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Cited by 103Antioxidant Activity and Oxidative StressTryptophan and brain disordersTreatment of Major Depression

Oxidative Stress Implications in the Affective Disorders: Main Biomarkers, Animal Models Relevance, Genetic Perspectives, and Antioxidant Approaches

Open access
Balmus, Ioana Miruna, Ciobica, Alin, Antioch, Iulia, Dobrin, Romeo, Timofte, Daniel·2016·Oxidative Medicine and Cellular Longevity
DOI 10.1155/2016/3975101PMC PMC4983669
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Abstract

The correlation between the affective disorders and the almost ubiquitous pathological oxidative stress can be described in a multifactorial way, as an important mechanism of central nervous system impairment. Whether the obvious changes which occur in oxidative balance of the affective disorders are a part of the constitutive mechanism or a collateral effect yet remains as an interesting question. However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease‐dependent manner. Still, there are a lot of controversies regarding the relevance of the oxidative stress status in most of the affective disorders and despite the fact that most of the studies are showing that the affective disorders development can be correlated to increased oxidative levels, there are various studies stating that oxidative stress is not linked with the mood changing tendencies. Thus, in this minireview we decided to describe the way in which oxidative stress is involved in the affective disorders development, by focusing on the main oxidative stress markers that could be used mechanistically and therapeutically in these deficiencies, the genetic perspectives, some antioxidant approaches, and the relevance of some animal models studies in this context.

AI snapshot

Written from the paper’s full text.

TL;DR

This minireview synthesizes evidence linking oxidative stress to affective disorders, focusing on biomarkers, animal models, genetic susceptibility, and antioxidant approaches. It concludes that oxidative stress is a disease-dependent component of these disorders, but causality and specific pathways remain unresolved.

Key findings

  • Oxidative stress is implicated across affective disorders including depressive disorder, anxiety, bipolar disorder, panic disorder, OCD, and PTSD, but findings are controversial; some studies report no link, for example with PTSD.
  • In major depressive disorder, most studies describe decreased GPX and increased MDA, while SOD activity is inconsistently reported as decreased, unchanged, or increased; lipid peroxidation, 8-OHdG, F2-isoprostanes, and nitric oxide are also highlighted as relevant markers.
  • Genetic heritability estimates cited are up to 80% for bipolar disorder by additive genetic factors, 40%–70% for major depression, and 40–50% for anxiety; familial cases are only 5 to 10% of all cases.
  • Antioxidant approaches include lithium, antidepressants, N-acetylcysteine, omega-3 fatty acids, melatonin, zinc, ascorbic acid, lycopene, diet, and exercise, with mixed evidence; one double-blind randomized placebo-controlled study found NAC improved standard therapy, while another found no significant antidepressant effect.

Methods

  • Narrative minireview; literature searched in ScienceDirect, PubMed/Medline, Embase, and Google Scholar, limited to English-language articles up to March 2016.
  • Publications were screened by title, then abstract, then full content by three separate researchers, with differences resolved by common consent.
  • Main analysis is a qualitative synthesis of oxidative stress markers, animal models, genetic perspectives, and antioxidant treatments in affective disorders.

Limitations

  • The paper states that controversies remain about the relevance of oxidative stress in most affective disorders, with some studies reporting no link, and that exact pathways in OCD, MDD, and other conditions are still unclear.
  • The paper notes that animal models cannot reproduce complex human psychiatric concepts such as self-esteem, recurrent thoughts of death, or fear of losing control, and that genetic correlations with oxidative stress are not clearly established due to extreme individual genetic variability.
  • Evident from the text: this is a narrative minireview without quantitative meta-analysis, and the search was restricted to English-language articles up to March 2016.

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

Integrity signals

Registry

Crossref · 10.1155/2016/3975101

Cites

313 of 313 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 240 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Increased oxidative damage occurs quite often in depression.

    “increased oxidative damage occurs quite often in depression [7–9]”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] Michel T. M. Pülschen D. Thome J. The role of oxidative stress in depressive disorders Current Pharmaceutical Design 2012 18 36 5890 5899 10.2174/138161212803523554 2-s2.0-84867696554 22681168 source

      Not checked in the free run.

    • cites [8] Black C. N. Bot M. Scheffer P. G. Cuijpers P. Penninx B. W. J. H. Is depression associated with increased oxidative stress? A systematic review and meta-analysis Psychoneuroendocrinology 2015 51 164 175 10.1016/j.psyneuen.2014.09.025 2-s2.0-84920572199 25462890 source

      Not checked in the free run.

    • cites [9] Vaváková M. Ďuračková Z. Trebatická J. Markers of oxidative stress and neuroprogression in depression disorder Oxidative Medicine and Cell Longevity 2015 2015 12 898393 10.1155/2015/898393 2-s2.0-84930959313 PMC4453280 26078821 source

      Not checked in the free run.

  • Premisecitation

    Increased oxidative damage occurs quite often in anxiety.

    “anxiety [9, 10]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Vaváková M. Ďuračková Z. Trebatická J. Markers of oxidative stress and neuroprogression in depression disorder Oxidative Medicine and Cell Longevity 2015 2015 12 898393 10.1155/2015/898393 2-s2.0-84930959313 PMC4453280 26078821 source

      Not checked in the free run.

    • cites [10] Bouayed J. Rammal H. Soulimani R. Oxidative stress and anxiety. Relationship and cellular pathways Oxidative Medicine and Cellular Longevity 2009 2 2 63 67 2-s2.0-63449091380 20357926 PMC2763246 source

      Not checked in the free run.

  • Premisecitation

    Increased oxidative damage occurs quite often in bipolar disorder.

    “bipolar disorder (BD) [10–14]”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [10] Bouayed J. Rammal H. Soulimani R. Oxidative stress and anxiety. Relationship and cellular pathways Oxidative Medicine and Cellular Longevity 2009 2 2 63 67 2-s2.0-63449091380 20357926 PMC2763246 source

      Not checked in the free run.

    • cites [11] Smaga I. Niedzielska E. Gawlik M. Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism Pharmacological Reports 2015 67 3 569 580 10.1016/j.pharep.2014.12.015 2-s2.0-84924330587 25933971 source

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    • cites [12] Andreazza A. C. Kauer-Sant'Anna M. Frey B. N. Oxidative stress markers in bipolar disorder: a meta-analysis Journal of Affective Disorders 2008 111 2-3 135 144 10.1016/j.jad.2008.04.013 2-s2.0-51349085199 18539338 source

      Not checked in the free run.

    • cites [13] Ng F. Berk M. Dean O. Bush A. I. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications International Journal of Neuropsychopharmacology 2008 11 6 851 876 10.1017/s1461145707008401 2-s2.0-50849139232 18205981 source

      Not checked in the free run.

    • cites [14] Berk M. Kapczinski F. Andreazza A. C. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors Neuroscience and Biobehavioral Reviews 2011 35 3 804 817 10.1016/j.neubiorev.2010.10.001 2-s2.0-78649938042 20934453 source

      Not checked in the free run.

  • Premisecitation

    Increased oxidative damage occurs quite often in panic disorder.

    “panic disorder (PD) [15, 16]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [15] Ersoy M. A. Selek S. Celik H. Role of oxidative and antioxidative parameters in etiopathogenesis and prognosis of panic disorder International Journal of Neuroscience 2008 118 7 1025 1037 10.1080/00207450701769026 2-s2.0-45849139343 18569158 source

      Not checked in the free run.

    • cites [16] Gul I. G. Karlidag R. Cumurcu B. E. The effect of agoraphobia on oxidative stress in panic disorder Psychiatry Investigation 2013 10 4 317 325 10.4306/pi.2013.10.4.317 2-s2.0-84892531472 24474979 PMC3902148 source

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  • Interpretationreasoning

    The correlation between oxidative stress status and affective disorders development could arise from the vulnerability of the central nervous system to oxidative damage.

    “In fact, the correlation between the oxidative stress status and affective disorders development could arise from the vulnerability of central nervous system (CNS) to oxidative damage.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [26] Bild W. Ciobica A. Padurariu M. Bild V. The interdependence of the reactive species of oxygen, nitrogen, and carbon Journal of Physiology and Biochemistry 2013 69 1 147 154 10.1007/s13105-012-0162-2 2-s2.0-84879470298 22456998 source

      Not checked in the free run.

    • cites [27] Massaad C. A. Klann E. Reactive oxygen species in the regulation of synaptic plasticity and memory Antioxidants and Redox Signaling 2011 14 10 2013 2054 10.1089/ars.2010.3208 2-s2.0-79954596666 20649473 PMC3078504 source

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    • cites [28] Halliwell B. Free radicals and antioxidants—quo vadis? Trends in Pharmacological Sciences 2011 32 3 125 130 10.1016/j.tips.2010.12.002 2-s2.0-79952442409 21216018 source

      Not checked in the free run.

    • cites [29] Lehtinen M. K. Bonni A. Modeling oxidative stress in the central nervous system Current Molecular Medicine 2006 6 8 871 881 10.2174/156652406779010786 2-s2.0-33845401465 17168738 source

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  • May combine two claims. 61
  • Classified as probably not a substantial claim. 27
  • The quote only partly states this claim. 1

  • May combine two claims.

    Interpretationnone given

    Oxidative stress is a component of affective disorders, with different aspects depending on the disease.

    “However it is now clear that oxidative stress is a component of these disorders, being characterized by different aspects in a disease-dependent manner.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    A close connection between glutamatergic hyperactivity and depression has been postulated.

    “a close connection between glutamatergic hyperactivity and depression has been postulated [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Deschwanden A. Karolewicz B. Feyissa A. M. Reduced metabotropic glutamate receptor 5 density in major depression determined by [11C]ABP688 PET and postmortem study The American Journal of Psychiatry 2011 168 7 727 734 10.1176/appi.ajp.2011.09111607 2-s2.0-79960539531 21498461 PMC3129412 source

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

    Premisecitation

    Some distinct studies report that oxidative stress may not be linked in any way with posttraumatic stress disorder.

    “there are also some distinct studies reporting that oxidative stress may not be linked in any way, for example, with PTSD [57, 58].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [57] Ozdemir P. G. Kaplan I. Uysal C. Serum total oxidant and antioxidant status in earthquake survivors with post-traumatic stress disorder Acta Neuropsychiatrica 2015 27 3 153 158 10.1017/neu.2014.47 2-s2.0-84929297072 25597474

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    • cites [58] Lang U. E. Borgwardt S. Molecular mechanisms of depression: perspectives on new treatment strategies Cellular Physiology and Biochemistry 2013 31 6 761 777 10.1159/000350094 2-s2.0-84878352105 23735822

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.

    Study design and conductnone given

    The review's literature search was conducted in ScienceDirect, PubMed/Medline, Embase, and Google Scholar, considering only English articles up to March 2016, and publications were screened by title, abstract, and full content by three researchers.

    “The information gathered for this review was searched in the main available databases (e.g., ScienceDirect, PubMed/Medline, Embase, and Google Scholar) taking into consideration just the articles in the English language.”
    • Also stated in: § 2. Methodology · plain
      “Firstly, the publications were screened by title, then by abstract content, and then by full content. This inquiry was conducted by three separate researchers (Ioana Miruna Balmus, Alin Ciobica, and Iulia Antioch).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Bilici et al. showed that administration of SSRIs for 3 months generates normalization in levels of some oxidative stress markers such as antioxidative enzyme activities and lipid markers.

    “Bilici et al. showed that the administration of some selective serotonin reuptake inhibitors (SSRIs) for 3 months is generating a normalization in levels for some oxidative stress markers such as some antioxidative enzyme activities and lipid markers [121]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [121] Bilici M. Efe H. Koroglu M. A. Uydu H. A. Bekaroglu M. Deger O. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments Journal of Affective Disorders 2001 64 1 43 51 10.1016/s0165-0327(00)00199-3 2-s2.0-0035065919 11292519

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    Premisecitation

    The Sarandol group stated no significant modifications in oxidative stress levels after venlafaxine and sertraline administration for 6 weeks.

    “the group of Sarandol stated no significant modifications in the oxidative stress levels after venlafaxine and sertraline administration for 6 weeks”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [123] Sarandol A. Sarandol E. Eker S. S. 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 10.1002/hup.829 2-s2.0-33947726165 17299810 source

      Not checked in the free run.

    • cites [124] 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 10.1016/S1734-1140(09)70084-2 2-s2.0-67651148093 19605942

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    Premisecitation

    Some oxidative stress markers normalize during or after specific therapy for affective episodes, suggesting antidepressants could reduce oxidative stress levels.

    “some oxidative stress markers are normalizing during or after the specific therapy applied for the affective episodes, suggesting that antidepressants could actually reduce oxidative stress levels [116].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [116] Sarris J. Mischoulon D. Schweitzer I. Adjunctive nutraceuticals with standard pharmacotherapies in bipolar disorder: a systematic review of clinical trials Bipolar Disorders 2011 13 5-6 454 465 10.1111/j.1399-5618.2011.00945.x 2-s2.0-80054869712 22017215

      Not checked in the free run.

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    Premisecitation

    Both 8-hydroxy-2-deoxyguanosine and F2-isoprostanes are increased in depression.

    “Black et al. in 2015 [8] revealed that both 8-hydroxy-2-deoxyguanosine (8-OHdG) and F2-isoprostanes are increased in depression”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] Black C. N. Bot M. Scheffer P. G. Cuijpers P. Penninx B. W. J. H. Is depression associated with increased oxidative stress? A systematic review and meta-analysis Psychoneuroendocrinology 2015 51 164 175 10.1016/j.psyneuen.2014.09.025 2-s2.0-84920572199 25462890 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing).

    Premisecitation

    Major depressive disorder could be considered an inflammatory disorder, as judged mainly by increased levels of proinflammatory cytokines such as interleukin-1b, interleukin-6, or tumor necrosis factor-alpha.

    “there are opinions in the literature that MDD could be considered an inflammatory disorder, as judged mainly by the increased levels of the proinflammatory cytokines, such as interleukin-1b, interleukin-6, or tumor necrosis factor-alpha [139].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [139] Maes M. Fišar Z. Medina M. Scapagnini G. Nowak G. Berk M. New drug targets in depression: inflammatory, cell-mediate immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. and new drug candidates-Nrf2 activators and GSK-3 inhibitors Inflammopharmacology 2012 20 3 127 150 10.1007/s10787-011-0111-7 2-s2.0-84862769027 22271002

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    Premisecitation

    In bipolar disorder animal models, the specific activity of SOD and CAT is increased and GPX activity is decreased.

    “in BD animal models there are various alterations for the protein oxidation markers, with the specific activity of SOD and CAT being increased and GPX activity decreased.”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [90] Frey B. N. Martins M. R. Petronilho F. C. Dal-Pizzol F. Quevedo J. Kapczinski F. Increased oxidative stress after repeated amphetamine exposure: possible relevance as a model of mania Bipolar Disorders 2006 8 3 275 280 10.1111/j.1399-5618.2006.00318.x 2-s2.0-33646567187 16696830

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    • cites [91] Frey B. N. Valvassori S. S. Réus G. Z. Changes in antioxidant defense enzymes after d-amphetamine exposure: implications as an animal model of mania Neurochemical Research 2006 31 5 699 703 10.1007/s11064-006-9070-6 2-s2.0-33745101692 16770742

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    • cites [92] Frey B. N. Valvassori S. S. Gomes K. M. Increased oxidative stress in submitochondrial particles after chronic amphetamine exposure Brain Research 2006 1097 1 224 229 10.1016/j.brainres.2006.04.076 2-s2.0-33745877318 16730669

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    • cites [93] Andreazza A. C. Kauer-Sant'Anna M. Frey B. N. Effects of mood stabilizers on DNA damage in an animal model of mania Journal of Psychiatry and Neuroscience 2008 33 6 516 524 2-s2.0-56349115455 18982174 PMC2575759

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    Premisecitation

    Phenelzine showed great antioxidative defense potential, being capable of reducing reactive oxygen species formation and scavenging hydrogen peroxide.

    “phenelzine, which is a monoamine oxidase inhibitor drug, showed great antioxidative defense potential, being capable of reducing the reactive oxygen species formation and the scavenging proprieties of hydrogen peroxide [170].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [170] Abdel-Wahab B. A. Salama R. H. Venlafaxine protects against stress-induced oxidative DNA damage in hippocampus during antidepressant testing in mice Pharmacology Biochemistry and Behavior 2011 100 1 59 65 10.1016/j.pbb.2011.07.015 2-s2.0-80052115992 21835191

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  • May combine two claims.

    Premisecitation

    In several models of depression in rats, animals exhibit glutathione depletion, decrease in GPX specific activity, lower levels of vitamin C, and increased rates of lipid peroxidation and nitric oxides.

    “in other several models of depression in rats it was showed that these animals exhibit alterations of some oxidative mechanisms in the form of glutathione levels depletion, decrease in GPX specific activity, lower levels of vitamin C, or increased rates of lipid peroxidation and nitric oxides [166, 167].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [166] Eren I. Nazıroğlu M. Demirdaş A. Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat Neurochemical Research 2007 32 3 497 505 10.1007/s11064-006-9258-9 2-s2.0-33847105552 17268845

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    • cites [167] Pal S. N. Dandiya P. C. Glutathione as a cerebral substrate in depressive behavior Pharmacology, Biochemistry and Behavior 1994 48 4 845 851 10.1016/0091-3057(94)90191-0 2-s2.0-0027971028 7972287

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    Premisecitation

    In an anxiety rat model of social stress, plasma 8-isoprostane and hippocampus protein carbonylation increased, without changes in prefrontal cortex and amygdala regions.

    “other evidences of oxidative stress in an anxiety rat model of social stress were demonstrated by an important increase of plasma 8-isoprostane and hippocampus protein carbonylation, but interestingly without any changes in prefrontal cortex and amygdala regions [107].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [107] Patki G. Allam F. H. Atrooz F. Grape powder intake prevents ovariectomy-induced anxiety-like behavior, memory impairment and high blood pressure in female wistar rats PLoS ONE 2013 8 9 e74522 10.1371/journal.pone.0074522 2-s2.0-84883615497 PMC3767647 24040270

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    Premisecitation

    Olanzapine reversed decreased hepatic glutathione levels but did not alter elevated hepatic proinflammatory cytokines.

    “they saw that although the drug was able to reverse decreased hepatic glutathione levels, it did not alter the elevated hepatic proinflammatory cytokines”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [176] Jeding I. Evans P. J. Akanmu D. Characterization of the potential antioxidant and pro-oxidant actions of some neuroleptic drugs Biochemical Pharmacology 1995 49 3 359 365 10.1016/0006-2952(94)00424-K 2-s2.0-0028797685 7857323

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    Premisecitation

    Typical antipsychotics presented mainly prooxidant effects, while atypical antipsychotics have important antioxidant capacity.

    “while the first ones presented mainly prooxidant effects [177–179], the latter has proven to have an important antioxidant capacity [180, 181].”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [177] Parikh V. Khan M. M. Mahadik S. P. Differential effects of antipsychotics on expression of antioxidant enzymes and membrane lipid peroxidation in rat brain Journal of Psychiatric Research 2003 37 1 43 51 10.1016/S0022-3956(02)00048-1 2-s2.0-0037212193 12482469

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    • cites [178] Pillai A. Parikh V. Terry A. V. Jr. Mahadik S. P. Long-term antipsychotic treatments and crossover studies in rats: differential effects of typical and atypical agents on the expression of antioxidant enzymes and membrane lipid peroxidation in rat brain Journal of Psychiatric Research 2007 41 5 372 386 10.1016/j.jpsychires.2006.01.011 2-s2.0-33846847640 16564057

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    • cites [179] Wang H. Xu H. Dyck L. E. Li X.-M. Olanzapine and quetiapine protect PC12 cells from β-amyloid peptide 25–35-induced oxidative stress and the ensuing apoptosis Journal of Neuroscience Research 2005 81 4 572 580 10.1002/jnr.20570 2-s2.0-24744433317 15948179

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    • cites [180] Xu H. Wang H. Zhuang L. Demonstration of an anti-oxidative stress mechanism of quetiapine: implications for the treatment of Alzheimer's disease The FEBS Journal 2008 275 14 3718 3728 10.1111/j.1742-4658.2008.06519.x 2-s2.0-50549100242 18554300

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    • cites [181] Ciobica A. Bild V. Hritcu L. Padurariu M. Bild W. Effects of angiotensin II receptor antagonists on anxiety and some oxidative stress markers in rat Central European Journal of Medicine 2011 6 3 331 340 10.2478/s11536-011-0010-8 2-s2.0-79957476286

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  • May combine two claims.

    Premisecitation

    Many genes involved in affective disorders pathology may be associated with brain growth factors, signal molecules, receptors, chelation, and transport factors, and some encode enzymes and factors implicated in brain oxidative status.

    “They may be associated with brain growth factors, signal molecules, receptors, chelation, and transport factors, while some of them are actually genes which encode several enzymes and factors implicated in brain oxidative status [187].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [187] McGuffin P. Rijsdijk F. Andrew M. Sham P. Katz R. Cardno A. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression Archives of General Psychiatry 2003 60 5 497 502 10.1001/archpsyc.60.5.497 2-s2.0-0037629099 12742871

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    Premisecitation

    Major depression is less probable to be inherited than bipolar disorder, with 40%-70% heritability.

    “while major depression (40%–70%) [189] and anxiety (40–50%) [190] are less probable to be inherited by the descendants.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] Eley T. C. Collier D. McGuffin P. McGuffin P. Owen M. J. Gottesman I. I. Anxiety and eating disorders Psychiatric Genetics and Genomics 2002 Oxford, UK Oxford University Press 303 340

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Anxiety is less probable to be inherited than bipolar disorder, with 40-50% heritability.

    “while major depression (40%–70%) [189] and anxiety (40–50%) [190] are less probable to be inherited by the descendants.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Norrholm S. D. Ressler K. J. Genetics of anxiety and trauma-related disorders Neuroscience 2009 164 1 272 287 10.1016/j.neuroscience.2009.06.036 2-s2.0-74049140846 19540311 PMC2760665

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

    Interpretationreasoning

    The genetic component, environmental risk factors, and their interaction in affective disorders development are rather variable.

    “In this way, it can be stated that the genetic component, the environmental risk factors, and their interaction in the affective disorders development context are rather variable.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Other groups correlated organophosphates exposure with oxidative stress and alterations in brain dopamine and serotonin receptors of young rats, but no actual correlation between oxidative stress and these receptors has been proposed.

    “In addition, other groups correlated organophosphates exposure with oxidative stress and alterations in brain dopamine and serotonin receptors of young rats, but still no actual correlation between oxidative stress and these receptors has been proposed [201].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [201] Sankhwar M. L. Yadav R. S. Shukla R. K. Monocrotophos induced oxidative stress and alterations in brain dopamine and serotonin receptors in young rats Toxicology and Industrial Health 2016 32 3 422 436 10.1177/0748233713500834 24105069

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    Premisecitation

    Twin and adoption studies revealed that a close interaction exists between the genetic background and the environment, raising several environmental risk factors which could play an important role in building up the risk for affective disorders development.

    “On the other hand, twin and adoption studies [204, 205] revealed that a close interaction exists between the genetic background and the environment, raising several environmental risk factors which could play an important role in building up the risk for affective disorders development.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [204] Smoller J. W. Finn C. T. Family, twin, and adoption studies of bipolar disorder American Journal of Medical Genetics Part C (Seminaries of Medical Genetics) 2003 123 1 48 58 2-s2.0-0242354132 14601036

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    • cites [205] Na H.-R. Kang E.-H. Lee J.-H. Yu B.-H. The genetic basis of panic disorder Journal of Korean Medical Science 2011 26 6 701 710 10.3346/jkms.2011.26.6.701 2-s2.0-79958277049 21655053 PMC3102861

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  • May combine two claims.

    Premisenone given

    Although a clear correlation between genetic components and PTSD has been made and all of these genes may be directly or indirectly implicated in oxidative stress modulation or development, no previous correlation between all of them is available.

    “In fact, although a clear correlation between genetic components and PTSD has been made and all of these genes may be directly or indirectly implicated in oxidative stress modulation or development, no previous correlation between all of them is available.”
    Quote in the paperNot a substantial claim

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    Premisereasoning

    The predisposition to PTSD through these gene polymorphisms has been shown, but the oxidative stress pathways in which they may be involved are almost unknown in PTSD conditions.

    “Therefore, since the predisposition to PTSD through these genes polymorphisms has been shown, the oxidative stress pathways in which they may be involved are almost unknown in PTSD conditions.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Familial cases are only 5 to 10% of all cases.

    “Unfortunately, as the familial cases are thought to be easier to screen and to prevent, these are only 5 to 10% of all cases.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Another previous study associated D2 and D3 dopamine receptor agonists with glutamate oxidative stress inhibition in oxygen/glucose deprivation models.

    “Another previous study also associated D2 and D3 dopamine receptor agonists with glutamate oxidative stress inhibition in oxygen/glucose deprivation models [200].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [200] Rosin C. Colombo S. Calver A. A. Bates T. E. Skaper S. D. Dopamine D2 and D3 receptor agonists limit oligodendrocyte injury caused by glutamate oxidative stress and oxygen/glucose deprivation GLIA 2005 52 4 336 343 10.1002/glia.20250 2-s2.0-30444448403 16078234

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

    Premisecitation

    One recent study correlated a dopamine D2 receptor antagonist and anti-Parkinson medication with reduced excitotoxicity and therefore reduced neuronal apoptosis in oxidative stress conditions.

    “Dopamine receptor D2 association with oxidative stress is rather controversial, considering, for example, that one recent study correlated a dopamine D2 receptor antagonist and anti-Parkinson medication with reduced excitotoxicity and therefore reduced neuronal apoptosis in oxidative stress conditions [199].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [199] Odaka H. Numakawa T. Adachi N. Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity PLoS ONE 2014 9 6 e99271 10.1371/journal.pone.0099271 2-s2.0-84902593610 PMC4051758 24914776

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

    Premisecitation

    An interaction between CCK and dopamine may be involved in panic attacks modulation.

    “It seems that an interaction between CCK and dopamine may be involved in panic attacks modulation [212].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [212] Vanderhaeghen J. J. Signeau J. C. Gepts W. New peptide in the vertebrate CNS reacting with antigastrin antibodies Nature 1975 257 5527 604 605 10.1038/257604a0 2-s2.0-0016737525 1165787

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  • May combine two claims.

    Premisecitation

    Although there are studies which negatively correlate COMT with PD, the COMT polymorphism remains one of the most consistent findings in PD genetics.

    “In this way, although there are studies which negatively correlate COMT with PD, it seems that this polymorphism remains as one of the most consistent findings in PD genetics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Plenty of studies revealed genetic component implications in affective disorders occurrence and rarely the same susceptibility locus shows up repeatedly.

    “There are plenty of studies that revealed the genetic component implications in the affective disorders occurrence and rarely the same susceptibility locus shows up repeatedly.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    COMT gene codes for a catecholamine catabolic breakdown enzyme, which is involved in anxiety development as high levels of COMT have been observed in patient's serum.

    “COMT gene, for example, codes for a catecholamine catabolic breakdown enzyme, which is known to be involved in anxiety development as high levels of COMT have been observed in patient's serum [206].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [206] Lehman C. L. Brown T. A. Palfai T. Barlow D. H. The effects of alcohol outcome expectancy on a carbon-dioxide challenge in patients with panic disorder Behavior Therapy 2002 33 3 447 463 10.1016/S0005-7894(02)80038-7 2-s2.0-0037625614

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

    Premisecitation

    Several studies report high COMT activity and high oxidative stress levels in vitiligo patients.

    “Still there are several studies which report high COMT activity and high oxidative stress levels in vitiligo patients [207, 208]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [207] Mehaney D. A. Darwish H. A. Hegazy R. A. Analysis of oxidative stress status, catalase and catechol-O-methyltransferase polymorphisms in Egyptian vitiligo patients PLoS ONE 2014 9 6 e99286 10.1371/journal.pone.0099286 2-s2.0-84902593754 PMC4051781 24915010

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    • cites [208] Colucci R. Dragoni F. Moretti S. Oxidative stress and immune system in vitiligo and thyroid diseases Oxidative Medicine and Cellular Longevity 2015 2015 7 631927 10.1155/2015/631927 2-s2.0-84925654814 PMC4370195 25838868

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

    Premisecitation

    The serotonin transporter gene codes for a protein affected by SSRI medications, which are frequently used in anxiety disorders treatment.

    “This gene is coding for a protein affected by selective serotonin reuptake inhibitor (SSRI) medications, which are of course frequently used in anxiety disorders treatment [215].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [215] Wendland J. R. Moya P. R. Kruse M. R. A novel, putative gain-of-function haplotype at SLC6A4 associates with obsessive-compulsive disorder Human Molecular Genetics 2008 17 5 717 723 10.1093/hmg/ddm343 2-s2.0-39749154209 18055562

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

    Premisecitation

    COMT activity is thought to be oxidative stress promoter in association with high catalase activity in melanocytes and melanin biosynthesis.

    “In the same way, COMT activity is thought to be oxidative stress promoter in association with high catalase activity in melanocytes and melanin biosynthesis [208].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [208] Colucci R. Dragoni F. Moretti S. Oxidative stress and immune system in vitiligo and thyroid diseases Oxidative Medicine and Cellular Longevity 2015 2015 7 631927 10.1155/2015/631927 2-s2.0-84925654814 PMC4370195 25838868

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  • May combine two claims.

    Premisecitation

    The exact correlation between CCK and PD is not known, although CCK A receptor and dopamine D5 genes are closely situated on the short arm of the fourth chromosome.

    “In fact, ambiguous results have been obtained through time in several studies and therefore the exact correlation between CCK and PD is not known, although it seems that CCK A receptor and dopamine D5 genes are closely situated on the short arm of the fourth chromosome [212].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [212] Vanderhaeghen J. J. Signeau J. C. Gepts W. New peptide in the vertebrate CNS reacting with antigastrin antibodies Nature 1975 257 5527 604 605 10.1038/257604a0 2-s2.0-0016737525 1165787

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    Premisecitation

    Menazza et al. showed that MAOA activity may increase mitochondrial ROS production, which will lead to increased oxidative stress and myofiber damage.

    “Moreover, Menazza et al. [221] showed that MAOA activity may increase mitochondrial ROS production, which will lead to increased oxidative stress and myofiber damage.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [221] Menazza S. Blaauw B. Tiepolo T. Oxidative stress by monoamine oxidases is causally involved in myofiber damage in muscular dystrophy Human Molecular Genetics 2010 19 21 4207 4215 10.1093/hmg/ddq339 2-s2.0-77957870248 20716577

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  • May combine two claims.

    Premisecitation

    D-amino acid oxidase activator gene and brain derived neurotrophic factor gene became of great interest, but no actual evidence was found in BD, mainly because most of these genes are reported as schizophrenia susceptibility genes too.

    “Later, D-amino acid oxidase activator gene and brain derived neurotrophic factor gene became also of great interest, but it seems that no actual evidence was found in this matter [223, 224], mainly due to the fact that most of these genes are reported as schizophrenia susceptibility genes too.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [223] Green E. Craddock N. Brain-derived neurotrophic factor as a potential risk locus for bipolar disorder: evidence, limitaions, and implications Current Psychiatry Reports 2003 5 6 469 476 10.1007/s11920-003-0086-1 2-s2.0-2942633780 14609502

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    • cites [224] Hattori E. Liu C. Badner J. A. Polymorphisms at the G72/G30 gene locus, on 13q33, are associated with bipolar disorder in two independent pedigree series American Journal of Human Genetics 2003 72 5 1131 1140 10.1086/374822 2-s2.0-0037730178 12647258 PMC1180266

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  • May combine two claims.

    Premisecitation

    No significant association with BDNF polymorphism or inconsistent evidence was reported in DD.

    “In this way, no significant association with BDNF polymorphism or inconsistent evidence was reported [226, 227].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [226] Schumacher J. Jamra R. A. Becker T. Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression Biological Psychiatry 2005 58 4 307 314 10.1016/j.biopsych.2005.04.006 2-s2.0-23644432395 16005437

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    • cites [227] Surtees P. G. Wainwright N. W. J. Willis-Owen S. A. G. No association between the BDNF Val66Met polymorphism and mood status in a non-clinical community sample of 7389 older adults Journal of Psychiatric Research 2007 41 5 404 409 10.1016/j.jpsychires.2006.01.004 2-s2.0-33846634095 16497333

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

    Interpretationreasoning

    It might be possible that high COMT activity is associated with both agitation/disorientation and oxidative stress.

    “it might be possible that high COMT activity is associated with both agitation/disorientation and oxidative stress.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Both D-amino acid oxidase activator and brain derived neurotrophic factor are involved in several oxidative stress pathways, but a direct correlation between these two and oxidative stress in BD has not yet been showed.

    “Surprisingly, it can be observed that both D-amino acid oxidase activator and brain derived neurotrophic factor are involved in several oxidative stress pathways [14, 225], but a direct correlation between these two and oxidative stress in BD has not been yet showed.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [14] Berk M. Kapczinski F. Andreazza A. C. Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors Neuroscience and Biobehavioral Reviews 2011 35 3 804 817 10.1016/j.neubiorev.2010.10.001 2-s2.0-78649938042 20934453

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    • cites [225] Cabungcal J.-H. Steullet P. Morishita H. Perineuronal nets protect fast-spiking interneurons against oxidative stress Proceedings of the National Academy of Sciences of the United States of America 2013 110 22 9130 9135 10.1073/pnas.1300454110 2-s2.0-84878429993 23671099 PMC3670388 source

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    Premisecitation

    Tryptophan hydroxylase gene encodes for an important rate-limiting enzyme of brain serotonin synthesis and is thought to be implicated in DD.

    “Another gene thought to be implicated in DD is tryptophan hydroxylase gene, which encodes for an important rate-limiting enzyme of brain serotonin synthesis [231].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [231] Lohoff F. W. Overview of the genetics of major depressive disorder Current Psychiatry Reports 2010 12 6 539 546 10.1007/s11920-010-0150-6 2-s2.0-78649906500 20848240 PMC3077049 source

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

    Premisecitation

    Numakawa et al. suggested that an interaction between BDNF and CAT could be associated with the positive and negative syndrome scale (PANSS) as a cognitive factor.

    “Also, they suggested that an interaction between BDNF and CAT could be associated with the positive and negative syndrome scale (PANSS) as a cognitive factor.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [230] Numakawa T. Richards M. Nakajima S. The role of brain-derived neurotrophic factor in comorbid depression: possible linkage with steroid hormones, cytokines, and nutrition Frontiers in Psychiatry 2014 5, article 136 10.3389/fpsyt.2014.00136 2-s2.0-84907096914 PMC4175905 25309465

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    Premisecitation

    Patients with schizophrenia exhibit a significant decrease in BDNF levels and also in the activities of SOD and GPX.

    “It seems that the patients exhibit a significant decrease in BDNF levels and also in the activities of SOD and GPX.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [229] Zhang X. Y. Chen D.-C. Tan Y.-L. The interplay between BDNF and oxidative stress in chronic schizophrenia Psychoneuroendocrinology 2015 51 201 208 10.1016/j.psyneuen.2014.09.029 2-s2.0-84920602922 25462893

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    Premisecitation

    Controversial results were obtained in the case of the polymorphisms for the RGS2 gene, which could be implicated in anxiety-like behaviours, but also in PTSD, emotional distress, and PD.

    “Also, controversial results were obtained in the case of the polymorphisms for the regulator of G-protein signalling 2 (RGS2) gene, which could be implicated in anxiety-like behaviours [240], but also in PTSD, emotional distress, and PD [241, 242].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [240] Leygraf A. Hohoff C. Freitag C. Rgs 2 gene polymorphisms as modulators of anxiety in humans? Journal of Neural Transmission 2006 113 12 1921 1925 10.1007/s00702-006-0484-8 2-s2.0-33749176495 16736243

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    • cites [241] Smoller J. W. Paulus M. P. Fagerness J. A. Influence of RGS2 on anxiety-related temperament, personality, and brain function Archives of General Psychiatry 2008 65 3 298 308 10.1001/archgenpsychiatry.2007.48 2-s2.0-40349100396 18316676

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    • cites [242] Koenen K. C. Amstadter A. B. Ruggiero K. J. RGS2 and generalized anxiety disorder in an epidemiologic sample of hurricane-exposed adults Depression & Anxiety 2009 26 4 309 315 10.1002/da.20528 2-s2.0-63849284108 18833580 PMC2666784

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  • May combine two claims.

    Premisecitation

    Kuhn et al. reported a possible implication of the oxidative stress status in TPH2 activity, whereas TPH2 oxidation leads to low TPH2 enzymatic activity.

    “Furthermore, Kuhn et al. [234] reported a possible implication of the oxidative stress status in TPH2 activity, whereas THP2 oxidation leads to low TPH2 enzymatic activity.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [234] Kuhn D. M. Sykes C. E. Geddes T. J. Jaunarajs K. L. E. Bishop C. Tryptophan hydroxylase 2 aggregates through disulfide cross-linking upon oxidation: Possible link to serotonin deficits and non-motor symptoms in Parkinson's disease Journal of Neurochemistry 2011 116 3 426 437 10.1111/j.1471-4159.2010.07123.x 2-s2.0-78651295081 21105877 PMC3019244

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  • May combine two claims.

    Premisecitation

    A very recent report showed increased systemic oxidative stress in TPH2 knock-out mice and also increased lipid metabolism impairments which might be implicated in serotonin deficiency.

    “Furthermore, a very recent report showed increased systemic oxidative stress in TPH2 knock-out mice and also increased lipid metabolism impairments which might be implicated in serotonin deficiency [235].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [235] Weng R. Shen S. Burton C. Lipidomic profiling of tryptophan hydroxylase 2 knockout mice reveals novel lipid biomarkers associated with serotonin deficiency Analytical and Bioanalytical Chemistry 2016 408 11 2963 2973 10.1007/s00216-015-9256-3 2-s2.0-84954434369 26780709

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  • May combine two claims.

    Premisecitation

    PPARGC1A has been connected to nuclear respiratory factors 1 (NRF1) and 2 (NRF2), which are linked to oxidative stress and also well correlated to ANX both in human and rodent models.

    “but it has been shortly connected to the nuclear respiratory factors 1 (NRF1) and 2 (NRF2), which are linked to oxidative stress and also well correlated to ANX both in human and rodent models [23, 38].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [23] Ciobica A. Hritcu L. Padurariu M. Dobrin R. Bild V. Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders Advances in Medical Sciences 2010 55 2 289 296 10.2478/v10039-010-0035-2 2-s2.0-78650491427 20934963

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    • cites [38] Distler M. G. Palmer A. A. Role of glyoxalase 1 (Glo1) and methylglyoxal (MG) in behavior: recent advances and mechanistic insights Frontiers in Genetics 2012 3 p. 250 10.3389/fgene.2012.00250 2-s2.0-84875842853 PMC3500958 23181072

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    Premisecitation

    A common lipid peroxidation product such as 4-hydroxy-2-nonenal can inhibit RGS4, which further impairs the GTPase activity.

    “In this way, it seems that a common lipid peroxidation product such as 4-hydroxy-2-nonenal can inhibit RGS4, which further impairs the GTPase activity [244].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [244] Monroy C. A. Mackie D. I. Roman D. L. A high throughput screen for RGS proteins using steady state monitoring of free phosphate formation PLoS ONE 2013 8 4 e62247 10.1371/journal.pone.0062247 2-s2.0-84876575524 PMC3633906 23626793

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

    Premisecitation

    PPARGC1A was discovered in muscle cells and brown fat and thought to stimulate mitochondrial biogenesis by increasing oxidative phosphorylation and enhancing oxidative respiration.

    “PPARGC1A was actually discovered in the muscle cells and brown fat and thought to stimulate mitochondrial biogenesis by increasing oxidative phosphorylation and by enhancing oxidative respiration [245]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [245] Wu Z. Puigserver P. Andersson U. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1 The Cell 1999 98 1 115 124 10.1016/s0092-8674(00)80611-x 2-s2.0-0033538473 10412986 source

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  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    At least hypothetically and theoretically, a link between the neuroprogression biomarkers and the decline observed in affective disorders can be made.

    “In this way, at least hypothetically and theoretically, a link between the neuroprogression biomarkers and the decline observed in affective disorders can be made.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    According to an estimative perspective given by the World Health Organization (WHO), major depressive disorder will be the second health problem worldwide by the year of 2020.

    “In this way, according to an estimative perspective given by the World Health Organization (WHO), major depressive disorder will be the second health problem worldwide by the year of 2020 [246].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [246] World Health Organization The Global Burden of Disease: 2004 Update 2008 Geneva, Switzerland World Health Organization

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  • May combine two claims.

    Premisecitation

    A six-week lithium therapy can successfully decrease lipid peroxidation markers and restore SOD plasma levels.

    “Thus, a six-week lithium therapy can successfully decrease lipid peroxidation markers and restore SOD plasma levels [253].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [253] Machado-Vieira R. Andreazza A. C. Viale C. I. Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects Neuroscience Letters 2007 421 1 33 36 10.1016/j.neulet.2007.05.016 2-s2.0-34250318164 17548157

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

    Premisenone given

    A strong correlation between genetics, oxidative stress, and affective disorders has not been made quite clear due to the extreme genetic variability of the individuals.

    “However, we have to mention that a strong correlation between genetics, oxidative stress, and affective disorders has not been made quite clear due to the extreme genetic variability of the individuals.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Lithium can exhibit mood stabilizing properties, but also antioxidant potential.

    “For instance, lithium can exhibit mood stabilizing properties, but also antioxidant potential, as some early phase studies regarding the oxidative stress status in BD showed [252].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [252] Kiełczykowska M. Pasternak K. Musik I. Wrońska-Tyra J. Hordyjewska A. The influence of different doses of lithium administered in drinking water on lipid peroxidation and the activity of antioxidant enzymes in rats Polish Journal of Environmental Studies 2006 15 5 747 751 2-s2.0-33750986480

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

    Premisecitation

    In Europe and USA anxiety disorders are the most prevalent psychiatric conditions.

    “Even more, it seems that in Europe and USA anxiety disorders are the most prevalent psychiatric conditions [247–249].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [247] Nutt D. J. Kessler R. C. Alonso J. Consensus statement on the benefit to the community of ESEMeD (European study of the epidemiology of mental disorders) survey data on depression and anxiety Journal of Clinical Psychiatry 2007 68 Supplement 2 42 48 2-s2.0-33847388521 17288507

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    • cites [248] Kessler R. C. The global burden of anxiety and mood disorders: putting the European Study of the Epidemiology of Mental Disorders (ESEMeD) findings into perspective Journal of Clinical Psychiatry 2007 68 supplement 2 10 19 10.4088/jcp.0407e10 2-s2.0-33847390799 17288502 PMC1852440

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    • cites [249] Kessler R. C. Chiu W. T. Demler O. Merikangas K. R. Walters E. E. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication Archives of General Psychiatry 2005 62 6 617 627 10.1001/archpsyc.62.6.617 2-s2.0-20344374645 15939839 PMC2847357 source

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    Premisecitation

    A classical case report of twin brothers diagnosed with mania demonstrated normalization of TBARS or SOD levels after medication in the brother who accepted therapy, whereas the brother who refused medication had unchanged markers and manic symptomatology.

    “In fact, this was presented as a situation where one brother accepted therapy and the TBARS or SOD levels came back to normal parameters after medication, whereas the other brother refused the medication and these markers remained unchanged, as well as the manic symptomatology [257].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [257] Khairova R. Pawar R. Salvadore G. Effects of lithium on oxidative stress parameters in healthy subjects Molecular Medicine Reports 2012 5 3 680 682 10.3892/mmr.2011.732 2-s2.0-84856243953 22200861 PMC3289682

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  • May combine two claims.

    Premisecitation

    Lithium can boost GSH rates and also the expression of glutamate-cysteine ligase.

    “It also appears that lithium can boost GSH rates and also the expression of glutamate-cysteine ligase [31]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Shao L. Martin M. V. Watson S. J. Mitochondrial involvement in psychiatric disorders Annals of Medicine 2008 40 4 281 295 10.1080/07853890801923753 2-s2.0-42449146057 18428021 PMC3098560

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  • May combine two claims.

    Premisecitation

    Lithium therapy can affect SOD activity in BD patients, but also in healthy volunteers exposed to this medication.

    “Also, it was noticed that the aforementioned lithium therapy can affect SOD activity in the BD patients, but also in healthy volunteers exposed to this medication [258].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [258] Wang P. S. Walker A. M. Tsuang M. T. Dopamine antagonists and the development of breast cancer Archives of General Psychiatry 2002 59 12 1147 1154 10.1001/archpsyc.59.12.1147 2-s2.0-0036897032 12470131

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    Premisecitation

    Anti-inflammatory and antioxidant properties were showed for antidepressants such as clomipramine and imipramine, which resulted in decreased NO levels.

    “Anti-inflammatory and antioxidant properties were also showed for the antidepressants such as clomipramine and imipramine, which resulted in decreased NO levels [263].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [263] Hadden J. W. Szentivanyi A. Immunopharmacology Reviews 1990 1 New York, NY, USA Plenum

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  • May combine two claims.

    Premisecitation

    Antioxidant properties and decreased NO levels were reported for several SSRIs such as fluoxetine, citalopram, fluvoxamine, or sertraline, together with reduced xanthine oxidase activity and lipid peroxidation processes.

    “In addition, antioxidant properties and decreased NO levels were reported for several SSRIs such as fluoxetine, citalopram, fluvoxamine, or sertraline, together with reduced xanthine oxidase activity [264] and lipid peroxidation processes [265].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [264] Bilici M. Efe H. Köroğlu M. A. Uydu H. A. Bekaroğlu M. Değer O. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments Journal of Affective Disorders 2001 64 1 43 51 10.1016/s0165-0327(00)00199-3 2-s2.0-0035065919 11292519

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    • cites [265] Inkielewicz-Stêpniak I. Impact of fluoxetine on liver damage in rats Pharmacological Reports 2011 63 2 441 447 10.1016/S1734-1140(11)70510-2 2-s2.0-79955931363 21602599

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

    Premisecitation

    Michel et al. group suggested that antidepressant therapy and modulation of oxidative stress are linked and are contributing in a specific way to the oxidative balance.

    “In fact, in a specific review, Michel et al. group suggested that antidepressant therapy and modulation of oxidative stress are linked and are contributing in a specific way to the oxidative balance [7, 127].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [7] Michel T. M. Pülschen D. Thome J. The role of oxidative stress in depressive disorders Current Pharmaceutical Design 2012 18 36 5890 5899 10.2174/138161212803523554 2-s2.0-84867696554 22681168

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    • cites [127] Srivastava N. Barthwal M. K. Dalal P. K. A study on nitric oxide, β-adrenergic receptors and antioxidant status in the polymorphonuclear leukocytes from the patients of depression Journal of Affective Disorders 2002 72 1 45 52 10.1016/s0165-0327(01)00421-9 2-s2.0-0036773956 12204316

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    Premisecitation

    In the treatment course with fluoxetine, the specifications of oxidative and antioxidant context did not modify flagrantly, while including acetylsalicylic acid in the treatment scheme resulted in a significant improvement for the oxidative stress status.

    “it can be noted that, in the treatment course with fluoxetine, the specifications of oxidative and antioxidant context did not modify flagrantly, while including acetylsalicylic acid in the treatment scheme resulted in a significant improvement for the oxidative stress status [124].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] 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 10.1016/S1734-1140(09)70084-2 2-s2.0-67651148093 19605942

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    Premisecitation

    In the context of depression, various studies highlighted that GPX activity becomes normal subsequently to subchronic therapy with antidepressants and NO levels substantially diminish.

    “Although, in the context of depression, various studies highlighted that GPX activity becomes normal subsequently to subchronic therapy with antidepressants [56] and NO levels substantially diminish [262]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [56] 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 38 247 252 17227736

      Not checked in the free run.

    • cites [262] Hwang J. Zheng L. T. Ock J. Inhibition of glial inflammatory activation and neurotoxicity by tricyclic antidepressants Neuropharmacology 2008 55 5 826 834 10.1016/j.neuropharm.2008.06.045 2-s2.0-51049098119 18639562

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Depressive episodes in human individuals are defined by the presence of inflammatory components, which represent an originating site for the reactive oxygen species.

    “One important argument for this could be represented by the fact that the depressive episodes in human individuals are defined by the presence of inflammatory components, which are representing of course an originating site for the reactive oxygen species [7, 270, 271].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] Michel T. M. Pülschen D. Thome J. The role of oxidative stress in depressive disorders Current Pharmaceutical Design 2012 18 36 5890 5899 10.2174/138161212803523554 2-s2.0-84867696554 22681168

      Not checked in the free run.

    • cites [270] Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression Neuroendocrinology Letters 2008 29 3 287 291 18580840

      Not checked in the free run.

    • cites [271] Peet M. Horrobin D. F. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs Archives of General Psychiatry 2002 59 10 913 919 10.1001/archpsyc.59.10.913 2-s2.0-0036790628 12365878

      Not checked in the free run.

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

    Premisecitation

    Antioxidant defense is also constituted in a nonenzymatic component (e.g., ascorbic acid, β-carotene, melatonin, coenzyme Q10, vitamin E, zinc, and glutathione).

    “As in the present paper we referred to the main antioxidant markers as being mainly enzymes, it must be stated of course that antioxidant defense is also constituted in a nonenzymatic component (e.g., ascorbic acid, β-carotene, melatonin, coenzyme Q10, vitamin E, zinc, and glutathione) [274].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [274] Maes M. Galecki P. Chang Y. S. 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 10.1016/j.pnpbp.2010.05.004 2-s2.0-79954568978 20471444 source

      Not checked in the free run.

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

    Premisecitation

    Many biological active molecules are implicated in oxidative stress such as folic acid (vitamin B9).

    “Furthermore, it seems that many biological active molecules are implicated in oxidative stress such as folic acid (vitamin B9) [276].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [276] Taylor M. J. Carney S. M. Goodwin G. M. Geddes J. R. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials Journal of Psychopharmacology 2004 18 2 251 256 10.1177/0269881104042630 2-s2.0-3242663365 15260915

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Several data add up to the fundaments of the hypothesis emphasizing intensified features for the association of antidepressant therapy with antioxidants such as omega-3 acid and N-acetylcysteine in depressed persons and also anxiety SSRI resistant adolescents, all resulting in a better outcome for the treatment course.

    “Several data are adding up to the fundaments of this hypothesis which are emphasising on the intensified features for the association of antidepressant therapy with antioxidants such as omega-3 acid [271] and N-acetylcysteine [272] in depressed persons and also anxiety SSRI resistant adolescents, all of these resulting in a better outcome for the treatment course [11].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [271] Peet M. Horrobin D. F. A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs Archives of General Psychiatry 2002 59 10 913 919 10.1001/archpsyc.59.10.913 2-s2.0-0036790628 12365878

      Not checked in the free run.

    • cites [272] Carvalho A. F. Macêdo D. S. Goulia P. Hyphantis T. N. N-Acetylcysteine augmentation to tranylcypromine in treatment-resistant major depression Journal of Clinical Psychopharmacology 2013 33 5 719 720 10.1097/JCP.0b013e31829839c6 2-s2.0-84883761730 23899640

      Not checked in the free run.

    • cites [11] Smaga I. Niedzielska E. Gawlik M. Oxidative stress as an etiological factor and a potential treatment target of psychiatric disorders. Part 2. Depression, anxiety, schizophrenia and autism Pharmacological Reports 2015 67 3 569 580 10.1016/j.pharep.2014.12.015 2-s2.0-84924330587 25933971 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NAC, which is a precursor of glutathione, can significantly improve the standard therapy, as a double-blind randomized placebo-controlled clinical study performed by Ng et al. in 2008 demonstrated.

    “Coming back to NAC, which is a precursor of glutathione, it has been shown that it can significantly improve the standard therapy, as a double-blind randomized placebo-controlled clinical study performed by Ng et al. in 2008 demonstrated [13].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Ng F. Berk M. Dean O. Bush A. I. Oxidative stress in psychiatric disorders: evidence base and therapeutic implications International Journal of Neuropsychopharmacology 2008 11 6 851 876 10.1017/s1461145707008401 2-s2.0-50849139232 18205981 source

      Not checked in the free run.

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

    Premisecitation

    In MDD it is important to observe the nonenzymatic antioxidant defense dynamics in order to evaluate the psychiatric treatment yielding and to determine future mood attacks.

    “In this way, for example, in MDD it is important to observe the nonenzymatic antioxidant defense dynamics in order to evaluate the psychiatric treatment yielding and to determine future mood attacks [275].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [275] Ibrahim W. Tousson E. El-Masry T. Arafa N. Akela M. The effect of folic acid as an antioxidant on the hypothalamic monoamines in experimentally induced hypothyroid rat Toxicology and Industrial Health 2012 28 3 253 261 10.1177/0748233711410913 2-s2.0-84858432250 21967841

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    NAC is considered a product which can modulate glutathione levels and it is already cited as an adjuvant in BD therapy.

    “In fact, NAC is considered a product which can modulate glutathione levels [149] and it is already cited as an adjuvant in BD therapy [278].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [149] Grande I. Magalhães P. V. Kunz M. Vieta E. Kapczinski F. Mediators of allostasis and systemic toxicity in bipolar disorder Physiology & Behavior 2012 106 1 46 50 10.1016/j.physbeh.2011.10.029 2-s2.0-84857112386 22079584

      Not checked in the free run.

    • cites [278] Odlaug B. L. Grant J. E. N-acetyl cysteine in the treatment of grooming disorders Journal of Clinical Psychopharmacology 2007 27 2 227 229 10.1097/01.jcp.0000264976.86990.00 2-s2.0-34247170051 17414258

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Inclusion of a nonsteroidal anti-inflammatory drug could counteract inflammation and therefore could exert antioxidant actions.

    “Consequently the inclusion of a nonsteroidal anti-inflammatory drug could counteract inflammation and therefore could exert antioxidant actions.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Copper is an essential element for the normal functioning of the antioxidant system, and also plays an important role in immune system modulation, myelin formation, erythropoiesis, and the synthesis of hormones.

    “In addition, copper is another essential element for the normal functioning of the antioxidant system, which also plays an important role in immune system modulation, myelin formation, erythropoiesis, and the synthesis of hormones [155, 156].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Krömer S. A. Keßler M. S. Milfay D. Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety The Journal of Neuroscience 2005 25 17 4375 4384 10.1523/jneurosci.0115-05.2005 2-s2.0-20944449099 15858064 PMC6725100

      Not checked in the free run.

    • cites [156] Ditzen C. Jastorff A. M. Kessler M. S. Protein biomarkers in a mouse model extremes in trait anxiety Molecular and Cellular Proteomics 2006 5 10 1914 1920 10.1074/mcp.m600088-mcp200 2-s2.0-33750610003 16775081

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Zinc could exert some antioxidant effects, with proven effectiveness in clinical and preclinical studies, through the potentiation of the classical antidepressant treatment.

    “Also in the case of zinc, there are reports demonstrating that it could exert some antioxidant effects, with proven effectiveness in clinical and preclinical studies, through the potentiation of the classical antidepressant treatment [289, 290].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [289] Lai J. Moxey A. Nowak G. Vashum K. Bailey K. McEvoy M. The efficacy of zinc supplementation in depression: systematic review of randomised controlled trials Journal of Affective Disorders 2012 136 1-2 e31 e39 10.1016/j.jad.2011.06.022 2-s2.0-84857064428 21798601

      Not checked in the free run.

    • cites [290] Siwek M. Dudek D. Paul I. A. Zinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study Journal of Affective Disorders 2009 118 1–3 187 195 10.1016/j.jad.2009.02.014 2-s2.0-69949143152 19278731 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Alterations in copper levels could lead to deficiencies related to anaemia, neuronal degeneration, and cardiac and immune dysfunctions, or exciding levels of copper could cause cellular instability.

    “In this way, knowing that alterations in copper levels could lead to deficiencies related to anaemia, neuronal degeneration, and cardiac and immune dysfunctions or that the exciding levels of copper could cause cellular instability [286, 287]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [286] Kodama H. Fujisawa C. Bhadhprasit W. Inherited copper transport disorders: biochemical mechanisms, diagnosis, and treatment Current Drug Metabolism 2012 13 3 237 250 10.2174/138920012799320455 2-s2.0-84860505334 21838703 PMC3290776

      Not checked in the free run.

    • cites [287] Młyniec K. Gaweł M. Doboszewska U. Essential elements in depression and anxiety. Part II Pharmacological Reports 2015 67 2 187 194 10.1016/j.pharep.2014.09.009 2-s2.0-84918495329 25712638

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Although the proof of copper implications in the oxidative mechanisms is pretty solid, some animal models studies contradicted the clinical findings, and there is still a need for the determination of the real benefits for copper therapy in patients with depression.

    “Moreover, although the proof of its implications in the oxidative mechanisms is pretty solid, some animal models studies contradicted the clinical findings [285] and therefore, there is still a need for the determination of the real benefits for the copper therapy in patients with depression [288].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [285] Collins J. F. Klevay L. M. Copper Advances in Nutrition 2011 2 6 520 522 10.3945/an.111.001222 2-s2.0-84862275347 22332094 PMC3226389

      Not checked in the free run.

    • cites [288] Swardfager W. Herrmann N. McIntyre R. S. Potential roles of zinc in the pathophysiology and treatment of major depressive disorder Neuroscience & Biobehavioral Reviews 2013 37 5 911 929 10.1016/j.neubiorev.2013.03.018 2-s2.0-84877091127 23567517 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    There are controversies regarding the usage of NAC in the affective disorders, since the same author conducted another study to evaluate the NAC potential to alleviate DD outbreaks, with no significant results obtained in regard to its antidepressant potential.

    “Still, there are also controversies regarding the usage of it in the affective disorders, since the same author conducted another study in order to evaluate the NAC potential to alleviate DD outbreaks, with no significant results obtained in regard to its antidepressant potential [280].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [280] Marshall K.-A. Reiter R. J. Poeggeler B. Aruoma O. I. Halliwell B. Evaluation of the antioxidant activity of melatonin in vitro Free Radical Biology and Medicine 1996 21 3 307 315 10.1016/0891-5849(96)00046-9 2-s2.0-1542312038 8855441

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Lycopene (a carotenoid antioxidant found in tomatoes and other fruits and vegetables) may be an important antioxidant compound, which exhibits no toxic reactions in the animal body.

    “Other studies showed that lycopene (a carotenoid antioxidant found in tomatoes and other fruits and vegetables [302]) may be an important antioxidant compound, which exhibits no toxic reactions in the animal body [303].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [302] Heber D. Lu Q.-Y. Overview of mechanisms of action of lycopene Experimental Biology and Medicine 2002 227 10 920 923 2-s2.0-0036846616 12424335

      Not checked in the free run.

    • cites [303] Niu K. Guo H. Kakizaki M. A tomato-rich diet is related to depressive symptoms among an elderly population aged 70 years and over: a population-based, cross-sectional analysis Journal of Affective Disorders 2013 144 1-2 165 170 10.1016/j.jad.2012.04.040 2-s2.0-84870294305 22840609

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ROS produced during exercise sessions provoke specific adaptation and increased regulation in antioxidant endogenous defenses, while antioxidant enzymes activity is leading to higher resistance to oxidative stress.

    “In fact, it seems that ROS produced during exercise sessions provoke specific adaptation and increased regulation in antioxidant endogenous defenses, while antioxidant enzymes activity is leading to higher resistance to oxidative stress [315, 316].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [315] Lopresti A. L. Hood S. D. Drummond P. D. A review of lifestyle factors that contribute to important pathways associated with major depression: diet, sleep and exercise Journal of Affective Disorders 2013 148 1 12 27 10.1016/j.jad.2013.01.014 2-s2.0-84876966334 23415826

      Not checked in the free run.

    • cites [316] Trofin F.-P. Chirazi M. Honceriu C. Pre-administration of vitamin C reduces exercise-induced oxidative stress in untrained subjects Archives of Biological Sciences 2014 66 3 1179 1185 10.2298/ABS1403179T 2-s2.0-84908155787

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Some studies supported the protective role of exercise against oxidative stress, while others demonstrated increased oxidative stress markers after acute aerobic and anaerobic exercise.

    “However, there are also some controversies about this matter, since some studies supported the protective role of exercise against oxidative stress, while others demonstrated increased oxidative stress markers after acute aerobic [310, 311] and anaerobic exercise [313, 314].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [310] Bloomer R. J. Effect of exercise on oxidative stress biomarkers Advances in Clinical Chemistry 2008 46 1 50 10.1016/s0065-2423(08)00401-0 2-s2.0-53849091705 19004186

      Not checked in the free run.

    • cites [311] Pittaluga M. Parisi P. Sabatini S. Cellular and biochemical parameters of exercise-induced oxidative stress: relationship with training levels Free Radical Research 2006 40 6 607 614 10.1080/10715760600623015 2-s2.0-33744831227 16753838

      Not checked in the free run.

    • cites [313] Bloomer R. J. Goldfarb A. H. Anaerobic exercise and oxidative stress: a review Canadian Journal of Applied Physiology 2004 29 3 245 263 10.1139/h04-017 2-s2.0-3042609590 15199226

      Not checked in the free run.

    • cites [314] Radak Z. Chung H. Y. Goto S. Systemic adaptation to oxidative challenge induced by regular exercise Free Radical Biology and Medicine 2008 44 2 153 159 10.1016/j.freeradbiomed.2007.01.029 2-s2.0-37849004479 18191751

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Francis and Stevenson found that a tomato-rich diet can prevent depressive manifestations and revealed an independent link to lower prevalence rates of depressive behaviours in an elderly community population aged 70 years and over, without any interconnection with intake of other vegetables and depressive symptomatology.

    “In this way, Francis and Stevenson found that a tomato-rich diet can prevent depressive manifestations and revealed an independent link to lower prevalence rates of depressive behaviours in an elderly community population aged 70 years and over, without any interconnection with intake of other vegetables and depressive symptomatology [304].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [304] Francis H. Stevenson R. The longer-term impacts of Western diet on human cognition and the brain Appetite 2013 63 119 128 10.1016/j.appet.2012.12.018 2-s2.0-84873823608 23291218

      Not checked in the free run.

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

    Premisecitation

    Some suspect the possible involvement of oxidative stress in the mechanisms underlying the relationship between the effects of exercising and the affective disorders.

    “Even though the mechanisms underlying the relationship between the effects of exercising and the affective disorders are unknown, some suspect also the possible involvement of oxidative stress [310–313].”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [310] Bloomer R. J. Effect of exercise on oxidative stress biomarkers Advances in Clinical Chemistry 2008 46 1 50 10.1016/s0065-2423(08)00401-0 2-s2.0-53849091705 19004186

      Not checked in the free run.

    • cites [311] Pittaluga M. Parisi P. Sabatini S. Cellular and biochemical parameters of exercise-induced oxidative stress: relationship with training levels Free Radical Research 2006 40 6 607 614 10.1080/10715760600623015 2-s2.0-33744831227 16753838

      Not checked in the free run.

    • cites [312] Eyre H. Baune B. T. Neuroimmunological effects of physical exercise in depression Brain, Behavior, and Immunity 2012 26 2 251 266 10.1016/j.bbi.2011.09.015 2-s2.0-84856013004 21986304

      Not checked in the free run.

    • cites [313] Bloomer R. J. Goldfarb A. H. Anaerobic exercise and oxidative stress: a review Canadian Journal of Applied Physiology 2004 29 3 245 263 10.1139/h04-017 2-s2.0-3042609590 15199226

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    By adopting a healthy diet, the oxidative stress levels may decrease resulting in a lower mood disorder development and even decreased predisposition.

    “Thus, by adopting a healthy diet, the oxidative stress levels may decrease resulting in a lower mood disorder development and even decreased predisposition.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    A significant pattern of oxidative stress involvement in affective disorders development can be theorized by further proposing several biological markers that could be assessed in indicating the oxidative status or antioxidant therapy efficiency.

    “Therefore, a significant pattern of oxidative stress involvement in affective disorders development can be theorized by further proposing several biological markers that could be assessed in indicating the oxidative status or antioxidant therapy efficiency.”
    Quote in the paperNot a substantial claim
82 of 82

  • The paper relies on this without support.

    Oxidative stress is an important component in many diseases.

    “In this way, by knowing that oxidative stress is an important component in many diseases, the idea of counteracting its effects emerged lately in the literature.”

  • The authors state this as an assumption.

    All living organisms are the result of a complex interaction between genome and environment, and mental disorders do not deviate from this pattern.

    “As all living organisms are the result of a complex interaction between genome and environment, the mental disorders seem not to deviate from this pattern.”

  • The authors state this as an assumption.

    Physical exercise might prevent affective disorders development.

    “From here an assumption could be made that they might also prevent affective disorders development.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • Grape-powder PTSD claim cites a depression case series

    Minor

    Reference [174] is a case series on venlafaxine and olanzapine in women with psychotic major depression, not the described grape-powder PTSD animal study. A grape-powder PTSD study is listed at [110].

  • Twin-brothers case report cites a healthy-subjects study

    Minor

    The twin-brothers account cites [257], whose listed title concerns lithium in healthy subjects. The bipolar twin-case report is listed at [256].

  • Venlafaxine claim cites a vitamin C reference

    Minor

    The cited entry [171] is about vitamin C, whereas the venlafaxine study described in the text is listed at [170].

  • Claimed randomized NAC trial cites a review

    Minor

    The text describes [13] as a double-blind randomized placebo-controlled clinical study performed by Ng and colleagues. The listed reference is instead a review of oxidative stress in psychiatric disorders.

  • Phenelzine claim cites a venlafaxine study

    Minor

    Reference [170] is titled as a study of venlafaxine, not phenelzine. The phenelzine study appears as reference [169].

  • Citalopram social-phobia claim cites a bipolar twin report

    Minor

    Reference [256] is a bipolar-disorder twin case report, not the cited citalopram treatment study in social phobia. That study is listed at [255].

  • Ascorbic-acid claim cites a vitamin E study

    Minor

    The claim about ascorbic acid in a depression model cites [108], whose listed title concerns vitamin E deficiency and anxiety. The reference list places the described ascorbic-acid depression study at [172].

  • Tomato-diet finding is attributed to the wrong cited paper

    Minor

    The text attributes the tomato-diet finding to Francis and Stevenson at [304], but their listed paper concerns Western diet and cognition. The tomato-rich-diet paper is listed at [303] under Niu and colleagues.

  • D2 receptor study is described as antagonist rather than agonist

    Minor

    The text calls the drug in reference [199] a D2 receptor antagonist, but the cited reference identifies cabergoline as a D2 receptor agonist. This reverses the stated mechanism of action.

9 of 9

Cites

Flagged first, then by citations

3 of the 316 references couldn’t be matched to a known paper.

Research works printed but not linked: 10

  1. Shah N., 1999, An overview of SSRIs for the treatment of depression, The Journal of the Pharmacy Society of Wisconsin, 33
  2. QuevedoJ. ReusG. AbelairaH.et al. Tianeptine treatment reverses increase on oxidative damage and decrease of antioxidant defense enzymes into the brain of rats submitted to the chronic mild stress model Proceedings of the 28th CINP World Congress of Neuropsychopharmacology 2012.
  3. Delattre J., 2005, Radicaux Libres et Stress Oxydant. Aspects Biologiques et Pathologiques
  4. 10.1007/s11064-006-9258-9 · DOI
  5. 10.1016/j.ejps.2015.10.010 · DOI
  6. Ravindran L. N., 2009, Kaplan and Sadock Comprehensive Textbook of Psychiatry, 1906
  7. World Health Organization, 2008, The Global Burden of Disease: 2004 Update
  8. 10.1016/s0165-0327(00)00199-3 · DOI · Paper page
  9. Maes M., 2008, The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression, Neuroendocrinology Letters, 29, 287
  10. 10.1080/07315724.2003.10719272 · DOI · Paper page

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Authors
Balmus, I. M., Ciobica, A., Antioch, I., Dobrin, R., & Timofte, D.
Affiliations
  • Grigore T. Popa University of Medicine and Pharmacy (RO)
  • Alexandru Ioan Cuza University (RO)
Corresponding author
Ciobica, Alin
ORCID
Venue
Oxidative Medicine and Cellular Longevity
Publisher
Wiley
Published
2016-01
Volume
2016
Issue
1
Pages
3975101-3975101
ISSN
  • 1942-0994 (ISSN-L)
  • 1942-0900
DOI
10.1155/2016/3975101
PMC
PMC4983669
OpenAlex
W2500331684
Semantic Scholar
4844192fc6327d0a73da6ef60dd336a8f824d527
Cited by
103
References
316
Citations by year
2026: 5 · 2025: 6 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 14 · 2020: 15 · 2019: 8 · 2018: 12 · 2017: 9
FWCI
0.90
Type
journal article
Language
en
Open access
Licence
Locations
  • Oxidative Medicine and Cellular Longevity (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (PN-II-RU-TE-2014-4-1886)
Topics
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
oxidative stress, mood disorders, biomarkers, antioxidant therapy, genetic susceptibility, animal models, central nervous system disorders
MeSH terms
Animals, Antioxidants, Disease Models, Animal, Humans, Biomarkers, Oxidative Stress, Mood Disorders

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.

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