Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls.
Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls.
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DOI：
10.1186/1471-244x-13-273
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发表时间：
2013-10-21
期刊：
影响因子：
4.4
通讯作者：
Light AR
中科院分区：
文献类型：
--
作者：
Iacob E;Light KC;Tadler SC;Weeks HR;White AT;Hughen RW;Vanhaitsma TA;Bushnell L;Light AR
抑郁症是一种巨大的经济和社会负担。女性抑郁症的发生率比男性高70%，其中超过30%的患者对传统药物没有反应。因此，药物耐药的女性患者是一个庞大的、服务不足的群体，非常需要新的干预生物靶点。我们用实时定量聚合酶链式反应(QPCR)检测了免疫、HPA轴、离子通道、生长和转录因子等27个基因在外周血白细胞中的基因表达。我们的样本包括23名患有药物难治性抑郁症的女性：13名患有严重抑郁障碍(MDD)，10名患有双相情感障碍(BPD)。我们的对照组是19名健康的、非抑郁症的女性对照组。我们检测了DD与对照组、MDD与BPD以及抑郁程度较重与较轻患者的mRNA表达差异。DD患者IL-10、IL-6、OXTR、P2RX7、P2RY1和TRPV1表达增加。BPD患者APP、CREB1、NFKB1、NR3C1和SPARC增加，而肿瘤坏死因子表达减少。抑郁的严重程度与IL-10、P2RY1、P2RX1和TRPV4的表达增加有关。这些结果支持了先前免疫基因失调的发现，并为女性药物难治性抑郁症患者的嘌呤能和其他离子通道以及BPD患者的转录和生长因子失调提供了初步证据。如果在未来检测蛋白质水平和mRNA水平的研究中复制这些途径，这些途径可能被用于探索抑郁症的生物学机制，并开发新的药物靶点。
Depressive Disorders (DD) are a great financial and social burden. Females display 70% higher rate of depression than males and more than 30% of these patients do not respond to conventional medications. Thus medication-refractory female patients are a large, under-served, group where new biological targets for intervention are greatly needed. We used real-time quantitative polymerase chain reaction (qPCR) to evaluate mRNA gene expression from peripheral blood leukocytes for 27 genes, including immune, HPA-axis, ion channels, and growth and transcription factors. Our sample included 23 females with medication refractory DD: 13 with major depressive disorder (MDD), 10 with bipolar disorder (BPD). Our comparison group was 19 healthy, non-depressed female controls. We examined differences in mRNA expression in DD vs. controls, in MDD vs. BPD, and in patients with greater vs. lesser depression severity. DD patients showed increased expression for IL-10, IL-6, OXTR, P2RX7, P2RY1, and TRPV1. BPD patients showed increased APP, CREB1, NFKB1, NR3C1, and SPARC and decreased TNF expression. Depression severity was related to increased IL-10, P2RY1, P2RX1, and TRPV4 expression. These results support prior findings of dysregulation in immune genes, and provide preliminary evidence of dysregulation in purinergic and other ion channels in females with medication-refractory depression, and in transcription and growth factors in those with BPD. If replicated in future research examining protein levels as well as mRNA, these pathways could potentially be used to explore biological mechanisms of depression and to develop new drug targets.