Quantitative Proteomic Approach for Discriminating Major Depressive Disorder and Bipolar Disorder by Multiple Reaction Monitoring-Mass Spectrometry

Author(s):  
Dongyoon Shin ◽  
Sang Jin Rhee ◽  
Jihyeon Lee ◽  
Injoon Yeo ◽  
Misol Do ◽  
...  
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 11 (1) ◽  
Author(s):  
Rona J. Strawbridge ◽  
Keira J. A. Johnston ◽  
Mark E. S. Bailey ◽  
Damiano Baldassarre ◽  
Breda Cullen ◽  
...  

AbstractUnderstanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.


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