|
|
REVIEW ARTICLE |
|
Year : 2016 | Volume
: 6
| Issue : 4 | Page : 139-145 |
|
An empirical review on oxidative stress markers and their relevance in obsessive-compulsive disorder
Sujita Kumar Kar1, Ipsita Choudhury2
1 Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India 2 Department of Biochemistry, Rama Medical College and Research Institute, Kanpur, Uttar Pradesh, India
Date of Submission | 23-May-2016 |
Date of Acceptance | 01-Jul-2016 |
Date of Web Publication | 7-Oct-2016 |
Correspondence Address: Sujita Kumar Kar Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2231-0738.191641
Abstract | | |
Oxidative stress results from imbalance in the generation of oxidative free radicals in the body and neutralizing antioxidant mechanisms. It hampers various cellular biochemical processes causing dysfunction of the neurons. Reactive oxygen species and reactive nitrogen species are the two important systems regulating the body's oxidative stress. Oxidative stress has a role in several psychiatric disorders including obsessive-compulsive disorder (OCD) and other anxiety disorders. Various studies have found elevated levels of malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase in patients with OCD, which are considered the markers of oxidative stress. This review discusses the relevance of oxidative stress in OCD.
Keywords: Markers of oxidative stress, obsessive-compulsive disorder, oxidative stress
How to cite this article: Kar SK, Choudhury I. An empirical review on oxidative stress markers and their relevance in obsessive-compulsive disorder. Int J Nutr Pharmacol Neurol Dis 2016;6:139-45 |
How to cite this URL: Kar SK, Choudhury I. An empirical review on oxidative stress markers and their relevance in obsessive-compulsive disorder. Int J Nutr Pharmacol Neurol Dis [serial online] 2016 [cited 2023 Feb 1];6:139-45. Available from: https://www.ijnpnd.com/text.asp?2016/6/4/139/191641 |
Introduction | |  |
Oxidative stress usually results from the excessive production of reactive oxygen species (ROS) or due to failure of the enzymatic and nonenzymatic systems regulating the ROS. [1] Oxidative stress is responsible for the causation of various physical as well as mental illnesses. To counter the oxidative stress, the body has its own antioxidant system, which tries to control the oxidative injury.
ROS and reactive nitrogen species are the two important systems that regulate the body's oxidative activity. [2],[3] Excessive production of ROS in the body leads to more oxidative stress, which results in intracellular signaling impairment and cellular aging that direct to apoptosis. [2] Free radicals are highly reactive species, generated from the metabolism of oxygen and nitrogen. They have a very short half-life and usually inactivated by the antioxidant system of the body. [3] The generation of free radicals may be due to accidental leakage of electrons from electron transport chain [Figure 1] or from the respiratory burst of neutrophils and macrophages as shown in [Figure 2]. [4] Respiratory burst (sometimes called oxidative burst) is the rapid release of ROS (superoxide radical and hydrogen peroxide) from the cells. | Figure 1: The formation of superoxide ion leaking from electron transport chain of mitochondria
Click here to view |
ROS generation commonly occurs at the mitochondria, which becomes dysfunctional under oxidative stress resulting in the release of calcium into the intracellular compartment and lysosomal activation, triggering the apoptotic process [Figure 1] and [Figure 2]. [5]
Antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and nonenzymatic antioxidants such as - Vitamin A, C, E, β-carotene, zinc, copper, selenium, and flavonoids act as scavengers of free radicals; hence reduce oxidative stress and resultant cell injury. [3],[5],[6] Protein molecules such as albumin, ceruloplasmin, haptoglobin, and transferrin also act as the scavengers of toxic free radicals. [5]
The neuronal tissue of the brain is rich in lipid and consumes large quantities of oxygen. When the brain's oxidative by-products over take the antioxidant mechanism, damage to the brain components occurs. [7] Oxidative stress-related damage to the brain can be in the form of disruption in the membrane integrity, oxidative damage of lipid, protein, & nucleic acid, and neuronal dysfunction leading to apoptosis. [3] The process of neuroplasticity (axonal sprouting, neurite formation, synaptogenesis, synaptic remodeling, and neuronogenesis) is impaired due to oxidative stress. [5] [Figure 3] shows the mechanism of the generation of oxidative free radicals and their impact on the cellular biochemical process. Failure in the regulation of the endogenous oxidative processes leads to brain insult, which may be implicated in various psychiatric disorders including anxiety disorder and depression [Figure 3]. [8] | Figure 3: Generation of oxidative free radicals and their impact on the cellular biochemical process
Click here to view |
Role of Oxidative Stress in Psychiatric Disorders with Focus on Anxiety Disorders | |  |
Oxidative stress has a close association with anxiety and depression. [3] Anxiety is a common manifestation of anxiety disorders, obsessive-compulsive disorder (OCD), depression, substance use disorder, stress-related disorder, bipolar disorder and schizophrenia. [1],[9] Even oxidative stress can mediate the psychotropic drug-induced side effects such as tardive dyskinesia. [9] Oxidative stress also has an influence on the genes responsible for various psychiatric disorders. Genetic polymorphism of disrupted-in-schizophrenia-1, neuregulin 1, and many other genes occurs due to oxidative stress, which is responsible for the causation of schizophrenia. [10] Some similar genetic mechanisms induced by oxidative stress also might be responsible for the generation of anxiety and depression. Oxidative stress plays a pivotal role in the interface of gene and environment interaction. [10] Both ROS and nitrogen species damage the DNA, proteins, and lipids by several mechanisms. [11] Activation of stress-sensitive genes further facilitates the oxidative injury of body tissues including the neuronal tissue, which may result in neurodegeneration. [11]
The biological markers of anxiety, such as the oxidative stress markers are expected to be clinically evident in these groups of psychiatric disorders and many other conditions where anxiety is prominent. [3] The cause and consequence relationship between anxiety and oxidative stress markers seems to be bidirectional. Low level of total antioxidant state is associated with depression and anxiety. [5] Oxidative stress can be the result as well as the cause of stress and anxiety. When an individual is under stress or experiences anxiety, the metabolic process of the body is adversely affected, which may facilitate the generation of oxidative free radicals causing dysfunction in cellular processing, which through a cascade of biochemical events lead to the generation of anxiety. Repetition of this vicious cycle leads to the persistence of oxidative stress as well as anxiety. Recent evidences suggest about the potential etiologic role of oxidative stress in anxiety disorders and depression. [1] Excessive glutaminergic transmission occurs during stressful situations, which causes mitochondrial dysfunction mediated by excessive calcium influx. Excessive calcium influx in the neurons triggers the apoptotic process resulting in neurodegeneration. [12] [Figure 4] shows the pathophysiology of anxiety, depression, and obsession induced by oxidative stress [Figure 4]. | Figure 4: Pathophysiology of anxiety, depression, and obsession induced by oxidative stress
Click here to view |
Oxidative Stress in Anxiety and Obsessive-Compulsive Disorder: Evidences from Animal Studies | |  |
Several studies have been conducted in experimental animals to find the association of oxidative stress markers with anxiety. Bouayed et al. in their study on mice found a positive correlation with peripheral oxidative markers and anxiety. [13] Hovatta et al. in their study on mice found that overexpression of two genes, glyoxalase 1 and glutathione reductase 1, has a major role in the production of anxiety, and these two genes have been associated with oxidative metabolism. [14] Glyoxalase 1 may be considered a biological marker of anxiety phenotype due to its consistent and close association with anxiety production in mice. [15],[16]
Studies on experimental animals (mice) suggest that an increased level of nitric oxide (NO) in the brain which is mostly generated from oxidative dysregulation may be responsible for the obsessive-compulsive behavior (marble-burying behavior in mice), [17],[18] and selective serotonin reuptake inhibitors (SSRIs) are effective in controlling the obsessive-compulsive behavior by decreasing the NO level in brain. [17] In another study on mice, it was found that high level of anxiety has a significant association with the generation of free radicals in leukocytes. [19]
Stereotypic behavior in experimental animals is considered the human counterpart of repetitive compulsive acts of OCD. [20] A study focused on the stereotypic behavior of deer mouse in relation with the oxidative biomarkers revealed that deficient glutathione system in the frontal cortex is responsible for this behavior, [20] which suggests the possible scope of antioxidants related to the glutathione in patients with OCD. Chronic fluoxetine treatment in deer mice reduces the stereotypic behavior by attenuating prefrontal cortical cyclic adenosine monophosphate level as well as phosphodiesterase Type 4 activity. [21]
A recent study on experimental animals (rats) has demonstrated that SSRI (escitalopram) is effective in normalizing the oxidative stress in the body. [22] Endothelial functions and vascular contractility are also found to be modulated by SSRIs such as fluoxetine and Escitalopram through the oxidative pathway. [22],[23] Some contradicting evidences also exist such as chronic treatment with fluoxetine may induce oxidative stress resulting in endothelial dysfunction. [23]
Oxidative Stress in Obsessive-Compulsive Disorder: Experiences from Human Studies | |  |
Extensive search in MEDLINE database using the keywords - oxidative stress, free radicals, Superoxide Dismutase, Glutathione Peroxidase, nitric oxide, Catalase, malondialdehyde, ascorbate, total oxidant status, serum thiobarbituric acid reacting substances (TBARS) individually with "obsessive compulsive disorder" found eleven original research articles. These studies have been published between the years 2002 and 2016, with each study having a control group along with the patient group.
Studies done to measure oxidative stress in patients with OCD were mostly cross-sectional and had sample sizes ranging from 20 to 42, [24],[25],[26],[27],[28],[29],[30],[31],[32],[33],[34] except one study which studied the genetic variants of oxidative markers in patients with OCD, where the sample size was more than 100. [33] These studies measured different antioxidants and products of oxidative process. The antioxidants that are measured in most of the studies are Vitamin E, [24] Vitamin C, [24],[25] SOD, [26],[27],[30],[33] GSH-Px, [26],[30],[33] CAT, [26],[30] and serum selenium. [26] Lipid peroxidation metabolites such as malondialdehyde (MDA) [24],[26],[27],[30],[33] and Thiobarbituric acid reacting substances (TBARS) [25],[31] were also measured in various studies. Atmaca et al., in their study on patients with OCD, studied the plasma NO level. [32]
Other than the above parameters, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were also studied in patients with OCD. [28],[29],[34] Among the above-mentioned studies, most were done in adult patients with OCD and only one study evaluated the oxidative stress parameter in pediatric population. [28] Most studies had included patients of OCD without any psychiatric comorbidities; however, Kuloglu et al. had included OCD along with major depressive disorder (MDD) in their study and compared them with the patients of OCD without MDD and healthy controls. [30] All the above studies are cross-sectional, measuring oxidative markers at baseline, except one study, where patients were followed up for 12 weeks with fluoxetine treatment and the oxidative markers were measured during the follow-up. [25]
Chakraborty et al. in their study found that newly diagnosed, drug-naive patients with OCD had a higher level of TBARS and lower ascorbate level. [25] Ozdemir et al. in their study compared the oxidative stress parameters of patients with OCD, who were drug-free for at least 1 month with healthy controls. It was found that the level of MDA and SOD was significantly higher in patients than healthy controls. [26] Other markers of oxidative stress (serum selenium, GSH-Px, and CAT) in patient group were significantly lower than the healthy controls. [26] A significantly increased level of MDA was reported in patients with OCD in comparison to healthy controls, which was also found in other studies. [26],[27],[30] Kandemir et al. in their study on children and adolescents with OCD found that the patient group had more oxidative stress than their healthy counterparts. The patient group had a significantly higher TOS and OSI as well as significantly lower TAS than that of controls. [28] However, Alici et al. refuted this finding in a recent study, as they did not find any significant difference in TOS, OSI, and TAS between the patient and control groups. [34] This study had revealed about the increased oxidative damage of DNA in patients with OCD in comparison to the healthy controls. [Table 1] shows the studies evaluating various oxidative parameters in patients with OCD [Table 1]. | Table 1: Oxidative parameters in patients with obsessive-compulsive disorder
Click here to view |
Hopes and Scopes | |  |
Published research data on oxidative stress in OCD are scarce. [34]
The same group of neurotransmitters (serotonin, noradrenaline, glutamate, and dopamine) is involved in the depression and anxiety disorders including OCD. Regulation of these neurotransmitters in the body is modulated by the ROS and NOS. [35]
Both depression and anxiety disorders are characterized by the deficiency of antioxidants such as Vitamin C, E, glutathione, and zinc; [24],[25],[35] hence, antioxidants possibly hold some promise in the management of depression as well as in anxiety disorder. Preclinical, clinical as well as epidemiological studies revealed the role of antioxidants in various neuropsychiatric disorders, where oxidative stress has an important role. [9] Therapies targeting the oxidative stress management may be effective in controlling the anxiety symptoms. [12]
Certain genotypes are encoding the antioxidant enzymes; mutation of these genotypes or genetic polymorphism of mitochondrial DNA or nuclear genes leads to oxidative stress. [33] This seems to be a new avenue for research. OCD is a chronic heritable illness, but it may follow a sporadic pattern (development of OCD without any family history). The sporadic variants of OCD need to be evaluated for mutation of genes responsible for the regulation of oxidative stress.
Recently, regulation of indolamine 2,3-dioxygenase enzyme is gaining interest among researchers. Indolamine 2,3-dioxygenase is a rate-limiting enzyme in the kynurenine pathway. [36] This enzyme metabolizes amino acid tryptophan, leading to a decrease in tryptophan level and an increase in kynurenine level. [36],[37] Increased breakdown of tryptophan results in fall in the level of serotonin in the brain, which may cause depression and anxiety. [36] The metabolites of kynurenine pathway (e.g., quinolinic acid) are neurotoxic and produce inflammatory changes in the brain by crossing the blood-brain barrier. [38] Activation of the enzyme indolamine 2,3-dioxygenase also impairs the immunoregulation, tumor defense as well as the oxidative regulation in the body. [36],[37] Many mediators of inflammation such as interferon gamma (IFN-γ), interleukin-6 (IL-6), and transforming growth factor regulate the activity of indolamine 2,3-dioxygenase. [36] It signifies the immuno-biological role of indolamine 2,3-dioxygenase in depression, anxiety as well as obsession. Immune mediators such as IL-6 and IFN-γ activate indolamine 2,3-dioxygenase and administration of agents that suppresses the activity of these immune mediators, which, in turn, deactivates indolamine 2,3-dioxygenase activity. [36],[39] Experimental animals deficient in indolamine 2,3-dioxygenase are resistant to depressive behavior, which might be due to the nondepletion of serotonin reserve of the brain. [40]
Oxidative stress may be induced in experimental animals by intraperitoneal injection of buthionine-(S, R)-sulfoximine, which provokes anxiety-like behavior. Regular exercise lead to diminution of this anxiety behavior. [41] Evidences suggest the pivotal role of regular physical exercise in reducing inflammation and oxidative stress, which improves neuroplasticity and optimizes neuronal functioning. [42] This may be beneficial in reducing the symptoms of anxiety disorders.
Hence, it may be reasonably argued that physical exercise, relaxation exercise as well as yoga may be beneficial in patients with OCD by reducing oxidative stress.
Conclusion | |  |
Oxidative stress has a major role in various neuropsychiatric disorders including anxiety disorders and OCD. It indicates the role of antioxidant medications and nonpharmacological measures (aerobic exercise, yoga, and relaxation techniques) that reduce oxidative stress in the treatment of these disorders. Antidepressants (e.g., SSRIs), which improve the anxiety and depressive symptoms as well as OCD, are known to attenuate the oxidative stress, other than their action through concerned neurotransmitter receptors. [43] It can be strongly recommended to see antidepressants beyond receptor modulators. Their anti-inflammatory as well as antioxidant properties are need to be evaluated.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References | |  |
1. | Hovatta I, Juhila J, Donner J. Oxidative stress in anxiety and comorbid disorders. Neurosci Res 2010;68:261-75.  [ PUBMED] |
2. | Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.  [ PUBMED] |
3. | Hassan W, Silva CE, Mohammadzai IU, da Rocha JB, Landeira-Fernandez J. Association of oxidative stress to the genesis of anxiety: Implications for possible therapeutic interventions. Curr Neuropharmacol 2014;12:120-39. |
4. | Inoguchi T, Sonta T, Tsubouchi H, Etoh T, Kakimoto M, Sonoda N, et al. Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: Role of vascular NAD(P) H oxidase. J Am Soc Nephrol 2003;14 8 Suppl 3:S227-32. |
5. | Xu Y, Wang C, Klabnik JJ, O'Donnell JM. Novel therapeutic targets in depression and anxiety: Antioxidants as a candidate treatment. Curr Neuropharmacol 2014;12:108-19.  [ PUBMED] |
6. | McCall MR, Frei B. Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic Biol Med 1999;26:1034-53.  [ PUBMED] |
7. | Ng F, Berk M, Dean O, Bush AI. Oxidative stress in psychiatric disorders: Evidence base and therapeutic implications. Int J Neuropsychopharmacol 2008;11:851-76.  [ PUBMED] |
8. | Bouayed J, Rammal H, Soulimani R. Oxidative stress and anxiety: Relationship and cellular pathways. Oxid Med Cell Longev 2009;2:63-7.  [ PUBMED] |
9. | Zhang XY, Yao JK. Oxidative stress and therapeutic implications in psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 2013;46:197-9.  [ PUBMED] |
10. | Nunomura A, Tamaoki T, Motohashi N. Role of oxidative stress in the pathophysiology of neuropsychiatric disorders. Seishin Shinkeigaku Zasshi 2014;116:842-58.  [ PUBMED] |
11. | Wang JY, Wen LL, Huang YN, Chen YT, Ku MC. Dual effects of antioxidants in neurodegeneration: Direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation. Curr Pharm Des 2006;12:3521-33.  [ PUBMED] |
12. | Krolow R, Arcego DM, Noschang C, Weis SN, Dalmaz C. Oxidative imbalance and anxiety disorders. Curr Neuropharmacol 2014;12:193-204. |
13. | Bouayed J, Rammal H, Younos C, Soulimani R. Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice. Eur J Pharmacol 2007;564:146-9.  [ PUBMED] |
14. | Hovatta I, Tennant RS, Helton R, Marr RA, Singer O, Redwine JM, et al. Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice. Nature 2005;438:662-6.  [ PUBMED] |
15. | Krömer SA, Kessler MS, Milfay D, Birg IN, Bunck M, Czibere L, et al. Identification of glyoxalase-I as a protein marker in a mouse model of extremes in trait anxiety. J Neurosci 2005;25:4375-84. |
16. | Ditzen C, Jastorff AM, Kessler MS, Bunck M, Teplytska L, Erhardt A, et al. Protein biomarkers in a mouse model of extremes in trait anxiety. Mol Cell Proteomics 2006;5:1914-20.  [ PUBMED] |
17. | Umathe SN, Bhutada PS, Jain NS, Mundhada YR, Borkar SS, Dhumal B. Role of nitric oxide in obsessive-compulsive behavior and its involvement in the anti-compulsive effect of paroxetine in mice. Nitric Oxide 2009;21:140-7.  [ PUBMED] |
18. | Salunke BP, Umathe SN, Chavan JG. Experimental evidence for involvement of nitric oxide in low frequency magnetic field induced obsessive compulsive disorder-like behavior. Pharmacol Biochem Behav 2014;122:273-8.  [ PUBMED] |
19. | Rammal H, Bouayed J, Younos C, Soulimani R. The impact of high anxiety level on the oxidative status of mouse peripheral blood lymphocytes, granulocytes and monocytes. Eur J Pharmacol 2008;589:173-5.  [ PUBMED] |
20. | Güldenpfennig M, Wolmarans de W, du Preez JL, Stein DJ, Harvey BH. Cortico-striatal oxidative status, dopamine turnover and relation with stereotypy in the deer mouse. Physiol Behav 2011;103:404-11. |
21. | Korff S, Stein DJ, Harvey BH. Cortico-striatal cyclic AMP-phosphodiesterase-4 signalling and stereotypy in the deer mouse: Attenuation after chronic fluoxetine treatment. Pharmacol Biochem Behav 2009;92:514-20.  [ PUBMED] |
22. | Matchkov VV, Kravtsova VV, Wiborg O, Aalkjaer C, Bouzinova EV. Chronic selective serotonin reuptake inhibition modulates endothelial dysfunction and oxidative state in rat chronic mild stress model of depression. Am J Physiol Regul Integr Comp Physiol 2015;309:R814-23. |
23. | Simplicio JA, Resstel LB, Tirapelli DP, D'Orléans-Juste P, Tirapelli CR. Contribution of oxidative stress and prostanoids in endothelial dysfunction induced by chronic fluoxetine treatment. Vascul Pharmacol 2015;73:124-37. |
24. | 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. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:1039-42.  [ PUBMED] |
25. | Chakraborty S, Dasgupta A, Das HN, Singh OP, Mandal AK, Mandal N. Study of oxidative stress in obsessive compulsive disorder in response to treatment with fluoxetine. Indian J Clin Biochem 2009;24:194-7.  [ PUBMED] |
26. | Ozdemir E, Cetinkaya S, Ersan S, Kucukosman S, Ersan EE. Serum selenium and plasma malondialdehyde levels and antioxidant enzyme activities in patients with obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:62-5.  [ PUBMED] |
27. | Behl A, Swami G, Sircar SS, Bhatia MS, Banerjee BD. Relationship of possible stress-related biochemical markers to oxidative/antioxidative status in obsessive-compulsive disorder. Neuropsychobiology 2010;61:210-4.  [ PUBMED] |
28. | Kandemir H, Abuhandan M, Aksoy N, Savik E, Kaya C. Oxidative imbalance in child and adolescent patients with obsessive compulsive disorder. J Psychiatr Res 2013;47:1831-4.  [ PUBMED] |
29. | Selek S, Herken H, Bulut M, Ceylan MF, Celik H, Savas HA, et al. Oxidative imbalance in obsessive compulsive disorder patients: A total evaluation of oxidant-antioxidant status. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:487-91.  [ PUBMED] |
30. | Kuloglu M, Atmaca M, Tezcan E, Gecici O, Tunckol H, Ustundag B. Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder. Neuropsychobiology 2002;46:27-32.  [ PUBMED] |
31. | Chakraborty S, Singh OP, Dasgupta A, Mandal N, Nath Das H. Correlation between lipid peroxidation-induced TBARS level and disease severity in obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:363-6.  [ PUBMED] |
32. | Atmaca M, Tezcan E, Kuloglu M, Ustundag B. Plasma nitrate values in patients with obsessive-compulsive disorder. Psychiatry Clin Neurosci 2005;59:621-3.  [ PUBMED] |
33. | Orhan N, Kucukali CI, Cakir U, Seker N, Aydin M. Genetic variants in nuclear-encoded mitochondrial proteins are associated with oxidative stress in obsessive compulsive disorders. J Psychiatr Res 2012;46:212-8.  [ PUBMED] |
34. | Alici D, Bulbul F, Virit O, Unal A, Altindag A, Alpak G, et al. Evaluation of oxidative metabolism and oxidative DNA damage in patients with obsessive-compulsive disorder. Psychiatry Clin Neurosci 2016;70:109-15. |
35. | Scapagnini G, Davinelli S, Drago F, De Lorenzo A, Oriani G. Antioxidants as antidepressants: Fact or fiction? CNS Drugs 2012;26:477-90.  [ PUBMED] |
36. | Loftis JM. Indolamine 2,3-dioxygenase regulation and neuropsychiatric symptoms. Psychoneuroendocrinology 2013;38:1829-30.  [ PUBMED] |
37. | Mbongue JC, Nicholas DA, Torrez TW, Kim NS, Firek AF, Langridge WH, et al. The role of indolamine 2, 3-dioxygenase in immune suppression and autoimmunity. Vaccines (Basel) 2015;3:703-29. |
38. | Kwidzinski E, Bechmann I. IDO expression in the brain: A double-edged sword. J Mol Med (Berl) 2007;85:1351-9. |
39. | Kwidzinski E, Bunse J, Aktas O, Richter D, Mutlu L, Zipp F, et al. Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation. FASEB J 2005;19:1347-9.  [ PUBMED] |
40. | O'Connor JC, Lawson MA, André C, Briley EM, Szegedi SS, Lestage J, et al. Induction of IDO by bacille Calmette-Guérin is responsible for development of murine depressive-like behavior. J Immunol 2009;182:3202-12. |
41. | Salim S, Sarraj N, Taneja M, Saha K, Tejada-Simon MV, Chugh G. Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats. Behav Brain Res 2010 2;208:545-52. |
42. | Moylan S, Eyre HA, Maes M, Baune BT, Jacka FN, Berk M. Exercising the worry away: How inflammation, oxidative and nitrogen stress mediates the beneficial effect of physical activity on anxiety disorder symptoms and behaviours. Neurosci Biobehav Rev 2013;37:573-84.  [ PUBMED] |
43. | Maes M, Fišar Z, Medina M, Scapagnini G, Nowak G, Berk M. New drug targets in depression: Inflammatory, cell-mediated immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. And new drug candidates - Nrf2 activators and GSK-3 inhibitors. Inflammopharmacology 2012;20:127-50. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1]
This article has been cited by | 1 |
Role of Sonic Hedgehog Signaling Activation in the Prevention of Neurological Abnormalities Associated with Obsessive–Compulsive Disorder |
|
| Ria Gupta, Sidharth Mehan, Swesha Chhabra, Aditi Giri, Kajal Sherawat | | Neurotoxicity Research. 2022; | | [Pubmed] | [DOI] | | 2 |
Effect of Multivoice Chorus on Interpersonal Communication Disorder |
|
| Huiling Lei, Sheng Bin | | Occupational Therapy International. 2022; 2022: 1 | | [Pubmed] | [DOI] | | 3 |
Alterations in Tryptophan Metabolism Affect Vascular Functions: Connected to Ageing Population Vulnerability to COVID-19 Infection? |
|
| Arehally M Mahalakshmi, Shasthara Paneyala, Bipul Ray, Musthafa Mohamed Essa, Mona Dehhaghi, Benjamin Heng, Gilles J Guillemin, Saravana Babu Chidambaram | | International Journal of Tryptophan Research. 2022; 15: 1178646922 | | [Pubmed] | [DOI] | | 4 |
Potential effects of noni (Morinda citrifolia L.) fruits extract against obsessive-compulsive disorder in marble burying and nestlet shredding behavior mice models |
|
| Srikanth Jeyabalan, Logeshwari Bala, Kavimani Subramanian, Sugin Lal Jabaris, Mahendran Sekar, Ling Shing Wong, Vetriselvan Subramaniyan, Kumarappan Chidambaram, Siew Hua Gan, Nur Najihah Izzati Mat Rani, M. Yasmin Begum, Sher Zaman Safi, Siddharthan Selvaraj, Adel Al Fatease, Ali Alamri, Kamini Vijeepallam, Shivkanya Fuloria, Neeraj Kumar Fuloria, Sinouvassane Djearamane | | Frontiers in Pharmacology. 2022; 13 | | [Pubmed] | [DOI] | | 5 |
The Role of Antioxidants in the Management of Obsessive-Compulsive Disorder |
|
| Fatemeh Baratzadeh,Sepideh Elyasi,Amir Hooshang Mohammadpour,Sofia Salari,Amirhossein Sahebkar,Guodong Zhang | | Oxidative Medicine and Cellular Longevity. 2021; 2021: 1 | | [Pubmed] | [DOI] | | 6 |
Malondialdehyde concentrations in obsessive–compulsive disorder: a systematic review and meta-analysis |
|
| Amir Hossein Mohammadi,Ebrahim Balandeh,Alireza Milajerdi | | Annals of General Psychiatry. 2021; 20(1) | | [Pubmed] | [DOI] | | 7 |
The Nrf2 pathway in psychiatric disorders: pathophysiological role and potential targeting |
|
| Ranjana Bhandari,Japneet Kaur,Simerpreet Kaur,Anurag Kuhad | | Expert Opinion on Therapeutic Targets. 2021; | | [Pubmed] | [DOI] | | 8 |
A SVM-Based Classification Approach for Obsessive Compulsive Disorder by Oxidative Stress Biomarkers |
|
| Abhijeet Shrivastava,Ajaya Kumar Tripathy,Pronob Kumar Dalal | | Journal of Computational Science. 2019; | | [Pubmed] | [DOI] | | 9 |
Low-density polyethylene microplastics as a source and carriers of agrochemicals to soil and earthworms |
|
| Andrés Rodríguez-Seijo,Bruna Santos,Eduardo Ferreira da Silva,Anabela Cachada,Ruth Pereira | | Environmental Chemistry. 2019; 16(1): 8 | | [Pubmed] | [DOI] | | 10 |
Antidepressant Effects of Vaccinium bracteatum via Protection Against Hydrogen Peroxide-Induced Oxidative Stress and Apoptosis |
|
| Dool-Ri Oh,Yujin Kim,Eun-Jin Choi,Ara Jo,Jawon Shin,Huwon Kang,Seul-Gi Lee,Jaeyong Kim,Young Ran Kim,Chul Yung Choi | | The American Journal of Chinese Medicine. 2018; : 1 | | [Pubmed] | [DOI] | |
|
 |
 |
|