scholarly journals Subfield-specific Effects of Chronic Mild Unpredictable Stress on Hippocampal Astrocytes

2020 ◽  
Author(s):  
Garima Virmani ◽  
Priyal D’almeida ◽  
Arnab Nandi ◽  
Swananda Marathe
Keyword(s):  
Antidepressant Drugs ◽  
Disease Outcome ◽  
Major Depressive ◽  
Hippocampal Subfields ◽  
Cell Radius ◽  
Specific Effects ◽  
Sholl Analysis ◽  
Confocal Images ◽  
Hippocampal Astrocytes ◽  
Novel Therapeutic Strategies

AbstractMajor Depressive Disorder (MDD) is a debilitating neuropsychiatric illness affecting over 20% of the population worldwide. Despite its prevalence, our understanding of its pathophysiology is severely limited, thus hampering the development of novel therapeutic strategies. Recent advances have clearly established astrocytes as major players in the pathophysiology, and plausibly pathogenesis, of major depression. In particular, astrocyte density in the hippocampus is severely diminished in MDD patients and correlates strongly with the disease outcome. Moreover, astrocyte densities from different subfields of the hippocampus show varying trends in terms of their correlation to the disease outcome. Given the central role that hippocampus plays in the pathophysiology of depression and in the action of antidepressant drugs, changes in hippocampal astrocyte density and physiology may have a significant effect on behavioral symptoms of MDD. In this study, we used Chronic Mild Unpredictable Stress (CMUS) in mice, which induces a depressive-like state, and examined its effects on astrocytes from different subfields of the hippocampus. We used S100β immunostaining to estimate the number of astrocytes per mm2 from various hippocampal subfields. Furthermore, using confocal images of fluorescently labeled GFAP-immunopositive hippocampal astrocytes, we quantified various morphology-related parameters and performed Sholl analysis. We found that CMUS exerts differential effects on astrocyte cell density, ramification, cell radius, surface area, and process width of hippocampal astrocytes from different hippocampal subfields. Taken together, our study reveals that chronic stress doesn’t uniformly affect all hippocampal astrocytes; but exerts its effects differentially on different astrocytic subpopulations within the hippocampus.

Children and adolescents with major depressive disorders: are some second generation antidepressants better than others?

2011 ◽  
Vol 26 (S2) ◽  
pp. 1251-1251
Author(s):  
A. Kaminski ◽  
G. Gartlehner
Keyword(s):  
Children And Adolescents ◽  
Comparative Effectiveness ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Depressive Disorders ◽  
Second Generation ◽  
Young Patients ◽  
Antidepressant Drugs ◽  
Cochrane Library ◽  
Major Depressive ◽  
Increased Risk

IntroductionSince the black box warning of the FDA (Food and Drug Administration) regarding an increased risk of suicidality in children and adolescents treated with antidepressants, cautious prescription of antidepressant drugs in young patients became even more important. In the light of potentially severe side effects the comparative effectiveness and harms of antidepressants should be known to clinicians to provide optimal treatment.ObjectivesTo compare the benefits and harms of second-generation antidepressants for the treatment of Major Depressive Disorder (MDD) in children and adolescents.AimsTo provide an evidence base for clinicians and policymakers when making informed decisions regarding the prescription of Selective Serotonin Reuptake Inhibitors and other newer antidepressants.MethodsWe updated a comparative effectiveness report of the Oregon Drug Effectiveness Review Project searching MEDLINE, Embase, The Cochrane Library, and the International Pharmaceutical Abstracts up to August 2010. Two persons independently reviewed the literature, abstracted data, and rated the risk of bias.ResultsWe could not identify any head-to-head trials. There is insufficient evidence to compare one second-generation antidepressant to another in pediatric outpatients with MDD. Evidence from a systematic review of published and unpublished data indicates, that in children and adolescents only fluoxetine shows a good risk-benefit ratio.ConclusionsTo date, the evidence is insufficient to make any clear inferences about the comparative benefits and harms of second-generation antidepressants for the treatment of MDD in children. Clinicians must be aware of the small benefits and the high potential risks when prescribing antidepressant medications to children and adolescents.

scholarly journals Risks of Antidepressant induced psychotic events in patients with depression and psychosis

2022 ◽  
Author(s):  
Sourav Dakua
Keyword(s):  
Literature Review ◽  
Depressive Disorders ◽  
Meta Analysis ◽  
Antidepressant Drug ◽  
Age Groups ◽  
Antidepressant Drugs ◽  
Individual Risk ◽  
Major Depressive ◽  
Compulsive Disorder ◽  
Drug Classes

The aim of this ‘literature review’-based argumentative paper has been to find out the risks of developing psychotic and depressive disorders in patients having been treated with antidepressants. In order to reach a resounding supposition, this literature review-based argumentative study had taken an incisive look into previous research works and meta-analysis, which in effect had underscored the risks of antidepressant-induced psychotic and depressive disorders in patients with depression as well as psychosis even as the protagonists of antidepressant drug classes could not be undermined given their upscaled magnitude of benefits. While following a probing interpretation of past studies, this might be demystified that antidepressants could lead to psychotic events and depressive disorders in patients of all age groups with children and young adults being more susceptible to develop psychosis. The psychotic episodes could even be developed during initial phase of treatments in patients suffering from depressive and psychotic disorders such as bipolar mood disorder, unipolar depression, major depressive disorders, mania, OCD (Obsessive Compulsive Disorder), delusional depression (psychotic depression), schizophrenia, schizoaffective disorders alongside multiple somatic symptoms among others as well. Concomitantly, with efficaciousness of antidepressants in major depressive disorder still remaining a subject to utter dubitability, different antidepressant drug classes were found to be associated with a considerable scale of adverse effects after carrying out protracted arguments on findings of evidence-based past studies, meta-analysis of previous researches and relevant clinical cases. Therefore, following a systematized approach towards past studies, this argumentative research has reached a coherent conclusion that antidepressants are likely to cause psychotic events and exaggeration of depressive disorders up to some extent in several cases. Hence, there is a stipulation of individual risk-benefit assessment and intricate history taking in patients being contemplated for antidepressant drugs alongside a close observation and follow-up in patients of all age groups after introducing antidepressant medications.

scholarly journals New Molecular Targets for Antidepressant Drugs

2021 ◽  
Vol 14 (9) ◽  
pp. 894
Author(s):  
Johannes Kornhuber ◽  
Erich Gulbins
Keyword(s):  
Psychological Symptoms ◽  
Antidepressant Drugs ◽  
Molecular Targets ◽  
Mechanisms Of Action ◽  
The Body ◽  
Whole Body ◽  
Severe Mental Disorder ◽  
Major Depressive ◽  
Markers Of Oxidative Stress ◽  
Peripheral Markers

Major depressive disorder (MDD) is a common and severe mental disorder that is usually recurrent and has a high risk of suicide. This disorder manifests not only with psychological symptoms but also multiple changes throughout the body, including increased risks of obesity, diabetes, and cardiovascular disease. Peripheral markers of oxidative stress and inflammation are elevated. MDD is therefore best described as a multisystem whole-body disease. Pharmacological treatment with antidepressants usually requires several weeks before the desired effects manifest. Previous theories of depression, such as the monoamine or neurogenesis hypotheses, do not explain these characteristics well. In recent years, new mechanisms of action have been discovered for long-standing antidepressants that also shed new light on depression, including the sphingolipid system and the receptor for brain-derived neurotrophic factor (BDNF).

scholarly journals Association between Glucocorticoid Receptor Methylation and Hippocampal Subfields in Major Depressive Disorder

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e85425 ◽  
Author(s):  
Kyoung-Sae Na ◽  
Hun Soo Chang ◽  
Eunsoo Won ◽  
Kyu-Man Han ◽  
Sunyoung Choi ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Glucocorticoid Receptor ◽  
Major Depressive ◽  
Hippocampal Subfields

scholarly journals Association Between Side Effects and Blood microRNA Expression Levels and Their Targeted Pathways in Patients With Major Depressive Disorder Treated by a Selective Serotonin Reuptake Inhibitor, Escitalopram: A CAN-BIND-1 Report

2019 ◽  
Vol 23 (2) ◽  
pp. 88-95
Author(s):  
Antoine Yrondi ◽  
Laura M Fiori ◽  
Benicio N Frey ◽  
Raymond W Lam ◽  
Glenda M MacQueen ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Messenger Rna ◽  
Antidepressant Drugs ◽  
Target Prediction ◽  
Major Depressive ◽  
Mrna Targets ◽  
Downstream Effects

Abstract Introduction Antidepressant drugs are effective therapies for major depressive disorder; however, they are frequently associated with side effects. Although there is some evidence for a relationship between genetic variation and side effects, little is known regarding the role of dynamic molecular factors as moderators of side effects. The aim of this study was to assess microRNA (miRNA) changes associated with side effects during escitalopram treatment and their downstream effects on target gene expression. Methods A total 160 patients with major depressive disorder from the CAN-BIND-1 cohort were included. Side effects were assessed with the Toronto Side Effect Scale after 2 weeks of treatment with escitalopram. We assessed the relationship between side effects and changes in peripheral expression of miRNAs between baseline and week 2. For miRNA whose expression changed, we used target prediction algorithms to identify putative messenger RNA (mRNA) targets and assessed their expression. Results Nausea was experienced by 42.5% of patients. We identified 45 miRNAs whose expression changed on initiation of escitalopram treatment, of which 10 displayed a negative association with intensity of nausea (miR15b-5p, miR17-5p, miR20a-5p, miR20b-5p, miR103a-3p, miR103b, miR106a-5p, miR182-5p, miR185-5p, and miR660-5p). Additionally, we found negative associations between 4 microRNAs (miR20a-5p, miR106a-5p, miR185-5p, miR660-5p) and mRNA targets. The expression of the miR185-5p target, CAMK2δ was significantly decreased [log 2 mean = −0.048 (0.233)] between weeks 0 and 2 (P = .01)]. Conclusions We identified an overexpression of miR185-5p during escitalopram treatment of major depressive disorder, which was negatively associated with intensity of nausea, and identified a potential mRNA target that may mediate this effect.

scholarly journals Changes in the neural correlates of implicit emotional face processing during antidepressant treatment in major depressive disorder

2013 ◽  
Vol 16 (10) ◽  
pp. 2195-2208 ◽  
Author(s):  
Teresa A. Victor ◽  
Maura L. Furey ◽  
Stephen J. Fromm ◽  
Arne Öhman ◽  
Wayne C. Drevets
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Treatment Condition ◽  
Functional Neuroimaging ◽  
Antidepressant Treatment ◽  
Antidepressant Drugs ◽  
Anterior Cingulate ◽  
Major Depressive ◽  
Pre Treatment ◽  
Emotional Face

Abstract An emerging hypothesis regarding the mechanisms underlying antidepressant pharmacotherapy suggests that these agents benefit depressed patients by reversing negative emotional processing biases (Harmer, 2008). Neuropsychological indices and functional neuroimaging measures of the amygdala response show that antidepressant drugs shift implicit and explicit processing biases away from the negative valence and toward the positive valence. However, few studies have explored such biases in regions extensively connected with the amygdala, such as the pregenual anterior cingulate cortex (pgACC) area, where pre-treatment activity consistently has predicted clinical outcome during antidepressant treatment. We used functional magnetic resonance imaging (fMRI) to investigate changes in haemodynamic response patterns to positive vs. negative stimuli in patients with major depressive disorder (MDD) under antidepressant treatment. Participants with MDD (n = 10) underwent fMRI before and after 8 wk sertraline treatment; healthy controls (n = 10) were imaged across an equivalent interval. A backward masking task was used to elicit non-conscious neural responses to sad, happy and neutral face expressions. Haemodynamic responses to emotional face stimuli were compared between conditions and groups in the pgACC. The response to masked-sad vs. masked-happy faces (SN-HN) in pgACC in the depressed subjects was higher in the pre-treatment condition than in the post-treatment condition and this difference was significantly greater than the corresponding change across time in the controls. The treatment-associated difference was attributable to an attenuated response to sad faces and an enhanced response to happy faces. Pre-treatment pgACC responses to SN-HN correlated positively with clinical improvement during treatment. The pgACC participates with the amygdala in processing the salience of emotional stimuli. Treatment-associated functional changes in this limbic network may influence the non-conscious processing of such stimuli by reversing the negative processing bias extant in MDD.

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