scholarly journals Discovery of Screening Biomarkers for Major Depressive Disorder in Remission by Proteomic Approach

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 539
Author(s):  
Hyebin Choi ◽  
Sora Mun ◽  
Eun-Jeong Joo ◽  
Kyu Young Lee ◽  
Hee-Gyoo Kang ◽  
...  

Major depressive disorder (MDD) is a common disorder involving depressive mood and decreased motivation. Due to its high heterogeneity, novel biomarkers are required to diagnose MDD. In this study, a proteomic method was used to identify a new MDD biomarker. Using sequential window acquisition of all theoretical mass spectra acquisitions and multiple reaction monitoring analysis via mass spectrometry, relative and absolute quantification of proteins in the sera was performed. The results of the relative quantitation by sequential window acquisition for all theoretical mass spectra data showed that seven proteins were significantly differently expressed between MDD patients and other patients with remission status. However, absolute quantification by multiple reaction monitoring analysis identified prothrombin as the only significantly upregulated protein in the depressive state compared to remission (p < 0.05) and was, thus, subsequently selected as an MDD biomarker. The area under the curve for prothrombin was 0.66. Additionally, increased prothrombin/thrombin induced hyper-activation of platelets via activating protease-activated receptors, a feature associated with MDD; specifically, activated platelets secrete various molecules related to MDD, including brain-derived neurotropic factors and serotonin. Therefore, prothrombin is a potential screening, prognostic, and diagnostic marker for MDD.

2020 ◽  
Author(s):  
Hye In Woo ◽  
Jisook Park ◽  
Shinn-Won Lim ◽  
Doh Kwan Kim ◽  
Soo-Youn Lee

Abstract Background: Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.Methods: A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine). Results: Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (p = 0.026). There was no significant difference in protein levels related to SSRIs treatment. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (p = 0.007).Conclusions: In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.


2021 ◽  
Author(s):  
Hye In Woo ◽  
Jisook Park ◽  
Shinn-Won Lim ◽  
Doh Kwan Kim ◽  
Soo-Youn Lee

Abstract Background: Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.Methods: A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine). Results: Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (p = 0.026). A few differences were observed in protein levels related to SSRIs treatment, although they were not statistically significant. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (p = 0.007).Conclusions: In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hye In Woo ◽  
Jisook Park ◽  
Shinn-Won Lim ◽  
Doh Kwan Kim ◽  
Soo-Youn Lee

Abstract Background Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals. Methods A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine). Results Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (P = 0.026). A few differences were observed in protein levels related to SSRIs treatment, although they were not statistically significant. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (P = 0.007). Conclusions In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.


2020 ◽  
Author(s):  
Hye In Woo ◽  
Jisook Park ◽  
Shinn-Won Lim ◽  
Doh Kwan Kim ◽  
Soo-Youn Lee

Abstract Background: Major depressive disorder (MDD), common mental disorder, lacks objective diagnostic and prognosis biomarkers. The objective of this study was to perform proteomic analysis to identify proteins with changed expression levels after antidepressant treatment and investigate differences in protein expression between MDD patients and healthy individuals.Methods: A total of 111 proteins obtained from literature review were subjected to multiple reaction monitoring (MRM)-based protein quantitation. Finally, seven proteins were quantified for plasma specimens of 10 healthy controls and 78 MDD patients (those at baseline and at 6 weeks after antidepressant treatment of either selective serotonin reuptake inhibitors (SSRIs) or mirtazapine). Results: Among 78 MDD patients, 35 patients were treated with SSRIs and 43 patients were treated with mirtazapine. Nineteen (54.3%) and 16 (37.2%) patients responded to SSRIs and mirtazapine, respectively. Comparing MDD patients with healthy individuals, alteration of transthyretin was observed in MDD (p = 0.026). A few differences were observed in protein levels related to SSRIs treatment, although they were not statistically significant. Plasma thyroxine-binding globulin (TBG) was different between before and after mirtazapine treatment only in responders (p = 0.007).Conclusions: In proteomic analysis of plasma specimens from MDD patients, transthyretin and TBG levels were altered in MDD and changed after antidepressant treatment.


2021 ◽  
Vol 12 ◽  
Author(s):  
Li-Juan Nie ◽  
Jun Liang ◽  
Feng Shan ◽  
Bao-Shi Wang ◽  
Yuan-Yuan Mu ◽  
...  

The lack of biomarkers greatly limits the diagnosis and treatment of major depressive disorder (MDD). Endogenous L-carnitine (LC) and its derivative acetyl-L-carnitine (ALC) play antidepressant roles by improving brain energy metabolism, regulating neurotransmitters and neural plasticity. The levels of ALC in people and rodents with depression are significantly reduced. It is necessary to determine whether serum LC and ALC might be used as novel biomarkers for the diagnosis of MDD. Here, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentration of LC and ALC in the serum of healthy controls and patients with MDD; among the latter, in patients who were responsive (effective group) and non-responsive (ineffective group) after 2 weeks of treatment. The diagnostic value of serum LC and ALC for MDD was assessed. Compared with healthy controls, the serum LC and ALC concentrations in patients with MDD were significantly decreased (P &lt; 0.001). Pearson correlation analysis shows that the HDRS-24 score was negatively associated with serum ALC (r = −0.325, P = 0.007). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.801 with 83.1% sensitivity and 66.3% specificity for LC, and an AUC of 0.898 with 88.8% sensitivity and 76.4% specificity for ALC, differentiating patients with MDD from healthy controls. Furthermore, the concentration of LC and ALC in patients with depression was significantly increased in the effective treatment group, and no significant change was observed in the ineffective treatment group. These results suggest that serum LC and ALC may be novel biomarkers for the diagnosis of MDD.


2019 ◽  
Vol 27 (4) ◽  
pp. 381-390 ◽  
Author(s):  
Mechthild Westhoff-Bleck ◽  
Lotta Winter ◽  
Lukas Aguirre Davila ◽  
Christoph Herrmann-Lingen ◽  
Jens Treptau ◽  
...  

Objective The purpose of this study was the diagnostic evaluation of the hospital anxiety and depression scale total score, its depression subscale and the Beck depression inventory II in adults with congenital heart disease. Methods This cross-sectional study evaluated 206 patients with congenital heart disease (mean age 35.3 ± 11.7 years; 58.3% men). Major depressive disorder was diagnosed by a structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders IV and disease severity with the Montgomery–Åsberg depression rating scale. Receiver operating characteristics provided assessment of diagnostic accuracy. Youden’s J statistic identified optimal cut-off points. Results Fifty-three participants (25.7%) presented with major depressive disorder. Of these, 28 (52.8%) had mild and 25 (47.2%) had moderate to severe symptoms. In the total cohort, the optimal cut-off of values was >11 in the Beck depression inventory II, >11 in the hospital anxiety and depression scale and >5 in the depression subscale. Optimal cut-off points for moderate to severe major depressive disorder were similar. The cut-offs for mild major depressive disorder were lower (Beck depression inventory II >4; hospital anxiety and depression scale >8; >2 in its depression subscale). In the total cohort the calculated area under the curve varied between 0.906 (hospital anxiety and depression scale) and 0.93 (Beck depression inventory II). Detection of moderate to severe major depressive disorder (area under the curve 0.965–0.98) was excellent; detection of mild major depressive disorder (area under the curve 0.851–0.885) was limited. Patients with major depressive disorder had a significantly lower quality of life, even when they had mild symptoms. Conclusion All scales were excellent for detecting moderate to severe major depressive disorder. Classification of mild major depressive disorder, representing 50% of cases, was limited. Therapy necessitating loss of quality of life is already present in major depressive disorder with mild symptoms. Established cut-off points may still be too high to identify patients with major depressive disorder requiring therapy. External validation is needed to confirm our data.


2018 ◽  
Vol 6 ◽  
pp. 205031211877395 ◽  
Author(s):  
Md Rabiul Islam ◽  
Md Reazul Islam ◽  
Imtiaz Ahmed ◽  
Abdullah Al Moktadir ◽  
Zabun Nahar ◽  
...  

Objectives: Major depressive disorder is diagnosed on the basis of patient’s self-reported experiences, behavior reported by relatives, and a mental status examination, and yet we do not have any reliable biomarker for this. Mood-regulating pathways are affected by oxidative injury to lipids and cortisol is released into the blood due to stimulation of corticotrophin receptors in the adrenal cortex. Here, we aimed to determine serum levels of malondialdehyde and cortisol in major depressive disorder patients and controls. Methods: We collected blood samples from 247 major depressive disorder patients and 248 controls. Serum levels of malondialdehyde and cortisol were measured by ultraviolet spectrophotometry and enzyme-linked immunosorbent assay kit, respectively. Results: We found malondialdehyde levels were significantly higher in patients than controls, with mean ± standard deviation at 4.49 ± 1.37 and 2.87 ± 0.82 µmol/L, respectively, p < 0.001. Cortisol levels were also found significantly higher in patients than controls, with mean ± SD at 19.22 ± 1.64 and 17.37 ± 1.34 µg/dL, respectively, p < 0.001. Significant negative correlation was observed between serum levels of malondialdehyde and cortisol in patients ( r =−0.170, p = 0.021). Receiver operating characteristic analysis showed good diagnostic value for malondialdehyde and cortisol, with the area under the curve at 0.853 and 0.819, respectively. Conclusion: The present study suggests that increased serum levels of malondialdehyde and cortisol are strongly associated with major depressive disorder. We believe elevations of malondialdehyde and cortisol in serum level arise independently and they could serve as biomarkers for major depressive disorder.


2020 ◽  
Author(s):  
Maliha Afrin Proma ◽  
Sohel Daria ◽  
Salsabil Islam ◽  
Zabun Nahar ◽  
Sardar Mohammad Ashraful Islam ◽  
...  

AbstractMajor depressive disorder (MDD) is a distressing condition characterized by persistent low mood, loss of interest in daily activities. Many biological, psycho-social, and genetic factors are thought to be involved with depression. The present study aimed to investigate the serum levels of monocyte chemoattractant protein-1 (MCP-1) in MDD patients to explore its role in the development of depression. This case-control study recruited 114 MDD patients and 106 healthy controls (HCs) matched by age and gender. A specialized psychiatrist diagnosed the cases and evaluated the controls based on the diagnostic and statistical manual for mental disorders, 5th edition. The serum MCP-1 levels were quantified by commercially available enzyme-linked immune sorbent assay kits. The Hamilton depression rating scale (Ham-D) was applied to measure the severity of depression. We observed the decreased levels of serum MCP-1 in MDD patients compared to HCs. A significant negative correlation was obtained between serum MCP-1 levels and Ham-D scores. Also, female MDD patients with higher Ham-D scores exhibited lower serum MCP-1 levels. The receiver operating characteristic analysis demonstrated the good diagnostic value of MCP-1 with the area under the curve at 0.837. The depression-related alteration of serum MCP-1 may be more complicated than the current assumption and depends on the characteristics of the individual patients. Our study suggests that the serum MCP-1 levels might be involved in the pathophysiology and mechanism of MDD. The present findings, along with the diagnostic evaluation, might be used to assess the depression risk.


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