| 1 | Mol. Psychiatry 2005 Mar 10: 309-22 |
|---|---|
| PMID | 15303102 |
| Title | Transcriptional profiling reveals evidence for signaling and oligodendroglial abnormalities in the temporal cortex from patients with major depressive disorder. |
| Abstract | Major depressive disorder is one of the most common and devastating psychiatric disorders. To identify candidate mechanisms for major depressive disorder, we compared gene expression in the temporal cortex from 12 patients with major depressive disorder and 14 matched controls using Affymetrix HgU95A microarrays. Significant expression changes were revealed in families of genes involved in neurodevelopment, signal transduction and cell communication. Among these, the expression of 17 genes related to oligodendrocyte function was significantly (P < 0.05, fold change > 1.4) decreased in patients with major depressive disorder. Eight of these 17 genes encode structural components of myelin (CNP, MAG, MAL, MOG, MOBP, PMP22, PLLP, PLP1). Five other genes encode enzymes involved in the synthesis of myelin constituents (ASPA, UGT8), or are essential in regulation of myelin formation (ENPP2，EDG2，TF，KLK6）。一个基因，即Sox10，编码调节其他髓鞘相关基因的转录因子。Olig2是一个独家存在于少突胶质细胞和少突胶质细胞前体中的转录因子。另一个基因ERBB3参与了少突胶质细胞分化。除了与髓鞘相关的基因外，轴突生长/突触功能涉及多个基因也发生了重大变化。这些发现表明，主要的抑郁症可能与细胞通信和信号转导机制的变化有关，这些机制导致少突齿和突触功能的异常。与其他研究一起，这些发现表明，重度抑郁症可能与常见的寡头异常异常精神分裂症and bipolar disorder. |
| SCZ关键字 | 精神分裂症 |
| 2 | Synapse 2008 1月62日：1-7 |
| PMID | 17948890 |
| Title | Effect of MK-801 on gene expressions in the amygdala of rats. |
| Abstract | Rodents treated with N-methyl-D-aspartate (NMDA) antagonists have been thought to be an animal model of精神分裂症. In this study, we examined gene expression in the amygdala of rats chronically treated with MK-801, as well as behavioral changes, such as social behavior, in these animals. The social interaction test, a measure of social behavior, and locomotor activity was performed in male Wistar rats injected with MK-801 (0.13 mg/kg i.p.) or saline for 14 days. Changes in mRNA levels were analyzed using a GeneChip microarray system. Real-time quantitative PCR (RT-qPCR) assay was subsequently conducted to confirm the results of the microarray analysis. MK-801 decreased social interaction and increased locomotor activity in rats, consistent with previous reports. We found 23 downregulated genes and 16 upregulated genes, with the gene encoding arginine-vasopressin (AVP) being most downregulated, and that for transthyretin (Ttr) most upregulated. mRNA levels, quantified by RT-qPCR assay, were altered for genes related to neuropeptides (AVP, Sstr2), the arachidonic cascade (Ptgds), myelination (Mobp,ENPP2), neurotrophic factors (Igfbp2), and hormonal milieu (Ttr). Downregulation of the AVP gene in the amygdala of MK-801-treated rats may provide a basis for the ability of AVP-analogues to ameliorate the behavioral disturbances caused by blockade of the NMDA receptor. The results of this study provide an insight into the neural substrates responsible for the generation of psychotic symptoms. |
| SCZ关键字 | 精神分裂症 |
| 3 | Pharmacogenomics 2011 Feb 12: 171-84 |
| PMID | 21332311 |
| Title | Genome-wide expression profiling of human lymphoblastoid cell lines identifies CHL1 as a putative SSRI antidepressant response biomarker. |
| Abstract | Selective serotonin reuptake inhibitors (SSRIs) are the most commonly used class of antidepressants for treating major depression. However, approximately 30% of patients do not respond sufficiently to first-line antidepressant drug treatment and require alternative therapeutics. Genome-wide studies searching for SSRI response DNA biomarkers or studies of candidate serotonin-related genes so far have given inconclusive or contradictory results. Here, we present an alternative transcriptome-based genome-wide approach for searching antidepressant drug-response biomarkers by using drug-effect phenotypes in human lymphoblastoid cell lines (LCLs). We screened 80 LCLs from healthy adult female individuals for growth inhibition by paroxetine. A total of 14 LCLs with reproducible high and low sensitivities to paroxetine (seven from each phenotypic group) were chosen for genome-wide expression profiling with commercial microarrays. 表现出较高的LCL与低帕罗西汀敏感性之间的最显着的全基因组转录组差异是CHL1的基础表达低6.3倍（P = 0.0000256），该基因是编码在正确的丘脑皮层回路中的神经元细胞粘附蛋白的基因，该基因编码为神经元细胞粘附蛋白，精神分裂症and autism. The microarray findings were confirmed by real-time PCR (36-fold lower CHL1 expression levels in the high paroxetine sensitivity group). Several additional genes implicated in synaptogenesis or in psychiatric disorders, including ARRB1, CCL5, DDX60, DDX60L, ENDOD1,ENPP2, FLT1, GABRA4, GAP43, MCTP2 and SPRY2, also differed by more than 1.5-fold and a p-value of less than 0.005 between the two paroxetine sensitivity groups, as confirmed by real-time PCR experiments. Genome-wide transcriptional profiling of in vitro phenotyped LCLs identified CHL1 and additional genes implicated in synaptogenesis and brain circuitry as putative SSRI response biomarkers. This method might be used as a preliminary tool for searching for potential depression treatment biomarkers. |
| SCZ关键字 | 精神分裂症 |