Oxidative stress markers in bipolar disorder: A meta-analysis
Abstract
Background Oxidative stress is thought to mediate neuropathological processes of a number of neuropsychiatric disorders and recent data suggest that oxidative stress may be involved in the pathophysiology of bipolar disorder (BD). In the present investigation, we conducted a meta-analysis of studies that evaluated markers of oxidative stress in individuals with BD, as compared to healthy controls.Methods A Medline search was conducted to identify studies that measured peripheral markers of oxidative stress in bipolar disorder. Data were subjected to meta-analysis using a random effects model to examine the effect sizes of the pooled results. Bias assessment (Egger's test) and assessment of heterogeneity (I(2)) were also carried out.Results Thiobarbituric acidic reactive substances (TBARS) (p = 0.001) as well as NO activity (p = 0.02) were significantly increased in BD with a large effect size for TBARS and a moderate effect size for increase in NO. No significant effect sizes were observed for the antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase (all p>0.05).Limitations Some caution is warranted in interpreting these results: (1) Egger's test was positive for SOD, suggesting that SOD results may have been influenced by a publication bias. (2) We analyzed the absolute values of each antioxidant enzyme separately and the literature suggests that an imbalance between the antioxidant enzymes is a better indication of the presence of oxidative stress.Conclusions The present meta-analysis suggests that oxidative stress markers are increased in BD and that oxidative stress may play a role in the pathophysiology of BD.
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Gclm KO mice represent a valid animal model, as low brain GSH levels and genetic association with GCLM have been reported in schizophrenia.
“and represent a valid animal model, as low brain GSH levels (18,19) and genetic association with GCLM have been reported in schizophrenia (22).”
From Perineuronal nets protect fast-spiking interneurons against oxidative stress (2013) · cites this paper as [18]
Reduced antioxidant enzymes have been reported in patients with schizophrenia.
“Reduced antioxidant enzymes are reported in schizophrenic patients (4–8)”
From Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons (2015) · cites this paper as [5]
Incidence of bipolar disorder is between 1 and 3% of world's population with average age between 20 and 30 years.
“The incidence of bipolar disorder is between 1 and 3% of the world’s population with average age between 20 and 30 years.”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Andreazza et al. 2008
Bipolar disorder is characterized by extreme swings in mood with emotional highs and lows.
“Bipolar disorder (BD) or manic depression is a mental health disorder characterized by extreme swings in mood with emotional highs (mania or hypomania) and lows (depression) (Andreazza et al. 2008).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Andreazza et al. 2008
Increased oxidative damage occurs quite often in bipolar disorder.
“bipolar disorder (BD) [10–14]”
From Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches (2016) · cites this paper as [12]
Cites
Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence
Passos, J. F., Saretzki, G., Ahmed, S., Nelson, G., Richter, T., Peters, H., Wappler, I., Birket, M. J., Harold, G., Schaeuble, K., et al. (2007) · PLoS Biology · doi:10.1371/journal.pbio.0050110 · Cited by 796 · see citing works
Belmaker, R. H. (2004) · New England Journal of Medicine · doi:10.1056/nejmra035354 · Cited by 473 · see citing works
Lipid peroxidation and antioxidant enzyme levels in patients with schizophrenia and bipolar disorder
Kuloglu, M., Ustundag, B., Atmaca, M., Canatan, H., Tezcan, A. E., & Cinkilinc, N. (2002) · Cell Biochemistry and Function · doi:10.1002/cbf.940 · Cited by 321 · see citing works
Oxidative Parameters Differences during Non-Lethal and Lethal Sepsis Development1
Andrades, M., Ritter, C., Moreira, J. C. F., & Dal-Pizzol, F. (2005) · Journal of Surgical Research · doi:10.1016/j.jss.2004.11.008 · Cited by 86 · see citing works
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Is depression associated with increased oxidative stress? A systematic review and meta-analysis
Black, C. N., Bot, M., Scheffer, P. G., Cuijpers, P., & Penninx, B. W. J. H. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.025 · Cited by 711 · see citing works
Gawryluk, J. W., Wang, J.-F., Andreazza, A. C., Shao, L., & Young, L. T. (2011) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145710000805 · Cited by 594 · see citing works
Self-citationOxidative Stress and Psychological Disorders
Salim, S. (2014) · Current Neuropharmacology · doi:10.2174/1570159x11666131120230309 · Cited by 557 · see citing works
Perineuronal nets protect fast-spiking interneurons against oxidative stress
Cabungcal, J.-H., Steullet, P., Morishita, H., Kraftsik, R., Cuenod, M., Hensch, T. K., & Do, K. Q. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300454110 · Cited by 512 · see citing works
Dean, O., Giorlando, F., & Berk, M. (2011) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.100057 · Cited by 494 · see citing works
Rose, S., Melnyk, S., Pavliv, O., Bai, S., Nick, T. G., Frye, R. E., & James, S. J. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.61 · Cited by 480 · see citing works
Adibhatla, R. M., & Hatcher, J. F. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2668 · Cited by 480 · see citing works
Therapeutic potential of mood stabilizers lithium and valproic acid:Beyond bipolar disorder
Chiu, C.-T., Wang, Z., Hunsberger, J. G., & Chuang, D.-M. (2013) · Pharmacological Reviews · doi:10.1124/pr.111.005512 · Cited by 404 · see citing works
Kananen, L., Surakka, I., Pirkola, S., Suvisaari, J., Lönnqvist, J., Peltonen, L., Ripatti, S., & Hovatta, I. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010826 · Cited by 270 · see citing works
Cytokines in bipolar disorder: A systematic review and meta-analysis
Munkholm, K., Vinberg, M., & Vedel Kessing, L. (2013) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.06.010 · Cited by 256 · see citing works
The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders
Morris, G., & Berk, M. (2015) · BMC Medicine · doi:10.1186/s12916-015-0310-y · Cited by 245 · see citing works
Frey, B. N., Andreazza, A. C., Houenou, J., Jamain, S., Goldstein, B. I., Frye, M. A., Leboyer, M., Berk, M., Malhi, G. S., Lopez-Jaramillo, C., et al. (2013) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867413478217 · Cited by 234 · see citing works
Self-citationGigante, A. D., Bond, D. J., Lafer, B., Lam, R. W., Young, L. T., & Yatham, L. N. (2012) · Bipolar Disorders · doi:10.1111/j.1399-5618.2012.01033.x · Cited by 226 · see citing works
Self-citationAntioxidants as potential therapeutics for neuropsychiatric disorders
Pandya, C. D., Howell, K. R., & Pillai, A. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.10.017 · Cited by 222 · see citing works
Gałecki, P., Szemraj, J., Bieńkiewicz, M., Florkowski, A., & Gałecka, E. (2009) · Pharmacological Reports · doi:10.1016/s1734-1140(09)70084-2 · Cited by 214 · see citing works
Magnetic field effects in biology from the perspective of the radical pair mechanism
Zadeh-Haghighi, H., & Simon, C. (2022) · Journal of The Royal Society Interface · doi:10.1098/rsif.2022.0325 · Cited by 197 · see citing works
Berk, M., Dean, O. M., Cotton, S. M., Jeavons, S., Tanious, M., Kohlmann, K., Hewitt, K., Moss, K., Allwang, C., Schapkaitz, I., et al. (2014) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13m08454 · Cited by 172 · see citing works
Oxidative stress in early stage Bipolar Disorder and the association with response to lithium
de Sousa, R. T., Zarate, C. A., Zanetti, M. V., Costa, A. C., Talib, L. L., Gattaz, W. F., & Machado-Vieira, R. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.11.011 · Cited by 169 · see citing works
Ghezzo, A., Visconti, P., Abruzzo, P. M., Bolotta, A., Ferreri, C., Gobbi, G., Malisardi, G., Manfredini, S., Marini, M., Nanetti, L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066418 · Cited by 164 · see citing works
Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview
Dias, V. V., Balanzá‐Martinez, V., Soeiro‐de‐Souza, M. G., Moreno, R. A., Figueira, M. L., Machado‐Vieira, R., & Vieta, E. (2012) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2012.01910.x · Cited by 146 · see citing works
The role of mitochondria in mood disorders: from physiology to pathophysiology and to treatment
Giménez-Palomo, A., Dodd, S., Anmella, G., Carvalho, A. F., Scaini, G., Quevedo, J., Pacchiarotti, I., Vieta, E., & Berk, M. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.546801 · Cited by 140 · see citing works
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Kulak, A., Steullet, P., Cabungcal, J.-H., Werge, T., Ingason, A., Cuenod, M., & Do, K. Q. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4858 · Cited by 124 · see citing works
A systemic toxicity index developed to assess peripheral changes in mood episodes
Kapczinski, F., Dal-Pizzol, F., Teixeira, A. L., Magalhaes, P. V. S., Kauer-Sant'Anna, M., Klamt, F., de Bittencourt Pasquali, M. A., Quevedo, J., Gama, C. S., & Post, R. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.112 · Cited by 117 · see citing works
Self-citationSowa-Kućma, M., Styczeń, K., Siwek, M., Misztak, P., Nowak, R. J., Dudek, D., Rybakowski, J. K., Nowak, G., & Maes, M. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.024 · Cited by 104 · see citing works
Maes, M., Landucci Bonifacio, K., Morelli, N. R., Vargas, H. O., Barbosa, D. S., Carvalho, A. F., & Nunes, S. O. V. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1051-7 · Cited by 102 · see citing works
Balmus, I. M., Ciobica, A., Antioch, I., Dobrin, R., & Timofte, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3975101 · Cited by 103 · see citing works
“In this way, one of these aspects is oxidative stress status, which seems to be implicated in most of the different affective disorders, since it has been shown that increased oxidative damage occurs quite often in depression [7–9], anxiety [9, 10], bipolar disorder (BD) [10–14], panic disorder (PD) [15, 16], and also…”
BackgroundProlonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons
Morishita, H., Cabungcal, J.-H., Chen, Y., Do, K. Q., & Hensch, T. K. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.12.026 · Cited by 92 · see citing works
Differences in the immune-inflammatory profiles of unipolar and bipolar depression
Brunoni, A. R., Supasitthumrong, T., Teixeira, A. L., Vieira, E. L., Gattaz, W. F., Benseñor, I. M., Lotufo, P. A., Lafer, B., Berk, M., Carvalho, A. F., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2019.10.037 · Cited by 94 · see citing works
Kulak, A., Cuenod, M., & Do, K. Q. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.10.020 · Cited by 90 · see citing works
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Saxena, A., Scaini, G., Bavaresco, D. V., Leite, C., Valvassoria, S. S., Carvalho, A. F., & Quevedo, J. (2017) · Complex Psychiatry · doi:10.1159/000480349 · Cited by 85 · see citing works
Valvassori, S. S., Elias, G., de Souza, B., Petronilho, F., Dal-Pizzol, F., Kapczinski, F., Trzesniak, C., Tumas, V., Dursun, S., Nisihara Chagas, M. H., et al. (2011) · Journal of Psychopharmacology · doi:10.1177/0269881109106925 · Cited by 80 · see citing works
Neurotrophins, inflammation and oxidative stress as illness activity biomarkers in bipolar disorder
Pfaffenseller, B., Fries, G. R., Wollenhaupt-Aguiar, B., Colpo, G. D., Stertz, L., Panizzutti, B., Magalhães, P. V., & Kapczinski, F. (2013) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2013.811981 · Cited by 68 · see citing works
Self-citationCecerska-Heryć, E., Polikowska, A., Serwin, N., Roszak, M., Grygorcewicz, B., Heryć, R., Michalczyk, A., & Dołęgowska, B. (2022) · Neurochemistry International · doi:10.1016/j.neuint.2021.105269 · Cited by 68 · see citing works
Singh, L., Kaur, A., Bhatti, M. S., & Bhatti, R. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02805-5 · Cited by 55 · see citing works
Overdiagnosis of Bipolar Disorder: A Critical Analysis of the Literature
Ghouse, A. A., Sanches, M., Zunta-Soares, G., Swann, A. C., & Soares, J. C. (2013) · The Scientific World Journal · doi:10.1155/2013/297087 · Cited by 50 · see citing works
Diagnostic biomarkers for obsessive-compulsive disorder: A reasonable quest or ignis fatuus?
Fullana, M. A., Abramovitch, A., Via, E., López-Sola, C., Goldberg, X., Reina, N., Fortea, L., Solanes, A., Buckley, M. J., Ramella-Cravaro, V., et al. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.08.008 · Cited by 44 · see citing works
Beyond the therapeutic shackles of the monoamines: new mechanisms in bipolar disorder biology
Data-Franco, J., Singh, A., Popovic, D., Ashton, M., Berk, M., Vieta, E., Figueira, M. L., & Dean, O. M. (2017) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.09.004 · Cited by 38 · see citing works
Akarsu, S., Bolu, A., Aydemir, E., Zincir, S. B., Kurt, Y. G., Zincir, S., Erdem, M., & Uzun, Ö. (2018) · Psychiatry Investigation · doi:10.30773/pi.2016.12.31 · Cited by 35 · see citing works
Korkmaz, Ş. A., Kızgın, S., Oğuz, E. F., Neşelioğlu, S., & Erel, Ö. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.07.079 · Cited by 24 · see citing works
Slyepchenko, A., Brunoni, A. R., McIntyre, R. S., Quevedo, J., & Carvalho, A. F. (2016) · Current Molecular Medicine · doi:10.2174/1566524016666160126144601 · Cited by 14 · see citing works
Zelfand, E. (2020) · Integrative Medicine · Cited by 8 · see citing works
Mitochondrial Dysfunction in Bipolar Disorder: Lessons from Brain Imaging and Molecular Markers
Minuzzi, L., Behr, G. A., Moreira, J. C. F., & Frey, B. N. (2011) · Revista Colombiana de Psiquiatría · doi:10.1016/s0034-7450(14)60201-8 · Cited by 7 · see citing works
Self-citation
- Authors
- Andreazza, A. C., Kauer-Sant'Anna, M., Frey, B. N., Bond, D. J., Kapczinski, F., Young, L. T., & Yatham, L. N.
- Affiliations
- Universidade Federal do Rio Grande do Sul (BR)
- Montreal Neurological Institute and Hospital (CA)
- University of British Columbia (CA)
- Corresponding author
- Yatham, Lakshmi N.
- Venue
- Journal of Affective Disorders
- Publisher
- Elsevier BV
- Published
- 2008-12
- Volume
- 111
- Issue
- 2-3
- Pages
- 135-144
- ISSN
- 0165-0327 (ISSN-L)
- OpenAlex
- W2131671310
- Cited by
- 526
- References
- 4
- Citations by year
- 2026: 18 · 2025: 16 · 2024: 17 · 2023: 16 · 2022: 27 · 2021: 26 · 2020: 45 · 2019: 26 · 2018: 25 · 2017: 37 · 2016: 39 · 2015: 36 · 2014: 48 · 2013: 49 · 2012: 30
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Affective Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Health Canada
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- oxidative stress, bipolar disorder, lipid peroxidation, TBARS, nitric oxide, antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase, pathophysiology
- MeSH terms
- Antioxidants, Bipolar Disorder, Erythrocytes, Glutathione Peroxidase, Humans, Nitric Oxide, Superoxide Dismutase, Lipid Peroxidation, Biomarkers, Thiobarbituric Acid Reactive Substances, Oxidative Stress, Control Groups, Protein Carbonylation
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