Antioxidants as potential therapeutics for neuropsychiatric disorders

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Abstract

Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and non-genetic factors have been found to cause increased cellular levels of reactive oxygen species beyond the capacity of antioxidant defense mechanism in patients of psychiatric disorders. These factors trigger oxidative cellular damage to lipids, proteins and DNA, leading to abnormal neural growth and differentiation. Therefore, novel therapeutic strategies such as supplementation with antioxidants can be effective for long-term treatment management of neuropsychiatric disorders. The use of antioxidants and PUFAs as supplements in the treatment of neuropsychiatric disorders has provided some promising results. At the same time, one should be cautious with the use of antioxidants since excessive antioxidants could dangerously interfere with some of the protective functions of reactive oxygen species. The present article will give an overview of the potential strategies and outcomes of using antioxidants as therapeutics in psychiatric disorders.

Highlights

► Overview of oxidative stress in major neuropsychiatric disorders ► Alterations in antioxidant defense mechanisms in schizophrenia and depression ► Antioxidants hold great promise for the treatment of schizophrenia and depression.

Introduction

Oxidative stress and constitutively produced reactive oxygen and nitrogen species (ROS and RNS) are known to affect cellular processes in a deleterious manner. Moreover, accumulating evidence indicate that oxidative free radicals play important roles in the pathophysiology of various neuropsychiatric disorders including schizophrenia, bipolar disorder and major depression. Such studies have also opened the possible avenues of new treatment strategies using antioxidants as adjunctive therapy in the above disorders. In this review, we present an overview of recent findings on the role of oxidative stress in the pathophysiology of neuropsychiatric disorders. We also discuss on the use of antioxidants as adjunctive therapy in the above psychiatric conditions.

This review has been prepared based on a literature search using the Medline, Pubmed, Google Scholar, BIOSIS Previews, and NIH Reporter databases, up until July 2012. Search terms included the following: oxidative stress, reactive oxygen species, reactive nitrogen species, antioxidants, antioxidant defense, lipid peroxidation, DNA damage, neuropsychiatric disorder, psychiatry, mental disorder, schizophrenia, bipolar disorder, depression, anxiety disorder, glutathione, N-acetylcysteine, alternative treatment, antipsychotic, antidepressant, and treatment, grouped in various combinations.

Section snippets

Free radicals

The main free radicals formed in the body are ROS and RNS. At least 5% of the inhaled oxygen is converted to reactive oxygen species (Harman, 1993). These radicals in excess result in oxidative stress, which has been implicated in the pathogenesis of several diseases including neuropsychiatric disorders. Most of the molecular oxygen consumed by aerobic cells during metabolism is reduced to water by using cytochrome oxidase in mitochondria. However, when the oxygen is partially reduced it

Antioxidants

The antioxidant defense mechanisms protect the cells by removing the free radicals. The antioxidant system comprises of different types of functional components such as enzymatic and nonenzymatic antioxidants. The enzymatic antioxidants comprise of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S transferase (GST). The non-enzymatic antioxidants include reduced glutathione (GSH), vitamin C (ascorbic acid), vitamin E (α

Oxidative stress in psychiatric disorders

The brain is considered particularly vulnerable to oxidative injury due to high oxygen utilization and hence generation of free radicals, insufficient antioxidant defense mechanisms, high lipid content and excitotoxicity. Increasing evidence indicates that disturbances of antioxidant defense mechanisms can play a part in a wide range of neuropsychiatric disorders (Table 1). Below, we discuss the role of free radicals and antioxidants in the pathophysiology of schizophrenia, bipolar disorder and

Therapeutic approach of antioxidants in psychiatric disorders

Previous findings suggest a strong correlation in the activity of free radicals and antioxidants in the pathophysiology of various neuropsychiatric disorders. However, due to the variations in findings among clinical subjects, it still leaves the exact mechanistic link to the pathophysiology of these complex disorders unclear. While there are pharmaceutical treatments available for those who have schizophrenia or mood disorders, these treatments have limitations in the long-term treatment

Conclusions

There is a growing body of evidence that oxidative stress is involved in the pathology of major neuropsychiatric disorders. Evidence from postmortem as well as peripheral tissues indicate alterations in both free radicals and antioxidant defense mechanisms in disorders such as schizophrenia and mood disorders. Strategies to ameliorate oxidative injury and thereby improve clinical symptoms are of considerable importance. As discussed above, antioxidants as supplements in the treatment of

Acknowledgments

This material is based upon work supported in part by the grants from National Institute of Health [MH087857 (AP)].

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