title: Oxidative stress, inflammation and treatment response in major depression.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States; Lund University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry, Lund, Sweden. Electronic address: daniel.lindqvist@ucsf.edu.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lindqvist
authors.affiliation: Department of Psychiatry & Behavioral Sciences, Sylvester Comprehensive Cancer Center, University of Miami, FL, United States.
authors.forename: Firdaus S
authors.initials: FS
authors.lastname: Dhabhar
authors.affiliation: Arkansas Children's Research Institute, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, United States.
authors.forename: S Jill
authors.initials: SJ
authors.lastname: James
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Hough
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Jain
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States; Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy.
authors.forename: F Saverio
authors.initials: FS
authors.lastname: Bersani
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Reus
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States; Department of Psychiatry and EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, The Netherlands.
authors.forename: Josine E
authors.initials: JE
authors.lastname: Verhoeven
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Elissa S
authors.initials: ES
authors.lastname: Epel
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Mahan
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rosser
authors.affiliation: Department of Psychiatry, UCSF Weill Institute for Neurosciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Owen M
authors.initials: OM
authors.lastname: Wolkowitz
authors.affiliation: Department of OB/GYN and Reproductive Sciences, University of California San Francisco (UCSF) School of Medicine, San Francisco, CA, United States.
authors.forename: Synthia H
authors.initials: SH
authors.lastname: Mellon
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D018384:Oxidative Stress / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors
keywords: Antidepressant response; Inflammation; Major depressive disorder; Oxidative stress; Selective serotonin reuptake inhibitor