Oxidative stress and anxiety -
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nd9 gi. The term Oxidative stress is an imbalance between the cellular production of reactive oxygen species ROS and counteracting antioxidant mechanisms. With high oxygen consumption and a lipid rich environment in brain is considered highly susceptible to oxidative stress or redox imbalances.
Thus, the fact that oxidative stress is implicated in several mental disorders including depression, anxiety disorders, schizophrenia and bipolar disorder, is not surprising. Although several elegant studies have been established a link between oxidative stress and psychiatric disorders, the causal relationship between oxidative stress and psychiatric diseases is not fully determined.
Within the mitochondria, oxidative phosphorylation takes place and it is a major source of ATP in aerobic organisms. It also produces free radicals as a byproduct, including reactive oxygen species [ROS], reactive nitrogen species [RNS], carbon centered and sulfur centered radicals.
With an unpaired number of electrons, free radicals are atoms or groups of atoms that are highly reactive substances which results in chain reactions, with each step forming a free radical. The oxygen reduction to water generates ROS as intermediates that can cause damage.
The primary ROS generated in humans are hydrogen peroxide, superoxide radical and hydroxyl radical. During the process of auto-oxidation of hemoglobin and photolysis the superoxide radical is generated. This superoxide is not peculiarly reactive by itself, but it can be catalytically converted by superoxidase dismutases [SOD] to H2O2, which decomposes to yield the highly reactive hydroxyl radical in the presence of iron.
Of the three drugs, lamotrigine was associated with the greatest antioxidative protective effects Eren et al. An in-vitro study of rat cerebrocortex neuronal and astroglial cultures showed that moclobemide could attenuate cell death induced by anoxia and glutamate, a process involving oxidative stress pathways Verleye et al.
The monoamine oxidase inhibitor phenelzine was able to attenuate the loss of differentiated rat PC12 cells exposed to chemical oxidative stress, and demonstrated antioxidant effects including the reduction of ROS formation and the scavenging of the pro-oxidant hydrogen peroxide Lee et al.
As no clinical trials of antioxidant therapies have been published for major depressive disorder, the primary evidence for antioxidant efficacy at present is derived from the previously cited animal study, which demonstrated the prevention and reversal of shock-induced behavioural depression with glutathione Pal and Dandiya, The beneficial effects of NAC on mood in a non-clinically depressed population have been reported from a double-blind, placebo-controlled study of NAC in patients with mild chronic bronchitis.
NAC recipients showed significantly superior outcomes on the General Health Questionnaire GHQ , which predominantly measures mood, compared with the placebo group Hansen et al.
The limitations to generalizing these indirect results to depression are apparent. The notion of oxidative stress mechanisms underlying anxiety disorder has been in existence for some years, with the earlier suggestion that NO and peroxynitrite might play a major role in setting up a vicious aetiological cycle involving free radicals and inflammatory cytokines in post-traumatic stress disorder Miller, ; Pall and Satterlee, However, oxidation biology research in anxiety disorders is still at its infancy, and the bulk of the limited literature originates from animal studies, which have nevertheless generated intriguing findings.
An interesting set of animal experiments have linked glyoxalase 1 Glo1 and glutathione reductase 1 GR genes, both of which protect against oxidative stress, with anxiety in mice Hovatta et al.
By using behavioural analysis of six inbred mouse strains to determine anxiety phenotypes and quantitative gene expression profiling of seven pertinent brain regions, 17 candidate genes were identified, of which both Glo1 and GR showed positive correlations between their expressed activity levels and phenotypic anxiety status.
The causal role that these genes may play in anxiety were supported by a series of experiments, which confirmed a highly significant positive correlation between the expressed activities of these genes and anxiety in cross-bred mice, and demonstrated that over-expression of Glo1 and GR in the cingulate cortex increased anxiety behaviours, while inhibition of Glo1 gene expression reduced such behaviours Hovatta et al.
The over-expression of Glo1 in innately anxious mice has also been reported by others Landgraf et al. Further evidence for oxidative pathways being involved in mouse models of anxiety can be derived from the association of vitamin E depletion and increased oxidative stress markers and anxiety behaviours in phospholipid transfer protein PLTP knock-out mice Desrumaux et al.
The pro-oxidative vitamin A has been demonstrated to induce oxidative stress in the rat hippocampus, as measured by increased lipid peroxidation, protein carbonylation, protein thiol oxidation, and altered SOD and CAT levels, as well as causing anxiety behaviours in the animal model de Oliveira et al.
In addition, green tea polyphenol — -epigallocatechin gallate EGCG , a potent antioxidant, showed anxiolytic effects on mice with a dose-dependent relationship Vignes et al. Anxiolytic effects have also been reported in mice with chlorogenic acid, a dietary polyphenol and antioxidant Bouayed et al.
Inconsistent results have been reported for whortleberry extracts in rats, and vitamin E was found to increase anxiety in the same study Kolosova et al. In humans, only a handful of relevant studies have been published.
These have reported elevated lipid peroxidation products and antioxidant changes in obsessive—compulsive disorder Ersan et al. The study on social phobia also found a reversal of these disturbances following 8 wk of citalopram treatment Atmaca et al.
A study of anxious women found reduced total antioxidant capacity among this group compared with non-anxious controls, in conjunction with several parameters of impaired immune functioning Arranz et al.
A case series has reported improvement in trichotillomania, pathological nail-biting and skin-picking, conditions that have similarities with obsessive—compulsive disorder, using NAC Odlaug and Grant, Substance abuse and dependence are important to consider in psychiatric disorders, given the substantial overlap between the two in terms of syndromal manifestations and causality.
A solid body of literature exists in support of the association between oxidative stress and common drugs of abuse, including nicotine Petruzzelli et al. Although their precise roles are yet to be fully understood, oxidative mechanisms have been proposed to mediate both the processes of drug addiction and toxicity Kovacic, ; Kovacic and Cooksy, , and antioxidants may thus have therapeutic potential in the management of these conditions.
Preclinical evidence has indicated antioxidants to be promising in alcohol Amanvermez and Agara, , heroin Zhou and Kalivas, and cocaine dependence Baker et al. Pilot clinical trial data of NAC in cocaine dependence have been promising, suggesting that craving and withdrawal symptoms LaRowe et al.
A growing literature has been published that cites evidence for oxidative disturbances in autism, including genetic polymorphisms affecting oxidative metabolic pathways James et al. Currently, the most robust and multi-dimensional evidence for the pathophysiological involvement of oxidative stress is for schizophrenia, followed by bipolar disorder, with both having support from preclinical and clinical research.
The data is less extensive for the other psychiatric disorders, but there is accumulating evidence indicating a role of oxidative stress in their aetiopathogenesis. In summary, there is evidence for glutathione depletion in schizophrenia; increased lipid peroxidation in schizophrenia, bipolar and major depressive disorders; and reduction in antioxidants such as albumin and bilirubin in schizophrenia and major depressive disorder.
Findings in relation to NO and antioxidative enzymes in these disorders have been less consistent. Data from molecular and genetic studies have implicated oxidative metabolic pathways in the aetiopathogenesis of schizophrenia, bipolar disorder and possibly anxiety disorders.
Antipsychotics, mood stabilizers and antidepressants have all been demonstrated to have antioxidative effects, and some antioxidants have been reported to be of therapeutic benefit, including vitamins C and E and EGb for schizophrenia, and NAC for schizophrenia and bipolar disorder.
In the interpretation of mass data, the context and limitations of each investigation must be borne in mind. In view of the complexities of psychiatric conditions and biological systems, and the diversity of research areas, the collective significance of study findings would be expected to have greater strength than individual results.
For instance, a substantial portion of the existing evidence base is derived from the comparison of oxidative biochemical status of patients with controls, and such studies have yielded apparently inconsistent results, with varying presence, directions or combinations of disturbances in markers of oxidant and antioxidant activities.
Moreover, psychiatric syndromes are aetiologically heterogeneous, commonly chronic and multiphasic, and often overlapping, thus further complicating the specificity of individual marker changes.
Alternatively, it is possible that the mixed findings may signify an indirect pathophysiological role of the relevant oxidative markers in the disorders. However, on balance, the literature as a whole seems to provide sufficient consistent evidence that oxidative stress balance is significantly altered in patient groups.
In particular, findings of elevated oxidative products across disorders supply fairly direct evidence of increased oxidative stress, while its aetiological significance is supported by genetic and molecular studies that link specific oxidative pathway polymorphisms or gene expression to specific disorders.
Genetic manipulation experiments demonstrating positive correlations between the expression of specific oxidative genes and anxiety behaviours in animal models further validate this aetiopathogenic hypothesis.
However, it is difficult to distinguish from current data whether oxidative stress results from primary excessive mitochondrial energy generation, primary dysfunction within oxidative homeostatic mechanisms, or both.
Impaired mitochondrial energy metabolism has also been suggested to be a fundamental defect in bipolar disorder Kato, ; Young, , with hypometabolism, energy imbalance and oxidative stress assuming secondary roles, and may present an alternative hypothesis.
In practical terms, pharmacological and clinical studies have established the antioxidant properties of efficacious pharmacotherapies, and antioxidant treatment data, although limited in quantity, have reported promising therapeutic potentials.
The implications of the expanding data on oxidative stress mechanisms in psychiatric disorders are twofold, having salience in both furthering their aetiopathogenic understanding and treatment options. In relation to the former, the aetiopathogenic mechanisms for psychiatric disorders remain largely elusive, despite the growth of hypotheses on multiple conceptual levels that include sociocultural systems, personality, cognitive schemata, behavioural learning, neuroanatomy, psychoneuroendoimmunology, biomolecules and genetics.
Given the complexities of human psychobehavioural systems and the infinite deterministic variability behind their manifestations, basic biopathway pathologies may present tangible and widely applicable pathophysiological models, as all psychobehavioural manifestations must have fundamental biological underpinnings.
There is gathering evidence for oxidative stress to be one such biopathway, as oxidative damage is believed to be a major mechanism underlying cell dysfunction and death in both ageing and disease processes, although its temporal role in and relative contribution to these processes is likely to vary.
Theoretically, oxidative stress may result from the overproduction of free radicals, defective oxidative homeostasis, or a combination of both. Each of these situations, in turn, is likely to stem from different causes, which may include overactive oxidative metabolism driven by physiological stress, pathogens or the inflammatory response, genetic polymorphisms and physiological factors that undermine the oxidative defence capacity of the individual, and differential expression of mitochondrial and metabolic enzymes.
Once established, secondary amplifications or self-perpetuating oxidative cascades may also play a role in the pathogenesis of illnesses, the continuation of symptoms and vulnerability to future illness relapses. Evidence for the interdependent relationships between oxidative pathways and those involving neurotransmitters, hormones and inflammatory mediators further enhance the plausibility of the oxidative stress hypothesis, and provide a unifying framework for the various conceptual theories of causality.
Dopaminergic, noradrenergic and glutamatergic overactivity have been demonstrated to induce cytotoxicity via oxidative stress among other mechanisms Chan et al. These connections provide a basis for explaining phenomena such as drug-induced and organic psychiatric syndromes, as well as comorbid somatic and psychiatric disorders.
The association of particular neurochemical pathways with oxidative stress induction, combined with the differing vulnerabilities of neuronal and glial cells to oxidative damage according to their types and anatomical positions, may help to explain the involvement of specific neurological sites in psychiatric syndromes.
This specificity of site can be observed in neuroimaging studies Ettinger et al. The involvement of similar sites across conditions may also account for their symptomatic overlap and diagnostic mutability. Apart from conceptual utility, a theory of value should also demonstrate practical applicability.
An appealing aspect of the oxidative stress theory is that regardless of the precise defect s , this state of disequilibrium can theoretically be corrected by bolstering the total antioxidant capacity, providing that the supplementary antioxidants are bioactive and able to access the brain.
The practical utility of this theory has already garnered support from the existing literature, which has found benefits from the use of vitamins C and E, EGb, NAC and other antioxidants in psychiatric disorders. NAC, in particular, seems to hold the most promising evidence for efficacy across diagnoses, with benefits recently reported for schizophrenia, bipolar disorder, cocaine dependence, and impulsive control disorders.
This may relate to its bioavailability and putative mechanisms of replenishing and enhancing glutathione stores Dean et al. Further clinical evidence is required to consolidate the efficacies of antioxidants for the various conditions, but their potential in acute and maintenance treatment settings are clearly implied on theoretical grounds.
Furthermore, these treatments may be useful in the prevention of long-term sequelae by minimizing cell damage and cell death, as well as primary prevention in vulnerable individuals. These treatments are generally associated with low occurrence of side-effects, which is an attractive feature conducive to long-term treatment adherence.
The investigation of antioxidants in psychiatric disorders has perhaps been hampered by several unfavourable factors, the main ones probably relating to the conventional aetiopathophysiological understanding of psychiatric disorders and to misconceptions about antioxidants.
Traditionally, psychiatric teachings and research have focused on neurotransmitter aetiological theories, such as the dopamine theory for schizophrenia and the monoamine hypothesis for depression, and these have provided a basis for therapeutic manipulations.
The unfamiliar mechanisms of action of antioxidants to clinical psychiatry may thus have contributed to their peripheral therapeutic status. Furthermore, the heterogeneity within antioxidants as a class is not widely appreciated. Differences exist among the antioxidants in their targets of action, as well as in their pharmacokinetic properties.
Vitamin E, for example, has a principal antioxidant action of scavenging peroxyl radicals in biological lipid phases Traber and Atkinson, , in addition to multiple non-antioxidant properties that include modulation of signal transduction, transcriptional and translational processes Zingg and Azzi, , yet its antioxidant efficacy in pathological redox states has not been established Azzi, Vitamin C, on the other hand, is a scavenger of free radicals in water phases Rodrigo et al.
The specific antioxidant actions of these agents, when applied to neuropsychiatric conditions where the precise oxidative defects are not yet clear, may account for some inefficacious trial findings Boothby and Doering, In this respect, glutathione may be the most generic of cellular antioxidants in terms of its molecular actions, which may explain the promising findings with NAC.
Besides pharmacological treatments, lifestyle and dietary manipulations are relevant in optimizing oxidative balance.
A diet rich in natural antioxidants and the avoidance of oxidative stress-inducing habits such as cigarette smoking and substance abuse are prudent measures. Diets high in saturated fats may increase oxidative stress Shih et al.
Physical exercise, specifically endurance training, has also been suggested to have a beneficial impact on oxidative stress status, possibly mediated by increasing total antioxidant capacity and GSH-Px activity Fatouros et al.
Although the current state of evidence is not yet mature enough to adopt this in clinical practice, findings of syndrome- Reddy et al.
Genetic polymorphisms of antioxidant enzymes, associated with psychiatric disorders Akyol et al. In research, broad areas remain to be explored on both preclinical and clinical levels, especially for mood and anxiety disorders which have an early evidence base.
The use of antioxidants in their treatment is both substantiated and promising, in view of the internally consistent theoretical framework, convincing early evidence, wide-ranging potential therapeutic benefits, the high population prevalence and overall disease burden associated with these disorders, and the limited efficacies of existing pharmacotherapies.
Abdalla DS Monteiro HP Oliveira JA Bechara EJ Activities of superoxide dismutase and glutathione peroxidase in schizophrenic and manic-depressive patients. Clinical Chemistry 32 , — Google Scholar. Adler LA Edson R Lavori P Peselow E Duncan E Rosenthal M Rotrosen J Long-term treatment effects of vitamin E for tardive dyskinesia.
Biological Psychiatry 43 , — Adler LA Rotrosen J Edson R Lavori P Lohr J Hitzemann R Raisch D Caligiuri M Tracy K Vitamin E treatment for tardive dyskinesia. Veterans Affairs Cooperative Study Study Group.
Archives of General Psychiatry 56 , — Akyol O Herken H Uz E Fadillioglu E Unal S Sogut S Ozyurt H Savas HA The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. Progress in Neuropsychopharmacology and Biological Psychiatry 26 , — Akyol O Yanik M Elyas H Namli M Canatan H Akin H Yuce H Yilmaz HR Tutkun H Sogut S et al.
Association between Ala-9Val polymorphism of Mn-SOD gene and schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry 29 , — Altuntas I Aksoy H Coskun I Caykoylu A Akcay F Erythrocyte superoxide dismutase and glutathione peroxidase activities, and malondialdehyde and reduced glutathione levels in schizophrenic patients.
Clinical Chemistry and Laboratory Medicine 38 , — Amanvermez R Agara E Advances in Therapy 23 , — Andreassen OA Jorgensen HA Neurotoxicity associated with neuroleptic-induced oral dyskinesias in rats. Implications for tardive dyskinesia? Progress in Neurobiology 61 , — Andreazza AC Cassini C Rosa AR Leite MC de Almeida LM Nardin P Cunha AB Cereser KM Santin A Gottfried C et al.
Serum SB and antioxidant enzymes in bipolar patients. Journal of Psychiatric Research 41 , — Arranz L Guayerbas N De la Fuente M Impairment of several immune functions in anxious women. Journal of Psychosomatic Research 62 , 1 — 8. Arvindakshan M Ghate M Ranjekar PK Evans DR Mahadik SP a.
Supplementation with a combination of omega-3 fatty acids and antioxidants vitamins E and C improves the outcome of schizophrenia. Schizophrenia Research 62 , — Arvindakshan M Sitasawad S Debsikdar V Ghate M Evans D Horrobin DF Bennett C Ranjekar PK Mahadik SP b.
Essential polyunsaturated fatty acid and lipid peroxide levels in never-medicated and medicated schizophrenia patients. Biological Psychiatry 53 , 56 — Atkuri KR Mantovani JJ Herzenberg LA Herzenberg LA Current Opinion in Pharmacology 7 , — Atmaca M Tezcan E Kuloglu M Ustundag B Kirtas O The effect of extract of ginkgo biloba addition to olanzapine on therapeutic effect and antioxidant enzyme levels in patients with schizophrenia.
Psychiatry and Clinical Neurosciences 59 , — Atmaca M Tezcan E Kuloglu M Ustundag B Tunckol H Antioxidant enzyme and malondialdehyde values in social phobia before and after citalopram treatment.
European Archives of Psychiatry and Clinical Neuroscience , — Azzi A Molecular mechanism of alpha-tocopherol action. Free Radical Biology and Medicine 43 , 16 — Baker DA Madayag A Kristiansen LV Meador-Woodruff JH Haroutunian V Raju I Contribution of cystine-glutamate antiporters to the psychotomimetic effects of phencyclidine.
Published online: 29 August doi: Baker DA McFarland K Lake RW Shen H Toda S Kalivas PW N-acetyl cysteine-induced blockade of cocaine-induced reinstatement.
Annals of the New York Academy of Sciences , — Barnham KJ Masters CL Bush AI Neurodegenerative diseases and oxidative stress. Nature Reviews. Drug Discovery 3 , — Ben Othmen L Mechri A Fendri C Bost M Chazot G Gaha L Kerkeni A Altered antioxidant defense system in clinically stable patients with schizophrenia and their unaffected siblings.
Progress in Neuropsychopharmacology and Biological Psychiatry. Published online: 14 August Benes FM Matzilevich D Burke RE Walsh J The expression of proapoptosis genes is increased in bipolar disorder, but not in schizophrenia. Molecular Psychiatry 11 , — Berk M The glutathione precursor N-acetyl cysteine as a treatment for oxidative stress in bipolar disorder: a double-blind randomised placebo controlled trial.
Bipolar Disorders 9 Suppl. Berk M Bodemer W Van Oudenhove T Butkow N The platelet intracellular calcium response to serotonin is augmented in bipolar manic and depressed patients. Human Psychopharmacology 10 , — Berk M Kirchmann NH Butkow N Clinical Neuropharmacology 19 , 48 — Bilici M Efe H Koroglu MA Uydu HA Bekaroglu M Deger O Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments.
Journal of Affective Disorders 64 , 43 — Boothby LA Doering PL Vitamin C and vitamin E for Alzheimer's disease. Annals of Pharmacotherapy 39 , — Bouayed J Rammal H Dicko A Younos C Soulimani R a. Chlorogenic acid, a polyphenol from Prunus domestica Mirabelle , with coupled anxiolytic and antioxidant effects.
Journal of the Neurological Sciences , 77 — Bouayed J Rammal H Younos C Soulimani R b. Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice. European Journal of Pharmacology , — Buckman TD Kling AS Eiduson S Sutphin MS Steinberg A Glutathione peroxidase and CT scan abnormalities in schizophrenia.
Biological Psychiatry 22 , — Chan AS Ng LW Poon LS Chan WW Wong YH Dopaminergic and adrenergic toxicities on SK-N-MC human neuroblastoma cells are mediated through G protein signaling and oxidative stress.
Apoptosis 12 , — Chauhan A Chauhan V Brown WT Cohen I Oxidative stress in autism: increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin—the antioxidant proteins.
Life Sciences 75 , — Chen B Wang JF Young LT Chronic valproate treatment increases expression of endoplasmic reticulum stress proteins in the rat cerebral cortex and hippocampus.
Biological Psychiatry 48 , — Chen G Zeng WZ Yuan PX Huang LD Jiang YM Zhao ZH Manji HK The mood-stabilizing agents lithium and valproate robustly increase the levels of the neuroprotective protein bcl-2 in the CNS. Journal of Neurochemistry 72 , — Chen J Wersinger C Sidhu A Chronic stimulation of D1 dopamine receptors in human SK-N-MC neuroblastoma cells induces nitric-oxide synthase activation and cytotoxicity.
Journal of Biological Chemistry , — Chovanova Z Muchova J Sivonova M Dvorakova M Zitnanova I Waczulikova I Trebaticka J Skodacek I Durackova Z Free Radical Research 40 , — Cui J Shao L Young LT Wang JF Role of glutathione in neuroprotective effects of mood stabilizing drugs lithium and valproate.
Neuroscience , — Dakhale G Khanzode S Khanzode S Saoji A Khobragade L Turankar A Oxidative damage and schizophrenia: the potential benefit by atypical antipsychotics. Neuropsychobiology 49 , — Dakhale GN Khanzode SD Khanzode SS Saoji A Supplementation of vitamin C with atypical antipsychotics reduces oxidative stress and improves the outcome of schizophrenia.
Psychopharmacology , — Davies KJ Oxidative stress: the paradox of aerobic life. Biochemical Society Symposium 61 , 1 — Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life 50 , — de Oliveira MR Silvestrin RB Mello EST Moreira JC Oxidative stress in the hippocampus, anxiety-like behavior and decreased locomotory and exploratory activity of adult rats: effects of sub acute vitamin A supplementation at therapeutic doses.
Neurotoxicology 28 , — de Vasconcellos AP Nieto FB Crema LM Diehl LA de Almeida LM Prediger ME da Rocha ER Dalmaz C Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress. Neurochemical Research 31 , — Dean O van den Buurse M Copolov D Berk M Bush AI N-acetylcysteine treatment inhibits depletion of brain glutathione levels in rats: implications for schizophrenia.
International Journal of Neuropsychopharmacology 7 , S Desrumaux C Risold PY Schroeder H Deckert V Masson D Athias A Laplanche H Le Guern N Blache D Jiang XC et al.
Phospholipid transfer protein PLTP deficiency reduces brain vitamin E content and increases anxiety in mice. FASEB Journal 19 , — Dietrich-Muszalska A Olas B Isoprostenes as indicators of oxidative stress in schizophrenia.
World Journal of Biological Psychiatry. Published online: 11 May Dietrich-Muszalska A Olas B Rabe-Jablonska J Oxidative stress in blood platelets from schizophrenic patients.
Platelets 16 , — Dietrich JB Mangeol A Revel MO Burgun C Aunis D Zwiller J Acute or repeated cocaine administration generates reactive oxygen species and induces antioxidant enzyme activity in dopaminergic rat brain structures.
Neuropharmacology 48 , — Do KQ Lauer CJ Schreiber W Zollinger M Gutteck-Amsler U Cuenod M Holsboer F gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders.
Journal of Neurochemistry 65 , — Do KQ Trabesinger AH Kirsten-Kruger M Lauer CJ Dydak U Hell D Holsboer F Boesiger P Cuenod M Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo.
European Journal of Neuroscience 12 , — Drieu K Vranckx R Benassayad C Haourigi M Hassid J Yoa RG Rapin JR Nunez EA Effect of the extract of Ginkgo biloba EGb on the circulating and cellular profiles of polyunsaturated fatty acids: correlation with the anti-oxidant properties of the extract.
Prostaglandins, Leukotrienes, and Essential Fatty Acids 63 , — Dvorakova M Sivonova M Trebaticka J Skodacek I Waczulikova I Muchova J Durackova Z The effect of polyphenolic extract from pine bark, Pycnogenol on the level of glutathione in children suffering from attention deficit hyperactivity disorder ADHD.
Redox Report 11 , — Eren I Naziroglu M Demirdas A a. Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochemical Research 32 , — Eren I Naziroglu M Demirdas A Celik O Uguz AC Altunbasak A Ozmen I Uz E b.
Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Ersan S Bakir S Erdal Ersan E Dogan O Examination of free radical metabolism and antioxidant defence system elements in patients with obsessive-compulsive disorder. Progress in Neuropsychopharmacology and Biological Psychiatry 30 , — Ettinger U Picchioni M Landau S Matsumoto K van Haren NE Marshall N Hall MH Schulze K Toulopoulou T Davies N et al.
Magnetic resonance imaging of the thalamus and adhesio interthalamica in twins with schizophrenia. Archives of General Psychiatry 64 , — Evans DR Parikh VV Khan MM Coussons C Buckley PF Mahadik SP Red blood cell membrane essential fatty acid metabolism in early psychotic patients following antipsychotic drug treatment.
Prostaglandins, Leukotrienes, and Essential Fatty Acids 69 , — Fatouros IG Jamurtas AZ Villiotou V Pouliopoulou S Fotinakis P Taxildaris K Deliconstantinos G Oxidative stress responses in older men during endurance training and detraining.
Medicine and Science in Sports and Exercise 36 , — Filomeni G Ciriolo MR Redox control of apoptosis: an update. Antioxidants and Redox Signaling 8 , — Finkel T Holbrook NJ Oxidants, oxidative stress and the biology of ageing. Nature , — Forlenza MJ Miller GE Psychosomatic Medicine 68 , 1 — 7.
Frey BN Andreazza AC Kunz M Gomes FA Quevedo J Salvador M Goncalves CA Kapczinski F Increased oxidative stress and DNA damage in bipolar disorder: a twin-case report. Progress in Neuropsychopharmacology and Biological Psychiatry 31 , — Frey BN Martins MR Petronilho FC Dal-Pizzol F Quevedo J Kapczinski F a.
Increased oxidative stress after repeated amphetamine exposure: possible relevance as a model of mania. Bipolar Disorders 8 , — Frey BN Valvassori SS Gomes KM Martins MR Dal-Pizzol F Kapczinski F Quevedo J b. Increased oxidative stress in submitochondrial particles after chronic amphetamine exposure.
Brain Research , — Frey BN Valvassori SS Reus GZ Martins MR Petronilho FC Bardini K Dal-Pizzol F Kapczinski F Quevedo J c. Changes in antioxidant defense enzymes after d-amphetamine exposure: implications as an animal model of mania. Frey BN Valvassori SS Reus GZ Martins MR Petronilho FC Bardini K Dal-Pizzol F Kapczinski F Quevedo J d.
Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania. Journal of Psychiatry and Neurosciences 31 , — Fukami G Hashimoto K Koike K Okamura N Shimizu E Iyo M Effect of antioxidant N-acetyl-L-cysteine on behavioral changes and neurotoxicity in rats after administration of methamphetamine.
Brain Research , 90 — Fukunaga K Yoshida M Nakazono N A simple, rapid, highly sensitive and reproducible quantification method for plasma malondialdehyde by high-performance liquid chromatography. Biomedical Chromatography 12 , — Gama CS Salvador M Andreazza AC Kapczinski F Silva Belmonte-de-Abreu P Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in schizophrenia: a study of patients treated with haloperidol or clozapine.
Gergerlioglu HS Savas HA Bulbul F Selek S Uz E Yumru M Changes in nitric oxide level and superoxide dismutase activity during antimanic treatment.
Goff DC Coyle JT The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. American Journal of Psychiatry , — Gysin R Kraftsik R Sandell J Bovet P Chappuis C Conus P Deppen P Preisig M Ruiz V Steullet P et al.
Impaired glutathione synthesis in schizophrenia: convergent genetic and functional evidence. Proceedings of the National Academy of Sciences USA , — Halliwell B
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Keywords: Antioxidant therapyanxiety disordersanxlety stress anxoety, toxicity. Title: Association of Oxidative Anxuety to the Genesis oxicative Anxiety: Implications for Possible Therapeutic Interventions.
Volume: 12 Issue: 2. Author s : Waseem Hassan, Carlos E. Silva, Imdad Ullah Mohammadzai, Joao B. da Rocha and Jesus Landeira-Fernandez. Abstract: Oxidative stress caused by reactive species, including reactive oxygen species, reactive nitrogen species, and unbound, adventitious metal ions e.
Hassan Waseem, E. Silva Carlos, Ullah Mohammadzai Imdad, da Rocha Joao B. and Landeira-Fernandez Jesus, Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions, Current Neuropharmacology ; 12 2.
Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions Author s : Waseem Hassan, Carlos E. da Rocha and Laboratorio de Neurociencia Comportamental, Departamento de Psicologia, Pontifícia Universidade Catolica do Rio de Janeiro, Rua Marques de Sao Vicente,Rio de Janeiro, RJ, Brazil.
Purchase PDF. Mark Item. Current Neuropharmacology. Title: Association of Oxidative Stress to the Genesis of Anxiety: Implications for Possible Therapeutic Interventions Volume: 12 Issue: 2 Author s : Waseem Hassan, Carlos E.
da Rocha and Jesus Landeira-Fernandez Affiliation: Keywords: Antioxidant therapyanxiety disordersoxidative stresstoxicity. Close Print this page. Export Options ×. Export File: RIS for EndNote, Reference Manager, ProCite.
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: Oxidative stress and anxiety| Human Verification | Article Streas. Zhang XY Zhou DF Cao Oxidative stress and anxiety Oidative PY Wu GY Shen YC beta-Carotene Organic Guarana Powder canthaxanthin alter the pro-oxidation and antioxidation balance in rats fed a high-cholesterol and high-fat diet. Dal-Pizzol F. Currently, there is increasing evidence that the advantageous effects of antioxidants on health are not only attributed to their antioxidant properties. Berk M Kirchmann NH Butkow N |
| Oxidative Imbalance and Anxiety Disorders | Bentham Science | References 1. Adler LA Edson R Lavori P Peselow Organic Guarana Powder Duncan E Rosenthal M Oxidatuve Organic Guarana Powder Reale M et al Ixidative of chemo-cytokine production Aging well blogs schizophrenic anxiegy versus healthy controls. Differences exist among the antioxidants in their targets of action, as well as in their pharmacokinetic properties. In agreement with these results, we have also found that the behaviour of anxious and non-anxious mice did not significantly vary in the tail suspension and forced swimming tests, the well-known predictive tests of depression-related behaviour unpublished results. |
| Oxidative Stress and Anxiety Disorder | A complex and heterogeneous disorder that has negative impact on quality of life, morbidity or mortality, and cognitive function is known as depression. Several years ago, the oxidative stress has received much attention with regards to psychiatric illnesses and also been proposed as a contributing factor in the pathogenesis of depression. Several lines of evidence specify the involvement of oxidative and nitrosative stress in the pathophysiology of major depression. Therefore, for novel anti-depressants the oxidative and nitrosative mechanisms have been proposed as targets. It was studied that the individuals who are suffering with depression has been displayed with lower serum or plasma antioxidant potentials and reduced brain GSH levels. In depressed patients the circulatory levels of F2- isoprostanes are increased and are correlated with the severity of depressive symptoms and urinary excretion of 8 hydroxydeoxyguanosine seems to be higher when compared to healthy controls. Bipolar disorder is characterized by intermittent episodes of mania or hypomania that usually interlaced with depressive episodes. This is also a serious mood disorder which is clinically presented as unusual shifts in mood, energy and cognitive levels, with or without depressive episodes. Symptoms are different from the normal ups and downs, and this disorder may seriously damage relationships, job life or school performance, and even tend to suicide. In several studies it has been reported that patients with bipolar disorder have significant alterations in lipid peroxidation, antioxidant enzymes, and nitric oxide levels, such as increased lipid peroxidation and increased Nitric Oxide levels. Here the accumulating evidence implicates of free radical mediated pathology, altered antioxidant capacity, neurotoxicity and inflammation in neuropsychiatric disorders. It is also stated up to what extent oxidative stress contributes to specific clinical symptomatology of these complex and debilitating psychiatric ailments remains to be seen. A major question remains still regarding the causal role of oxidative stress in these illnesses, which is highly critical for early and preventive intervention. Export Options ×. Export File: RIS for EndNote, Reference Manager, ProCite. Content: Citation Only. Citation and Abstract. About this article ×. Cite this article as: Krolow R. Close About this journal. Related Journals Anti-Cancer Agents in Medicinal Chemistry. Current Bioactive Compounds. Current Cancer Drug Targets. Current Cancer Therapy Reviews. Current Diabetes Reviews. Current Drug Safety. Current Drug Targets. Current Drug Therapy. View More. Related Books Advanced Pharmacy. Plant-derived Hepatoprotective Drugs. The Role of Chromenes in Drug Discovery and Development. New Avenues in Drug Discovery and Bioactive Natural Products. Practice and Re-Emergence of Herbal Medicine. Methods for Preclinical Evaluation of Bioactive Natural Products. Nanopharmacology and Nanotoxicology: Clinical Implications and Methods. Frontiers in Clinical Drug Research - CNS and Neurological Disorders. Traditional Medicine for Neuronal Health. The sensitivity of brain to oxygen increases with increasing age following the natural consequence of brain aging, which is characterized among others by the declining ability of the antioxidant system to prevent against oxidative damages resulting from non-detoxified ROS Mariani et al. The present chapter focuses on the link between OS and anxiety, discussing and reviewing different findings obtained from humans and rodents in this field. The emerging role of antioxidants as a potential new strategy for the prevention and treatment of anxiety is also debated. GABAergic and serotoninergic systems are considered among the principal regulatory systems of anxiety. However, following to recent findings of Kuloglu et al. This hypothesis has gained interest due to the intrinsic oxidative vulnerability of the brain see above. When the production of ROS prevails over the brain defense systems, the lipid-rich constitution of brain may favour lipid peroxidation, constituting a free radical chain reaction that may result in decrease in membrane fluidity and damage in membrane proteins inactivating receptors, enzymes and ion channels, even disrupting membrane integrity resulting eventually in cell death. In addition to oxidative damage of neuronal membrane lipids and proteins, oxidation of other sensitive components such as nucleic acids and neurotransmitters can occur. As a result, OS can alter neurotransmission, neuronal function and overall brain activity Bouayed et al. Therefore, brain oxidative damage might be also a plausible pathogenic factor for certain multifactorial neurological diseases including neuropsychiatric troubles. Interestingly, OS state was recently linked to other behavioural disorders, such as aggressive behaviour and depression, and also to deterioration of short-term spatial memory Bouayed et al. Moreover, patients suffering from major depression have presented OS in both their peripheral as well as their central systems Bilici et al. Curiously, some of these conditions e. aggressiveness and depressed mood could also be associated with anxiety. For instance, Bayani et al. In animals, it has been shown that dominant rodents had high levels of anxiety and they often exhibited aggressive behaviour toward subaltern subjects Ferrari et al. Anxiety may also coexist with depression and for defining these states the term comorbidity is usually used. Such mixed states of anxiety and depression make coping of the disease more difficult. It concerns both general prognosis, as well as treatment response in this cohort of patients. For example, in the Finnish population-wide Health Survey, it has been estimated that In their studies, Kuloglu et al. superoxide dismutase and glutathione peroxidase in erythrocytes and the level of malondialdehyde in plasma as markers of oxidative status of human subjects healthy volunteers versus patients suffering from obsessive—compulsive disorder and panic disorder. Other human studies have shown the validity of these biomarkers to assess OS state. In the light of results from Kuloglu et al a and b establishing a relationship between OS and anxiety disorder, other recent studies have focused on the link between redox status and normal anxiety, and also on a possible causal relationship between cellular oxidative stress and emotional stress using rodents as animal model. Mice and rats are often used as translational models for studying anxiety in humans due to the similarity in the extremely complex mechanisms involved in anxiety in these species. Indeed, the principal brain areas e. the amygdala implicated in the processing or the suppression of fear and anxiety, the comparable brain circuits involved with anxiety, and the similar neurochemical substrates e. GABA, serotonin among others, make rodents a good model to study anxiety in humans Mathew et al. These behavioural tests are also sensitive to pharmacological agents with anxiolytic or anxiogenic properties, causing a decrease or an increase in the anxiety-related behaviour of animals, respectively. Afterwards, they have demonstrated a close correlation between brain expression of genes of the antioxidative defense system glutathione reductase 1 and glyoxalase 1 and anxiety-related phenotypes across all mouse strains. They further found that the activity of the antioxidative enzymes of glutathione reductase 1 and glyoxalase 1 is highest in the most anxious strain and lowest in the least anxious strains. A link between OS and emotional stress is not surprising per se; since it is well accepted that oxidative damage in the brain may cause an impairment of the nervous system. For example, abnormalities in the regulatory systems of anxiety in rodents e. GABAergic and serotoninergic systems can result in anxious behaviour. Furthermore, alteration of the function of the hypothalamic-pituitary-adrenal HPA axis, which is implicated in stress responses and anxiety disorders, could also impact the emotional response. However, the second part of results of Hovatta et al. Indeed, they found that local overexpression of glutathione reductase 1 and glyoxalase 1 in the cingulated cortex of the murine brain results in an increase of anxiety-like behaviour, while inhibition of glyoxalase 1 expression produces low-anxiety. Thus, Hovatta et al. However, in vivo , antioxidant genes e. superoxide dismutase, glutathione peroxidase and glutathione reductase are normally overexpressed in response to an uncontrolled production of ROS. In certain cases, OS leads to silencing of genes encoding antioxidant defensive enzymes. In the lentivirus experiments of Hovatta et al. Clearly, the mechanism by which these antioxidant defensive enzymes regulate anxiety is of great interest. Additionally, Hovatta et al. Enzymatic activity of glyoxalase 1 aims to protect against carbonyl stress resulting from excessive accumulation of reactive dicarbonyl compounds. Carbonyl stress leads to protein and nucleotide damages by dicarbonyl glycation, which is associated with several pathologies including diabetes Thornalley, a, b and c. Glutathione GSH , which is a major antioxidant in the brain, constitutes a determinant cofactor for the enzymatic reaction that is catalyzed by glyoxalase 1. However, a close relation between oxidative stress and carbonyl stress was established. Curiously, other findings from another laboratory Krömer et al. Contradictory, they have proposed that the level of expression of glyoxalase 1 could be used as a physiological marker of trait anxiety level, with high protein expression indicating low trait anxiety level and low expression for high trait anxiety. Indeed, comparing two Swiss CD1 mouse lines with extremes in trait anxiety, these authors found that glyoxalase 1 was more expressed in the line with low-anxiety-related behavioural phenotype than in the line with high-anxiety-related behavioural phenotype. The expression of glyoxalase 1 has been assessed in several brain areas and also in red blood cells of mice. Differences in the genotype of this strain and those used by Hovatta et al. Thus, it would be interesting to compare in the same strain, anxiety-related behaviour of mice with their oxidative status rather than compare the redox status of strains differing in their anxiety-related phenotypes. This approach takes into account the intra-variability between individuals of the same strain. Because of the large heterogeneity in their anxiety levels, Swiss albino male mice OF1 constitute an interesting behavioural model to study the link between oxidative status and anxiety-related behaviour. Our results suggested a positive relationship between peripheral oxidative status and level of anxiety in mice. To confirm the relationship between OS and emotional stress, we comparatively evaluated the peripheral oxidative status of mice with contrasting levels of anxiety anxious and non-anxious. Following strict selection criteria from a general population of mice Rammal et al. We found that high anxiety level was associated with a significant generation of ROS in the peripheral blood lymphocytes, granulocytes and monocytes in mice compared to low anxiety level Rammal et al. Our results confirm that there is a relationship between the level of intracellular ROS in peripheral blood cells and anxiety-related behaviour in mice. These results prompted us to study the oxidative status of the brain in mice with distinct levels of anxiety. Using the same behavioural approach to distinguish between anxious and non-anxious mice, we found that anxiety levels were associated with the oxidative status in both neuronal and glial cells in the cerebellum and hippocampus, in neurons of the cerebral cortex and in peripheral leucocytes monocytes, granulocytes and lymphocytes Rammal et al. Our results clearly indicated the presence of OS in the central and peripheral systems of anxious mice. OS in the brain and blood immune cells could predispose anxious mice to neuroinflammation and neurodegeneration as well as recurrent infections. We considered that type of anxiety evaluated in mice with contrasting levels of anxiety is a trait-anxiety, for two reasons. First, we have verified that the level of anxiety of anxious and non-anxious mice was stable during time a period of 15 days. We have also found that the general activity, both horizontal locomotion and vertical rears , of anxious mice was significantly lower than of non-anxious mice unpublished results , which was in keeping with the findings of do-Rego et al. These authors also found that these groups of mice did not significantly differ with regard to their immobility time, marker of depressive behaviour, in the forced swimming test. In agreement with these results, we have also found that the behaviour of anxious and non-anxious mice did not significantly vary in the tail suspension and forced swimming tests, the well-known predictive tests of depression-related behaviour unpublished results. From the above, it could be suggested that high trait anxiety level in anxious mice from Swiss albino male mice OF1 was not associated with depressive symptoms. The results of our studies are in good concordance with the initial findings of Hovatta et al. In keeping with the animal experiments, the link between OS and human trait anxiety was also determined. Indeed, Yasunari et al. To study the causal relation between OS and anxiety, Masood et al. Surprisingly, BSO-treated mice developed anxious behaviour in several mouse models of anxiety including elevated plus maze, hole-board and open field tests. The NADPH oxidase was suggested to be the principal oxidative pathway responsible for the anxiogenic behaviour following BSO treatment. Depletion of GSH was also reported to cause cognitive impairment short-term spatial memory disturbances in rodents as assessed in the Y-maze test Dean et al. It is also suggested that GSH might play a role in psychiatric illnesses including schizophrenia and bipolar disorder Dean et al. However, despite that GSH is considered as a major antioxidant in aerobic cells functioning as an important cellular redox buffer, GSH depletion can cause other cellular stresses, including nitrosative and carbonyl stresses, as GSH is also an important determinant of the nitrogen and dicarbonyl metabolism. Excessive production of ROS induces oxidative damage of cellular structures; production of reactive nitrogen species triggers nitrosylation reactions, which can alter the structure of proteins to inhibit their normal function; excessive accumulation of reactive dicarbonyl compounds leads to damage of protein and nucleotides by dicarbonyl glycation. Additionally, GSH may also have an additional double role in the central nervous system by acting as a neurotransmitter and neuromodulator, e. by regulating the release of other neurotransmitters such as dopamine and gamma-aminobutyric acid GABA , which is an important regulator of anxiety Oja et al. Therefore, the anxiogenic behaviour resulting from depletion of GSH in mice could be independent from oxidative metabolism disturbances generated by BSO treatment. Thus, it is difficult to deduce, from this study, a direct causal relationship between oxidative stress and anxiety. Other studies have mentioned that OS state could cause anxiogenic behaviour, however the link is indirect. Desrumaux et al. Souza et al. Berry et al. In addition, Berry et al. At physiologic conditions, antioxidants play a crucial role in maintaining redox homeostasis by maintaining the level of ROS at physiological doses necessary for optimal cellular functioning. Thus, the excess of ROS is neutralized by antioxidants avoiding the oxidation of cellular components and consequently their damage. Exogenous antioxidants complete the antioxidative action of endogenous antioxidants by acting together, e. additively or synergistically. The principal source of exogenous antioxidants is our diet. However, diets relatively deficient in antioxidants may favour oxidative stress. Vitamin E, vitamin C, carotenoids, zinc, selenium, and polyphenols e. phenolic acids and flavonoids constitute the principal dietary antioxidants existing in food. Of course, these antioxidants can be found naturally e. in plant foods or animal products such as eggs and honey , however, other sources can also exist e. supplementation and fortification. Currently, there is increasing evidence that the advantageous effects of antioxidants on health are not only attributed to their antioxidant properties. This is due to the fact that antioxidants can also act e. The effect of dietary antioxidants on the central nervous system has gained interest in the last decades. In this sense, it has been demonstrated that dietary antioxidants can also exhibit cognitive enhancing effect, psychostimulant activity, and antidepressant and anti-anxiety properties. For example, it has been shown that antioxidants e. vitamin C, rutin, caffeic acid and rosmarinic acid possess antidepressant activity with relatively lower doses 0. The mechanism of action of antioxidants on the central nervous system is not well elucidated, however, it has been demonstrated that rutin exerts its antidepressant activity similarly to conventional antidepressants by increasing the availability of serotonin and noradrenalin in the synaptic cleft reviewed by Bouayed, Interestingly, antioxidant effects of conventional antidepressants have been reported in several studies Atmaca et al. The antioxidant effects of anxiolytic treatments with citalopram also used as an antidepressant have been emphasized by Atmaca et al. Polyphenols have also shown their ability to reverse anxiety-related behaviour of rodents. Some polyphenols have a pharmacological profile that suggests a partial agonistic action that may produce the anxiolytic-like effects, but without the side effects such as dependency, which are a feature of full agonists such as benzodiazepines. However, a fold increase in dosage of this flavonoid produced slight sedative effects. Polyphenols may present a dose-effect response on the central nervous system. The ability of polyphenols to cross the blood-brain barrier might explain the difference in their active concentration. The intranasal administration of polyphenols in the form of liposomes could be an effective strategy both to facilitate the movement of these substances across the blood-brain barrier and to effectively reduce the active dose. Therefore, the use of liposomes is a potentially novel strategy which can facilitate the delivery of polyphenols across the blood-brain barrier and also can effectively reduce the active dose reviewed by Bouayed, Although psychopharmacological studies present antioxidants as a potential new strategy for the treatment of anxiety and depression, the use of these substances has to be with caution. Several studies are required to investigate the toxicity of antioxidants at non-nutritional doses. At high doses, it has been discussed that antioxidants could enact deleterious effects on health, acting e. as prooxidants. Therefore, antioxidants from a normal diet could prevent from anxiety development. In this respect, it has been demonstrated that some specific foods prevent aging-accompanying anxiety. Viggiano et al. The decrease of anxiety was not associated with a change in general activity, however a reduction of OS was also found. Indeed, these authors found that brain superoxide dismutase SOD activity of aged rats fed with an apples enriched diet was not different from young animals feed with the standard diet with or without apples, while SOD activity of aged rats fed with the standard diet was significantly elevated. Pitozzi et al. Interestingly, the reduction of anxiety was associated with significant decreased glutathione reductase activity and expression in the brain. Chepulis et al. They found that anxiety of rats fed with the diet supplemented with honey was significantly lower than in the other groups. No information was given on the oxidative status of different groups; however, the antioxidant power of honey has already been stressed in other reports. It has been suggested that the anti-anxiety effect of long intake of apples, olive oil and honey may be attributed to the whole food matrix containing complex mixtures of nutrients and non-nutrients including vitamins, flavonoids, phenolic acids, several carotenoids, and many more acting on a synergistic or additive manner, rather than to specific compounds. Anxiety has a multifactorial origin and can result e. from pharmacological treatment with some drugs e. methyl-β-carbolinecarboxylate , stressful situations e. immobilization stress or natural conditions e. |
| Oxidative Imbalance and Anxiety Disorders | N Engl J Med — Monda M. Koskinen S. Supplementation with a combination of omega-3 fatty acids and antioxidants vitamins E and C improves the outcome of schizophrenia. FASEB, J 19 Get help with access Accessibility Contact us Advertising Media enquiries. |
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