Molecular serum signature of treatment resistant depression

Ruland, Tillmann; Chan, Man K.; Stocki, Paweł; Grosse, Laura; Rothermundt, Matthias; Cooper, Jason D.; Arolt, Volker; Bahn, Sabine

doi:10.1007/s00213-016-4348-0

Cited by 21 publications

(13 citation statements)

References 54 publications

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“…However, increase in pro-inflammatory cytokines and other inflammatory factors in plasma/serum from patients with depression have been reported in several studies ( Dowlati et al, 2010 ; Dahl et al, 2014 ). Plasma and serum proteomic studies of patients with major depressive disorders have found altered levels of acute phase, complement, and metabolic proteins similar to our study ( Lee et al, 2015 ; Ruland et al, 2016 ). These studies indicate that changed anxiety or depression status could affect proteins systemically.…”

Section: Discussionsupporting

confidence: 88%

“…As mentioned above, psychological distress is common in CWP and is often measured using the Hospital Anxiety and Depression Scale (HADS) ( Zigmond and Snaith, 1983 ). Because the association between depression and several serum proteins has been shown in patients with major depression disorder, ( Lee et al, 2015 ; Ruland et al, 2016 ) it is important to investigate whether the protein pattern in blood correlates with psychological distress in CWP patients and to what extent these proteins influence pain intensity. The same principal reasoning goes for Body Mass Index (BMI) since increased BMI is often found in patients with CWP/FMS ( Neumann et al, 2008 ) and the correlation between limited numbers of plasma/serum metabolites and proteins and BMI have been reported ( Xiao et al, 2013 ; Rus et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain

Wåhlén

Ghafouri

et al. 2018

Front. Psychol.

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Objectives: Although generalized muscle pain, tiredness, anxiety, and depression are commonly present among chronic widespread pain (CWP) patients, the molecular mechanisms behind CWP are not fully elucidated. Moreover, the lack of biomarkers often makes diagnosis and treatment problematic. In this study, we investigated the correlation between pain intensity, psychological distress, and plasma proteins among CWP patients and controls (CON).Methods: The plasma proteome of CWP (n = 15) and CON (n = 23) was analyzed using two-dimensional gel electrophoresis. Orthogonal Partial Least Square analysis (OPLS) was used to determine proteins associated with pain intensity (numeric rating scale) in CWP and psychological distress (Hospital and Depression Scale, HADS) in CWP and CON. Significant proteins were identified by MALDI-TOF and tandem MS.Results: In CWP, pain intensity was associated with plasma proteins mostly involved in metabolic and immunity processes (e.g., kininogen-1, fibrinogen gamma chain, and ceruloplasmin), and psychological distress was associated with plasma proteins related to immunity response, iron ion, and lipid metabolism (e.g., complement factor B, complement C1r subcomponent, hemopexin, and clusterin).Discussion: This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome. Using the plasma proteome profile of CWP to study potential biomarker candidates provides a snapshot of ongoing systemic mechanisms in CWP.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain

Wåhlén

Ghafouri

et al. 2018

Front. Psychol.

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“…Although, there were no significant differences in weight or BMI in this cohort, it is generally known that one of the risk factors is obesity in females with CWP/FMS 44,45. Several studies have also found a correlation between higher levels of CERU, haptoglobin and complement proteins in plasma and serum to be associated with major depressive disorders 46–50. In this study, the CWP group reported statistically significant higher HADS scores (anxiety and depression) compared to CON.…”

Section: Discussionmentioning

confidence: 56%

Systemic alterations in plasma proteins from women with chronic widespread pain compared to healthy controls: a proteomic study

Wåhlén¹,

Olausson²,

Carlsson³

et al. 2017

JPR

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Chronic widespread pain (CWP) is a complex pain condition that is difficult to treat. The prevalence of CWP approximates ~10% of the general population, with higher prevalence in women. Lack of understanding of molecular mechanisms has been a challenge for diagnosis and treatment of chronic pain. The aim of this study was to explore the systemic protein changes in CWP compared to those in healthy controls (CON). By applying 2-dimensional gel electrophoresis, we analyzed the protein pattern of plasma samples from women with CWP (n=16) and healthy women (n=23). The proteomic data were analyzed using multivariate statistical models, and altered proteins were identified using mass spectrometry. The proteome analysis was further validated by gel-free Western blot. Multivariate statistical data analysis of quantified proteins revealed 22 altered proteins in women with CWP, compared to CON group. Many of the identified proteins are previously known to be involved in different parts of the complement system and metabolic and inflammatory processes, e.g., complement factor B, vitamin D-binding protein, ceruloplasmin, transthyretin and alpha-2-HS-glycoprotein. These results indicate that important systemic protein differences exist between women with CWP and healthy women. Further, this study illustrates the potential use of proteomics to detect biomarkers that may provide new insights into the molecular mechanism(s) of chronic pain. However, further larger investigations are required in order to confirm these findings before it will be possible to identify proteins as potential pain biomarkers for clinical use.

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“…Most of these proteins are related to the innate immune response, inflammation and the coagulation cascade. Effects on protein components of these pathways have been reported previously for MDD patients at risk of suicide (Yang et al, 2016 ) and as markers of treatment resistance (Ruland et al, 2016 ). Furthermore, in a previous study, we found that levels of fibrinogen, a key component of the clotting cascade, may be predictive of antidepressant treatment response (Martins-de-Souza et al, 2014 ).…”

Section: Resultsmentioning

confidence: 68%

“…In addition, three proteins associated with a transport function were lower including apolipoprotein A-IV, apolipoprotein B-100 and retinol-binding protein 4. Previous studies have identified lower levels of all of these proteins in major depression patients (Lopez-Vilchez et al, 2014 ; Frye et al, 2015 ; Lee et al, 2016 ; Ruland et al, 2016 ; Kim et al, 2017 ). In addition, the finding of lower levels of apolipoprotein A-IV in responders is consistent with the findings of a recent study showing that this protein may be a marker of response to different antidepressants (Ruland et al, 2016 ).…”

Section: Resultsmentioning

confidence: 94%

Proteomic Differences in Blood Plasma Associated with Antidepressant Treatment Response

Turck

Guest

Maccarrone

et al. 2017

Front. Mol. Neurosci.

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The current inability of clinical psychiatry to objectively select the most appropriate treatment is a major factor contributing to the severity and clinical burden of major depressive disorder (MDD). Here, we have attempted to identify plasma protein signatures in 39 MDD patients to predict response over a 6-week treatment period with antidepressants. LC-MS/MS analysis showed that differences in the levels of 29 proteins at baseline were found in the group with a favorable treatment outcome. Most of these proteins were components of metabolism or immune response pathways as well as multiple components of the coagulation cascade. After 6 weeks of treatment, 43 proteins were altered in responders of which 2 (alpha-actinin and nardilysin) had been identified at baseline. In addition, 46 proteins were altered in non-responders and 9 of these (alpha-actinin, alpha-2-macroglobulin, apolipoprotein B-100, attractin, C-reactive protein, fibrinogen alpha chain, fibrinogen beta chain, nardilysin and serine/threonine-protein kinase Chk1) had been identified at baseline. However, it should be stressed that the small sample size precludes generalization of the main results. Further studies to validate these as potential biomarkers of antidepressant treatment response are warranted considering the potential importance to the field of psychiatric disorders. This study provides the groundwork for development of novel objective clinical tests that can help psychiatrists in the clinical management of MDD through improved prediction and monitoring of patient responses to antidepressant treatments.

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Molecular serum signature of treatment resistant depression

Cited by 21 publications

References 54 publications

Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain

Plasma Protein Pattern Correlates With Pain Intensity and Psychological Distress in Women With Chronic Widespread Pain

Systemic alterations in plasma proteins from women with chronic widespread pain compared to healthy controls: a proteomic study

Proteomic Differences in Blood Plasma Associated with Antidepressant Treatment Response

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