Biomarker Genes in Mood Disorder: Lymphocyte and Brain

情绪障碍的生物标志基因：淋巴细胞和大脑

• 批准号: 7089915
• 负责人: MARQUIS PHILIP VAWTER
• 金额: $ 15.82万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7089915
• 关键词: biomarker; bipolar depression; brain; clinical research; diagnosis design /evaluation; diagnostic tests; gene expression; gene expression profiling; human subject; human tissue; lymphocyte; major depression; mental disorder diagnosis; messenger RNA; microarray technology; mood disorders; patient oriented research; postmortem; tissue /cell culture

DESCRIPTION (provided by applicant): The mRNA profile of postmortem brain shows evidence of neural signatures in certain psychiatric disorders such as bipolar disorder, major depression, schizophrenia, and other neuropsychiatric disorders. This suggests that diagnostic specificity might be present in the reported neural signatures. The neural signature could be further examined using peripheral lymphocytes as a neural probe. The broad goal of this application is to test for biomarkers and stability in postmortem brain using gene expression profiling by microarray. Aims 1 through 4 incorporate novel approaches to fill in existing gaps in scientific knowledge using an accessible tissue source of lymphocytes for a neural probe and organotypic brain culture as an extension to current postmortem studies to study candidate biomarkers. The present scientific gaps will be addressed in: Aim 1. Compare gene expression profiles in post-mortem human brain and outpatient lymphocyte tissue between controls, major depressive disorder (MDD), and bipolar disorder (BPD) groups for unique gene profiles that may act as diagnostic biomarkers for these disorders greatly facilitating better treatments. Aim 2. Simultaneous gene expression from brain and lymphocyte within the same subjects and analysis of lymphocyte expression between controls, MDD, and BPD subjects. Aim 3. Comparison between 2 sources of lymphocytes (outpatient and post-mortem) and effects of transformation on gene expression profiling. Aim 4. Stability testing of potential biomarkers using organotypic brain tissue culture to study the impact of agonal factors on mRNA profiling and biomarkers. The 4 aims of this application are inter-related, i.e. biomarker evaluation and the potential impact of agonal factors on the stability of biomarkers in peripheral and central gene expression. The potential use of biomarkers in lymphocytes will provide clinical researchers a tool to better address questions concerning diagnostic subgroups and treatment responders and non-responders.

描述（由申请人提供）：事后大脑的mRNA概况显示了某些精神疾病中神经信号的证据，例如躁郁症，严重抑郁症，精神分裂症和其他神经精神疾病。这表明诊断特异性可能存在于报告的神经信号中。可以使用外周淋巴细胞作为神经探针进一步检查神经特征。该应用的广泛目标是使用微阵列使用基因表达分析来测试死后大脑中的生物标志物和稳定性。目标1至4融合了新的方法，使用可访问的淋巴细胞的组织来源来填补科学知识中的现有空白，以扩展到当前的后死后研究，以扩展研究候选生物标志物。目前的科学差距将在以下方面解决：AIM 1。比较在对照组，重度抑郁症（MDD）和双相情感障碍（MDD）和双相情感障碍（BPD）组之间在验尸后的基因表达谱和独特的基因概况中，这些基因概况可能是这些疾病的诊断生物标志物的独特基因概况。 AIM 2。来自相同受试者中脑和淋巴细胞的同时基因表达以及对照，MDD和BPD受试者之间淋巴细胞表达的分析。 AIM 3。2个淋巴细胞（门诊和验尸）的比较与转化对基因表达分析的影响。 AIM 4。使用器官脑组织培养物对潜在生物标志物进行稳定性测试，以研究激动因素对mRNA分析和生物标志物的影响。该应用的4个目标是相互关联的，即生物标志物评估以及激动因素对外周和中央基因表达中生物标志物稳定性的潜在影响。生物标志物在淋巴细胞中的潜在用途将为临床研究人员提供一种工具，以更好地解决有关诊断亚组，治疗响应者和无反应者的问题。

项目成果

The first decade and beyond of transcriptional profiling in schizophrenia.

• DOI: 10.1016/j.nbd.2011.03.001
• 发表时间: 2012-01
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Sequeira, P. Adolfo;Martin, Maureen V.;Vawter, Marquis P.
• 通讯作者: Vawter, Marquis P.

Dysregulation of X-linked gene expression in Klinefelter's syndrome and association with verbal cognition.

克兰费尔特综合征中 X 连锁基因表达失调及其与言语认知的关系。

• DOI: 10.1002/ajmg.b.30454
• 发表时间: 2007
• 期刊: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
• 作者: Vawter,MarquisP;Harvey,PhilipD;DeLisi,LynnE
• 通讯作者: DeLisi,LynnE

Genome scans and gene expression microarrays converge to identify gene regulatory loci relevant in schizophrenia.

基因组扫描和基因表达微阵列结合起来识别与精神分裂症相关的基因调控位点。

• DOI: 10.1007/s00439-006-0172-7
• 发表时间: 2006
• 期刊: Human genetics
• 影响因子: 5.3
• 作者: Vawter,MarquisP;Atz,MaryE;Rollins,BrandiL;Cooper-Casey,KathleenM;Shao,Ling;Byerley,WilliamF
• 通讯作者: Byerley,WilliamF

Peripheral biomarkers revisited: integrative profiling of peripheral samples for psychiatric research.

• DOI: 10.1016/j.biopsych.2013.09.035
• 发表时间: 2014-06-15
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Hayashi-Takagi A;Vawter MP;Iwamoto K
• 通讯作者: Iwamoto K

Olanzapine Reversed Brain Gene Expression Changes Induced by Phencyclidine Treatment in Non-Human Primates.

奥氮平逆转了非人类灵长类动物中苯环己哌啶治疗引起的脑基因表达变化。

• DOI: 10.1159/000430786
• 发表时间: 2015
• 期刊: Molecular neuropsychiatry
• 作者: Martin,MaureenV;Mirnics,Karoly;Nisenbaum,LauraK;Vawter,MarquisP
• 通讯作者: Vawter,MarquisP