Blood Biomarkers for Psychosis: Specificity vs Overlap with Mood Disorders

精神病的血液生物标志物：特异性与与情绪障碍的重叠

• 批准号: 8811010
• 负责人: Alexander B Niculescu
• 金额: --
• 依托单位: RLR VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811010
• 关键词: Address; Adverse effects; Affect; Animal Model; Animals; Anxiety; Area; Biological Markers; Biology; Bipolar Disorder; Blood; Blood Tests; Brain; Candidate Disease Gene; Caring; Clinic; Clinical; Clinical Treatment; Clinical assessments; Clozapine; Complex; Data; Development; Diagnosis; Disease; Early Intervention; Future; Gene Chips; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic study; Genomic approach; Goals; Hallucinations; Harvest; Health; Health Care Costs; Healthcare; Hospitalization; Human; Individual; Inflammatory; Interview; Laboratories; Lead; Lymphocyte; Measurement; Measures; Mental Depression; Mental disorders; Meta-Analysis; Modality; Molecular; Mood Disorders; Moods; Nature; Paper; Pathway interactions; Patient Self-Report; Patients; Peripheral; Personal Satisfaction; Pharmaceutical Preparations; Phencyclidine; Post-Traumatic Stress Disorders; Predictive Value; Probability; Psychiatry; Psychotic Disorders; Publishing; Quality of life; Recruitment Activity; Relapse; Research; Risk; Running; Safety; Sampling; Schizoaffective Disorders; Schizophrenia; Series; Severities; Solid; Source; Specificity; Study Subject; Symptoms; Testing; Time; Validation; Veterans; Visit; Whole Blood; Work; base; cohort; differential expression; disease classification; drug development; follow-up; functional genomics; human data; human subject; immune activation; impression; improved; information gathering; interest; lymphoblastoid cell line; male; peripheral blood; prevent; psychotic symptoms; public health relevance; response; trait; translational approach

DESCRIPTION (provided by applicant): We have previously proposed, and provide proof for, an approach to help identify blood biomarkers for mood state. Such biomarkers can serve as a basis for objective clinical laboratory tests. We are interested in carrying out similar studies to identify blood biomarkers for psychosis and to address the important scientific and clinical issue of specificity vs. overlap between the biomarkers for these disorders. There are to date no clinical laboratory blood tests for psychosis Given the complex nature of psychotic disorders, the current reliance on patient self-report of symptoms and the clinician's impression on interview of patient is a rate limiting step in deliverig the best possible care with existing treatment modalities, as well as in developing new and improved treatment approaches, including new medications. We propose to identify biomarkers using Convergent Functional Genomics (CFG), an approach developed by us over the last decade, which is based on comprehensive integration of gene expression and genetic data, from human and animal model studies. We have provided proof of principle for this approach helping to identify blood biomarkers for mood disorders (Le- Niculescu et al. 2009)1 and more recently for psychosis (Kurian et al. 2011)2. In that latter work, we have identified a series of high probability blood candidate biomarker genes for psychosis that deserve future scrutiny. A predictive score developed based on a panel of seven top candidate biomarkers for hallucinations (a key symptom for psychosis), shows good sensitivity and moderate specificity, in independent patient cohorts. Our preliminary studies suggest that blood biomarkers may offer an unexpectedly informative window into brain functioning and psychosis state. This exciting preliminary work needs to be carefully extended and replicated in a larger independent cohort, as well as compared to normal controls to derive additional normative data, which is what we propose to do in this project. Moreover, there was overlap between our lists of candidate genes and biomarkers for mood disorders and for psychosis, suggesting that we need to better understand the overlap between bipolar disorder and schizophrenia, and, as a field, explore and refine our integration of nosology with biology. Potential Impact on Veterans Health Care: The development of clinical laboratory blood tests for psychosis will lead to more targeted treatments for veterans affected by psychiatric disorders involving psychotic symptoms, such as schizophrenia and schizoaffective disorder, as well as severe forms of bipolar disorder, depression and PTSD, with improved efficacy and decreased side-effects. This will have an impact on patient health, well-being, safety, quality of life, and independent functioning, as well as decrease hospitalizations and overall health-care costs. Moreover, biomarker profiling may help with assessing response to treatment, risk of relapse, and early intervention efforts to prevent the full-blown development of illness in susceptible individuals.

描述（由申请人提供）：