Association of Antioxidant to the Genesis of Psychiatric Disorder

Ranjit S. Ambad1, Sonal Muley2, Lata Kanyal Butola*3, Ajinkya S. Ghogare4 1Department of Biochemistry, Datta Meghe Medical College, Shalinitai Meghe Hospital & Research Centre, Hingana, Nagpur-441110, Maharashtra, India 2Department of Ophthalmology, Datta Meghe Medical College, Shalinitai Meghe Hospital & Research Centre, Hingana Nagpur-441110, Maharashtra, India 3Department of Biochemistry, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi, Wardha-442001, Maharashtra, India 4Department of Psychiatry, Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi, Wardha-442001, Maharashtra, India


INTRODUCTION
Mental disorders were associated with a wide range of chronic illnesses, Alcohol usage disruptions, disability, and even mortality, particularly among elderly people (Patel et al., 2018). Depression will be the second cause of disease identi ied by the WHO in 2020 (World Health Organization, 2017). The risk of suicide rises with depression (Behere et al., 2017). Anxiety is an emotional state of antipathy in which the sense of fear is disproportionate to the magnitude of the risk. In certain psychological conditions, anxiety is involved (Weinberger, 2001). About one-eighth of the total population worldwide have excessive anxiety (Eisenberg et al., 1990).
Oxidative stress arises when the reactive oxygen species (ROS) are overproduced, or the cellular antioxidant defense mechanisms are de icient (Berg et al., 2004;Kohen and Nyska, 2002). Maternal antioxidant protection mechanism, which through enzymatic induction counteracts the effects of free radicals, may prevent nitrosative stress (Gaikwad et al., 2017).
Accumulating evidence indicates heightened oxidative stress could be involved in schizophrenia pathophysiology (Steullet et al., 2017;Yao and Reddy, 2011). Schizophrenia is a psychiatric illness that weakens and affects around one per cent of the people. It is described by positive side effects (e.g., irregular attitudes and thinking), negative side effects (e.g. inability to feel pleasure and detachment from society), and impairment mental processes (Bitanihirwe and Woo, 2011). In its etiology, it is considered as multifactorial and heterogeneous, so that various pathological processes converge on a cluster of allied symptoms. Schizophrenia and other psychotic disorders are generally known as neurodevelopmental disorders, where several hits mount up throughout the crucial phase of development of CNS triggering the disorders (Hovatta et al., 2010;Valko et al., 2007). Most schizophrenic sufferers begin with a prodromal process marked by subclinical symptoms of the condition, which we will consign to after this clinically elevated psychosis risk state (Hassan et al., 2014;Inoguchi, 2003).
In some trials, 22% of those who meet the CHR criterion lead to a year of record psychotic illness, compared with 0.015% healthy individuals (Xu et al., 2014). Neurons are usually less resistant to free radical attacks and damaged antioxidant systems or disclosure to free radicals can cause destructive reactions with substrates critical for the continued existence of cells such as proteins, lipids, nucleic acids and lead to neuronal death (McDaniel, 1995;Lohr, 1991). Freshly, OS has involved and evidence is emerging to hold the role it plays in bipolar disorder (Cheeseman and Slater, 1993;Jesberger and Richardson, 1991). SOD and GPx form an antioxidant protection mechanism next to essential harm and defend against damage to the cells and molecules (Andreazza et al., 2007;Selek et al., 2008). Oxidative stress typically results from excessive development of reactive oxygen species (ROS) or failure of the ROS controlling enzymatic and non-enzymatic processes (Savas et al., 2006;Kensler et al., 1983). The cause of multiple physical and mental disorders is responsible for oxidative stress. To counter the oxidative stress, the body has its antioxidant system, which tries to control the oxidative injury. ROS and reactive nitrogen species are the two main mechanisms that control oxidative activity in the body (Cotgreave et al., 1988;Wendel et al., 1980). Excessive development of ROS in the body leads to further oxidative stress, resulting in loss of intracellular signalling and cellular ageing leading to apoptosis (Cotgreave et al., 1988). Antioxidants like SOD, GPx, CAT, and non-antioxidants such as vitamin A, C, E, β-carotene, zinc, copper, selenium, and lavonoids act as free-scavengers, thereby reducing oxidative stress and resulting in cell injury (Riecher et al., 1989;Häfner et al., 1992). Reduced levels of Vit-C and E may not be adequate to ight ROS (Wasnik and Akarte, 2017).
A large proportion of the disorder has not been diagnosed by primary care doctors. Appropriate attention to psycho-neuro-endocrinological problems may help clinicians develop a more reliable and holistic view of patients and improve the likelihood of delivering the most appropriate care (Ambad et al., 2020a). This highlights the need for more training to enhance early detection at this stage (Pal et al., 2018). Knowledge of the endocrine system and minerals are important for the proper treatment of psychiatric disorders (Ambad et al., 2020c,b).
In this study, we have observed levels of SOD, GPx, Vitamin C, and Vitamin E.

Aim and Objective
Aim 1. To study levels of SOD, GPx, Vitamin C, and Vitamin E in psychiatric disorders.
2. To study the levels of Vit-C and E before and after vitamin supplementations.

Objective
To correlate the levels of SOD, GPx, Vitamin C, and Vitamin E between psychiatric patients and healthy controls (age-matched) attending AVBRH Wardha and SMHRC Nagpur.

MATERIALS AND METHODS
The current study was done in the Department of Biochemistry and Dept. of Psychiatry at Datta Meghe Medical College, Shalinitai Meghe Hospital &Research Centre, Nagpur in collaboration with Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi (Meghe) Wardha Maharashtra.
Total of 100 subjects was selected for the study. Out of which 50 patients are age and gender-matched healthy control, 50were suffered from psychiatric disorders. Informed consent was taken from all participants included in the study.

Sample Collection
Blood sample was collected and all patients and controls (n=100) gave informed consent for participation to the study.

GPx Measurement
GSH-Px movement was estimated by the strategy for Paglia and Valentine. The enzymatic response was started by adding H2O2 to the reaction mixture containing decreased GSH, diminished nicotinamide adenine dinucleotide phosphate and GR. The adjustment in the absorbance at 340 nm was checked by Shimadzu UV 1601 spectrophotometer. One unit of GSH-Px is characterized as micromoles of NADPH oxidized every moment. Action was given in units per liter plasma volume (Pal et al., 2018).

SOD Measurement
SOD was resolved by the technique for Sun and partners. One unit of SOD was characterized as the measure of compound causing half inhibition in the NBT decrease rate. Activity was given in units per liter plasma volume (Ambad et al., 2020c).

Estimation of vitamin C
Vitamin C was estimated by HPLC with electrochemical or ultraviolet light exposure (Ambad et al., 2020b).

Estimation of vitamin E
Vitamin E was estimated by Modi ied simple method by baker and frank method and the technique by using 2,2'-bipyridyl, FeCl3 and C8H10. The complex of Fe +2 generated in this reaction with 2,2'-bipyridyl is determined by using a plain ELISA microplate at 492nm (Paglia and Valentine, 1967).

Statistical Analysis
All approximate indings were as mean ±SD. Mean values are determined by unpaired Student -t-test for meaning. Statistical analysis will be carried out using the Social Science software Statistical Kit (SPSS, 24.0). The categorical indicators would be used with frequencies and percentages. Probability values p < 0.05 is known as statistically important.

OBSERVATION AND RESULTS
Graph 1: Scatter diagram of Vitamin E before and after supplementation Graph 2: Scatter diagram of Vitamin C before and after supplementation Table 1 showed the levels of Antioxidants in Psychiatric patients was highly signi icant than the normal control group.
There is a signi icant correlation between vitamins in psychiatric patients and healthy controls with a p-value of <0.05 shown in Table 2. Table 3 showed after the supplementation with different doses of vitamins, there is a slight increase in the values of Vitamins. There is a signi icant correlation between vitamins in psychiatric patients before and after supplementation with a p-value of <.05.

DISCUSSION
In a healthy being, the development and a variety of interactions with free radicals are closely regulated by enzymatic defence mechanisms such as SOD, GPx, or via the role of non-enzymatic antioxidants such   as Vit-C, E and GSH. Graph 1 shows the effect of Vit E on psychiatry patients. Graph 2 shows the effect of Vit C on psychiatry patients. Highly development of free radicals and compromised defence mechanisms, however, a guide to oxidative stress and effect in radical, induced lipid, protein and DNA damage (Sun et al., 1988).
Vit-C is a co-substrate for lots of enzymes, serving to stimulate antioxidants and increasing the effects of other compounds, such as Vit-E (Robitaille and Hoffer, 2015). Vit-E is viewed as the primary line of guard against lipid peroxidation, it shields cell ilms from free radical harm (Jargar et al., 2012). Vit-C and Vit-E work together by having both hydrophilic and hydrophobic properties, providing a complete antioxidant defence (Powers et al., 2004). Tocopherols and tocotrienols (vit-E) and Vit-C respond with free radicals, prominently peroxyl radicals, and with singlet atomic oxygen, this being the premise of their capacity as a cancer prevention agent.
Vit-C is a fundamental cofactor for α-ketoglutaratesubordinate dioxygenases. Vit-C-subordinate inhibition of the HIF pathway may give elective or extra ways to deal with controlling tumor movement, contaminations, and irritation. Vit-E works as a basic lipid-dissolvable cancer prevention agent, searching hydroperoxyl radicals in a lipid milieu. Human manifestations of Vit-E lack propose that its cancer prevention agent properties assume a key job in securing erythrocyte ilms and sensory issues. As a cancer prevention agent, Vit-C gives the security against oxidative pressure prompted cell harm by searching ROS, by Vit-E-subordinate balance of lipid hydroperoxyl radicals, and by shielding proteins from alkylation by electrophilic lipid peroxidation items. These bioactivities bear pertinence to in lammatory disorders (Powers et al., 2004;Traber and Stevens, 2011).

CONCLUSIONS
The result of this study indicates that, in psychiatric disorders, the serum levels of SOD, GPx, Vit-C and Vit-E decrease, Low level of vit-C and E levels can not suf ice to counter ROS and the level of antioxidant in the serum has been compromised to ight oxidative stress.
Antioxidants supplementation has provided some positive results in the treatment of neuropsychiatric disorders. These indings indicate that antioxidants should be studied either as an alternative therapy or as an adjunct to traditional medications, telepsychiatry diagnosis method has the ability to allow correctly and effectively diagnose psychological condi-tions antioxidants are usually Extremely low chance drugs and their use may before effective compared to the medicines that have been developed.

Funding Support
The authors declare that they have no funding support for this study.