PDF(Pubmed)
Abstract：
The biological mechanisms underlying the onset of major depressive disorder (MDD) have predominantly been studied in adult populations from high-income countries, despite the onset of depression typically occurring in adolescence and the majority of the world\'s adolescents living in low- and middle-income countries (LMIC). Taking advantage of a unique adolescent sample in an LMIC (Brazil), this study aimed to identify biological pathways characterizing the presence and increased risk of depression in adolescence, and sex-specific differences in such biological signatures. We collected blood samples from a risk-stratified cohort of 150 Brazilian adolescents (aged 14-16 years old) comprising 50 adolescents with MDD, 50 adolescents at high risk of developing MDD but without current MDD, and 50 adolescents at low risk of developing MDD and without MDD (25 females and 25 males in each group). We conducted RNA-Seq and pathway analysis on whole blood. Inflammatory-related biological pathways, such as role of hypercytokinemia/hyperchemokinemia in the pathogenesis of influenza (z-score = 3.464, p < 0.001), interferon signaling (z-score = 2.464, p < 0.001), interferon alpha/beta signaling (z-score = 3.873, p < 0.001), and complement signaling (z-score = 2, p = 0.002) were upregulated in adolescents with MDD compared with adolescents without MDD independently from their level of risk. The up-regulation of such inflammation-related pathways was observed in females but not in males. Inflammatory-related pathways involved in the production of cytokines and in interferon and complement signaling were identified as key indicators of adolescent depression, and this effect was present only in females.
摘要：
主要在高收入国家的成人人群中研究了抑郁症（MDD）发病的生物学机制。尽管抑郁症的发作通常发生在青春期，世界上大多数青少年生活在低收入和中等收入国家（LMIC）。利用LMIC（巴西）中独特的青少年样本，这项研究旨在确定青春期抑郁症的存在和风险增加的生物学途径，以及此类生物学特征中的性别特异性差异。我们从150名巴西青少年（年龄14-16岁）的风险分层队列中收集血液样本，其中包括50名患有MDD的青少年，50名青少年患MDD风险高，但目前没有MDD，50名青少年患MDD风险低，无MDD（每组25名女性和25名男性）。我们对全血进行了RNA-Seq和途径分析。炎症相关生物通路,如高细胞因子血症/高化疗激酶血症在流感发病机制中的作用（z评分=3.464，p<0.001），干扰素信号（z分数=2.464，p<0.001），干扰素α/β信号（z分数=3.873，p<0.001），与没有MDD的青少年相比,患有MDD的青少年中补体信号(z-score=2,p=0.002)上调,且与风险水平无关.在女性中观察到此类炎症相关途径的上调,但在男性中未观察到。参与细胞因子产生以及干扰素和补体信号传导的炎症相关途径被确定为青少年抑郁症的关键指标。这种效应只存在于女性身上。
