Biological mechanisms of atypical and melancholic major depressive disorder

2021 ◽  
Vol 27 ◽  
Author(s):  
Vadim V. Tarasov ◽  
Nikolay N. Ivanets ◽  
Andrey A. Svistunov ◽  
Vladimir N. Chubarev ◽  
Marina A. Kinkulkina ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Psychiatric Clinic ◽  
Biological Mechanisms ◽  
Major Depressive ◽  
Diagnosis And Prognosis ◽  
Depressive Subtypes ◽  
Different Origins

Background: This review summarizes recent findings in molecular biology and neuroimaging and their applicability to the classification and identification of depression. We discuss whether there is reliable evidence that could become a basis for biomarkers or subtyping that may enhance our understanding of the biological foundations of depression and may be useful for clinical practice with respect to diagnosis and prognosis as well as the selection of treatments. Objective: The purpose of this investigation is to present molecular mechanisms that contribute to different origins of depressions that could prove useful in daily psychiatric clinic based practices. Method: The authors analyzed and summarized electronic publications available via PubMed, Science Direct, Google Scholar, and Scopus. Results: The introduction of molecular diagnostics methods into medical practice is a promising method to improve the accuracy of the diagnosis of depression in clinical settings. The literature analysis revealed structural changes in some areas of the brain, its neuroplasticity, as well as changes at the molecular, epigenetic, and genetic levels. However, there are no current reliable biomarkers for differential diagnosis of the types and subtypes of depression. Conclusion: Major depressive disorder is a biologically and genetically heterogeneous disorder. Given its complexity, subtyping is worthwhile to identify biological bases of conditions. The literature review provides ample findings that reveal possible underlying biological mechanisms associated with atypical and melancholic depression. Additional, focused research should be continued with respect to the molecular and genetic biology of different types of depression. There already are promising findings, but additional research to define biologically based depressive subtypes is needed and worthwhile.

scholarly journals Cortical structural differences in major depressive disorder correlate with cell type-specific transcriptional signatures

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiao Li ◽  
Jakob Seidlitz ◽  
John Suckling ◽  
Feiyang Fan ◽  
Gong-Jun Ji ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Brain Regions ◽  
Cell Type ◽  
Major Depressive ◽  
Structural Differences ◽  
Neuroimaging Data ◽  
Cell Type Specific

AbstractMajor depressive disorder (MDD) has been shown to be associated with structural abnormalities in a variety of spatially diverse brain regions. However, the correlation between brain structural changes in MDD and gene expression is unclear. Here, we examine the link between brain-wide gene expression and morphometric changes in individuals with MDD, using neuroimaging data from two independent cohorts and a publicly available transcriptomic dataset. Morphometric similarity network (MSN) analysis shows replicable cortical structural differences in individuals with MDD compared to control subjects. Using human brain gene expression data, we observe that the expression of MDD-associated genes spatially correlates with MSN differences. Analysis of cell type-specific signature genes suggests that microglia and neuronal specific transcriptional changes account for most of the observed correlation with MDD-specific MSN differences. Collectively, our findings link molecular and structural changes relevant for MDD.

scholarly journals Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1089 ◽  
Author(s):  
Elisabetta Maffioletti ◽  
Alessandra Minelli ◽  
Daniela Tardito ◽  
Massimo Gennarelli
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Molecular Mechanisms ◽  
Pharmacological Treatments ◽  
Major Depressive ◽  
Reciprocal Interactions ◽  
Evidence Based Treatments ◽  
Molecular Effects ◽  
Molecular Bases ◽  
The Brain

Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field.

scholarly journals Association of GSK3β Polymorphisms With Brain Structural Changes in Major Depressive Disorder

2009 ◽  
Vol 66 (7) ◽  
pp. 721 ◽  
Author(s):  
Becky Inkster ◽  
Thomas E. Nichols ◽  
Philipp G. Saemann ◽  
Dorothee P. Auer ◽  
Florian Holsboer ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Structural Changes ◽  
Major Depressive

scholarly journals Pharmacogenetics of Major Depressive Disorder (MDD): Progress in Two Serotonergic Targets

2018 ◽  
Vol 8 (2) ◽  
pp. 35-39
Author(s):  
Chidiebere Michael Iro ◽  
Rami Hamati
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Molecular Mechanisms ◽  
Conclusive Evidence ◽  
Nucleotide Polymorphisms ◽  
Social Psychological ◽  
Major Depressive ◽  
Genetic Components ◽  
The One

Major depressive disorder (MDD) is a multifaceted, debilitating condition affecting over 300 million people worldwide. It contributes significantly to social, psychological and economic burdens on individuals and on society at large. Currently, the most widely prescribed antidepressant medications are selective serotonin reuptake inhibitors (SSRIs), which act by blocking serotonin (5-HT) reuptake into presynaptic neurons, thereby increasing the extracellular 5-HT concentration in the brain. However, response to SSRIs and other psychotropic medications used to treat depression is highly variable, with only about one third of patients responding to treatment with an SSRI. This may reflect, at least in part, the genetic heterogeneity of depressed individuals. Studies investigating the genetic components of depression aim to improve treatment outcomes and possibly pave the way for personalized medicine in which the first medication prescribed is the one most likely to result in remission. This review presents the results of several studies on two 5-HT related genes: SLC6A4 and HTR2A, which encode for the serotonin transporter and the serotonin-2A receptor, respectively. Extensive studies have demonstrated that possessing two copies of the long allele (L/L) of the SLC6A4 gene can predict better responses to the SSRI Escitalopram. However, this finding was significant only in the Caucasian population. In addition to this, several single nucleotide polymorphisms in the HTR2A gene also predict clinical outcome, although molecular mechanisms remain unclear. Hence, the results indicate that while there is significant potential for predicting treatment response associated with these and other genetic targets, there is much work left to be done to establish conclusive evidence for and feasibility of pharmacogenetic testing.

Telomeres: the role of shortening and senescence in major depressive disorder and its therapeutic implications

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jessica Daniela Schroder ◽  
Julia Beatrice de Araújo ◽  
Tacio de Oliveira ◽  
Airam Barbosa de Moura ◽  
Gabriel Rodrigo Fries ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Telomerase Activity ◽  
Biological Aging ◽  
Biological Mechanisms ◽  
Major Depressive ◽  
Number Of Patients ◽  
Telomere Biology

Abstract Major depressive disorder (MDD) is one of the most prevalent and debilitating psychiatric disorders, with a large number of patients not showing an effective therapeutic response to available treatments. Several biopsychosocial factors, such as stress in childhood and throughout life, and factors related to biological aging, may increase the susceptibility to MDD development. Included in critical biological processes related to aging and underlying biological mechanisms associated with MDD is the shortening of telomeres and changes in telomerase activity. This comprehensive review discusses studies that assessed the length of telomeres or telomerase activity and function in peripheral blood cells and brain tissues of MDD individuals. Also, results from in vitro protocols and animal models of stress and depressive-like behaviors were included. We also expand our discussion to include the role of telomere biology as it relates to other relevant biological mechanisms, such as the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, inflammation, genetics, and epigenetic changes. In the text and the discussion, conflicting results in the literature were observed, especially considering the size of telomeres in the central nervous system, on which there are different protocols with divergent results in the literature. Finally, the context of this review is considering cell signaling, transcription factors, and neurotransmission, which are involved in MDD and can be underlying to senescence, telomere shortening, and telomerase functions.

scholarly journals Identification of Core Genes and Pathways in Major Depressive Disorder Applying Bioinformatics

2020 ◽  
Author(s):  
Wenshan Yang ◽  
Hong Yin ◽  
Yichen Wang ◽  
Ping Liu ◽  
Yuan Hu
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Ppi Network ◽  
Biological Mechanisms ◽  
Major Depressive ◽  
Kegg Pathway Analysis ◽  
Depressive Patients

Abstract Background: Although extensive study efforts on major depressive disorder (MDD), the pathogenesis related to the biological factors are not fully understood and present therapeutic regimen are ineffective in some depressive patients. This study aims to identify key genes and pathways associated with the molecular biological mechanisms of major depressive disorder through bioinformatics analysis in the Gene Expression Omnibus (GEO) public database of the National Center for Biotechnology Information (NCBI) website.Materials and methods: The whole-transcriptome brain expression profile dataset (GSE101521) was obtained from the GEO database. Differentially-expressed genes (DEGs) in normal group (non-psychiatric human) and MDD group (depressive patients) were identified applying Networkanalyst online database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to function annotation and enrichment analysis. After that, STRING online database was conducted to protein–protein interaction (PPI) network, and Cytoscape.3.7.2 software was performed to module analysis. Results: Out of the 41 DEGs identified from normal tissue samples and MDD, 39 were upregulated and 2 were downregulated. GO enrichment analysis discovered that DEGs were primarily involved in inflammatory response, and KEGG pathway analysis suggested that the most chiefly pathway related to MDD were IL-17 signaling pathway, TNF signaling pathway and NOD-like receptor signaling pathway. Six hub genes (IL6, CXCL8, IL1B, FOS, CCL2 and CXCL2) were identified by PPI network and module analysis. Conclusion: Our current study detected novel markers and targets involved immune system, which are involved in pivotal biological mechanisms related to the pathogenesis of major depression. Looking forward, these findings still need to be validated in future experimental studies.

The Role of Depressive Subtypes within the Neuroinflammation Hypothesis of Major Depressive Disorder

Neuroscience ◽  
2019 ◽  
Vol 403 ◽  
pp. 93-110 ◽  
Author(s):  
Marie Woelfer ◽  
Vanessa Kasties ◽  
Sascha Kahlfuss ◽  
Martin Walter
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Major Depressive ◽  
Depressive Subtypes
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