Elevated level of DNA damage and impaired repair of oxidative DNA damage in patients with recurrent depressive disorder
Open accessAbstract
BACKGROUND: Depressive disorder (DD), including recurrent DD (rDD), is a severe psychological disease, which affects a large percentage of the world population. Although pathogenesis of the disease is not known, a growing body of evidence shows that inflammation together with oxidative stress may contribute to development of DD. Since reactive oxygen species produced during stress may damage DNA, we wanted to evaluate the extent of DNA damage and efficiency of DNA repair in patients with depression. MATERIAL AND METHODS: We measured and compared the extent of endogenous DNA damage--single- and double-strand breaks, alkali-labile sites, and oxidative damage of the pyrimidines and purines--in peripheral blood mononuclear cells isolated from rDD patients (n=40) and healthy controls (n=46) using comet assay. We also measured DNA damage evoked by hydrogen peroxide and monitored changes in DNA damage during repair incubation. RESULTS: We found an increased number DNA breaks, alkali-labile sites, and oxidative modification of DNA bases in the patients compared to the controls. Exposure to hydrogen peroxide evoked the same increased damage in both groups. Examination of the repair kinetics of both groups revealed that the lesions were more efficiently repaired in the controls than in the patients. CONCLUSIONS: For the first time we showed that patients with depression, compared with non-depresses individuals, had more DNA breaks, alkali-labile sites, and oxidative DNA damage, and that those lesions may be accumulated by impairments of the DNA repair systems. More studies must be conducted to elucidate the role of DNA damage and repair in depression.
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Higher oxidative stress, lower antioxidants, and more oxidative stress-related DNA/RNA damage are linked to clinical markers of major depressive disorder progression such as greater chronicity, more episodes, and treatment resistance.
“greater oxidative stress, lower antioxidant, and greater oxidative stress-related DNA/RNA damage have been linked to clinical markers of MDD illness progression, including greater chronicity, more MDEs, and treatment resistance (98,108–113).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [109]
Oxidative stress after mTBI can lead to widespread DNA damage.
“This can lead to widespread DNA damage [28].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [28]
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“In the ETC, complexes donate electrons to oxygen producing radicals like superoxide and peroxidases, and high levels of such radicals and oxidative stress cause damage to lipids, enhance DNA breaks, and oxidize nuclear and mtDNA (Tobe, 2013; Czarny et al., 2015).”
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“Similarly, another study reported higher number of single and double-stranded breaks in DNA along with oxidative damage with reduced DNA repair activity in patients with depressive disorder (Czarny et al. 2015b).”
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“ence of not only oxidatively modified purines and pyrimidines but also other types of DNA damage, like DNA strand breaks [16].”
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“This can lead to widespread DNA damage [28].”
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Czarny, P. L., Kwiatkowski, D., Gałecki, P., Talarowska, M. E., Orzechowska, A., Bobińska, K., Bielecka-Kowalska, A., Szemraj, J., Maes, M. H. J., Su, K., et al. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.05.044 · Cited by 36 · see citing works
“We also revealed that the patients repaired oxidative DNA damage in less efficient way than the controls, which may indicate impairments of BER pathway (Czarny et al., 2015).”
BackgroundResultInfluentialSelf-citationCeylan, D., Yılmaz, S., Tuna, G., Kant, M., Er, A., Ildız, A., Verim, B., Akış, M., Akan, P., Islekel, H., et al. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104600 · Cited by 33 · see citing works
Oxidatively-induced DNA damage and base excision repair in euthymic patients with bipolar disorder
Ceylan, D., Tuna, G., Kırkalı, G., Tunca, Z., Can, G., Arat, H. E., Kant, M., Dizdaroğlu, M., & Özerdem, A. (2018) · DNA repair · doi:10.1016/j.dnarep.2018.03.006 · Cited by 32 · see citing works
The compensatory antioxidant response system with a focus on neuroprogressive disorders
Morris, G., Puri, B. K., Walker, A. J., Berk, M., Walder, K. R., Bortolasci, C. C., Marx, W., Carvalho, A. F., & Maes, M. H. J. (2019) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109708 · Cited by 31 · see citing works
Czarny, P. L., Białek, K. I., Ziółkowska, S., Strycharz, J., & Śliwiński, T. (2019) · Mutagenesis · doi:10.1093/mutage/gez035 · Cited by 30 · see citing works
Self-citationNLRs as Helpline in the Brain: Mechanisms and Therapeutic Implications
Singh, S., & Jha, S. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-0957-4 · Cited by 29 · see citing works
An altered peripheral IL6 response in major depressive disorder
Money, K. M., Galik-Olah, Z., Korade, Ž., Garbett, K. A., Shelton, R. C., & Mirnics, K. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.01.015 · Cited by 27 · see citing works
Moreno‐Villanueva, M., von Scheven, G., Feiveson, A. H., Bürkle, A., Wu, H., & Goel, N. (2018) · SLEEP · doi:10.1093/sleep/zsy067 · Cited by 28 · see citing works
“Clinical studies have also demonstrated that some psychiatric disorders are associated with DNA damage [27]; for example, patients with recurrent depression had more single and double strand DNA breaks and impaired DNA repair compared with healthy controls [28].”
BackgroundHe, Z., Wang, W., Hu, W., Yang, L., Li, Y., Zhang, W., Yang, Y.-S., Liu, S., Zhang, F., Mei, R., et al. (2016) · Scientific Reports · doi:10.1038/srep34558 · Cited by 27 · see citing works
“Furthermore, oxidative DNA/RNA damage increases in peripheral blood of depressive patients 9,10 .”
RetractedCzarny, P. L., Kwiatkowski, D., Toma, M. M., Gałecki, P., Orzechowska, A., Bobińska, K., Bielecka-Kowalska, A., Szemraj, J., Berk, M., Anderson, G., et al. (2016) · Medical Science Monitor · doi:10.12659/msm.898091 · Cited by 27 · see citing works
“In a previous study, we showed that PBMCs of rDD patients’ cells repaired DNA damage induced by hydrogen peroxide (H2O2) less efficiently than in control patients’ cells [15].”
BackgroundResultSelf-citationOrtmann, C. F., Abelaira, H. M., Réus, G. Z., Ignácio, Z. M., Chaves, V. C., dos Santos, T. C., de Carvalho, P., Carlessi, A. S., Bruchchen, L., Danielski, L. G., et al. (2017) · Biomedical Chromatography · doi:10.1002/bmc.3982 · Cited by 24 · see citing works
Barańska, A., Pawlos, A., Mokra, K., & Michałowicz, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.869741 · Cited by 23 · see citing works
“Based on literature data (45) we decided to use 1 U of each enzyme per gel, which guaranteed their use in excess.”
MethodCell Model of Depression: Reduction of Cell Stress with Mirtazapine
Correia, A. S., Fraga, S., Teixeira, J. P., & Vale, N. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094942 · Cited by 20 · see citing works
Vieira, É. L. M., Mendes‐Silva, A. P., Ferreira, J. D. R., Bertola, L., Barroso, L., Vieira, M., Teixeira, A. L., & Diniz, B. S. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.09.084 · Cited by 19 · see citing works
Bielecka-Kowalska, A., Czarny, P. L., Wigner, P., Synowiec, E., Bielecki-Kowalski, B., Szwed, M., Krupa, R., Toma, M. M., Drzewiecka, M., Majsterek, I., et al. (2017) · Toxicology in Vitro · doi:10.1016/j.tiv.2017.10.028 · Cited by 18 · see citing works
“9 The level of DNA damage induced by either EGDMA or DEGDMA in HGFs was estimated using an alkaline version of the comet assay as described previously, with later modifications [14-17].”
MethodSelf-citationThe role of base excision repair in major depressive disorder and bipolar disorder
Küçüker, M. U., Özerdem, A., Ceylan, D., Cabello-Arreola, A., Ho, A. M., Joseph, B., Webb, L. M., Croarkin, P. E., Frye, M. A., & Veldić, M. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.03.033 · Cited by 18 · see citing works
Introducing the Role of Genotoxicity in Neurodegenerative Diseases and Neuropsychiatric Disorders
Kisby, G. E., Wilson, D. M., & Spencer, P. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137221 · Cited by 16 · see citing works
“Czarny and colleagues have reported that DNA repair of oxidative DNA damage in peripheral blood mononuclear cells of subjects with depressive disorder is reduced in comparison to samples from control subjects [190,191].”
ResultImproving Activity of Lycium Barbarum. Polysaccharide on Depressive Mice Induced by Reserpine.
Zhao, R., Master, B. Q., Master, B. M., & Cai, Y. (2019) · PubMed Central · doi:10.22037/ijpr.2019.1100763 · Cited by 12 · see citing works
Genotoxic and oxidative effect of duloxetine on mouse brain and liver tissues
Álvarez‐González, I., Camacho-Cantera, S., Gómez-González, P., Rendón-Barrón, M. J., Morales‐González, J. A., Madrigal‐Santillán, E., Paniagua‐Pérez, R., & Madrigal‐Bujaidar, E. (2021) · Scientific Reports · doi:10.1038/s41598-021-86366-0 · Cited by 12 · see citing works
Czarny, P. L., Ziółkowska, S., Kołodziej, Ł., Watała, C. W., Wigner, P., Bliźniewska-Kowalska, K. M., Wachowska, K., Gałecka, M., Synowiec, E., Gałecki, P., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914752 · Cited by 11 · see citing works
“Our research team was one of the first to show that the elevated DNA damage observed in depression is not only the result of increased oxidative stress, but also impairments in nuclear DNA (nDNA) damage repair [18,19].”
Self-citationFreitas, R. D. S., & da Silva, J. (2025) · Nutrition · doi:10.1016/j.nut.2025.112800 · Cited by 11 · see citing works
Czarny, P. L., Wigner, P., Strycharz, J., Watała, C. W., Świderska, E., Synowiec, E., Gałecki, P., Talarowska, M. E., Szemraj, J., Su, K., et al. (2018) · PeerJ · doi:10.7717/peerj.5116 · Cited by 11 · see citing works
Self-citationAssessment of type 1 and type 3 deiodinase expression levels in depressive disorders
Gałecka, E., Kumor‐Kisielewska, A., Orzechowska, A., Maes, M. H. J., Górski, P., & Szemraj, J. (2017) · Acta Neurobiologiae Experimentalis · doi:10.21307/ane-2017-056 · Cited by 9 · see citing works
“Oxidative stress, which is also characteristically observed in depression (Czarny et al. 2015), is an important factor that may affect and re‐ duce DIO1 levels.”
BackgroundSantos¹, L. F. D. S., Behrens, L. M. P., Barbosa, C. P., Ribeiro, C. T., da Rosa, H. T., Somensi, N., Brum, P. O., Silveira, A. K., Rodrigues, M. S., de Oliveira, J., et al. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-03912-3 · Cited by 8 · see citing works
“Evidence supports that microglial reactivity increases oxidative stress and may play a pivotal role in the pathogenesis of MDD [65–67].”
Lorenzo, E. C., Figueroa, J. E., Demirci, D. A., El-Tayyeb, F., Huggins, B., Illindala, M., Bartley, J. M., Haynes, L., & Diniz, B. S. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1376086 · Cited by 7 · see citing works
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DNA damage and repair mechanisms in bipolar disorder
Özerdem, A., & Ceylan, D. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821398-8.00005-9 · Cited by 7 · see citing works
Panwar, R., Sivakumar, M., Menon, V., & Vairappan, B. (2020) · Anatomy & Cell Biology · doi:10.5115/acb.19.217 · Cited by 5 · see citing works
“Czarny [11] estimated elevated levels of breakage in DNA strands, alkali-labile sites and oxidative DNA damage in the recurrent depressive disorder patients the help of comet assay method.”
BackgroundMethodInfluentialMa, W., Chu, S., Ma, Y., Wang, S., & Ma, X. (2025) · Current Neuropharmacology · doi:10.2174/011570159x386374250623095520 · Cited by 4 · see citing works
“It is widely known that patients with depression have more DNA breaks and oxidative DNA damage, which may be caused by impairments of the DNA repair systems [129, 130].”
Premature aging in serious mental illness
Diniz, B. S., Fries, G. R., Kuo, C.-L., Xu, M., & Lenze, E. J. (2026) · Neuropsychopharmacology · doi:10.1038/s41386-026-02322-4 · Cited by 4 · see citing works
PARP1 and OGG1 in Medicated Patients With Depression and the Response to ECT
Ryan, K. M., & McLoughlin, D. M. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac078 · Cited by 4 · see citing works
“Polymorphisms in OGG1 that can modulate the risk for depression have been noted (Czarny et al., 2015b).”
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Potential Involvement of Mitochondrial Dysfunction in Major Depressive Disorder: Recent Evidence
Kambe, Y. (2015) · Archives of Depression and Anxiety · doi:10.17352/2455-5460.000004 · Cited by 4 · see citing works
“DNA oxidation is increased in urine [51], mononuclear cells [52] and leukocytes (Especially in mtDNA) [53].”
BackgroundMitochondrial dysfunction and affective disorders: Focus on diet, exercise, and aging
Allen, J., Kalynchuk, L. E., & Caruncho, H. J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85666-9.00017-6 · Cited by 3 · see citing works
Retinal microvascular abnormalities in major depression
Sadykov, E., Hosák, L., Stěpanov, A., Zapletalová, J., & Studnička, J. (2023) · Biomedical Papers · doi:10.5507/bp.2023.026 · Cited by 2 · see citing works
THE ROLE OF OXIDATIVE STRESS IN THE ETIOPATHOGENESIS OF DEPRESSION
Komsiyska, D., & Petkov, Y. (2019) · Trakia Journal of Sciences · doi:10.15547/tjs.2019.01.013 · Cited by 2 · see citing works
“oxidative stress of lymphocytes are clearly demonstrated in depression (53, 54).”
BackgroundComet Parameters and Plasma 8-Iso-Prostaglandins F2α
Panwar, R., & Sivakumar, M. (2021) · National Journal of Clinical Anatomy · doi:10.4103/njca.njca_44_21 · Cited by 2 · see citing works
Mohammadi, Y., Kooshkaki, O., Esmaeili, A., Sarab, H. A., & Sarab, G. A. (2026) · Immunity Inflammation and Disease · doi:10.1002/iid3.70477 · Cited by 1 · see citing works
Genotoxicity of psychotropic drugs in experimental and clinical studies
Durnev, A. D., Eremina, N. V., Жанатаев, А. К., & Колик, Л. Г. (2022) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro20221221017 · Cited by 1 · see citing works
Metabolomics-based alleviation of depression by Xiaoyaosan through regulation of XDH and GRIA2
Lei, C., Liu, Y., Ma, Q., Chen, Z., Kong, Q., Jia, Y., Wang, X., Li, X., Xue, Z., & Chen, J. (2023) · Pharmacological Research - Modern Chinese Medicine · doi:10.1016/j.prmcm.2023.100284 · Cited by 1 · see citing works
Yeşiloğlu, B., Gör, C., Babalioglu, R. N., Şenol, Ş. H., Frye, M. A., Jørgensen, A., Özerdem, A., & Ceylan, D. (2025) · medRxiv · doi:10.1101/2025.05.20.25327903 · Cited by 1 · see citing works
“9 out of 15 studies were excluded due to being reviews or meta-analyses, 2 were not a follow-up study [31, 32], 3 had the wrong patient population [33-35], and 1 didn't measure 8-OHdG levels [36].”
Pergolizzi, J. V., Tabor, A., LeQuang, J. A., Annabi, M., & Annabi, H. M. (2019) · OBM Integrative and Complementary Medicine · doi:10.21926/obm.icm.1904062
Analysis of Genotoxic Damage in Different Diseases
GÖNEY, G., & Halisdemir, N. (2021) · Journal of General Health Sciences (JGEHES) Necmettin Erbakan University · doi:10.51123/jgehes.2021.23
“, 2017), and psychiatric diseases (Andreazza et al., 2007; Czarny et al., 2015).”
BackgroundOxygen - Mitochondrial fuel as a missing link in depressive pathophysiologyPreprint
Mavioğlu, R. N., Mack, M., Behnke, A., & Kolassa, I. (2021) · doi:10.31234/osf.io/m5t3h
(2018) · PeerJ · doi:10.7287/peerj.5116v0.2/reviews/1
“…found that the presence of single-nucleotide 59 polymorphisms (SNPs) encoding proteins involved in base excision repair (BER), a primary 60 pathway used to ameliorate oxidative DNA damage, also appear to affect the occurrence and 61 onset of depression (Czarny et al., 2015b; Czarny et al., 2016).”
BackgroundMethodGenotoxicity of Psychotropic Drugs in Experimental and Clinical Studies
Дурнев, А. Д., Eremina, N. V., Жанатаев, А. К., & Колик, Л. Г. (2023) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-023-01469-7
Behnke, A., Rappel, M., Ramo‐Fernández, L., Mavioğlu, R. N., Weber, B., Neuner, F., Bisle, E., Mack, M., Radermacher, P., Witt, S. H., et al. (2025) · medRxiv · doi:10.1101/2025.01.29.25321066
- Authors
- Śliwiński, T.
- Affiliations
- University of Łódź (PL)
- Corresponding author
- Śliwiński, Tomasz
- ORCID
- Śliwiński, Tomasz
- Venue
- Medical Science Monitor
- Published
- 2015
- Volume
- 21
- Pages
- 412-418
- ISSN
- 1234-1010 (ISSN-L)
- 1643-3750
- PMC
- PMC4329942
- OpenAlex
- W1992949421
- Cited by
- 78
- References
- 38
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 7 · 2022: 9 · 2021: 7 · 2020: 4 · 2019: 8 · 2018: 18 · 2017: 7 · 2016: 6 · 2015: 3
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Medical Science Monitor (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Lodz Repository (University of Łódź) (submittedVersion, cc-by)
- Funders
- Uniwersytet Medyczny w Lodzi (2011/01/D/HS6/05484, 2012/05/B/NZ5/01452)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- recurrent depression, DNA damage, DNA repair, oxidative DNA damage, oxidative stress, inflammation, single-strand breaks, DNA double-strand breaks, alkali-labile sites, hydrogen peroxide, peripheral blood mononuclear cells, comet assay
- MeSH terms
- Adult, Depressive Disorder, DNA Damage, DNA Repair, Humans, Hydrogen Peroxide, Leukocytes, Mononuclear, Middle Aged, Oxidation-Reduction, Poland, Recurrence, Statistics, Nonparametric, Comet Assay
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