Oxidative stress, inflammation and treatment response in major depression

Daniel Lindqvist, Firdaus Dhabhar, S. Jill James, Christina M. Hough, Felipe A. Jain, F. Saverio Bersani, Victor I. Reus, Josine E. Verhoeven, Elissa S. Epel, Laura Mahan, Rebecca Rosser, Owen M. Wolkowitz, Synthia H. Mellon

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Objective Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. Methods Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment “response” was defined as ≥50% decrease in HDRS ratings over 8 weeks of treatment. Results After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p < 0.001), TNF-α (p < 0.001), 8-OHdG (p = 0.018), and F2-isoprostanes (p = 0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p = 0.006), and after eight weeks of treatment (p = 0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p = 0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p = 0.019). Conclusion Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.

Original languageEnglish (US)
Pages (from-to)197-205
Number of pages9
JournalPsychoneuroendocrinology
Volume76
DOIs
StatePublished - Feb 1 2017

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Major Depressive Disorder
Oxidative Stress
Antidepressive Agents
Depression
Inflammation
F2-Isoprostanes
Deoxyguanosine
Interleukin-6
Therapeutics
Serotonin Uptake Inhibitors
Lymphotoxin-beta
Glutathione Peroxidase
C-Reactive Protein
Ascorbic Acid
Glutathione
Healthy Volunteers
Body Mass Index
Tumor Necrosis Factor-alpha
Smoking

Keywords

  • Antidepressant response
  • Inflammation
  • Major depressive disorder
  • Oxidative stress
  • Selective serotonin reuptake inhibitor

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Lindqvist, D., Dhabhar, F., James, S. J., Hough, C. M., Jain, F. A., Bersani, F. S., ... Mellon, S. H. (2017). Oxidative stress, inflammation and treatment response in major depression. Psychoneuroendocrinology, 76, 197-205. https://doi.org/10.1016/j.psyneuen.2016.11.031

Oxidative stress, inflammation and treatment response in major depression. / Lindqvist, Daniel; Dhabhar, Firdaus; James, S. Jill; Hough, Christina M.; Jain, Felipe A.; Bersani, F. Saverio; Reus, Victor I.; Verhoeven, Josine E.; Epel, Elissa S.; Mahan, Laura; Rosser, Rebecca; Wolkowitz, Owen M.; Mellon, Synthia H.

In: Psychoneuroendocrinology, Vol. 76, 01.02.2017, p. 197-205.

Research output: Contribution to journalArticle

Lindqvist, D, Dhabhar, F, James, SJ, Hough, CM, Jain, FA, Bersani, FS, Reus, VI, Verhoeven, JE, Epel, ES, Mahan, L, Rosser, R, Wolkowitz, OM & Mellon, SH 2017, 'Oxidative stress, inflammation and treatment response in major depression', Psychoneuroendocrinology, vol. 76, pp. 197-205. https://doi.org/10.1016/j.psyneuen.2016.11.031
Lindqvist, Daniel ; Dhabhar, Firdaus ; James, S. Jill ; Hough, Christina M. ; Jain, Felipe A. ; Bersani, F. Saverio ; Reus, Victor I. ; Verhoeven, Josine E. ; Epel, Elissa S. ; Mahan, Laura ; Rosser, Rebecca ; Wolkowitz, Owen M. ; Mellon, Synthia H. / Oxidative stress, inflammation and treatment response in major depression. In: Psychoneuroendocrinology. 2017 ; Vol. 76. pp. 197-205.
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abstract = "Objective Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. Methods Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment “response” was defined as ≥50{\%} decrease in HDRS ratings over 8 weeks of treatment. Results After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p < 0.001), TNF-α (p < 0.001), 8-OHdG (p = 0.018), and F2-isoprostanes (p = 0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p = 0.006), and after eight weeks of treatment (p = 0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p = 0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p = 0.019). Conclusion Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.",
keywords = "Antidepressant response, Inflammation, Major depressive disorder, Oxidative stress, Selective serotonin reuptake inhibitor",
author = "Daniel Lindqvist and Firdaus Dhabhar and James, {S. Jill} and Hough, {Christina M.} and Jain, {Felipe A.} and Bersani, {F. Saverio} and Reus, {Victor I.} and Verhoeven, {Josine E.} and Epel, {Elissa S.} and Laura Mahan and Rebecca Rosser and Wolkowitz, {Owen M.} and Mellon, {Synthia H.}",
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T1 - Oxidative stress, inflammation and treatment response in major depression

AU - Lindqvist, Daniel

AU - Dhabhar, Firdaus

AU - James, S. Jill

AU - Hough, Christina M.

AU - Jain, Felipe A.

AU - Bersani, F. Saverio

AU - Reus, Victor I.

AU - Verhoeven, Josine E.

AU - Epel, Elissa S.

AU - Mahan, Laura

AU - Rosser, Rebecca

AU - Wolkowitz, Owen M.

AU - Mellon, Synthia H.

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N2 - Objective Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. Methods Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment “response” was defined as ≥50% decrease in HDRS ratings over 8 weeks of treatment. Results After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p < 0.001), TNF-α (p < 0.001), 8-OHdG (p = 0.018), and F2-isoprostanes (p = 0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p = 0.006), and after eight weeks of treatment (p = 0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p = 0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p = 0.019). Conclusion Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.

AB - Objective Increased inflammation and oxidative stress have been shown in Major Depressive Disorder (MDD), although there is significant heterogeneity across studies. Whether markers of inflammation and oxidative stress are associated with antidepressant treatment response in MDD is currently unclear. The goals of the present study are to investigate markers of inflammation and oxidative stress in unmedicated MDD subjects and controls and test the relationship between these markers and antidepressant response in MDD subjects. Methods Interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein, F2-isoprostanes, 8-OH 2-deoxyguanosine (8-OHdG), glutathione peroxidase, glutathione, and vitamin C were quantified in blood samples from 50 unmedicated MDD subjects and 55 healthy controls. Depression symptom severity was rated with the 17-item Hamilton Depression Rating Scale (HDRS). All subjects were somatically healthy and free from medications that could interfere with inflammation and oxidative stress markers. A subgroup of 22 MDD subjects underwent open-label selective serotonin reuptake inhibitor (SSRI) antidepressant treatment for eight weeks, after which blood sampling and the HDRS were repeated. Antidepressant treatment “response” was defined as ≥50% decrease in HDRS ratings over 8 weeks of treatment. Results After controlling for the effects of age, sex, body mass index and smoking, MDD subjects had significantly higher levels of IL-6 (p < 0.001), TNF-α (p < 0.001), 8-OHdG (p = 0.018), and F2-isoprostanes (p = 0.012). Compared to Responders, Non-responders to SSRI antidepressant treatment had higher levels of F2-isoprostanes at baseline (p = 0.006), and after eight weeks of treatment (p = 0.031). Non-responders showed a significant increase in 8-OHdG over the course of treatment (p = 0.021), whereas Responders showed a significant decrease in IL-6 over the course of treatment (p = 0.019). Conclusion Our results are in line with previous reports of increased levels of markers of inflammation and oxidative stress in MDD. Moreover, poorer antidepressant treatment response was related to higher baseline levels of the major oxidative stress marker, F2-isoprostanes, in vivo. Further, antidepressant response was associated with changes in oxidative (8-OHdG) and inflammatory (IL-6) markers.

KW - Antidepressant response

KW - Inflammation

KW - Major depressive disorder

KW - Oxidative stress

KW - Selective serotonin reuptake inhibitor

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