Department of Pharmacology, Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119991, Russian Federation.
Curr Pharm Des. 2021;27(2):305-318. doi: 10.2174/1381612826666201124110437.
Modern medicine has provided considerable knowledge of the pathophysiology of mental disorders at the body, systemic, organ and neurochemical levels of the biological organization of the body. Modern clinical diagnostics of depression have some problems, that is why psychiatric society makes use of diagnostics and taxonomy of different types of depression by implemention of modern molecular biomarkers in diagnostic procedures. But up to now, there are no reliable biomarkers of major depressive disorder (MDD) and other types of depression.
The purpose of this review is to find fundamentals in pathological mechanisms of depression, which could be a basis for development of molecular and genetic biomarkers, being the most feasible for clinical use.
This review summarizes the published data using PubMed, Science Direct, Google Scholar and Scopus.
In this review, we summarized and discussed findings in molecular biology, genetics, neuroplasticity, neurotransmitters, and neuroimaging that could increase our understanding of the biological foundations of depression and show new directions for the development of reliable biomarkers. We did not find any molecular and genetic biomarker approved for the clinic. But the Genome-Wide Association Study method promises some progress in the development of biomarkers based on SNP in the future. Epigenetic factors also are a promising target for biomarkers. We have found some differences in the etiology of different types of atypical and melancholic depression. This knowledge could be the basis for development of biomarkers for clinical practice in diagnosis, prognosis and selection of treatment.
Depression is not a monoetiological disease. Many pathological mechanisms are involved in depression, thus up to now, there is no approved and reliable biomarker for diagnosis, prognosis and correction of treatment of depression. The structural and functional complexity of the brain, the lack of invasive technology, poor correlations between genetic and clinical manifestation of depression, imperfect psychiatric classification and taxonomy of subtypes of disease are the main causes of this situation. One of the possible ways to come over this situation can be to pay attention to the trigger mechanism of disease and its subtypes. Researchers and clinicians should focus their efforts on searching the trigger mechanism of depression and different types of it . HPA axis can be a candidate for such trigger in depression caused by stress, because it influences the main branches of disease: neuroinflammation, activity of biogenic amines, oxidative and nitrosative stress, epigenetic factors, metabolomics, etc. But before we shall find any trigger mechanism, we need to create complex biomarkers reflecting genetic, epigenetic, metabolomics and other pathological changes in different types of depression. Recently the most encouraging results have been obtained from genetics and neuroimaging. Continuing research in these areas should be forced by using computational, statistical and systems biology approaches, which can allow to obtain more knowledge about the neurobiology of depression. In order to obtain clinically useful tests, search for biomarkers should use appropriate research methodologies with increasing samples and identifying more homogeneous groups of depressed patients.
现代医学在身体的生理病理学方面提供了大量关于精神障碍的知识，包括身体的系统、器官和神经化学水平。现代临床抑郁症诊断存在一些问题，这就是为什么精神病学会利用现代分子生物标志物在诊断程序中对不同类型的抑郁症进行诊断和分类。但到目前为止，还没有可靠的重度抑郁症（MDD）和其他类型抑郁症的生物标志物。
本综述的目的是寻找抑郁症病理机制的基础，这可能是开发分子和遗传生物标志物的基础，是最有可能用于临床的。
本综述总结了使用 PubMed、Science Direct、Google Scholar 和 Scopus 发表的数据。
在本综述中，我们总结和讨论了分子生物学、遗传学、神经可塑性、神经递质和神经影像学方面的发现，这些发现可以增进我们对抑郁症生物学基础的理解，并为开发可靠的生物标志物指明新的方向。我们没有发现任何临床批准的分子和遗传生物标志物。但是，全基因组关联研究方法有望在未来基于 SNP 开发生物标志物方面取得一些进展。表观遗传因素也是生物标志物的一个有前途的靶点。我们发现了不同类型非典型性和忧郁性抑郁症病因的一些差异。这些知识可以为临床实践中的诊断、预后和治疗选择开发生物标志物提供基础。
抑郁症不是单病因疾病。许多病理机制都与抑郁症有关，因此到目前为止，还没有用于抑郁症诊断、预后和治疗修正的临床批准和可靠的生物标志物。大脑的结构和功能复杂性、缺乏侵入性技术、遗传与抑郁症临床表现之间的相关性差、精神科疾病分类和亚型分类不完善是造成这种情况的主要原因。克服这种情况的一种可能方法是关注疾病及其亚型的触发机制。研究人员和临床医生应将精力集中在寻找抑郁症及其不同类型的触发机制上。HPA 轴可能是应激引起的抑郁症的一个候选触发因素，因为它影响疾病的主要分支：神经炎症、生物胺活性、氧化和硝化应激、表观遗传因素、代谢组学等。但是在我们找到任何触发机制之前，我们需要创建反映不同类型抑郁症的遗传、表观遗传、代谢组学和其他病理变化的复杂生物标志物。最近，遗传学和神经影像学方面取得了最令人鼓舞的结果。通过使用计算、统计和系统生物学方法，继续在这些领域的研究应该是强制性的，这可以使我们获得更多关于抑郁症神经生物学的知识。为了获得临床上有用的测试，生物标志物的研究应该使用适当的研究方法，增加样本量，识别出更同质的抑郁患者群体。
