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Cited by 206Treatment of Major DepressionTryptophan and brain disordersAntioxidant Activity and Oxidative Stress

Preclinical and Clinical Evidence of Antioxidant Effects of Antidepressant Agents: Implications for the Pathophysiology of Major Depressive Disorder

Open access
Behr, Guilherme A., Moreira, José C. F., Frey, Benicio N.·2012·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2012/609421PMC PMC3368202
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Abstract

Major depressive disorder (MDD) is a common mental disorder associated with a significant negative impact on quality of life, morbidity/mortality, and cognitive function. Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials and reduced brain GSH levels. Also, F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms. Urinary excretion of 8-OHdG seems to be higher in patients with MDD compared to healthy controls. Despite the fact that antidepressant drugs have been used for more than 50 years, their mechanism of action is still not fully understood. This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD. Substantial data support that MDD seems to be accompanied by elevated levels of oxidative stress and that antidepressant treatments may reduce oxidative stress. These studies suggest that augmentation of antioxidant defences may be one of the mechanisms underlying the neuroprotective effects of antidepressants in the treatment of MDD.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes preclinical and clinical evidence that major depressive disorder (MDD) is accompanied by elevated oxidative stress and that antidepressant treatment, especially longer-term, may reduce oxidative stress and augment antioxidant defences. It suggests that augmentation of antioxidant defences may be one mechanism underlying the neuroprotective effects of antidepressants in MDD.

Key findings

  • MDD has been associated with lower serum/plasmatic total antioxidant potentials, reduced brain GSH levels, lower plasma coenzyme Q10, increased serum xanthine oxidase, increased F2-isoprostanes correlated with depressive symptom severity, and higher urinary 8-OHdG versus healthy controls.
  • In vitro and animal studies mostly support antioxidant-related effects of antidepressants, but some show prooxidant effects at high doses, particularly fluoxetine in rat liver; for example, chronic fluoxetine increased liver TBARS, carbonyl groups, and uric acid, with effects more pronounced at 24 versus 8 mg/kg.
  • Clinical studies suggest treatment duration matters: short-term treatments (4 to 8 weeks) do not seem to alter antioxidant/oxidative parameters, whereas longer treatments (12 to 24 weeks) seem to induce robust antioxidant effects.
  • Specific clinical findings include restoration of plasmatic GPx and MDA after 12 weeks of SSRIs in 32 MDD patients; in 57 MDD patients, TOS and OSI were higher and TAC lower, with severity correlations of r = 0.58, r = 0.63, and r = −0.553, and after 3 months of treatment TOS/OSI decreased and TAC increased.

Methods

  • Narrative review of preclinical (in vitro and animal model), post-mortem, and clinical literature on oxidative/antioxidant effects associated with antidepressant agents in MDD.
  • Data include studies summarized in tables, with human cohorts ranging from small samples to 96 MDD patients and treatment durations from 4 to 24 weeks.
  • Main analysis is qualitative synthesis of reported oxidative stress markers, antioxidant enzymes, and treatment effects; no systematic search strategy or meta-analysis is described.

Limitations

  • The paper states that post-mortem studies are not conclusive mostly because of small sample sizes, lack of control groups, and lack of relevant information such as treatment duration and specific drugs used.
  • The paper states that many clinical studies were short in duration and likely underpowered to address differences in antioxidant potential among particular drugs, and that larger studies are warranted.
  • The paper notes that peripheral markers may not necessarily correlate with central nervous system changes, citing Teyssier et al. (2011), who found oxidative stress-response genes were not altered in the prefrontal cortex of individuals with MDD, although all patients had received antidepressant treatment. Evident from the text: the review is narrative and heterogeneous across drugs, doses, tissues, and outcome markers, limiting direct comparability.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1155/2012/609421

Cites

69 of 69 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 112 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Increased serum xanthine oxidase (XO) levels are observed in MDD subjects.

    “increased serum XO levels observed in MDD subjects suggest increased systemic ROS production [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Herken H Gurel A Selek S Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment Archives of Medical Research 2007 38 2 247 252 17227736 source

      Not checked in the free run.

  • Premisecitation

    Increased XO activity is found in the thalamus and putamen of patients with recurrent MDD.

    “A recent post-mortem study found increased XO activity in the thalamus and putamen patients with recurrent MDD [35].”
    • Also stated in: § 4.3. Post-Mortem Studies · plain
      “Michel et al. (2010) showed increased XO activity in the thalamus and putamen of seven individuals with an ante-mortem diagnosis of recurrent MDD (age range = 61–93 y.o.).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Michel TM Camara S Tatschner T Increased xanthine oxidase in the thalamus and putamen in depression World Journal of Biological Psychiatry 2010 11 2 314 320 20218795 source

      Not checked in the free run.

  • Premisecitation

    Plasmatic coenzyme Q10 (CoQ10) is significantly lower in major depressive patients.

    “Plasmatic coenzyme Q10 (CoQ10), a strong antioxidant and a key molecule in the mitochondrial electron transport chain, is significantly lower in major depressive patients [34]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Maes M Mihaylova I Kubera M Uytterhoeven M Vrydags N Bosmans E Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness Neuroendocrinology Letters 2009 30 4 462 469 20010493

      Not checked in the free run.

  • Premisecitation

    Urinary excretion of 8-OHdG is higher in patients with MDD than in healthy controls.

    “urinary excretion of 8-OHdG, a marker of oxidative damage to DNA, was found to be higher in patients with MDD than healthy controls [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Maes M Mihaylova I Kubera M Uytterhoeven M Vrydags N Bosmans E Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome Neuroendocrinology Letters 2009 30 6 715 722 20035260

      Not checked in the free run.

  • Premisecitation

    Individuals with MDD display lower serum/plasmatic total antioxidant potentials than matched controls.

    “Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials [28, 32, 48] and reduced brain GSH levels [31] as compared to matched controls.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [28] Sarandol A Sarandol E Eker SS Erdinc S Vatansever E Kirli S Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems Human Psychopharmacology 2007 22 2 67 73 17299810 source

      Not checked in the free run.

    • cites [32] Cumurcu BE Ozyurt H Etikan I Demir S Karlidag R Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment Psychiatry and Clinical Neurosciences 2009 63 5 639 645 19674383 source

      Not checked in the free run.

    • cites [48] Gałecki P Szemraj J Bieńkiewicz M Florkowski A Gałecka E Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment Pharmacological Reports 2009 61 3 436 447 19605942 source

      Not checked in the free run.

  • May combine two claims. 24
  • Classified as probably not a substantial claim. 2
  • The quote only partly states this claim. 2

  • May combine two claims.

    Premisecitation

    The pathophysiology of depression is multifactorial and includes increased oxidative stress.

    “The pathophysiology of depression is multifactorial and includes changes in brain monoaminergic transmission (e.g., 5-HT, NE, DA), abnormalities in neurotransmitter receptors function (e.g., AC-cAMP pathway), reduced neurotrophic factors (e.g., BDNF), dysregulation of HPA axis (cortisol), increased proinflammatory cytokines (e.g., IL-6, TNF-α, NF-κB), increased NO (e.g., L-arginine-NO-cGMP pathway”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [45] Coyle JT Puttfarcken P Oxidative stress, glutamate, and neurodegenerative disorders Science 1993 262 5134 689 695 7901908 source

      Not checked in the free run.

    • cites [46] Gardner A Boles RG Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 3 730 743 20691744 source

      Not checked in the free run.

    • cites [47] Chopra K Kumar B Kuhad A Pathobiological targets of depression Expert Opinion on Therapeutic Targets 2011 15 4 379 400 21254923 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    F2-isoprostanes circulatory levels are increased in MDD subjects and are correlated with the severity of depressive symptoms.

    “Dimopoulos et al. (2008) have found that F2-isoprostanes (F2-iso) circulatory levels were increased in major depressive patients and were significantly correlated with the severity of depressive symptoms [50].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [50] Dimopoulos N Piperi C Psarra V Lea RW Kalofoutis A Increased plasma levels of 8-iso-PGF2α and IL-6 in an elderly population with depression Psychiatry Research 2008 161 1 59 66 18783834 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Imipramine treatment may induce changes in substrate oxidation pattern, increase rate of ATP synthesis, and can potentially increase mitochondrial ROS production.

    “These results suggest that imipramine treatment may induce changes in substrate oxidation pattern, increase rate of ATP synthesis, and can potentially increase mitochondrial ROS production.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [20] Katyare SS Rajan RR Effect of long-term in vivo treatment with imipramine on the oxidative energy metabolism in rat brain mitochondria Comparative Biochemistry and Physiology Part C 1995 112 3 353 357 8838689

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High dose (10 mg/kg) of venlafaxine decreases BDNF immunostaining in all subareas of the hippocampus and increases Cu/Zn-SOD immunostaining in the dentate granular cell layer.

    “High dose (10 mg/kg) of venlafaxine, however, decreased the intensity of BDNF immunostaining in all subareas of the hippocampus and increased the intensity of Cu/Zn-SOD immunostaining in the dentate granular cell layer [21].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Xu H Steven Richardson J Li XM Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus Neuropsychopharmacology 2003 28 1 53 62 12496940 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Fluoxetine may be potentially hepatotoxic at high doses.

    “Souza et al. (1994) reported that fluoxetine may be potentially hepatotoxic at high doses [7].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [7] Souza MEJ Polizello ACM Uyemura SA Castro-Silva O Curti C Effect of fluoxetine on rat liver mitochondria Biochemical Pharmacology 1994 48 3 535 541 8068040 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Low dose (5 mg/kg) of amitriptyline and venlafaxine increases BDNF immunostaining in hippocampal pyramidal neurons and Bcl-2 immunostaining in hippocampal mossy fibers, but does not alter Cu/Zn-SOD immunoreactivity.

    “low dose (5 mg/kg) of amitriptyline and venlafaxine increased the intensity of BDNF immunostaining in hippocampal pyramidal neurons and the intensity of Bcl-2 immunostaining in hippocampal mossy fibers, but did not alter the Cu/Zn-SOD immunoreactivity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Xu H Steven Richardson J Li XM Dose-related effects of chronic antidepressants on neuroprotective proteins BDNF, Bcl-2 and Cu/Zn-SOD in rat hippocampus Neuropsychopharmacology 2003 28 1 53 62 12496940 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Venlafaxine decreases MDA and total nitrite levels, increases total antioxidant potential and GSH content, and restores GST activity in hippocampus of stressed animals.

    “At all doses tested, venlafaxine decreased MDA and total nitrite levels, increased total antioxidant potential and GSH content, and restored GST activity in hippocampus of stressed animals.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Abdel-Wahab BA Salama RH Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice Pharmacology Biochemistry and Behavior 2011 100 1 59 65 21835191 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Fluoxetine inhibits the opening of the mitochondrial permeability transition (MPT) pore, the release of cytochrome c, and protects against staurosporine-induced apoptotic cell death.

    “Nahon et al. (2005) demonstrated that fluoxetine was able to inhibit the opening of the mitochondrial permeability transition (MPT) pore, the release of cytochrome c (cytC) and protected against staurosporine-induced apoptotic cell death [8].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Nahon E Israelson A Abu-Hamad S Shoshan-Barmatz V Fluoxetine (Prozac) interaction with the mitochondrial voltage-dependent anion channel and protection against apoptotic cell death FEBS Letters 2005 579 22 5105 5110 16139271 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Venlafaxine increases total antioxidant potential and GSH levels in the control, nonstressed group.

    “Venlafaxine also promoted increased total antioxidant potential and GSH levels in the control, nonstressed group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Abdel-Wahab BA Salama RH Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice Pharmacology Biochemistry and Behavior 2011 100 1 59 65 21835191 source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    In control and stressed animals, fluoxetine treatment decreases SOD activity and increases GPx activity.

    “Control animals and stressed animals displayed decreased activity of SOD and increased activity of GPx.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Djordjevic J Djordjevic A Adzic M Elaković I Matić G Radojcic MB Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver European Journal of Pharmacology 2011 659 1 61 66 21414309 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    After 21 days of fluoxetine treatment, male rat liver displays altered antioxidant status and increased apoptotic signalling.

    “Djordjevic et al. (2011) showed altered antioxidant status and increased apoptotic signalling in male rat liver after 21 days of fluoxetine treatment.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Djordjevic J Djordjevic A Adzic M Elaković I Matić G Radojcic MB Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver European Journal of Pharmacology 2011 659 1 61 66 21414309 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Imipramine treatment increases brain creatine kinase and increases activity of mitochondrial respiratory chain complexes.

    “Additionally, imipramine treatment increased brain creatine kinase and increased activity of mitochondrial respiratory chain complexes [18, 53].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [18] Reus GZ Stringari RB Gonçalves CL Administration of harmine and imipramine alters creatine kinase and mitochondrial respiratory chain activities in the rat brain Depression Research and Treatment 2012 2012 7 pages Article ID 987397. PMC3182396 21969912

      Not checked in the free run.

    • cites [53] Reus GZ Stringari RB Rezin GT Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain Journal of Neural Transmission 2012 119 4 481 491 21953515 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ebselen decreases immobility time in rodents, an effect dependent on its interaction with the noradrenergic and dopaminergic systems.

    “Ebselen (2-phenyl-1,2-benzisoselenazol-3[2H]-one), a substance that mimics the activity of the antioxidant enzyme GPx [56], decreased immobility time in rodents, an effect that was dependent on its interaction with the noradrenergic and dopaminergic systems [57].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Posser T Kaster MP Baraúna SC Rocha JBT Rodrigues ALS Leal RB Antidepressant-like effect of the organoselenium compound ebselen in mice: evidence for the involvement of the monoaminergic system European Journal of Pharmacology 2009 602 1 85 91 19026628 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rats displaying depressive-like behaviour induced by chronic mild stress, administration of liquiritin decreases immobility time, increases sucrose consumption, increases SOD activity, and attenuates MDA production in the peripheral blood.

    “In rats displaying depressive-like behaviour induced by chronic mild stress, administration of liquiritin, an antioxidant derived from Glycyrrhiza uralensis, decreased immobility time, increased sucrose consumption, increased SOD activity, and attenuated MDA production in the peripheral blood [55].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Zhao Z Wang W Guo H Zhou D Antidepressant-like effect of liquiritin from Glycyrrhiza uralensis in chronic variable stress induced depression model rats Behavioural Brain Research 2008 194 1 108 113 18655806 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    GST levels are reduced in MDD patients and no effects of antidepressant treatment were observed.

    “In a subsequent study with the same cohort, GST levels were also reduced in MDD patients and no effects of antidepressant treatment were observed [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Gawryluk JW Wang JF Andreazza AC Shao L Yatham LN Young LT Prefrontal cortex glutathione S-transferase levels in patients with bipolar disorder, major depression and schizophrenia The International Journal of Neuropsychopharmacology 2011 14 8 1069 1074 21733244 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    A major limitation of the animal studies is that not all studies measured oxidative stress markers; therefore, prooxidant effects need further investigation.

    “However, a major limitation of the studies above mentioned is that not all studies measured oxidative stress markers (i.e., MDA, carbonyl); therefore, these prooxidant effects need further investigation.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    No differences in locomotor activity were observed with Ginkgo biloba extract, suggesting a selective antidepressant-like effect.

    “No differences in locomotor activity were observed, suggesting a selective antidepressant-like effect.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Rojas P Serrano-García N Medina-Campos ON Pedraza-Chaverri J Ögren SO Rojas C Antidepressant-like effect of a Ginkgo biloba extract (EGb761) in the mouse forced swimming test: role of oxidative stress Neurochemistry International 2011 59 5 628 638 21672588 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a 24-week follow-up study, plasmatic MDA, serum OxLDL levels, and erythrocyte SOD activity were increased in MDD patients before treatment.

    “Plasmatic MDA, serum oxidized LDL (OxLDL) levels, and erythrocyte SOD activity were increased in MDD patients before treatment”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Kotan VO Sarandol E Kirhan E Ozkaya G Kirli S Effects of long-term antidepressant treatment on oxidative status in major depressive disorder: a 24-week follow-up study Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 5 1284 1290 21515329 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    BDNF, oxidative stress, and inflammation tend to be abnormal among individuals with multiple mood episodes and correlate with length of illness.

    “there is also evidence suggesting that BDNF, oxidative stress, and inflammation tend to be abnormal among individuals with multiple mood episodes and correlate with length of illness [51, 66, 67].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [51] Praticò D Rokach J Lawson J FitzGerald GA F2-isoprostanes as indices of lipid peroxidation in inflammatory diseases Chemistry and Physics of Lipids 2004 128 1-2 165 171 15037161 source

      Not checked in the free run.

    • cites [66] Frey BN Zunta-Soares GB Caetano SC Illness duration and total brain gray matter in bipolar disorder: evidence for neurodegeneration? European Neuropsychopharmacology 2008 18 10 717 722 18554875 source

      Not checked in the free run.

    • cites [67] Minuzzi L Behr GA Moreira JCF Frey BN Mitochondrial dysfunction in bipolar disorder: lessons from brain imaging and molecular markers Revista Colombiana de Psiquiatría 2011 40 166 182 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxidative (and nitrosative) stress may cause neurodegeneration and reduced neurogenesis.

    “Considering that the presence of oxidative (and nitrosative) stress may cause neurodegeneration and reduced neurogenesis [63, 64]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [63] Maes M Ruckoanich P Chang YS Mahanonda N Berk M Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 3 769 783 20561554 source

      Not checked in the free run.

    • cites [64] Maes M Galecki P Chang YS Berk M A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degenerative processes in that illness Progress in Neuro-Psychopharmacology and Biological Psychiatry 2011 35 3 676 692 20471444 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    In the post-mortem study by Teyssier et al., all patients had received antidepressant treatment, which may have normalized oxidative stress parameters.

    “However, in this post-mortem study all of the patients had received antidepressant treatment, which may have normalized oxidative stress parameters.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    SOD activity was increased in patients with MDD, and there was a positive correlation between the severity of depressive symptoms and SOD activity (r = 0.419).

    “Also, SOD activity was increased in patients with MDD, and there was a positive correlation between the severity of depressive symptoms and SOD activity (r = 0.419).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] Sarandol A Sarandol E Eker SS Erdinc S Vatansever E Kirli S Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems Human Psychopharmacology 2007 22 2 67 73 17299810 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    MDD patients had increased plasmatic MDA levels and increased susceptibility of red blood cells to oxidation.

    “In this study, MDD patients had increased plasmatic MDA levels and increased susceptibility of red blood cells (RBCs) to oxidation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Sarandol A Sarandol E Eker SS Erdinc S Vatansever E Kirli S Major depressive disorder is accompanied with oxidative stress: short-term antidepressant treatment does not alter oxidative—antioxidative systems Human Psychopharmacology 2007 22 2 67 73 17299810 source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    There was a positive correlation between the severity of the disease and serum TOS and OSI (r = 0.58, and r = 0.63, respectively) at the pretreatment stage.

    “Furthermore, the authors found a positive correlation between the severity of the disease and serum TOS and OSI (r = 0.58, and r = 0.63, resp.).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [32] Cumurcu BE Ozyurt H Etikan I Demir S Karlidag R Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment Psychiatry and Clinical Neurosciences 2009 63 5 639 645 19674383 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a group of 50 MDD patients who achieved remission after 3 months of fluoxetine, before treatment they displayed increased erythrocyte SOD and CAT activities, increased MDA levels, and decreased plasmatic TAS level.

    “Before treatment, MDD patients displayed increased erythrocyte SOD and CAT activities, increased MDA levels, and decreased plasmatic total antioxidant status (TAS) level.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Gałecki P Szemraj J Bieńkiewicz M Florkowski A Gałecka E Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment Pharmacological Reports 2009 61 3 436 447 19605942 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment with citalopram, fluoxetine, fluvoxamine, or sertraline for 8 weeks increased SOD activity and decreased XO levels in MDD patients.

    “Treatment with citalopram (20 mg/day, n = 10), fluoxetine (20 mg/day, n = 11), fluvoxamine (150 mg/day, n = 7), or sertraline (50 mg/day, n = 8) for 8 weeks increased SOD activity whereas decreased XO levels”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Herken H Gurel A Selek S Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment Archives of Medical Research 2007 38 2 247 252 17227736 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The pathogenic role of oxidative stress in the neurobiology of depression could not be inferred from alterations in the periphery.

    “They concluded that the pathogenic role of oxidative stress in the neurobiology of depression could not be inferred from alterations in the periphery [65].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [65] Teyssier JR Ragot S Chauvet-Gélinier JC Trojak B Bonin B Expression of oxidative stress-response genes is not activated in the prefrontal cortex of patients with depressive disorder Psychiatry Research 2011 186 2-3 244 247 20800905 source

      Not checked in the free run.

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  • The paper relies on this without support.

    Findings from animal models and in vitro studies about antidepressant antioxidant effects are relevant to human MDD treatment.

    “This paper examines preclinical (in vitro and animal model) and clinical literature on oxidative/antioxidant effects associated with antidepressant agents and discusses their potential antioxidant-related effects in the treatment of MDD.”

  • The paper relies on this without support.

    Peripheral markers of oxidative stress (serum/plasmatic) reflect central/brain oxidative stress in MDD.

    “Individuals who suffer with MDD display lower serum/plasmatic total antioxidant potentials [28, 32, 48] and reduced brain GSH levels [31] as compared to matched controls.”
2 of 2

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Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Sex counts exceed the stated cohort size

    Minor

    The stated female and male counts sum to 36, not 20. The four treatment-group counts later in the same cohort also sum to 36.

    Reported 20 · recomputed 36

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Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. 2005, Journal of Psychiatry and Neuroscience, 30, 196
  2. 2012, Depression Research and Treatment, 2012
  3. 1995, Comparative Biochemistry and Physiology Part C, 112, 353
  4. 2009, Neuroendocrinology Letters, 30, 462
  5. 2009, Neuroendocrinology Letters, 30, 715

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Authors
Behr, G. A., Moreira, J. C. F., & Frey, B. N.
Affiliations
  • Universidade Federal do Rio Grande do Sul (BR)
  • McMaster University (CA)
Corresponding author
Behr, Guilherme A.
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2012
Volume
2012
Pages
1-13
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2012/609421
PMC
PMC3368202
OpenAlex
W1977657096
Semantic Scholar
8844560d54d30597299b29b489c8ee918eb74996
Cited by
205
References
69
Citations by year
2026: 7 · 2025: 9 · 2024: 16 · 2023: 10 · 2022: 14 · 2021: 12 · 2020: 18 · 2019: 10 · 2018: 12 · 2017: 20 · 2016: 17 · 2015: 24 · 2014: 17 · 2013: 16 · 2012: 3
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BEX 5383/10-2)
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
major depressive disorder, antidepressants, antioxidant activity, oxidative stress, glutathione, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine, oxidative DNA damage, neuroprotection, antioxidant defense, antidepressant mechanism
MeSH terms
Animals, Antidepressive Agents, Antioxidants, Brain, Clinical Trials as Topic, Major Depressive Disorder, Depressive Disorder, Major, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Oxidative Stress

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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