scholarly journals Identifying Potential Novel Pathways and Therapeutic Targets of Major Depressive Disorder with Functional Genomics

2021 ◽  
Author(s):  
Kevin Bao
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Antidepressant Treatment ◽  
Interaction Network ◽  
Functional Enrichment ◽  
Future Research ◽  
Integrative Genomics ◽  
Major Depressive

Abstract Background: Major depressive disorder (MDD) is a debilitating illness and a leading cause of disability, but its pathophysiology remains to be completely elucidated. Resistance to traditional antidepressant treatment is highly prevalent within patient populations. Ketamine, a rapid-acting antidepressant that has shown success in treating resistant patients, is hypothesized to function by modulating excitatory and inhibitory neurotransmitters. This has led to a paradigm shift from the monoaminergic hypothesis, towards a glutamate and neuroplasticity hypothesis, though this picture may still be incomplete. The purpose of this study is to identify novel systems potentially implicated in MDD and suggest potential therapeutic mechanisms.Methods: An integrative genomics and systems biology approach was used to identify genes and pathways that may be relevant to MDD. Starting with genes implicated in current, well-established paradigms, a correlation analysis was used to query publicly available microarray datasets to identify potential genes that may be relevant to MDD. Systems and pathways of interest were identified through functional enrichment. Through a manual review, genes of systems and pathways potentially relevant to MDD were used to generate a protein interaction network. Interesting genes identified from the network were functionally enriched and clustered to identify new high-level themes. Genes from the protein interaction network were then classified into sets based on different paradigms using functional annotations. Genes belonging to multiple sets – and thus being involved in multiple different paradigms relevant to MDD – were identified for future research.Results: The highest-ranked enrichment cluster contained GABAeric signaling, retrograde endocannabinoid signaling, and morphine addiction. Other interesting pathways identified were T cell receptor signaling, cocaine addiction, and nicotine addiction. Other broad themes identified in other clusters were calcium, serotonin, the immune system, TGF beta, glutamate, telomeres, the guanine nucleotide exchange factor, the extracellular matrix, and DNA regulation. Potential genes of interest are listed in Chart 3.Conclusions: Throughout the study, interesting genes, groups of genes, and systems were identified manually and systematically, some of which validate existing literature and some give possible directions for future research. Further experiments are required to confirm causal links.

scholarly journals Drug Response-Related DNA Methylation Changes in Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
Jiaqi Zhou ◽  
Miao Li ◽  
Xueying Wang ◽  
Yuwen He ◽  
Yan Xia ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bipolar Disorder ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Clinical Improvement ◽  
Drug Response ◽  
Epigenetic Modification ◽  
Antidepressant Treatment ◽  
Future Research ◽  
Major Depressive

Pharmacotherapy is the most common treatment for schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD). Pharmacogenetic studies have achieved results with limited clinical utility. DNA methylation (DNAm), an epigenetic modification, has been proposed to be involved in both the pathology and drug treatment of these disorders. Emerging data indicates that DNAm could be used as a predictor of drug response for psychiatric disorders. In this study, we performed a systematic review to evaluate the reproducibility of published changes of drug response-related DNAm in SCZ, BD and MDD. A total of 37 publications were included. Since the studies involved patients of different treatment stages, we partitioned them into three groups based on their primary focuses: (1) medication-induced DNAm changes (n = 8); (2) the relationship between DNAm and clinical improvement (n = 24); and (3) comparison of DNAm status across different medications (n = 14). We found that only BDNF was consistent with the DNAm changes detected in four independent studies for MDD. It was positively correlated with clinical improvement in MDD. To develop better predictive DNAm factors for drug response, we also discussed future research strategies, including experimental, analytical procedures and statistical criteria. Our review shows promising possibilities for using BDNF DNAm as a predictor of antidepressant treatment response for MDD, while more pharmacoepigenetic studies are needed for treatments of various diseases. Future research should take advantage of a system-wide analysis with a strict and standard analytical procedure.

Pharmacological Interventions for Cognitive Dysfunction in Major Depressive Disorder

2019 ◽  
pp. 225-240
Author(s):  
Marco Solmi ◽  
Beatrice Bortolato ◽  
Nicola Veronese ◽  
Brendon Stubbs ◽  
Nathan Herrmann ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Cognitive Impairment ◽  
Depressive Disorder ◽  
Cognitive Dysfunction ◽  
Verbal Memory ◽  
Antidepressant Treatment ◽  
Future Research ◽  
Major Depressive ◽  
Memory And Attention ◽  
Psychosocial Dysfunction

Major depressive disorder (MDD) is a severe, chronic, and recurring mental disorder, which is frequently accompanied by co-occurring mental and somatic illnesses. Compelling evidence indicates that patients with MDD exhibit cognitive impairment encompassing several domains, including but not limited to, executive function, verbal memory, and attention. In addition, cognitive impairment may be evident even during remission and appears to play a major role in the persistence of psychosocial dysfunction (including impairment in workforce). Therefore, several compounds have been tested as putative cognitive enhancers for MDD. Although antidepressant treatment may be associated with modest improvements in some cognitive domains (namely psychomotor speed and delayed recall), evidence thus far remains unclear owing to methodological limitations across clinical trials. These methodological limitations include: (i) lack of adequate screening for cognitive dysfunction at baseline; (ii) the inclusion of samples that were not in remission at baseline; pseudospecificity (i.e. observed effects on cognition could be due to secondary improvement in mood); (iii) cognitive function was not the primary outcome in some trials; and (iv) lack of standardization of cognitive measures employed across studies. Replicated evidence from randomized controlled trials (RCTs) indicates that vortioxetine and duloxetine may have procognitive effects. Furthermore, data from RCTs suggest that lisdexamfetamine, modafinil, metformin, and erythropoietin may also have beneficial cognitive effects. In conclusion, the achievement of cognitive remission remains an unmet goal in the treatment of MDD. Future research directions, including methodological improvements in the conduct of RCTs targeting MDD-related cognitive dysfunction, are discussed.

Reduced latency to first antidepressant treatment in Italian patients with a more recent onset of major depressive disorder

2017 ◽  
Vol 41 (S1) ◽  
pp. S529-S529
Author(s):  
B. Grancini ◽  
B. Dell’Osso ◽  
L. Cremaschi ◽  
F. De Cagna ◽  
B. Benatti ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Antidepressant Treatment ◽  
Stressful Events ◽  
Major Depressive ◽  
Recent Onset ◽  
Valid Predictor ◽  
Before And After ◽  
Competing Interest ◽  
Year 2000

IntroductionMajor depressive disorder (MDD) is a prevalent burdensome disease, which frequently remains untreated. The duration of untreated illness (DUI) is modifiable parameter and a valid predictor of outcome. Previous investigation in patients with MDD revealed a DUI of different years, while recent reports have documented a reduction of DUI across time, in patients with different psychiatric disorders.Objectives/aimsThe present study was aimed to investigate potential differences in terms of DUI and related variables in patients with MDD across time.MethodsAn overall sample of 188 patients with MDD was divided in two subgroups on the basis of their epoch of onset (onset before and after year 2000). DUI and other onset-related variables were assessed through a specific questionnaire and compared between the two subgroups.ResultsThe whole sample showed a mean DUI of approximately 4.5 years, with a lower value in patients with more recent onset compared to the other subgroup (27.1 ± 42.6 vs. 75.8 ± 105.2 months, P < .05). Moreover, patients with onset after 2000 reported higher rates of onset-related stressful events and lower ones for benzodiazepines prescription (65% vs. 81%; P = 0.02; 47% vs. 30%; P = 0.02).ConclusionsThe comparison of groups with different epochs of onset showed a significant reduction in terms of DUI and benzodiazepines prescription, and a higher rate of onset-related stressful events in patients with a more recent onset. Reported findings are of epidemiologic and clinical relevance in order to evaluate progress and developments in the diagnostic and therapeutic pathways of MDD in Italian and other countries.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Network Pharmacology study of Curcuma longa L.: Potential Target Proteins and their Functional Enrichment Analysis.

2020 ◽  
Author(s):  
SANGEETA KUMARI
Keyword(s):  
Signaling Pathway ◽  
Mechanism Of Action ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Curcuma Longa ◽  
Interaction Network ◽  
Functional Enrichment ◽  
Target Proteins ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network

Abstract Objective This study’s primary goal is unraveling the mechanism of action of bioactives of Curcuma longa L. at the molecular level using protein-protein interaction network.Results We used target proteins to create protein-protein interaction network (PPIN) and identified significant node and edge attributes of PPIN. We identified the cluster of proteins in the PPIN, which were used to identify enriched pathways. . We identified closeness centrality and jaccard score as most important node and edge attribute of the PPIN respectively. The enriched pathways of various clusters were overlapped suggesting synergistic mechanism of action. The three pathways found to be common among three clusters were Gonadotropin-releasing hormone receptor pathway, Endothelin signaling pathway, and Inflammation mediated by chemokine and cytokine signaling pathway.

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