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）：死后大脑的 mRNA 图谱显示了某些精神疾病（如双相情感障碍、重度抑郁症、精神分裂症和其他神经精神疾病）中神经特征的证据。这表明所报告的神经特征中可能存在诊断特异性。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。该应用的主要目标是使用微阵列的基因表达谱来测试死后大脑中的生物标志物和稳定性。目标 1 至 4 采用新方法来填补科学知识中现有的空白，使用可获取的淋巴细胞组织来源进行神经探针和器官型脑培养，作为当前尸检研究的延伸，以研究候选生物标志物。目前的科学差距将在以下方面得到解决： 目标 1. 比较对照组、重度抑郁症 (MDD) 和双相情感障碍 (BPD) 组之间死后人脑和门诊淋巴细胞组织的基因表达谱，以找出可能发挥作用的独特基因谱作为这些疾病的诊断生物标志物极大地促进了更好的治疗。目标 2. 同一受试者中大脑和淋巴细胞的同步基因表达以及对照、MDD 和 BPD 受试者之间淋巴细胞表达的分析。目标 3. 两种淋巴细胞来源（门诊和死后）之间的比较以及转化对基因表达谱的影响。目标 4. 使用器官型脑组织培养物对潜在生物标志物进行稳定性测试，以研究临终因子对 mRNA 谱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枢基因表达中生物标志物稳定性的潜在影响。淋巴细胞中生物标志物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以及治疗反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