Silva-Costa Licia C, Smith Bradley J, Carregari Victor Corasolla, Souza Gustavo H M F, Vieira Erica M, Mendes-Silva Ana Paula, de Almeida Valéria, Carvalho Benilton S, Diniz Breno S, Martins-de-Souza Daniel
Laboratory of Neuroproteomics, Institute of Biology, Department of Biochemistry and Tissue Biology, University of Campinas (UNICAMP), Campinas, Brazil.
SpectraMass Ltd., Campinas, SP, Brazil.
J Proteomics. 2022 Oct 30;269:104713. doi: 10.1016/j.jprot.2022.104713. Epub 2022 Sep 1.
Depression is a complex and multifactorial disease, affecting about 6.5% of the elderly population in what is referred to as late-life depression (LLD). Despite its public health relevance, there is still limited information about the molecular mechanisms of LLD. We analyzed the blood plasma of 50 older adults, 19 with LLD and 31 controls, through untargeted mass spectrometry, and used systems biology tools to identify biochemical pathways and biological processes dysregulated in the disease. We found 96 differentially expressed proteins between LLD patients and control individuals. Using elastic-net regression, we generated a panel of 75 proteins that comprises a potential model for determining the molecular signature of LLD. We also showed that biological pathways related to vesicle-mediated transport and voltage-dependent calcium channels may be dysregulated in LLD. These data can help to build an understanding of the molecular basis of LLD, offering an integrated view of the biomolecular alterations that occur in this disorder. SIGNIFICANCE: Major depressive disorder in the elderly, called late-life depression (LLD), is a common and disabling disorder, with recent prevalence estimates of 6.5% in the general population. Despite the public health relevance, there is still limited information about the molecular mechanisms of LLD. The findings in this paper shed light on LLD heterogeneous biological mechanisms. We uncovered a potential novel biomolecular signature for LLD and biological pathways related to this condition which can be targets for the development of novel interventions for prevention, early diagnosis, and treatment of LLD.
抑郁症是一种复杂的多因素疾病，在所谓的老年期抑郁症（LLD）中影响着约6.5%的老年人口。尽管其具有公共卫生相关性，但关于老年期抑郁症分子机制的信息仍然有限。我们通过非靶向质谱分析了50名老年人的血浆，其中19名患有老年期抑郁症，31名作为对照，并使用系统生物学工具来识别该疾病中失调的生化途径和生物学过程。我们发现老年期抑郁症患者与对照个体之间有96种差异表达的蛋白质。使用弹性网络回归，我们生成了一个由75种蛋白质组成的面板，该面板构成了一个用于确定老年期抑郁症分子特征的潜在模型。我们还表明，与囊泡介导的转运和电压依赖性钙通道相关的生物学途径在老年期抑郁症中可能失调。这些数据有助于增进对老年期抑郁症分子基础的理解，提供对该疾病中发生的生物分子改变的综合看法。意义：老年人中的重度抑郁症，即老年期抑郁症（LLD），是一种常见且致残的疾病，最近在普通人群中的患病率估计为6.5%。尽管具有公共卫生相关性，但关于老年期抑郁症分子机制的信息仍然有限。本文的研究结果揭示了老年期抑郁症的异质性生物学机制。我们发现了一种潜在的新型老年期抑郁症生物分子特征以及与此病症相关的生物学途径，这些可作为开发预防、早期诊断和治疗老年期抑郁症新干预措施的靶点。
