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A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 39933

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Special Issue Editors

Prof. Dr. Xiangyang Zhang

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Guest Editor

Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
Interests: schizophrenia; drug addiction; oxidative stress; antioxidant; cognition

Dr. Zezhi Li

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Guest Editor

1. Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou 510370, China
2. Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou 510370, China
Interests: schizophrenia; mood disorders; molecular psychiatry; biological psychiatry; neuropsychopharmacology; oxidative stress; antioxidant

Dr. Dongmei Wang

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Guest Editor

Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China
Interests: drug addiction; schizophrenia; oxidative stress; cognition; neuromodulation

Special Issue Information

Dear Colleagues,

There is growing evidence that oxidative stress and antioxidant defense system disturbance play an important role in the pathogenesis and pathology of psychiatric disorders, including schizophrenia, bipolar disorder, major depressive disorder, and anxiety disorders, side effects caused by antipsychotic medications, such as tardive dyskinesia (TD), and metabolic syndromes (e.g., obesity and diabetes). In addition, evidence from clinical, preclinical, and epidemiological studies suggests that treatment with antioxidants can be used as an adjunctive therapy for psychiatric disorders with good clinical outcomes.

In this Special Issue, we aim to collect a variety of papers on psychiatric research related to oxidative stress, including experimental studies and clinical studies (e.g., interventional or observational studies), as well as meta-analyses and review papers, to provide an up-to-date overview of the importance of oxidative stress in the pathophysiology of psychiatric disorders, with the aim of providing more effective treatments for psychiatric disorders.

Prof. Dr. Xiangyang Zhang
Dr. Zezhi Li
Dr. Dongmei Wang
Guest Editors

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Keywords

antioxidants
antioxidant defense system
psychiatric symptoms
clinical treatment
oxidative stress
reactive oxygen species

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Published Papers (11 papers)

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Research

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12 pages, 1677 KiB

Open AccessArticle

Age of Onset Moderates the Association between Total Antioxidant Capacity and Cognitive Deficits in Patients with Drug-Naïve Schizophrenia

by Jiaxin Li, Deyang Li, Junru Guo, Dongmei Wang and Xiangyang Zhang

Antioxidants 2023, 12(6), 1259; https://doi.org/10.3390/antiox12061259 - 12 Jun 2023

Cited by 5 | Viewed by 1586

Abstract

Schizophrenia patients with an earlier age of onset have been found to have more serious negative symptoms and cognitive deficits. Oxidative stress is thought to be implicated in cognitive impairment in schizophrenia. Total antioxidant capacity (TAOC) is an essential indicator of oxidative stress. However, the association between age of onset, TAOC, and cognitive performance in schizophrenia remains unexplored. In this study, 201 patients (age: 26.5 ± 9.6 years; male: 53.2%) with drug-naïve schizophrenia were recruited. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive functioning was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Plasma TAOC levels were analyzed using established procedures. Results showed that early-onset (EO) patients had higher TAOC levels, more severe negative symptoms and performed worse on visuospatial/constructional, language and RBANS total scores than non-EO patients. After Bonferroni correction, only non-EO patients showed a significant inverse relationship between TAOC levels and RBANS language, attention, and total scores. Our findings suggest that an early/late age of onset may be correlated with psychopathological symptoms, cognitive impairment and oxidative responses in schizophrenia. Furthermore, the age of onset may moderate the relationship between TAOC and cognitive function in patients with schizophrenia. These findings suggest that improving oxidative stress status in non-EO schizophrenia patients may enhance their cognitive function. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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23 pages, 2922 KiB

Open AccessArticle

Anxiety, Insomnia, and Memory Impairment in Metabolic Syndrome Rats Are Alleviated by the Novel Functional Ingredients from Anacardium occidentale

by Pratthana Srichomphu, Jintanaporn Wattanathorn, Wipawee Thukham-mee and Supaporn Muchimapura

Antioxidants 2022, 11(11), 2203; https://doi.org/10.3390/antiox11112203 - 7 Nov 2022

Cited by 5 | Viewed by 2637

Abstract

Despite an increase in the coexistence of metabolic syndrome (MetS) and psychological disorders, together with their great impact on socio-economic burdens, no protective strategies that focus on these situations are available. Due to the role of oxidative stress in the pathophysiology of metabolic syndrome (MetS) and psychological disorders, we hypothesized that substances possessing antioxidant activity such as the novel functional ingredients from Anacardium occidentale (AO) could mitigate common psychological disorders in MetS rats. Male Wistar rats, weighing 200–250 g, were induced with MetS through a 12-week high-fat and high-cholesterol diet (HFHC). Then, they were given AO orally via a gastric gavage needle at doses of 1, 10 and 100 mg/kg BW for 14 days. Spatial memory, anxiety, depression, and sleep behaviors, together with changes in oxidative stress status and neurotransmitters, were assessed. All doses of AO significantly improved memory, anxiety, and sleep, together with the suppression of oxidative stress, AChE, and GABA-T in the cerebral cortex and hippocampus. These results suggest the protective effect of AO against anxiety, insomnia, and memory impairment that coexist with the MetS condition via an improvement in oxidative stress and the functions of the cholinergic and GABAergic systems. However, this benefit requires clinical confirmation. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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13 pages, 570 KiB

Open AccessArticle

Association between MnSOD Activity and Cognitive Impairment in Unmedicated First-Episode Schizophrenia: Regulated by MnSOD Ala-9Val Gene Polymorphism

by Dong Mei Wang, Rong Rong Zhu, Yang Tian, Kadir Uludag, Jia Jing Chen, Hui Xia Zhou, Li Wang, Thomas R. Kosten and Xiang Yang Zhang

Antioxidants 2022, 11(10), 1981; https://doi.org/10.3390/antiox11101981 - 4 Oct 2022

Cited by 6 | Viewed by 2291

Abstract

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and MnSOD Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients’ psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. MnSOD Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by MnSOD Ala-9Val polymorphism. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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18 pages, 2632 KiB

Open AccessArticle

Sirtuin 3 Plays a Critical Role in the Antidepressant- and Anxiolytic-like Effects of Kaempferol

by Hao-Yuan Li, Jing Wang, Ling-Feng Liang, Shi-Yu Shen, Wei Li, Xiao-Rong Chen, Bing Li, Yu-Qiu Zhang and Jin Yu

Antioxidants 2022, 11(10), 1886; https://doi.org/10.3390/antiox11101886 - 23 Sep 2022

Cited by 23 | Viewed by 2580

Abstract

An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, Sirt3 depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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12 pages, 3282 KiB

Open AccessArticle

Oxidative Stress and Psychiatric Disorders: Evidence from the Bidirectional Mendelian Randomization Study

by Zhe Lu, Chengcheng Pu, Yuyanan Zhang, Yaoyao Sun, Yundan Liao, Zhewei Kang, Xiaoyang Feng and Weihua Yue

Antioxidants 2022, 11(7), 1386; https://doi.org/10.3390/antiox11071386 - 18 Jul 2022

Cited by 36 | Viewed by 5645

Abstract

Observational studies have shown that oxidative stress is highly related to psychiatric disorders, while its cause–effect remains unclear. To this end, a Mendelian randomization study was performed to investigate the causal relationship between oxidative stress and psychiatric disorders. On the one hand, all causal effects of oxidative stress injury biomarkers (OSIB) on psychiatric disorders were not significant (p > 0.0006), while the findings suggested that part of OSIB was nominally associated with the risk of psychiatric disorders (causal OR of uric acid (UA), 0.999 for bipolar disorder (BD), and 1.002 for attention-deficit/hyperactivity disorder (ADHD); OR of catalase was 0.903 for anorexia nervosa (AN); OR of albumin was 1.162 for autism; p < 0.05). On the other hand, major depressive disorder (MDD) was significantly associated with decreased bilirubin (p = 2.67 × 10⁻⁴); ADHD was significantly associated with decreased ascorbate (p = 4.37 × 10⁻⁵). Furthermore, there were also some suggestively causal effects of psychiatric disorders on OSIB (BD on decreased UA and increased retinol; MDD on increased UA and decreased ascorbate; schizophrenia on decreased UA, increased retinol and albumin; ADHD on increased UA, and decreased catalase, albumin, and bilirubin; AN on decreased UA). This work presented evidence of potential causal relationships between oxidative stress and psychiatric disorders. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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8 pages, 659 KiB

Open AccessArticle

Association between Changes in Total Antioxidant Levels and Clinical Symptom Improvement in Patients with Antipsychotic-Naïve First-Episode Schizophrenia after 3 Months of Risperidone Monotherapy

by Keqiang Wang, Meihong Xiu, Xiuru Su, Fengchun Wu and Xiangyang Zhang

Antioxidants 2022, 11(4), 646; https://doi.org/10.3390/antiox11040646 - 28 Mar 2022

Cited by 3 | Viewed by 1972

Abstract

Schizophrenia (SCZ) is associated with aberrant redox regulation in the early stages of brain development. There is growing evidence that the antioxidant defense system is closely associated with the therapeutic response to antipsychotics in SCZ patients. The aim of this study was to examine the effect of risperidone monotherapy on total antioxidant status (TAS) and the relationship between symptom improvement and changes in TAS in patients with antipsychotic-naïve first-episode (ANFE) SCZ. Clinical symptoms were evaluated using the Positive and Negative Syndrome Scale (PANSS). Two hundred and forty-six ANFE patients were treated with risperidone for 3 months. PANSS and TAS levels were assessed at baseline and at a 3-month follow-up. Relative to healthy controls, ANFE patients had higher TAS levels, which increased even further during the treatment. Moreover, baseline TAS levels were a predictor of symptom reduction after risperidone treatment. In addition, there was a significant association between increased TAS levels and the decreased cognitive factor. Our findings suggest that antioxidant protection is possibly associated with clinical improvement in ANFE patients after risperidone treatment. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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Review

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33 pages, 1101 KiB

Open AccessReview

Discovering the Potential Mechanisms of Medicinal Mushrooms Antidepressant Activity: A Review

by Jan Lazur, Kamil Hnatyk, Katarzyna Kała, Katarzyna Sułkowska-Ziaja and Bożena Muszyńska

Antioxidants 2023, 12(3), 623; https://doi.org/10.3390/antiox12030623 - 2 Mar 2023

Cited by 7 | Viewed by 7904

Abstract

Major Depression Disease is a common mental illness that affects more than 322 million people worldwide and it is one of the leading causes of mental and physical disability. The etiology of depression is a complex interplay of psychological, social, and biological factors. Currently, psychopharmacotherapy is based mainly on the monoamine theory, which states that depression is caused by an insufficient level of monoamines such as serotonin, norepinephrine, and/or dopamine. Due to the relatively low efficacy of the typical antidepressant and the high prevalence of treatment-resistant depression (~30%), seeking new ways of prophylaxis, adjuvant therapy, or novel compounds with antidepressant activity, is a priority. According to studies that analyzed mushroom consumption patterns and depression prevalence, it was concluded that mushroom ingestion lowers the odds of depression. Medicinal mushrooms are considered functional foods because of their ability to synthesize and accumulate different types of metabolites, which enhance their health-promoting properties. The review aims to explain the antidepressant activity of edible/medicinal mushrooms by elucidating the mechanism from different perspectives: edible mushrooms as a source of serotonin precursors and psilocybin as a rapid-acting antidepressant. These compounds exhibit anti-neuroinflammatory and antioxidant activities that impact neurotrophin expression, the neurogenesis process, and influence on the gut–brain axis. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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15 pages, 1495 KiB

Open AccessReview

Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders

by Simeng Gu, Yumeng Li, Yao Jiang, Jason H. Huang and Fushun Wang

Antioxidants 2022, 11(11), 2296; https://doi.org/10.3390/antiox11112296 - 20 Nov 2022

Cited by 28 | Viewed by 4181

Abstract

Major Depression disorder (MDD) is a potentially life-threatening mental illness, however, many patients have a poor response to current treatments. Recent studies have suggested that stress- or trauma-induced oxidative stress and inflammation could be important factors involved in the development of MDD, but the mechanisms remain unclear. We showed that the glymphatic system is a recently discovered structure in the brain that may be involved in the clearance of large molecular and cell debris in extracellular space. In addition, the glymphatic system can help with the removal of reactive oxygen species (ROS) and cytokines such as IL-1β and HIF-1α. Glymphatic impairment can lead to ROS accumulation in the microenvironment, inducing cellular injury signaling and activating NLRP3 in microglia to induce inflammation and, thus, many brain diseases, including psychiatric disorders. Therefore, trauma-induced glymphatic impairment could induce oxidative stress and inflammation, and thus MDD. This paper will review recent advances with regard to stress-induced glymphatic system impairment and ROS-mediated inflammation in MDD. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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19 pages, 2585 KiB

Open AccessReview

The Status of Oxidative Stress in Patients with Alcohol Dependence: A Meta-Analysis

by Mi Yang, Xiaofei Zhou, Xi Tan, Xincheng Huang, Lu Yuan, Zipeng Zhang, Yan Yang, Min Xu, Ying Wan and Zezhi Li

Antioxidants 2022, 11(10), 1919; https://doi.org/10.3390/antiox11101919 - 28 Sep 2022

Cited by 10 | Viewed by 2563

Abstract

Alcohol-induced oxidative stress (OS) plays a pivotal role in the pathophysiology of alcohol dependence (AD). This meta-analysis was aimed at investigating the changes in the levels of OS biomarkers in AD patients. We included relevant literature published before 1 April 2022, from the PubMed, Web of Science, and EBSCO databases following PRISMA guidelines. Finally, 15 eligible articles were enrolled in this meta-analysis, including 860 patients and 849 controls. Compared with healthy controls, AD patients had lower activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes, and lower levels of albumin, while levels of malondialdehyde (MDA), vitamin B12, homocysteine, and bilirubin were significantly increased in serum/plasma samples of AD subjects (all p < 0.05). In male patients, the activities of SOD and GPx were increased in serum/plasma but decreased in erythrocytes (all p < 0.05). The opposite trends in the level of SOD and GPx activities in serum/plasma and erythrocytes of male patients could be used as the biomarker of alcohol-induced OS injury, and the synergistic changes of MDA, vitamin B12, albumin, bilirubin, and homocysteine levels should also be considered. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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25 pages, 1423 KiB

Open AccessReview

Neuropharmacological Effects of Terpenoids on Preclinical Animal Models of Psychiatric Disorders: A Review

by Tamanna Jahan Mony, Fazle Elahi, Ji Woong Choi and Se Jin Park

Antioxidants 2022, 11(9), 1834; https://doi.org/10.3390/antiox11091834 - 18 Sep 2022

Cited by 16 | Viewed by 3507

Abstract

Terpenoids are widely distributed in nature, especially in the plant kingdom, and exhibit diverse pharmacological activities. In recent years, screening has revealed a wide variety of new terpenoids that are active against different psychiatric disorders. This review synthesized the current published preclinical studies of terpenoid use in psychiatric disorders. This review was extensively investigated to provide empirical evidence regarding the neuropharmacological effects of the vast group of terpenoids in translational models of psychiatric disorders, their relevant mechanisms of action, and treatment regimens with evidence of the safety and psychotropic efficacy. Therefore, we utilized nine (9) electronic databases and performed manual searches of each. The relevant data were retrieved from the articles published until present. We used the search terms “terpenoids” or “terpenes” and “psychiatric disorders” (“psychiatric disorders” OR “psychiatric diseases” OR “neuropsychiatric disorders” OR “psychosis” OR “psychiatric symptoms”). The efficacy of terpenoids or biosynthetic compounds in the terpenoid group was demonstrated in preclinical animal studies. Ginsenosides, bacosides, oleanolic acid, asiatic acid, boswellic acid, mono- and diterpenes, and different forms of saponins and triterpenoids were found to be important bioactive compounds in several preclinical studies of psychosis. Taken together, the findings of the present review indicate that natural terpenoids and their derivatives could achieve remarkable success as an alternative therapeutic option for alleviating the core or associated behavioral features of psychiatric disorders. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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13 pages, 1829 KiB

Open AccessSystematic Review

Dietary Intake of Carotenoids and Risk of Depressive Symptoms: A Systematic Review and Meta-Analysis

by Qiong Yu, Fengyu Xue, Zhijun Li, Xinwei Li, Lizhe Ai, Mengdi Jin, Mengtong Xie and Yaqin Yu

Antioxidants 2022, 11(11), 2205; https://doi.org/10.3390/antiox11112205 - 7 Nov 2022

Cited by 5 | Viewed by 3326

Abstract

Given the important role of oxidative stress in the pathogenesis of depression, the potential role of dietary antioxidant supplementation in the prevention of depression has attracted considerable attention. Most studies suggest that dietary carotenoids may play a role in maintaining depressive symptoms due to their antioxidant activity, but some studies concluded the contrary. This study conducted a meta-analysis of observational studies to test the relationship between carotenoid supplements and depressive symptoms. After a comprehensive search of the Cochrane Library, PubMed, Embase Scopus, and Web of Science databases from their inception to 28 July 2022, 12 publications met the inclusion and exclusion criteria, of which 8 were cross-sectional studies, 3 were case–control studies, and 1 was a cohort study, involving a total of 33,466 participants. Pooled meta-analysis found that intake of total carotenoids (OR = 0.61, 95% CI [0.53, 0.71], p < 0.01), beta-carotene (OR = 0.61, 95% CI [0.52, 0.70], p < 0.01), alpha-carotene (OR = 0.71, 95% CI [0.60, 0.83], p < 0.01), lycopene (OR = 0.71, 95% CI [0.55, 0.90], p < 0.01), lutein, and/or corn xanthin (OR = 0.53, 95% CI [0.43, 0.66], p < 0.01) was significantly inversely associated with depressive symptoms, while beta-cryptoxanthin (OR = 1.07, 95% CI [0.52, 2.21], p = 0.86) had no significance. At the same time, this meta-analysis was free of publication bias and heterogeneity. Although further studies are needed to elucidate the causal relationship between carotenoids and depressive symptoms, and to further reveal the mechanism of their association, the results of our meta-analysis suggest that carotenoids are protective factors for depressive symptoms, and dietary intake may help in reducing the risk of depressive symptoms. Full article

(This article belongs to the Special Issue Oxidative Stress and Psychiatric Research)

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