Background: 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.
Objective: 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.
Method: This review summarizes the published data using PubMed, Science Direct, Google Scholar and Scopus.
Results: 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.
Conclusion: 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.