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Biomarkers for Suicidality

自杀的生物标志物

基本信息

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
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/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

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.

全世界每40秒就有一人自杀。看精神病医生