scholarly journals Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 647 ◽  
Author(s):  
Yi-Yung Hung ◽  
Ming-Kung Wu ◽  
Meng-Chang Tsai ◽  
Ya-Ling Huang ◽  
Hong-Yo Kang

Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.

2015 ◽  
Vol 76 (12) ◽  
pp. 1658-1667 ◽  
Author(s):  
Sara Jiménez-Fernández ◽  
Manuel Gurpegui ◽  
Francisco Díaz-Atienza ◽  
Lucía Pérez-Costillas ◽  
Miriam Gerstenberg ◽  
...  

2004 ◽  
Vol 34 (7) ◽  
pp. 1299-1308 ◽  
Author(s):  
MAURIZIO FAVA ◽  
JONATHAN E. ALPERT ◽  
CHERYL N. CARMIN ◽  
STEPHEN R. WISNIEWSKI ◽  
MADHUKAR H. TRIVEDI ◽  
...  

Background. Anxious depression, defined as Major Depressive Disorder (MDD) with high levels of anxiety symptoms, may represent a relatively common depressive subtype, with distinctive features.Objective. The objective of this study was to determine the prevalence of anxious depression and to define its clinical correlates and symptom patterns.Method. Baseline clinical and sociodemographic data were collected on 1450 subjects participating in the STAR*D study. A baseline Hamilton Rating Scale for Depression (HAM-D) Anxiety/Somatization factor score of [ges ]7 was considered indicative of anxious depression. The types and degree of concurrent psychiatric symptoms were measured using the Psychiatric Diagnostic Screening Questionnaire (PDSQ), by recording the number of items endorsed by study participants for each diagnostic category. MDD symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology (IDS-C30).Results. The prevalence of anxious depression in this population was 46%. Patients with anxious MDD were significantly more likely to be older, unemployed, less educated, more severely depressed, and to have suicidal ideation before and after adjustment for severity of depression. As far as concurrent psychiatric symptoms are concerned, patients with anxious depression were significantly more likely to endorse symptoms related to generalized anxiety, obsessive compulsive, panic, post-traumatic stress, agoraphobia, hypochondriasis, and somatoform disorders before and after adjustment for severity of depression. Anxious-depression individuals were also significantly less likely to endorse IDS-C30 items concerning atypical features, and were significantly more likely to endorse items concerning melancholic/endogenous depression features.Conclusion. This study supports specific clinical and sociodemographic correlates of MDD associated with high levels of anxiety (anxious depression).


2021 ◽  
Vol 12 (01) ◽  
pp. 122-128
Author(s):  
Ralte Lalthankimi ◽  
Padmavathi Nagarajan ◽  
Vikas Menon ◽  
Jeby Jose Olickal

Abstract Objectives Mental disorders have a large impact on death by suicide. Hence, this study aims to determine the prevalence of suicidal behaviors among major depressive disorder (MDD) patients and the associated factors. Materials and Methods This cross-sectional analytical study was conducted among individuals aged 18 to 65 years, diagnosed with MDD in the Psychiatry Outpatient Department of a Tertiary Care Center, Puducherry during March to October 2019. Severity of depression was assessed using Hamilton Depression Rating Scale and Columbia-Suicide Severity Rating Scale was used to find the suicidal behaviors. Results For 166 participants in the study, mean (standard deviation) age was 40 (11) years and majority were females (76%). More than one-third (37%) had severe or very severe depression, and the prevalence of suicidal ideation, plan, and attempts were 83, 24, and 35%, respectively. After adjusting the covariates, the severity of depression and unemployment were significantly associated with suicidal attempts (adjusted prevalence ratios [aPR] = 11.4 and 1.9), and very severe depression was associated with suicidal ideation (aPR = 1.6). Among 140 individuals with suicidal ideation, 45 (32%) had an ideation frequency of 2 to 3 times/week, 69 (50%) had ideation for 1 hour, 36 (26%) could control ideation with little difficulty, and 12% had suicidal ideation mostly to end or stop their pain. Conclusion Suicidal ideation and attempts were significantly high in MDD patients, and the severity of depression was significantly associated with it. Early identification of high-risk suicidal behavior and implementation of effective preventive interventions are necessary to reduce death by suicide in these groups.


2017 ◽  
Vol 41 (S1) ◽  
pp. S529-S529
Author(s):  
B. Grancini ◽  
B. Dell’Osso ◽  
L. Cremaschi ◽  
F. De Cagna ◽  
B. Benatti ◽  
...  

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.


CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 313-314
Author(s):  
Marlene P. Freeman ◽  
Maurizio Fava ◽  
Bryan Dirks ◽  
Manish K. Jha ◽  
Richard C. Shelton ◽  
...  

Abstract:Study Objectives:Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.Method:Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.Results:Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).Conclusions:These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.Funding Acknowledgements:ACADIA Pharmaceuticals Inc.


2020 ◽  
pp. 1-9 ◽  
Author(s):  
Le Xiao ◽  
Xuequan Zhu ◽  
Amy Gillespie ◽  
Yuan Feng ◽  
Jingjing Zhou ◽  
...  

Abstract Background This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment. Methods This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization. Results A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects. Conclusions After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.


2011 ◽  
Vol 89 (9) ◽  
pp. 647-653 ◽  
Author(s):  
Chuanjun Zhuo ◽  
Ying Wang ◽  
Hongjun Tian ◽  
Xiaohui Wang ◽  
Yuhui Chen ◽  
...  

This study used a model of ischemia–reperfusion injury to the brachial artery endothelium to investigate whether the protective role of ischemic postconditioning (IPostC) is impaired in patients with major depressive episode. Flow-mediated dilation (FMD) was measured before and after ischemia–reperfusion in the absence or presence of IPostC in 24 patients with major depressive disorder and 20 healthy controls. In addition, the severity of the depression, as assessed by the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI) scores, and plasma nitrogen dioxide (NOx) levels were also determined. Ischemia–reperfusion resulted in a significant decrease in FMD in both patients with a major depressive episode and healthy controls. IPostC effectively prevented this decrease in FMD in healthy controls, but not in patients with a major depressive episode. HDRS and BDI scores were markedly increased, but plasma NOx levels decreased, in patients with a major depressive episode compared with those in healthy controls. Correlation analysis showed that HDRS and BDI scores and plasma NOx levels were significantly associated with post-ischemia–reperfusion FMD. These results suggest that endothelial protection by IPostC is impaired in patients with major depressive disorder, which may be related to the decrease in endothelial nitric oxide production and the severity of the depression.


2015 ◽  
Vol 28 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Bun-Hee Lee ◽  
Jin-Pyo Hong ◽  
Jung-A Hwang ◽  
Kyoung-Sae Na ◽  
Won-Joong Kim ◽  
...  

BackgroundSome clinical studies have reported reduced peripheral glial cell line-derived neurotrophic factor (GDNF) level in elderly patients with major depressive disorder (MDD). We verified whether a reduction in plasma GDNF level was associated with MDD.MethodPlasma GDNF level was measured in 23 healthy control subjects and 23 MDD patients before and after 6 weeks of treatment.ResultsPlasma GDNF level in MDD patients at baseline did not differ from that in healthy controls. Plasma GDNF in MDD patients did not differ significantly from baseline to the end of treatment. GDNF level was significantly lower in recurrent-episode MDD patients than in first-episode patients before and after treatment.ConclusionsOur findings revealed significantly lower plasma GDNF level in recurrent-episode MDD patients, although plasma GDNF levels in MDD patients and healthy controls did not differ significantly. The discrepancy between our study and previous studies might arise from differences in the recurrence of depression or the ages of the MDD patients.


2002 ◽  
Vol 32 (6) ◽  
pp. 1049-1057 ◽  
Author(s):  
M. FAVA ◽  
A. H. FARABAUGH ◽  
A. H. SICKINGER ◽  
E. WRIGHT ◽  
J. E. ALPERT ◽  
...  

Background. Personality disorders (PDs) were assessed among depressed out-patients by clinical interview before and after antidepressant treatment with fluoxetine to assess the degree of stability of PD diagnoses and determine whether changes in PD diagnoses across treatment are related to the degree of improvement in depressive symptoms.Method. Three hundred and eighty-four out-patients (55% women; mean age = 39.9±10.5) with major depressive disorder (MDD) diagnosed with the SCID-P were enrolled into an 8 week trial of open treatment with fluoxetine 20 mg/day. The SCID-II was administered to diagnose PDs at baseline and endpoint.Results. A significant proportion (64%) of our depressed out-patients met criteria for at least one co-morbid personality disorder. Following 8 weeks of fluoxetine treatment, there was a significant reduction in the proportion of patients meeting criteria for avoidant, dependent, passive-aggressive, paranoid and narcissistic PDs. From baseline to endpoint, there was also a significant reduction in the mean number of criteria met for paranoid, schizotypal, narcissistic, borderline, avoidant, dependent, obsessive–compulsive, passive aggressive and self-defeating personality disorders. While changes in cluster diagnoses were not significantly related to improvement in depressive symptoms, there were significant relationships between degree of reduction in depressive symptoms (percentage change in HAM-D-17 scores) and degree of change in the number of criteria met for paranoid, narcissistic, borderline and dependent personality disorders.Conclusions. Personality disorder diagnoses were found to be common among untreated out-patients with major depressive disorder. A significant proportion of these patients no longer met criteria for personality disorders following antidepressant treatment, and changes in personality disorder traits were significantly related to degree of improvement in depressive symptoms in some but not all personality disorders. These findings suggest that the lack of stability of PD diagnoses among patients with current MDD may be attributable in part to a direct effect of antidepressant treatment on behaviours and attitudes that comprise PDs.


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