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Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial.

ABSTRACT: Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via a multiplex assay comprised of inflammatory markers using a 27-plex standard assay panel plus a 4-plex human acute phase xMAP technology based platform. We carried out analyses in two steps. First, t-tests were used to identify inflammatory marker levels that changed between baseline and week 12. For markers that were altered, logistic regression models were then conducted to look for associated changes in remission at week 12. Among the 31 inflammatory markers analyzed, several cytokines (IL-5, IFN-?, IL-13), two chemokines (Eotaxin-1/CCL11, RANTES) and an acute-phase reactant (serum amyloid P component) showed change from baseline to week 12. However, only two indicated differential remission responses. Interestingly, increased levels of Eotaxin-1/CCL11 correlated with remission at week 12, whereas decreased levels of IFN-? correlated with non-remission at week 12. Results suggest that these inflammatory proteins may serve as predictors of treatment response.

SUBMITTER: Gadad BS

PROVIDER: S-EPMC5804347 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial.

Gadad Bharathi S BS Jha Manish K MK Grannemann Bruce D BD Mayes Taryn L TL Trivedi Madhukar H MH

Journal of psychiatric research 20170526

Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via ...[more]

PMID: 28628884

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Project description:ObjectiveCurrently, no valid measures inform treatment selection for depressed patients. Whether C-reactive protein (CRP) in particular and two other acute phase reactants (inflammatory markers) could differentiate between patients responding to either of two treatments with different mechanisms of action was assessed.MethodSubjects included Combining Medications to Enhance Depression Outcomes (CO-MED) trial participants randomly assigned to either escitalopram plus placebo (SSRI monotherapy, n=51) or bupropion plus escitalopram combination (bupropion-SSRI combination, n=55) with baseline plasma samples. CRP, serum amyloid P component, and alpha-2-macroglobulin were measured using the Bioplex Pro™ human acute-phase 4-plex panel. We conducted mixed model analyses of depressive symptom (Quick Inventory of Depressive Symptomatology Self-Report) and side-effect burden (Frequency, Intensity, and Burden of Side-Effects Rating Scale) obtained weekly or every other week over the 12-week acute-phase of CO-MED trial to evaluate the relationship between these outcomes and baseline CRP and other acute-phase reactants.ResultsThe treatment arms did not differ in depressive symptom or side effect outcomes. Most participants (69.8%, 74/106) had baseline CRP levels greater than 1mg/L (indicative of systemic inflammatory activity). Higher baseline CRP levels were associated lower depression severity (correlation coefficient=-0.63) with bupropion-SSRI combination but not with SSRI monotherapy (correlation coefficient=0.40). The overall remission rate was 41.5%. The estimated remission rate with CRP threshold based assignment (SSRI monotherapy for <1mg/L and Bupropion-SSRI for ≥1mg/L) was 53.1%, with a number needed to treat of 8.6. Side effect burden was unrelated to any baseline inflammatory marker.ConclusionsBaseline CRP levels relate differentially to antidepressant treatment outcomes in persons with major depressive disorder. Clinicaltrials.gov identifier: NCT00590863.

Project description:Sub-threshold hypomanic symptoms are common in major depressive disorder. This study evaluated the prevalence, the clinical and sociodemographic correlates, and the overall and differential effects of the presence/absence of sub-threshold hypomanic symptoms at baseline on acute-phase treatment outcomes with bupropion-plus-escitalopram combination, escitalopram monotherapy, and venlafaxine-plus-mirtazapine combination. Combining medications to enhance depression outcomes (CO-MED) trial participants (n = 665) were designated as sub-threshold hypomanic symptoms present (Altman Self-Rating Mania Scale score (ASRM) ≥ 1) or absent (ASRM = 0) and compared on clinical and sociodemographic features and remission rates. Participants with sub-threshold hypomanic symptoms (n = 335/665, 50.4%) were more likely to be black and non-Hispanic, have comorbid medical and psychiatric disorders, experience longer index episodes, and report lower depression severity and psychosocial impairment. Intent-to-treat remission rates were lower overall (absent = 42.7%, present = 34.0%, p = 0.02), with escitalopram monotherapy (absent = 45.8%, present = 31.6%, p = 0.03), and with venlafaxine-XR-plus-mirtazapine combination (absent = 44.4%, present = 30.1%, p = 0.03) but not with bupropion-plus-escitalopram combination (absent = 37.7%, present = 40.0%, p = 0.73). Participants without sub-threshold hypomanic symptoms were more likely to remit than those with such symptoms overall [odds ratio (OR) = 1.49], with escitalopram monotherapy (OR = 1.71), and with venlafaxine-plus-mirtazapine combination (OR = 1.97) but not with bupropion-plus-escitalopram combination (OR = 0.96), even after controlling for baseline depression severity, psychosocial impairment, and number of comorbid psychiatric disorders. Sub-threshold hypomanic symptoms (found in about 50% of patients in this report) were associated with lower remission rates with escitalopram monotherapy and with venlafaxine-plus-mirtazapine combination but not with the bupropion-plus-escitalopram combination.

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Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial.

Publications

Proteomics profiling reveals inflammatory biomarkers of antidepressant treatment response: Findings from the CO-MED trial.

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