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Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial
Background: Elevated S100 calcium binding protein B (S100B) levels in systemic circulation may induce neuroinflammation and reflect greater blood–brain barrier (BBB) dysfunction. Neuroinflammation in patients with major depressive disorder (MDD), in turn, may reduce likelihood of improvement with se...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958482/ https://www.ncbi.nlm.nih.gov/pubmed/31861074 http://dx.doi.org/10.3390/ph12040184 |
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author | Jha, Manish K. Minhajuddin, Abu Gadad, Bharathi S. Chin Fatt, Cherise Trivedi, Madhukar H. |
author_facet | Jha, Manish K. Minhajuddin, Abu Gadad, Bharathi S. Chin Fatt, Cherise Trivedi, Madhukar H. |
author_sort | Jha, Manish K. |
collection | PubMed |
description | Background: Elevated S100 calcium binding protein B (S100B) levels in systemic circulation may induce neuroinflammation and reflect greater blood–brain barrier (BBB) dysfunction. Neuroinflammation in patients with major depressive disorder (MDD), in turn, may reduce likelihood of improvement with serotonergic antidepressants. Methods: Levels of S100B were measured in plasma samples obtained prior to initiation of treatment with bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine in participants of Combining Medications to Enhance Depression Outcomes trial (n = 153). Depression severity was measured with 16-item Quick Inventory of Depressive Symptomatology Self-Report and anhedonia was measured with 3 items of 30-item Inventory of Depressive Symptomatology. Differential changes in depression severity and anhedonia over acute-phase (baseline, weeks 1, 2, 4, 6, 8, 10, and 12) in the three treatment arms were tested with logS100B-by-treatment-arm interaction in mixed model analyses after controlling for age, gender, and body mass index. Results: There was a significant logS100B-by-treatment-arm interaction for anhedonia (F = 3.21; df = 2, 142; p = 0.04) but not for overall depression severity (F = 1.99; df = 2, 142; p = 0.14). Higher logS100B levels were associated with smaller reductions in anhedonia (effect size = 0.67, p = 0.047) in escitalopram monotherapy but not in the other two arms. Correlation coefficients of anhedonia severity averaged over acute-phase (including baseline) with baseline S100B levels were 0.57, −0.19, and 0.22 for escitalopram monotherapy, bupropion-plus-escitalopram and venlafaxine-plus-mirtazapine arms respectively. Conclusion: Higher baseline S100B levels in depressed patients resulted in poorer response to escitalopram monotherapy. Addition of bupropion, a dopaminergic antidepressant, partially mitigated this effect. |
format | Online Article Text |
id | pubmed-6958482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-69584822020-01-23 Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial Jha, Manish K. Minhajuddin, Abu Gadad, Bharathi S. Chin Fatt, Cherise Trivedi, Madhukar H. Pharmaceuticals (Basel) Article Background: Elevated S100 calcium binding protein B (S100B) levels in systemic circulation may induce neuroinflammation and reflect greater blood–brain barrier (BBB) dysfunction. Neuroinflammation in patients with major depressive disorder (MDD), in turn, may reduce likelihood of improvement with serotonergic antidepressants. Methods: Levels of S100B were measured in plasma samples obtained prior to initiation of treatment with bupropion-plus-escitalopram, escitalopram-plus-placebo, or venlafaxine-plus-mirtazapine in participants of Combining Medications to Enhance Depression Outcomes trial (n = 153). Depression severity was measured with 16-item Quick Inventory of Depressive Symptomatology Self-Report and anhedonia was measured with 3 items of 30-item Inventory of Depressive Symptomatology. Differential changes in depression severity and anhedonia over acute-phase (baseline, weeks 1, 2, 4, 6, 8, 10, and 12) in the three treatment arms were tested with logS100B-by-treatment-arm interaction in mixed model analyses after controlling for age, gender, and body mass index. Results: There was a significant logS100B-by-treatment-arm interaction for anhedonia (F = 3.21; df = 2, 142; p = 0.04) but not for overall depression severity (F = 1.99; df = 2, 142; p = 0.14). Higher logS100B levels were associated with smaller reductions in anhedonia (effect size = 0.67, p = 0.047) in escitalopram monotherapy but not in the other two arms. Correlation coefficients of anhedonia severity averaged over acute-phase (including baseline) with baseline S100B levels were 0.57, −0.19, and 0.22 for escitalopram monotherapy, bupropion-plus-escitalopram and venlafaxine-plus-mirtazapine arms respectively. Conclusion: Higher baseline S100B levels in depressed patients resulted in poorer response to escitalopram monotherapy. Addition of bupropion, a dopaminergic antidepressant, partially mitigated this effect. MDPI 2019-12-17 /pmc/articles/PMC6958482/ /pubmed/31861074 http://dx.doi.org/10.3390/ph12040184 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Jha, Manish K. Minhajuddin, Abu Gadad, Bharathi S. Chin Fatt, Cherise Trivedi, Madhukar H. Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial |
title | Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial |
title_full | Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial |
title_fullStr | Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial |
title_full_unstemmed | Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial |
title_short | Higher S100B Levels Predict Persistently Elevated Anhedonia with Escitalopram Monotherapy Versus Antidepressant Combinations: Findings from CO-MED Trial |
title_sort | higher s100b levels predict persistently elevated anhedonia with escitalopram monotherapy versus antidepressant combinations: findings from co-med trial |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958482/ https://www.ncbi.nlm.nih.gov/pubmed/31861074 http://dx.doi.org/10.3390/ph12040184 |
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