Biomarker Genes in Mood Disorder: Lymphocyte and Brain

描述（由申请人提供）：死后大脑的mRNA谱显示了某些精神疾病的神经特征，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。这表明诊断特异性可能存在于报道的神经特征中。使用外周淋巴细胞作为神经探针可以进一步检查神经特征。该应用的广泛目标是通过微阵列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到目标4结合了新的方法来填补现有的科学知识空白，利用可获得的组织淋巴细胞来源进行神经探针和器官型脑培养，作为当前死后研究的延伸，研究候选生物标志物。目前的科学差距将在目标1中得到解决。比较对照、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中的基因表达谱，以获得可能作为这些疾病的诊断生物标志物的独特基因谱，从而极大地促进更好的治疗。目标2。同一受试者脑和淋巴细胞的同时基因表达以及对照组、重度抑郁症和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）的比较及其转化对基因表达谱的影响。目标4。利用器官型脑组织培养进行潜在生物标志物的稳定性测试，研究非特异性因素对mRNA谱和生物标志物的影响。该应用的4个目的是相互关联的，即生物标志物评估和agonal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和治疗反应和无反应的问题。

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.