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Discovery of blood transcriptomic markers for depression in animal models and pilot validation in subjects with early-onset major depression

机译:在动物模型中发现抑郁症的血液转录组标记物,并在患有早期发作的严重抑郁症的受试者中进行初步验证

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Early-onset major depressive disorder (MDD) is a serious and prevalent psychiatric illness in adolescents and young adults. Current treatments are not optimally effective. Biological markers of early-onset MDD could increase diagnostic specificity, but no such biomarker exists. Our innovative approach to biomarker discovery for early-onset MDD combined results from genome-wide transcriptomic profiles in the blood of two animal models of depression, representing the genetic and the environmental, stress-related, etiology of MDD. We carried out unbiased analyses of this combined set of 26 candidate blood transcriptomic markers in a sample of 15–19-year-old subjects with MDD (N=14) and subjects with no disorder (ND, N=14). A panel of 11 blood markers differentiated participants with early-onset MDD from the ND group. Additionally, a separate but partially overlapping panel of 18 transcripts distinguished subjects with MDD with or without comorbid anxiety. Four transcripts, discovered from the chronic stress animal model, correlated with maltreatment scores in youths. These pilot data suggest that our approach can lead to clinically valid diagnostic panels of blood transcripts for early-onset MDD, which could reduce diagnostic heterogeneity in this population and has the potential to advance individualized treatment strategies.. ? 2012 Macmillan Publishers Limited
机译:早发性重性抑郁症(MDD)是青少年和年轻人中的一种严重且普遍的精神疾病。目前的治疗方法并非最佳效果。早发性MDD的生物标记物可以提高诊断的特异性,但尚无此类生物标记物。我们针对早发性MDD的生物标记物发现的创新方法结合了两种抑郁症动物模型血液中全基因组转录组谱的结果,这些结果代表了MDD的遗传和环境,与压力相关的病因。我们对15至19岁患有MDD(N = 14)和无障碍(ND,N = 14)的受试者样本中的这26种候选血液转录组标记物组合进行了公正的分析。由11个血液标记组成的小组将参与者与ND组的早发性MDD区别开来。此外,由18个成绩单组成的单独但部分重叠的小组区分患有或不患有合并焦虑症的MDD患者。从慢性应激动物模型中发现的四个转录本与青少年的虐待分数相关。这些初步数据表明,我们的方法可以为早期发病的MDD带来临床有效的血液转录物诊断面板,这可以减少该人群的诊断异质性,并有可能推进个性化治疗策略。 2012 Macmillan Publishers Limited

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