标志物在自然界中更为普遍，有效跨性别和各种精神科诊断，并且具有独立的预测性队列。其次，按性别和性别划分的更加个性化的发现和测试方法将进行精神科诊断。我们将比较个性化的结果方法与通用方法的比较，以确定哪种方法可以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以及与其他疾病的共病作为药物基因组学和药物再利用方面的线索。这项工作将使我们建立普遍性、歧视性和潜在的个性化与该领域的发展高度相关的生物标志物和生物标志物组作为精准医学的完全临床适用性。鉴于自杀是一种潜在的死因是可预防的，因此我们做出这样的努力的必要性怎么强调也不为过。