The mRNA expression levels of GABAA receptor α1 and α2 subunits in patients with major depressive disorder during onset and remission

2020 ◽  
pp. 1-12
Author(s):  
Jiwu Liao ◽  
Sisi Wang ◽  
Haihua Yang ◽  
Ping Ma ◽  
Congrui Li ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mrna Expression ◽  
Gabaa Receptor ◽  
Major Depressive ◽  
Expression Levels ◽  
Mrna Expression Levels

scholarly journals Correlations Among mRNA Expression Levels of ATP7A, Serum Ceruloplasmin Levels, and Neuronal Metabolism in Unmedicated Major Depressive Disorder

2020 ◽  
Vol 23 (10) ◽  
pp. 642-652 ◽  
Author(s):  
Xuanjun Liu ◽  
Shuming Zhong ◽  
Lan Yan ◽  
Hui Zhao ◽  
Ying Wang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mrna Expression ◽  
Brain Regions ◽  
Regions Of Interest ◽  
Major Depressive ◽  
Expression Levels ◽  
Neuronal Metabolism ◽  
The Brain ◽  
Mrna Expression Levels

Abstract Background Previous studies have found that elevated copper levels induce oxidation, which correlates with the occurrence of major depressive disorder (MDD). However, the mechanism of abnormal cerebral metabolism of MDD patients remains ambiguous. The main function of the enzyme ATPase copper-transporting alpha (ATP7A) is to transport copper across the membrane to retain copper homeostasis, which is closely associated with the onset of mental disorders and cognitive impairment. However, less is known regarding the association of ATP7A expression in MDD patients. Methods A total of 31 MDD patients and 21 healthy controls were recruited in the present study. Proton magnetic resonance spectroscopy was used to assess the concentration levels of N-acetylaspartate, choline (Cho), and creatine (Cr) in brain regions of interest, including prefrontal white matter (PWM), anterior cingulate cortex (ACC), thalamus, lentiform nucleus, and cerebellum. The mRNA expression levels of ATP7A were measured using polymerase chain reaction (SYBR Green method). The correlations between mRNA expression levels of ATP7A and/or ceruloplasmin levels and neuronal biochemical metabolite ratio in the brain regions of interest were evaluated. Results The decline in the mRNA expression levels of ATP7A and the increase in ceruloplasmin levels exhibited a significant correlation in MDD patients. In addition, negative correlations were noted between the decline in mRNA expression levels of ATP7A and the increased Cho/Cr ratios of the left PWM, right PWM, and right ACC in MDD patients. A positive correlation between elevated ceruloplasmin levels and increased Cho/Cr ratio of the left PWM was noted in MDD patients. Conclusions The findings suggested that the decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels induced oxidation that led to the disturbance of neuronal metabolism in the brain, which played important roles in the pathophysiology of MDD. The decline in the mRNA expression levels of ATP7A and the elevated ceruloplasmin levels affected neuronal membrane metabolic impairment in the left PWM, right PWM, and right ACC of MDD patients.

scholarly journals Interleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder—Preliminary Results of the PROVIT Study

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2575
Author(s):  
Alexandra Reiter ◽  
Susanne A. Bengesser ◽  
Anne-Christin Hauschild ◽  
Anna-Maria Birkl-Töglhofer ◽  
Frederike T. Fellendorf ◽  
...  
Keyword(s):  
Gene Expression ◽  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Interleukin 6 ◽  
Intervention Group ◽  
Additional Treatment ◽  
Major Depressive ◽  
Efficient Treatment ◽  
Expression Levels ◽  
Gene Expression Levels

Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.

scholarly journals Association of circulating let-7b-5p with major depressive disorder: a nested case-control study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sanne Roumans ◽  
Kristina Sundquist ◽  
Ashfaque A. Memon ◽  
Anna Hedelius ◽  
Jan Sundquist ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Case Control Study ◽  
Case Control ◽  
Major Depressive ◽  
Expression Levels ◽  
Nested Case Control ◽  
Underlying Pathophysiology ◽  
Control Study

Abstract Background Major depressive disorder (MDD) is one of the most common psychiatric disorders and is a great disease burden. However, its underlying pathophysiology and aetiology remain poorly understood. Available evidence suggests that circulating microRNAs (miRNAs) are associated with MDD, but it is still unknown whether miRNAs can predict subsequent incident MDD. Methods In this nested case-control study, a total of 104 individuals, who were free of MDD at baseline, from the Women’s Health in Lund Area (WHILA) cohort were included. Among them, 52 individuals developed MDD (cases) during the 5 years follow-up and 52 individuals did not develop MDD (controls). Plasma expression levels of miR-17-5p, miR-134-5p, miR-144-5p, let-7b-5p and let-7c-5p at baseline were assessed using qRT-PCR. Logistic regression was used to estimate the odds of developing MDD among individuals with different levels of miRNA expression. Results Plasma expression levels of let-7b-5p were significantly lower (p = 0.02) at baseline in cases compared to controls. After adjustment for age and BMI, let-7b-5p was negatively associated with odds for developing MDD (OR = 0.33, p = 0.03, 95% CI = 0.12–0.91). Moreover, let-7b-5p expression levels showed a trend over time with larger differences between cases and controls for the earlier cases (MDD diagnosis <2 years from baseline) than MDD cases developed later (MDD diagnosis 2–5 years from baseline). Conclusions These findings show that lower plasma levels of let-7b-5p are associated with a higher future risk of MDD. Results need to be validated in a large cohort to examine its potential as a peripheral biomarker for MDD.

scholarly journals Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

2018 ◽  
Author(s):  
Héléna A Gaspar ◽  
Zachary Gerring ◽  
Christopher Hübel ◽  
Christel M Middeldorp ◽  
Eske M Derks ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Drug Target ◽  
Model Systems ◽  
Genome Wide Association ◽  
Multiple Testing Correction ◽  
Major Depressive ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome

AbstractThe major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics and genetically predicted expression levels in different tissues, using our online tool Drug Targetor (drugtargetor.com). We also investigated drug-target relationships and drug effects on gene expression that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 25 druggable genes were significantly associated with MDD after multiple testing correction, and 19 were suggestively significant. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new – and better – treatment options.

Elevated TREM2 mRNA expression in leukocytes in schizophrenia but not major depressive disorder

2016 ◽  
Vol 123 (6) ◽  
pp. 637-641 ◽  
Author(s):  
Yuta Yoshino ◽  
Kentaro Kawabe ◽  
Kiyohiro Yamazaki ◽  
Shinya Watanabe ◽  
Shusuke Numata ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Mrna Expression ◽  
Major Depressive

Excessive activation of the loop between the NR2B subunit of the N-methyl-d-aspartate receptor and glycogen synthase kinase-3β in the hippocampi of patients with major depressive disorder

2012 ◽  
Vol 24 (1) ◽  
pp. 26-33 ◽  
Author(s):  
Dong Hoon Oh ◽  
Seon-Cheol Park ◽  
Yong Chon Park ◽  
Seok Hyeon Kim
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Animal Studies ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Data Sets ◽  
Major Depressive ◽  
Expression Levels ◽  
Nitric Oxide Synthase 1 ◽  
Excessive Activation

Objective: We showed previously that glycogen synthase kinase-3β (GSK-3β) levels are significantly elevated in the hippocampi of patients with major depressive disorder (MDD). However, the exact cause of this elevation and its function are unknown. Recent animal studies have suggested a mechanism involving the N-methyl-d-aspartate (NMDA) NR2B–GSK-3β loop.Methods: To investigate the existence of an NR2B–GSK-3β loop in the hippocampi of patients with MDD, we examined the expression of NR2B. We also attempted to identify markers that correlate with NR2B levels in the hippocampus, using the Stanley Neuropathology Consortium Integrative Database (SNCID). The SNCID is a web-based tool used to integrate Stanley Medical Research Institute (SMRI) data sets.Results: We found that hippocampal levels of NR2B and DLGAP1 mRNA were higher in the MDD group (n = 8) than in unaffected controls (n = 12) (p < 0.05). NR2B expression levels were correlated with the expression levels of NR2A, NR1, DLGAP1, GSK-3β and nitric oxide synthase 1, as well as with the number of calretinin-immunoreactive neurons in the hippocampus in all subjects in the SNC (n = 42, p < 0.001).Conclusion: The results of our study show the possible involvement of excessive activation of the NR2B–GSK-3β loop in the overexpression of GSK-3β in the hippocampi of patients with MDD.

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