Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-18T19:50:37.271Z Has data issue: false hasContentIssue false
  • English
  • Français

Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort

Published online by Cambridge University Press:  08 December 2016

C. N. Black ,
M. Bot ,
P. G. Scheffer  and
B. W. J. H. Penninx
C. N. Black*
Affiliation:
Department of Psychiatry and EMGO+ Institute for Health and Care Research, VU University Medical Center, and GGZ inGeest, Amsterdam, The Netherlands
M. Bot
Affiliation:
Department of Psychiatry and EMGO+ Institute for Health and Care Research, VU University Medical Center, and GGZ inGeest, Amsterdam, The Netherlands
P. G. Scheffer
Affiliation:
Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
B. W. J. H. Penninx
Affiliation:
Department of Psychiatry and EMGO+ Institute for Health and Care Research, VU University Medical Center, and GGZ inGeest, Amsterdam, The Netherlands
*
*Address for correspondence: C. N. Black, M.D., Department of Psychiatry, VU University Medical Center, Postbus 74077, 1070 BB Amsterdam, The Netherlands. (Email: catherine.n.black@gmail.com; c.black@ggzingeest.nl)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Oxidative stress has been implicated in the pathophysiology of major depressive disorder (MDD) and anxiety disorders and may be influenced by antidepressant use. This study investigated the association of oxidative stress, measured by plasma levels of F2-isoprostanes and 8-hydroxy-2′-deoxyguanosine (8-OHdG) reflecting oxidative lipid and DNA damage respectively, with MDD, anxiety disorders and antidepressant use in a large cohort.

Method

Data was derived from the Netherlands Study of Depression and Anxiety including patients with current (N = 1619) or remitted (N = 610) MDD and/or anxiety disorder(s) (of which N = 704 antidepressant users) and 612 controls. Diagnoses were established with the Composite International Diagnostic Interview. Plasma 8-OHdG and F2-isoprostanes were measured using LC-MS/MS. ANCOVA was performed adjusted for sampling, sociodemographic, health and lifestyle variables.

Results

F2-isoprostanes did not differ between controls and patients, or by antidepressant use. Patients with current disorders had lower 8-OHdG (mean 42.1 pmol/l, 95% CI 40.4–43.8) compared to controls (45.0 pmol/l, 95% CI 42.9–47.2; p < 0.001) after adjustment for sampling, sociodemographics and lifestyle, but these differences disappeared after further adjustment for antidepressant use (p = 0.562). Antidepressant users had lower 8-OHdG levels (38.2 pmol/l, 95% CI 36.5–39.9) compared to controls (44.9 pmol/l, 95% CI 43.2–46.6; Cohen's d = 0.21, p < 0.001). Results for 8-OHdG were comparable across disorders (MDD and/or anxiety disorders), and all antidepressant types (SSRIs, TCAs, other antidepressants).

Conclusion

Contrary to previous findings this large-scale study found no increased oxidative stress in MDD and anxiety disorders. Antidepressant use was associated with lower oxidative DNA damage, suggesting antidepressants may have antioxidant effects.

Keywords

Anxiety disordersmajor depressive disorderoxidative DNA damageoxidative lipid damageoxidative stress
Type
Original Articles
Information
Psychological Medicine , Volume 47 , Issue 5 , April 2017 , pp. 936 - 948
Copyright
Copyright © Cambridge University Press 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdel-Wahab, BA, Salama, RH (2011). Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice. Pharmacology, Biochemistry, and Behavior 100, 59–65.Google Scholar
Aseervatham, GSB, Sivasudha, T, Jeyadevi, R, Arul Ananth, D (2013). Environmental factors and unhealthy lifestyle influence oxidative stress in humans – an overview. Environmental Science and Pollution Research International 20, 4356–4369.Google Scholar
Basu, S (2008). F2-isoprostanes in human health and diseases: from molecular mechanisms to clinical implications. Antioxidants & Redox Signaling 10, 1405–1434.Google Scholar
Beck, AT, Epstein, N, Brown, G, Steer, RA (1988). An inventory for measuring clinical anxiety: psychometric properties. Journal of Consulting and Clinical Psychology 56, 893–897.Google Scholar
Beck, AT, Steer, RA (1993). Manual for the Beck Anxiety Inventory. Psychological Corporation: San Antonio.Google Scholar
Black, CN, Bot, M, Scheffer, PG, Cuijpers, P, Penninx, BWJH (2015). Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology 51, 164–175.CrossRefGoogle ScholarPubMed
Black, CN, Bot, M, Scheffer, PG, Penninx, BWJH (2016 a). Sociodemographic and lifestyle determinants of plasma oxidative stress markers 8-OHdG and F2-Isoprostanes and associations with metabolic syndrome. Oxidative Medicine and Cellular Longevity 2016, 7530820.CrossRefGoogle ScholarPubMed
Black, CN, Penninx, BWJH, Bot, M, Odegaard, AO, Gross, MD, Matthews, KA, Jacobs, DR (2016 b). Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the CARDIA study. Translational Psychiatry 6, e743.CrossRefGoogle ScholarPubMed
Chung, CP, Schmidt, D, Stein, CM, Morrow, JD, Salomon, RM (2013). Increased oxidative stress in patients with depression and its relationship to treatment. Psychiatry Research 206, 213–216.CrossRefGoogle ScholarPubMed
Cohen, J (1988). Statistical Power Analysis for the Behavioral Sciences (2nd ed.). Taylor & Francis Inc. Google Scholar
Davies, SS, Roberts, LJ (2011). F2-isoprostanes as an indicator and risk factor for coronary heart disease. Free radical Biology & Medicine 50, 559–566.Google Scholar
Dimopoulos, N, Piperi, C, Psarra, V, Lea, RW, Kalofoutis, A (2008). Increased plasma levels of 8-iso-PGF2alpha and IL-6 in an elderly population with depression. Psychiatry Research 161, 59–66.Google Scholar
Dowlati, Y, Herrmann, N, Swardfager, W, Liu, H, Sham, L, Reim, EK, Lanctot, KL (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry 67, 446–457.CrossRefGoogle ScholarPubMed
Feng, Z, Hu, W, Marnett, LJ, Tang, M (2006). Malondialdehyde, a major endogenous lipid peroxidation product, sensitizes human cells to UV- and BPDE-induced killing and mutagenesis through inhibition of nucleotide excision repair. Mutation Research 601, 125–136.Google Scholar
Forlenza, MJ, Miller, GE (2006). Increased serum levels of 8-hydroxy-2′-deoxyguanosine in clinical depression. Psychosomatic Medicine 68, 1–7.Google Scholar
Glassman, AH, Helzer, JE, Covey, LS, Cottler, LB, Stetner, F, Tipp, JE, Johnson, J (1990). Smoking, smoking cessation, and major depression. Journal of the American Medical Association 264, 1546–1549.Google Scholar
Guney, E, Fatih Ceylan, M, Tektas, A, Alisik, M, Ergin, M, Goker, Z, Senses Dinc, G, Ozturk, O, Korkmaz, A, Eker, S, Kizilgun, M, Erel, O (2014). Oxidative stress in children and adolescents with anxiety disorders. Journal of Affective Disorders 156, 62–66.CrossRefGoogle ScholarPubMed
Hannestad, J, DellaGioia, N, Bloch, M (2011). The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36, 2452–2459.CrossRefGoogle ScholarPubMed
Hashioka, S, Klegeris, A, Monji, A, Kato, T, Sawada, M, McGeer, PL, Kanba, S (2007). Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Experimental Neurology 206, 33–42.Google Scholar
Herken, H, Akyol, O, Yilmaz, HR, Tutkun, H, Savas, HA, Ozen, ME, Kalenderoglu, A, Gulec, M (2006). Nitric oxide, adenosine deaminase, xanthine oxidase and superoxide dismutase in patients with panic disorder: alterations by antidepressant treatment. Human Psychopharmacology 21, 53–59.CrossRefGoogle ScholarPubMed
Herken, H, Gurel, A, Selek, S, Armutcu, F, Ozen, ME, Bulut, M, Kap, O, Yumru, M, Savas, HA, Akyol, O (2007). Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment. Archives of Medical Research 38, 247–252.Google Scholar
Hiles, SA, Baker, AL, de Malmanche, T, Attia, J (2012). Interleukin-6, C-reactive protein and interleukin-10 after antidepressant treatment in people with depression: a meta-analysis. Psychological Medicine 42, 2015–2026.Google Scholar
Horikawa, H, Kato, TA, Mizoguchi, Y, Monji, A, Seki, Y, Ohkuri, T, Gotoh, L, Yonaha, M, Ueda, T, Hashioka, S, Kanba, S (2010). Inhibitory effects of SSRIs on IFN-γ induced microglial activation through the regulation of intracellular calcium. Progress in Neuro-Psychopharmacology & Biological Psychiatry 34, 1306–1316.CrossRefGoogle ScholarPubMed
Hovatta, I, Juhila, J, Donner, J (2010). Oxidative stress in anxiety and comorbid disorders. Neuroscience Research. Ireland, 68, 261–275.Google Scholar
Howren, MB, Lamkin, DM, Suls, J (2009). Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosomatic Medicine 71, 171–186.Google Scholar
Janicki-Deverts, D, Cohen, S, Matthews, KA, Gross, MD, Jacobs, DRJ (2009). Socioeconomic status, antioxidant micronutrients, and correlates of oxidative damage: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Psychosomatic Medicine 71, 541–548.Google Scholar
Jiménez-Fernández, S, Gurpegui, M, Díaz-Atienza, F, Pérez-Costillas, L, Gerstenberg, M, Correll, CU (2015). Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis. Journal of Clinical Psychiatry 76, 1658–1667.Google Scholar
Jorgensen, A, Krogh, J, Miskowiak, K, Bolwig, TG, Kessing, LV, Fink-Jensen, A, Nordentoft, M, Henriksen, T, Weimann, A, Poulsen, HE, Jorgensen, MB (2013). Systemic oxidatively generated DNA/RNA damage in clinical depression: associations to symptom severity and response to electroconvulsive therapy. Journal of Affective Disorders 149, 355–362.CrossRefGoogle ScholarPubMed
Kadiiska, MB, Gladen, BC, Baird, DD, Germolec, D, Graham, LB, Parker, CE, Nyska, A, Wachsman, JT, Ames, BN, Basu, S, Brot, N, Fitzgerald, GA, Floyd, RA, George, M, Heinecke, JW, Hatch, GE, Hensley, K, Lawson, JA, Marnett, LJ, Morrow, JD, Murray, DM, Plastaras, J, Roberts, LJ II, Rokach, J, Shigenaga, MK, Sohal, RS, Sun, J, Tice, RR, Van Thiel, DH, Wellner, D, Walter, PB, Tomer, KB, Mason, RP, Barrett, JC (2005). Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radical Biology & Medicine 38, 698–710.CrossRefGoogle ScholarPubMed
Kessler, RC, Wittchen, H-U, Abelson, JM, Mcgonagle, K, Schwarz, N, Kendler, KS, Knäuper, B, Zhao, S (1998). Methodological studies of the Composite International Diagnostic Interview (CIDI) in the US national comorbidity survey (NCS). International Journal of Methods in Psychiatric Research 7, 33–55.Google Scholar
Kroese, LJ, Scheffer, PG (2014). 8-hydroxy-2′-deoxyguanosine and cardiovascular disease: a systematic review. Current Atherosclerosis Reports 16, 452.CrossRefGoogle ScholarPubMed
Lamers, F, van Oppen, P, Comijs, HC, Smit, JH, Spinhoven, P, van Balkom, AJLM, Nolen, WA, Zitman, FG, Beekman, ATF, Penninx, BWJH (2011). Comorbidity patterns of anxiety and depressive disorders in a large cohort study: the Netherlands Study of Depression and Anxiety (NESDA). Journal of Clinical Psychiatry. United States, 72, 341–348.Google Scholar
Lee, CH, Park, JH, Yoo, K-Y, Choi, JH, Hwang, IK, Ryu, PD, Kim, D-H, Kwon, Y-G, Kim, Y-M, Won, M-H (2011). Pre- and post-treatments with escitalopram protect against experimental ischemic neuronal damage via regulation of BDNF expression and oxidative stress. Experimental Neurology 229, 450–459.CrossRefGoogle ScholarPubMed
Lee, HB, Oei, TPS (1994). Factor structure, validity, and reliability of the fear questionnaire in a Hong Kong Chinese population. Journal of Psychopathology and Behavioral Assessment 16, 189–199.Google Scholar
Liu, T, Zhong, S, Liao, X, Chen, J, He, T, Lai, S, Jia, Y (2015). A meta-analysis of oxidative stress markers in depression. PLoS ONE 10, e0138904.Google Scholar
Loft, S, Vistisen, K, Ewertz, M, Tjønneland, A, Overvad, K, Poulsen, HE (1992). Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index. Carcinogenesis 13, 2241–2247.Google Scholar
Luppino, FS, de Wit, LM, Bouvy, PF, Stijnen, T, Cuijpers, P, Penninx, BWJH, Zitman, FG (2010). Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Archives of General Psychiatry 67, 220–229.Google Scholar
Lyketsos, C, Nestadt, G, Cwi, J, Heithoff, K, Eaton, WW (1994). The life chart interview: a standardized method to describe the course of psychopathology. International Journal of Methods in Psychiatric Research 4, 143–155.Google Scholar
Meagher, EA, Barry, OP, Burke, A, Lucey, MR, Lawson, JA, Rokach, J, FitzGerald, GA (1999). Alcohol-induced generation of lipid peroxidation products in humans. Journal of Clinical Investigation 104, 805–813.CrossRefGoogle ScholarPubMed
Milne, GL, Yin, H, Brooks, JD, Sanchez, S, Jackson Roberts, L, Morrow, JD (2007). Quantification of F2-isoprostanes in biological fluids and tissues as a measure of oxidant stress. Methods in Enzymology 433, 113–126.Google Scholar
Niki, E (2014). Biomarkers of lipid peroxidation in clinical material. Biochimica et Biophysica Acta – General Subjects 1840, 809–817.Google Scholar
Pahor, M, Chrischilles, EA, Guralnik, JM, Brown, SL, Wallace, RB, Carbonin, P (1994). Drug data coding and analysis in epidemiologic studies. European Journal of Epidemiology 10, 405–411.Google Scholar
Palta, P, Samuel, LJ, Miller, ER III, Szanton, SL (2014). Depression and oxidative stress: results from a meta-analysis of observational studies. Psychosomatic Medicine 76, 12–19 Google Scholar
Penninx, BWJH, Beekman, ATF, Smit, JH, Zitman, FG, Nolen, WA, Spinhoven, P, Cuijpers, P, De Jong, PJ, Van Marwijk, HWJ, Assendelft, WJJ, Van Der Meer, K, Verhaak, P, Wensing, M, De Graaf, R, Hoogendijk, WJ, Ormel, J, Van Dyck, R (2008). The Netherlands Study of Depression and Anxiety (NESDA): rationale, objectives and methods. International Journal of Methods in Psychiatric Research 17, 121–140.CrossRefGoogle ScholarPubMed
Poulsen, HE, Nadal, LL, Broedbaek, K, Nielsen, PE, Weimann, A (2014). Detection and interpretation of 8-oxodG and 8-oxoGua in urine, plasma and cerebrospinal fluid. Biochimica et Biophysica Acta – General Subjects 1840, 801–808.Google Scholar
Rawdin, BJ, Mellon, SH, Dhabhar, FS, Epel, ES, Puterman, E, Su, Y, Burke, HM, Reus, VI, Rosser, R, Hamilton, SP, Nelson, JC, Wolkowitz, OM (2013). Dysregulated relationship of inflammation and oxidative stress in major depression. Brain, Behavior, and Immunity 31, 143–152.Google Scholar
Reiter, RJ, Tan, DX, Cabrera, J, D'Arpa, D (1999). Melatonin and tryptophan derivatives as free radical scavengers and antioxidants. Advances in Experimental Medicine and Biology 467, 379–387.CrossRefGoogle ScholarPubMed
Rush, AJ, Gullion, CM, Basco, MR, Jarrett, RB, Trivedi, MH (1996). The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychological Medicine 26, 477–486.Google Scholar
Rush, AJ, Trivedi, MH, Ibrahim, HM, Carmody, TJ, Arnow, B, Klein, DN, Markowitz, JC, Ninan, PT, Kornstein, S, Manber, R, Thase, ME, Kocsis, JH, Keller, MB (2003). The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biological Psychiatry 54, 573–583.CrossRefGoogle ScholarPubMed
Sakano, N, Wang, D-H, Takahashi, N, Wang, B, Sauriasari, R, Kanbara, S, Sato, Y, Takigawa, T, Takaki, J, Ogino, K (2009). Oxidative stress biomarkers and lifestyles in Japanese healthy people. Journal of Clinical Biochemistry and Nutrition 44, 185–195.CrossRefGoogle ScholarPubMed
Schmidt, AJ, Heiser, P, Hemmeter, UM, Krieg, J-C, Vedder, H (2008). Effects of antidepressants on mRNA levels of antioxidant enzymes in human monocytic U-937 cells. Progress in Neuro-Psychopharmacology & Biological Psychiatry 32, 1567–1573.Google Scholar
Smaga, I, Niedzielska, E, Gawlik, M, Moniczewski, A, Krzek, J, Przegaliński, E, Pera, J, Filip, M (2015). Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism. Pharmacological Reports 67, 569–580.CrossRefGoogle Scholar
Sullivan, LE, Fiellin, DA, O'Connor, PG (2005). The prevalence and impact of alcohol problems in major depression: a systematic review. American Journal of Medicine 118, 330–341.Google Scholar
Valavanidis, A, Vlachogianni, T, Fiotakis, C (2009). 8-hydroxy-2′ -deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis. Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews 27, 120–139.Google Scholar
Valko, M, Leibfritz, D, Moncol, J, Cronin, MTD, Mazur, M, Telser, J (2007). Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry & Cell Biology 39, 44–84.CrossRefGoogle ScholarPubMed
Van Zuuren, FJ (1988). The fear questionnaire. Some data on validity, reliability and layout. British Journal of Psychiatry 153, 659–662.CrossRefGoogle ScholarPubMed
Vogelzangs, N, Duivis, HE, Beekman, ATF, Kluft, C, Neuteboom, J, Hoogendijk, W, Smit, JH, de Jonge, P, Penninx, BWJH (2012). Association of depressive disorders, depression characteristics and antidepressant medication with inflammation. Translational Psychiatry 2, e79.CrossRefGoogle ScholarPubMed
Vreeburg, SA, Hoogendijk, WJG, van Pelt, J, Derijk, RH, Verhagen, JCM, van Dyck, R, Smit, JH, Zitman, FG, Penninx, BWJH (2009). Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Archives of General Psychiatry 66, 617–626.Google Scholar
Wertheimer, AI (1986). The defined daily dose system (DDD) for drug utilization review. Hospital Pharmacy 21, 233–234, 239–41, 258.Google Scholar
Whiteford, HA, Degenhardt, L, Rehm, J, Baxter, AJ, Ferrari, AJ, Erskine, HE, Charlson, FJ, Norman, RE, Flaxman, AD, Johns, N, Burstein, R, Murray, CJL, Vos, T (2013). Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet 382, 1575–1586.CrossRefGoogle ScholarPubMed
Wolkowitz, OM, Mellon, SH, Epel, ES, Lin, J, Dhabhar, FS, Su, Y, Reus, VI, Rosser, R, Burke, HM, Kupferman, E, Compagnone, M, Nelson, JC, Blackburn, EH (2011). Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress–preliminary findings. PLoS ONE 6, e17837.Google Scholar
WHO (2004). The global burden of disease: 2004 update (http://www.who.int/entity/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf).Google Scholar
WHO Centre for Drug Statistics Methodology (2010). Anatomical Therapeutic Chemical (ATC) classification (http://www.whocc.no/atcddd).Google Scholar
Yager, S, Forlenza, MJ, Miller, GE (2010). Depression and oxidative damage to lipids. Psychoneuroendocrinology 35, 1356–1362.Google Scholar
Supplementary material: File

Black supplementary material

Table S1

Download Black supplementary material(File)
File 20.8 KB