scholarly journals SIGIRR and TNFAIP3 Are Differentially Expressed in Both PBMC and TNF-α Secreting Cells of Patients With Major Depressive Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Chin-Chuen Lin ◽  
Tiao-Lai Huang

Background: Major depressive disorder (MDD) is associated with the activation of the immune/inflammatory system. TNF-α is associated with MDD and poor treatment response. Toll-like receptors (TLR) are responsible in innate immune response, and is associated with MDD and antidepressant response. Some negative regulators of TLR pathway such as SOCS1, TOLLIP, SIGIRR, TNFAIP3, and MyD88s, are reported to be differentially expressed in the peripheral blood samples of patients of MDD.Methods: We recruited patients with MDD and healthy controls, collect their demographic data, and measured their mRNA levels of negative TLR regulators, using peripheral blood mononuclear cells (PBMC) and isolated TNF-α secreting cells. Clinical symptoms were evaluated using Halmiton Depression Rating Scale (Ham-D). Some patients were evaluated again after 4 weeks of antidepressant treatment.Results: Forty-seven patients with MDD and 52 healthy controls were recruited. Between the PBMC samples of 37 MDD patients and 42 controls, mRNA levels of SOCS1, SIGIRR, TNFAIP3, and MyD88s were significantly different. Between TNF-α secreting cells of 10 MDD patients and 10 controls, mRNA levels of SIGIRR and TNFAIP3 were significantly different. Change of Ham-D score only correlated significantly with TOLLIP mRNA level after treatment.Conclusion: SIGIRR and TNFAIP3, two negative regulators of TLR immune response pathways, were differentially expressed in both PBMC and TNF-α secreting cells of patients with MDD as compared to healthy controls. The negative regulations of innate immune response could contribute to the underlying mechanism of MDD.

2019 ◽  
Vol 8 (5) ◽  
pp. 568 ◽  
Author(s):  
Men-Ting Hsieh ◽  
Chin-Chuen Lin ◽  
Chien-Te Lee ◽  
Tiao-Lai Huang

Brain-derived neurotrophic factor (BDNF) exon IX promoter methylation levels, serum BDNF protein levels, and serum mRNA levels were investigated in patients with major depressive disorder (MDD) and healthy controls. Over two years, 51 patients with MDD and 62 healthy controls were recruited. Peripheral blood was drawn from all participants to analyze the BDNF exon IX promoter methylation levels as well as serum BDNF protein and mRNA levels, at baseline and after four weeks of antidepressant treatment. Methylation sequential analysis showed that patients with MDD (n = 39) had a higher methylation level at CpG site 217 and lower methylation levels at CpG site 327 and CpG site 362. Drug responders (n = 25) had a higher methylation level at CpG site 24 and CpG site 324 than the non-responders (n = 11). Patients with MDD had a lower serum BDNF protein and mRNA levels than the healthy controls. In conclusion, these results showed that BDNF exon IX promoter methylation levels, serum BDNF protein level, and serum BDNF mRNA level could contribute to the pathophysiology of a major depressive disorder.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nicolas Salvetat ◽  
Fabrice Chimienti ◽  
Christopher Cayzac ◽  
Benjamin Dubuc ◽  
Francisco Checa-Robles ◽  
...  

AbstractMental health issues, including major depressive disorder, which can lead to suicidal behavior, are considered by the World Health Organization as a major threat to global health. Alterations in neurotransmitter signaling, e.g., serotonin and glutamate, or inflammatory response have been linked to both MDD and suicide. Phosphodiesterase 8A (PDE8A) gene expression is significantly decreased in the temporal cortex of major depressive disorder (MDD) patients. PDE8A specifically hydrolyzes adenosine 3′,5′-cyclic monophosphate (cAMP), which is a key second messenger involved in inflammation, cognition, and chronic antidepressant treatment. Moreover, alterations of RNA editing in PDE8A mRNA has been described in the brain of depressed suicide decedents. Here, we investigated PDE8A A-to-I RNA editing-related modifications in whole blood of depressed patients and suicide attempters compared to age-matched and sex-matched healthy controls. We report significant alterations of RNA editing of PDE8A in the blood of depressed patients and suicide attempters with major depression, for which the suicide attempt took place during the last month before sample collection. The reported RNA editing modifications in whole blood were similar to the changes observed in the brain of suicide decedents. Furthermore, analysis and combinations of different edited isoforms allowed us to discriminate between suicide attempters and control groups. Altogether, our results identify PDE8A as an immune response-related marker whose RNA editing modifications translate from brain to blood, suggesting that monitoring RNA editing in PDE8A in blood samples could help to evaluate depressive state and suicide risk.


2020 ◽  
pp. 1-10
Author(s):  
V. H. Dam ◽  
D. S. Stenbæk ◽  
K. Köhler-Forsberg ◽  
C. Ip ◽  
B. Ozenne ◽  
...  

Abstract Background Cognitive disturbances are common and disabling features of major depressive disorder (MDD). Previous studies provide limited insight into the co-occurrence of hot (emotion-dependent) and cold (emotion-independent) cognitive disturbances in MDD. Therefore, we here map both hot and cold cognition in depressed patients compared to healthy individuals. Methods We collected neuropsychological data from 92 antidepressant-free MDD patients and 103 healthy controls. All participants completed a comprehensive neuropsychological test battery assessing hot cognition including emotion processing, affective verbal memory and social cognition as well as cold cognition including verbal and working memory and reaction time. Results The depressed patients showed small to moderate negative affective biases on emotion processing outcomes, moderate increases in ratings of guilt and shame and moderate deficits in verbal and working memory as well as moderately slowed reaction time compared to healthy controls. We observed no correlations between individual cognitive tasks and depression severity in the depressed patients. Lastly, an exploratory cluster analysis suggested the presence of three cognitive profiles in MDD: one characterised predominantly by disturbed hot cognitive functions, one characterised predominantly by disturbed cold cognitive functions and one characterised by global impairment across all cognitive domains. Notably, the three cognitive profiles differed in depression severity. Conclusion We identified a pattern of small to moderate disturbances in both hot and cold cognition in MDD. While none of the individual cognitive outcomes mapped onto depression severity, cognitive profile clusters did. Overall cognition-based stratification tools may be useful in precision medicine approaches to MDD.


2020 ◽  
Author(s):  
Kuk-In Jang ◽  
Chany Lee ◽  
Sangmin Lee ◽  
Seung Huh ◽  
Jeong-Ho Chae

Abstract Background: Electroencephalography (EEG) frontal alpha asymmetry (FAA) has been observed in several psychiatric disorders. Dominance in left or right frontal alpha activity remains inconsistent in patients with major depressive disorder (MDD), patients with schizophrenia, and healthy controls. This study compared FAA among patients with MDD and schizophrenia, and healthy controls.Methods: We recruited 20 patients with MDD, 18 patients with schizophrenia, and 16 healthy individuals. The EEG alpha frequency ranged from 8 Hz to 12 Hz. FAA was expressed as the difference between absolute power values of right and left hemisphere electrodes in the alpha frequency range (common-log-transformed frontal right- and left-hemisphere electrodes: F4–F3, F8–F7, FP2–FP1, AF4–AF3, F6–F5, and F2–F1). Hamilton depression and anxiety rating scales were evaluated in patients with MDD. Positive and negative syndrome scales were evaluated in patients with schizophrenia.Results: Patients with schizophrenia showed significantly lower left FAA than healthy controls (F4–F3, schizophrenia vs. healthy controls: -0.10 ± 0.04 vs. -0.05 ± 0.05). There were no significant differences in FAA between patients with schizophrenia and MDD as well as between patients with MDD and healthy controls.Conclusions: The present study suggests that FAA indicates a relatively lower activation of left frontal electrodes in schizophrenia. The left-lateralized FAA could be a neuropathological attribute in patients with schizophrenia, but a lack of sample size and information such as medication and duration of illness might obscure the interpretation and generalization of our findings. Thus, further studies to verify the findings would be warranted.


2004 ◽  
Vol 65 (4) ◽  
pp. 492-499 ◽  
Author(s):  
Thomas Frodl ◽  
Eva M. Meisenzahl ◽  
Thomas Zetzsche ◽  
Tom Höhne ◽  
Sandra Banac ◽  
...  

2018 ◽  
Vol 46 (5) ◽  
pp. 1734-1746 ◽  
Author(s):  
Mi Li ◽  
Lei Feng ◽  
Xingwang Liu ◽  
Ming Zhang ◽  
Bingbing Fu ◽  
...  

Objective This study was performed to examine the working memory (WM) encoding and retrieval abilities in patients with major depressive disorder (MDD) and determine whether a mood-congruent memory effect is present. Methods The modified Sternberg WM paradigm with positive, negative, and neutral emotional pictures was used to investigate the WM abilities of 26 patients with MDD and 26 healthy controls (HCs). Results No significant difference in picture WM was found between the MDD and HC groups; however, the accuracy of picture position WM was significantly lower and the response time was significantly longer in the MDD than HC group, regardless of the picture or position WM. Additionally, in the MDD group, the accuracy of negative picture/position WM was significantly higher than that of positive picture/position WM. Conclusions These results suggest that in patients with MDD, spatial WM impairment was more severe than object WM. In addition, these patients’ WM retrieval was impaired, resulting in a decrease in WM retrieval ability, which may be an important cause of the slow thought in patients with MDD. Moreover, patients with depression have a mood-congruent memory effect, which may be an important factor in the occurrence and maintenance of depression.


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