Antioxidants and Bipolar.
Oxidative stress has been implicated in the pathophysiology of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, major depression etc. Both genetic and nongenetic 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.
Free radicals.
Oxidative stress and constitutively produced reactive oxygen and nitrogen species (ROS and RNS) are known to affect cellular processes in a deleterious manner. 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. 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 becomes ‘activated’ and reacts readily with a variety of biomolecules such as proteins, carbohydrates, lipids and DNA. In the sequential univalent process by which oxygen undergoes reduction, several reactive intermediates such as superoxide, hydrogen peroxide, and extremely reactive hydroxyl radical are formed. The nitric oxide radical is produced in higher organisms by the oxidation of one of the terminal guanidonitrogen atoms of L-arginine. This process is catalyzed by the enzyme nitric oxide synthase. Depending on the microenvironment, NO can be converted to various other reactive nitrogen species such as nitrosonium cation (NO+), nitroxyl anion (NO−) or peroxynitrite (ONOO−). Some of the physiological effects may be mediated through the intermediate formation of S-nitroso-cysteine or S-nitroso-glutathione.
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 tocopherol), N-acetyl-cysteine (NAC), uric acid, carotenoids, flavanoids ubiquinol etc. Oxidative stress occurs when the production of ROS exceeds the natural antioxidant defense mechanisms, causing damage to macromolecules such as DNA, proteins and lipids. The oxidation of lipids by ROS, notably lipid peroxidation of polyunsaturated fatty acids (PUFA), results in reactive products such as croton aldehyde, malondialdehyde and 4-hydroxyalkenals. These intermediates can reac with DNA bases in vitro and in vivo to form exocyclic DNA adducts characterized as propano and etheno DNA-base adducts.
Although ROS are generally known for their destructive effects in the cells a number of biological reactions require ROS for their protective functions. It is known that phagocytes as well as neutrophils protect cells from intruding bacteria via NADPH dependent ROS mechanism. ROS play an important role in cytochorme P450-dependent detoxification reactions. It has been shown that ROS are essential mediators of apoptosis. Therefore, 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.
While there are pharmaceutical treatments available for those who have schizophrenia or mood disorders, these treatments have limitations in the longterm treatment management of the above disorders. In an attempt to find alternative approaches to better treatment for these patients, researchers have embarked on using antioxidant treatment as adjunct therapy for psychiatry disorders. Evidence from clinical, pre-clinical and epidemiological studies suggest that a benefit of using antioxidant compounds, which enhance neuroprotection, should be considered as adjunctive therapy.
Several compounds possessing antioxidant properties that could be used as possible therapeutics are vitamin E, vitamin C, Omega-3 fatty acid, coenzyme Q10, NAC, GSH, rutin, ginkgo biloba, melatonin, hydroxytyrosol, caffeic acid phenethyl ester, resveratrol, quercetin and lycopene. Metal ions such as Zinc and Manganese are also useful through improvement of antioxidant defense.