Department of Psychiatry, Dalhousie University Faculty of Medicine, Northwestern University, Chicago, IL, USA.
Transl Psychiatry. 2012 Apr 17;2(4):e101. doi: 10.1038/tp.2012.26.
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.
早发性重度抑郁症（MDD）是青少年和年轻成年人中一种严重且普遍的精神疾病。目前的治疗方法并不十分有效。早发性 MDD 的生物标志物可以提高诊断的特异性，但目前还没有这样的生物标志物。我们开创性的早发性 MDD 生物标志物发现方法结合了两种抑郁症动物模型血液的全基因组转录组谱的结果，代表了 MDD 的遗传和环境、与应激相关的病因。我们对 26 个候选血液转录组标记物的这一组合进行了无偏分析，这些标记物来自 15-19 岁的 MDD 患者（N=14）和无疾病（ND，N=14）的受试者。一个由 11 个血液标记物组成的小组将早发性 MDD 患者与 ND 组区分开来。此外，另一个单独但部分重叠的 18 个转录本小组将 MDD 患者与伴有或不伴有共病焦虑的患者区分开来。从慢性应激动物模型中发现的 4 个转录本与青少年的虐待评分相关。这些初步数据表明，我们的方法可以为早发性 MDD 提供临床有效的血液转录物诊断小组，这可以减少该人群的诊断异质性，并有可能推进个体化治疗策略。
