The Role of Brain-Derived Neurotrophic Factor in Mediating the Action of Antidepressants in the Treatment of Depression

According to the neurotrophic hypothesis of depression proposed two decades ago, the most important role in the pathogenesis of depressive disorders is played by abnormalities in the maintenance of neuronal plasticity regulated by brain neurotrophic factor (BDNF). Although the decline in BDNF activity in depression is now widely documented, it remains unclear whether it is a factor contributing to the onset of depression, or a consequence of the chronic course of the disease. In preclinical studies, it was found that exogenous BDNF infusions causes antidepressant-like effects, prevents the depressogenic effects of chronic stress and increases cell survival in the hippocampus and the prefrontal cortex, but the mechanisms mediating these effects have not been fully studied. The results of molecular genetic studies confirmed that BDNF is essential in mediating the therapeutic effect of antidepressants, while the role of genetic polymorphisms in predicting antidepressant efficacy in depression remains uncertain. The mechanisms of action of monoaminergic antidepressants are related to their effect on the expression of BDNF and its TrkB receptor, however, apparently, the effect size varies for different drugs. Peripheral BDNF levels increase during treatment with antidepressants, and this increase is clearly observed only during the acute phase treatment of depression, but not during the period of maintenance therapy. The serum level of BDNF is a potentially useful marker for diagnosing depression and prediction of a therapeutic response.

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From the clinic to the research laboratory. The role of the clinician in molecular genetic studies

Archives of Dermatology ◽

10.1001/archderm.129.11.1424 ◽

1993 ◽

Vol 129 (11) ◽

pp. 1424-1429

Author(s):

S. E. Palmer

Keyword(s):

Research Laboratory ◽

Molecular Genetic ◽

Genetic Studies

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Prospects for the Personalized Multimodal Therapy Approach to Pain Management via Action on NO and NOS

Molecules ◽

10.3390/molecules26092431 ◽

2021 ◽

Vol 26 (9) ◽

pp. 2431

Author(s):

Natalia A. Shnayder ◽

Marina M. Petrova ◽

Tatiana E. Popova ◽

Tatiana K. Davidova ◽

Olga P. Bobrova ◽

...

Keyword(s):

Chronic Pain ◽

Molecular Genetic ◽

Pain Syndrome ◽

Medical Problem ◽

Single Nucleotide Variants ◽

Genetic Studies ◽

Pain Syndromes ◽

Nos Inhibitors ◽

Peripheral Pain

Chronic pain syndromes are an important medical problem generated by various molecular, genetic, and pathophysiologic mechanisms. Back pain, neuropathic pain, and posttraumatic pain are the most important pathological processes associated with chronic pain in adults. Standard approaches to the treatment of them do not solve the problem of pain chronicity. This is the reason for the search for new personalized strategies for the prevention and treatment of chronic pain. The nitric oxide (NO) system can play one of the key roles in the development of peripheral pain and its chronicity. The purpose of the study is to review publications devoted to changes in the NO system in patients with peripheral chronical pain syndromes. We have carried out a search for the articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar databases. The search was carried out using keywords and their combinations. The role of NO and NO synthases (NOS) isoforms in peripheral pain development and chronicity was demonstrated primarily from animal models to humans. The most studied is the neuronal NOS (nNOS). The role of inducible NOS (iNOS) and endothelial NOS (eNOS) is still under investigation. Associative genetic studies have shown that single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes encoding nNOS, iNOS, and eNOS may be associated with acute and chronic peripheral pain. Prospects for the use of NOS inhibitors to modulate the effect of drugs used to treat peripheral pain syndrome are discussed. Associative genetic studies of SNVs NOS1, NOS2, and NOS3 genes are important for understanding genetic predictors of peripheral pain chronicity and development of new personalized pharmacotherapy strategies.

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The role of genetic research with family design in the study of affective disorders

V M BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY ◽

10.31363/2313-7053-2019-4-1-106-108 ◽

2019 ◽

pp. 106-108

Author(s):

E. D. Kasyanov ◽

G. E. Maso ◽

A. O. Kibitov

Keyword(s):

Affective Disorders ◽

Bipolar Affective Disorder ◽

Molecular Genetic ◽

Genetic Research ◽

Important Criterion ◽

Genetic Studies ◽

The Family ◽

Polygenic Diseases ◽

Potential Biomarkers

Affective disorders (recurrent depressive disorder and bipolar affective disorder) are multifactorial and polygenic diseases, which suggests the involvement of multiple neurobiological mechanisms. The phenotype of affective disorders is a heterogeneous group of clinically similar psychopathological symptoms, which also makes it difficult to detect potential biomarkers and new therapeutic targets. To study families at high risk of developing affective disorders using both clinical and molecular genetic approaches can help to study the neurobiological basis of depressive conditions, as well as to identify endophenotypes of affective disorders. The most important criterion for an endophenotype is its heritability, which can be proved only within the framework of the family design of the study. Comprehensive clinical and molecular genetic studies based on family design have the best prospects.

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Self-Directed Approaches to the Treatment of Depression

The Oxford Handbook of Mood Disorders ◽

10.1093/oxfordhb/9780199973965.013.40 ◽

2016 ◽

pp. 468-477

Author(s):

Pim Cuijpers ◽

Annet Kleiboer

Keyword(s):

Depressive Disorders ◽

Future Research ◽

Evidence Based ◽

Advantages And Disadvantages ◽

Self Help ◽

Treatment Of Depression ◽

High Prevalence ◽

Evidence Based Treatments ◽

The Common

This article examines self-directed approaches to the treatment of depression. It first considers some of the reasons why the uptake of mental health services by depressed people is low, despite the high prevalence of depressive disorders and the availability of evidence-based treatments. It then looks at the role of self-management in increasing access to evidence-based treatments for depression. It also defines what self-directed treatments are and goes on to discuss the different types of self-directed therapy, the common components of self-directed interventions for depression, Internet-based interventions for depression, and the advantages and disadvantages of self-directed interventions. Finally, it summarizes the findings from research on self-directed interventions for depression and suggests directions for future research and development in this area. Some titles of self-help books that can be used in self-directed interventions are presented.

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Assessing the Evidence of Micronutrients on Depression among Children and Adolescents: An Evidence Gap Map

Advances in Nutrition ◽

10.1093/advances/nmaa021 ◽

2020 ◽

Vol 11 (4) ◽

pp. 908-927

Author(s):

Susan C Campisi ◽

Clare Zasowski ◽

Shailja Shah ◽

Ashka Shah ◽

Glyneva Bradley-Ridout ◽

...

Keyword(s):

Children And Adolescents ◽

Depressive Disorders ◽

Unipolar Depression ◽

Eligibility Criteria ◽

Treatment Of Depression ◽

Comprehensive Search ◽

Major Depressive Disorders ◽

Severity Of Depression ◽

The Impact

ABSTRACT There is some evidence indicating that nutrition may have the ability to prevent, treat, and/or influence the severity of depression. The aims of this evidence gap map (EGM) are to provide an overview and to determine evidence gaps in the existing research on micronutrients and their impact on depression among children and adolescents. We conducted a comprehensive search in multiple databases of primary and secondary literature assessing the impact of micronutrients on depression-related outcomes such as unipolar depression, major depressive disorders, dysthymia, acute depression, and mood disorders. Abstracts and full-text articles were dual-screened based on predefined eligibility criteria. A total of 30 primary research publications were included in the EGM. About 47% of included studies focused on late adolescents (15–19 y), ∼40% on early adolescents (10–14 y), and ∼13% on children aged 6–9 y. Among the included studies, 8 studies examined a single micronutrient intervention and 22 studies examined micronutrient concentrations (either intake or serum), and their impact on depression. The most frequently studied micronutrients were vitamin D (n = 8), zinc (n = 8), iron (n = 6), folate (n = 7), and vitamin B-12 (n = 5). More longitudinal studies and trials are needed to determine the role of micronutrients in the etiology and treatment of depression among children and adolescents.

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The Role Of rs1799883 Polymorphism Of The FABP2 Gene In The Pathogenesis Of Nosological Syntropy Of Gallstone Disease And Metabolic Syndrome

The American Journal of Medical Sciences and Pharmaceutical Research ◽

10.37547/tajmspr/volume03issue06-07 ◽

2021 ◽

Vol 03 (06) ◽

pp. 46-51

Author(s):

Raximov Anvar Pulatboevich ◽

◽

Ismailov O’ktam Safaevich ◽

Batirov Davronbek Yusupovich ◽

◽

...

Keyword(s):

Gallstone Disease ◽

Molecular Genetic ◽

Case Control ◽

Control Model ◽

Molecular Medicine ◽

Genetic Studies ◽

Homozygous Genotype ◽

Risk Of Disease ◽

Fabp2 Gene

Objective: to study the role of the rs1799883 polymorphism of the FABP2 gene in the pathogenesis of gallstone disease in combination with MS. Material and methods. Molecular genetic studies were carried out in the Department of Molecular Medicine and Cell Technologies of the RSNPMC Hematology. The analysis of the associations of the rs1799883 polymorphisms of the FABP2 gene was carried out using a case-control model. The main group consisted of 118 patients with cholelithiasis in combination with MS living in the Khorezm region. Results: As a result of our research, we identified a significant association of the homozygous genotype for the Thr allele with the development of gallstone disease in combination with MS. The indicator of the ratio of the chances of developing gallstone disease in combination with MS in carriers of this genotype was OR = 2.9 at 95% CI: 1.122- 7.424. The relative risk of disease was RR = 2.5 with 95% CI: 1.11-5.76. Conclusion: Our results allow us to conclude that the homozygous Thr/Thr genotype plays an important role in the formation of gallstone disease and obesity in people of Uzbek nationality.

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Molecular genetic differentiation of depression in affective pathology and schizophrenia with depressive disorders: the role of polymorphism IL-1β –511C/T

Medical news of the North Caucasus ◽

10.14300/mnnc.2021.16088 ◽

2021 ◽

Vol 16 (4) ◽

Author(s):

Tatiana Viktorovna Lezheiko ◽

Denis Tikhonov ◽

Vera Cabrael Jello ◽

Marina Vladimirovna Gabaeva ◽

Galina Ivanovna Korovaitseva ◽

...

Keyword(s):

Genetic Differentiation ◽

Depressive Disorders ◽

Molecular Genetic

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Biochemical and molecular genetic studies of the metabolic role of methylcrotonyl-CoA carboxylase

10.31274/rtd-180813-13656 ◽

2000 ◽

Cited By ~ 1

Author(s):

Ping Che

Keyword(s):

Molecular Genetic ◽

Genetic Studies ◽

Metabolic Role

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The Low Molecular Weight Brain-derived Neurotrophic Factor Mimetics with Antidepressant-like Activity

Current Pharmaceutical Design ◽

10.2174/1381612825666190329122852 ◽

2019 ◽

Vol 25 (6) ◽

pp. 729-737 ◽

Cited By ~ 5

Author(s):

Tatiana A. Gudasheva ◽

Polina Povarnina ◽

Alexey V. Tarasiuk ◽

Sergey B. Seredenin

Keyword(s):

Small Molecules ◽

Neurotrophic Factor ◽

Antidepressant Drugs ◽

Brain Derived Neurotrophic Factor ◽

Therapeutic Agents ◽

Low Molecular Weight ◽

Promising Therapeutic Target ◽

Treatment Of Depression ◽

Fast Acting

The search for new highly-effective, fast-acting antidepressant drugs is extremely relevant. Brain derived neurotrophic factor (BDNF) and signaling through its tropomyosin-related tyrosine kinase B (TrkB) receptor, represents one of the most promising therapeutic targets for treating depression. BDNF is a key regulator of neuroplasticity in the hippocampus and the prefrontal cortex, the dysfunction of which is considered to be the main pathophysiological hallmark of this disorder. BDNF itself has no favorable drug-like properties due to poor pharmacokinetics and possible adverse effects. The design of small, proteolytically stable BDNF mimetics might provide a useful approach for the development of therapeutic agents. Two small molecule BDNF mimetics with antidepressant-like activity have been reported, 7,8-dihydroxyflavone and the dimeric dipeptide mimetic of BDNF loop 4, GSB-106. The article reflects on the current literature on the role of BDNF as a promising therapeutic target in the treatment of depression and on the current advances in the development of small molecules on the base of this neurotrophin as potential antidepressants.

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