Redox-Oxidative Stress and Micronutrients Interplay in the Clinical Phenotype of Schizophrenia in Nigeria Subjects

Redox-Oxidative Stress and Micronutrients Interplay in the Clinical Phenotype of Schizophrenia in Nigeria Subjects | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Redox-Oxidative Stress and Micronutrients Interplay in the Clinical Phenotype of Schizophrenia in Nigeria Subjects Tolutope Adebimpe Oso, Adeleye Sunday Joshua, Bamidele Musa Sikiru, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6646822/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Redox-oxidative dysregulation is implicated in the aetiology of several diseases including schizophrenia with possible influence on clinical symptoms. This study investigated the influence of redox, lipid peroxidation and micronutrient antioxidants in the expression of clinical phenotypes of schizophrenia. Methods A total number of 220 consented drug naïve volunteers including 120 participants with Schizophrenia and 100 apparently healthy controls were recruited. Schizophrenia symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS). MDA, glutathione, total antioxidant capacity (TAC), enzymatic antioxidants (SOD, Catalase) and non-enzymatic antioxidants (Vit C, Vit E, Zn, Se) were measured by ELISA and Atomic Absorption spectrophotometry technique, respectively. Results Enzymatic antioxidants; SOD (19.58 ± 0.80; 10.12 ± 0.045µmol/ml/min) and CAT (41.73 ± 1.8; 21.33 ± 0.98 µmol/ml/min) increased in schizophrenia compared with controls (p < 0.05) but decreased non-enzymatic antioxidants; Glutathione (GSH: 145.15 ± 0.28; 159.07 ± 1.59, P < 0.05). Furthermore, serum level of Zinc (0.18 ± 0.01; 0.27 ± 0.02 ppm), Selenium (0.08 ± 0.01; 0.10 ± 0.01 ppm) and Vitamin C (12.98 ± 0.49; 15.08 ± 0.37 mg/dl) were lowered in the schizophrenia compared with controls (P < 0.05). Glutathione had a negative correlation with positive symptoms (r=-0.285, p = 0.013) while SOD (r = 0.281, p = 0.001) and CAT (r = 0.179, p = 0.034) correlated positively with MDA (p < 0.05). In contrast, GSH (r=-0.247, p = 0.003) and TAC (r=-0.221, p = 0.009) correlated negatively with MDA (p < 0.05). Conclusion The study implicates redox and antioxidant imbalance in schizophrenia. There was evidence that natural defense against oxidative damage and antioxidant responses is compromised influencing the clinical phototypes of the disease, A meticulous supplementation of micronutrients and antioxidants may be a useful adjunct treatment in the management of schizophrenia. Antioxidants Clinical Phenotypes Redox-oxidative Stress Schizophrenia Micronutrient Lipid Peroxidation Figures Figure 1 Figure 2 Introduction Schizophrenia is a disorder that affects social and emotional function ( 1 ). It is a constellation of features which may be characterized as positive, negative and general psychopathological symptoms ( 2 ). Positive symptoms include hallucinations, delusions and paranoia, while alogia, anhedonia, avolition, and blunted affect mark the negative domain. General psychopathology tends to refer to impairments such as poor memory and poor executive functioning ( 3 ). It is the most common diagnosis resulting in help seeking in Nigeria ( 4 ), and affects 1% of the general population worldwide and has been known to contribute significantly to years lost to disability ( 5 ). Schizophrenia is a disorder with widespread structural and functional alterations, which are not completely understood. However, studies have shown numerous biochemical pathways in the neurobiology of the disorder. Some of which are not directly causative but act as risk factors for the disorder ( 6 ). In the past, much focus and emphasis had been placed on the dopamine system alterations based on indirect evidence from the role most antipsychotics medications play by acting on the dopamine receptor and specifically the D 2 sub-type ( 7 ). However, efforts have been made to identify other biological processes that may contribute to the process and symptomatology in schizophrenia. One of such is the redox-oxidative stress and micronutrients antioxidants in schizophrenia ( 8 ). Redox dysregulation as a potential pathway in symptomatology manifestation rises when there is increased oxidative damage and decreased capacity of intracellular antioxidant defense system. This give rise to oxidative stress which results from the disequilibrium between pro-oxidant processes and the antioxidant defense system in favor of the former ( 9 ). There are several consequences of oxidative stress due to increased free radical production and inefficient antioxidant systems which lead to lipid peroxidation ( 10 ). Oxidative stress has been linked to low levels of antioxidant vitamins such as C, E, and beta carotene ( 11 ). People with schizophrenia have also been found to have altered antioxidant levels in the blood and brain and altered antioxidant enzyme activity. Additionally, oxidative stress has been suggested as a potential connection between schizophrenia and vitamin deficiency. Studies have also shown that antioxidant vitamins such as C and E offer protection against cellular damage due to either inflammation or highly reactive oxygen species ( 12 ). Redox dysregulation is linked to reduction of parvalbumin, containing GABA interneurons and volumes of their perineuronal nets, white matter abnormalities and microglia activation. Activity of transcription factors, kinases and phosphatases regulating diverse aspect of neurodevelopment and synaptic pathway vary according to cellular redox state ( 13 ). Furthermore, the mechanism through which nutrition and nutritional deficiencies induce schizophrenia or exacerbate its symptoms is not completely understood but several modalities have been suggested. These include poor diet, bad eating habits, and nutritional deficiencies that have been connected to the onset of hyperhomocysteinemia, oxidant-antioxidant status derangement, immunological dysregulation, and changes in the levels of pro-inflammatory markers. The neuroprogressive hypothesis, which regarded abnormalities in oxidative stress and immune-inflammatory indicators as potential pathways in the pathophysiology of schizophrenia has previously discussed the significance of inflammation and oxidative stress in schizophrenia ( 14 ). According to current theories, the connection between nutrition and schizophrenia may involve the stimulation of neuro-inflammation and modification of the gut microbiota, both of which have been linked in some instances to the exacerbation of schizophrenia symptoms ( 14 ). Oxidative stress and redox imbalance can disrupt the normal functioning of neurotransmitter systems in the brain, particularly the glutamate system. Glutamate is an excitatory neurotransmitter that plays a crucial role in synaptic transmission and cognitive processes. Imbalances in glutamate levels or receptor functioning have been implicated in the pathophysiology of schizophrenia and may contribute to symptoms such as cognitive impairments, hallucinations, and disorganized thinking ( 15 ). In addition, increased oxidative stress can lead to damage to neuronal structures, including lipid peroxidation and protein oxidation. This can disrupt neuronal membrane integrity and impair cellular functions. Oxidative stress can also trigger inflammatory processes in the brain, leading to neuroinflammation. Neuroinflammation has been associated with the development and progression of schizophrenia and may contribute to the positive symptoms of the disorder ( 9 ). Furthermore, redox imbalance in schizophrenia may involve a deficiency in the antioxidant defense system. Antioxidants such as glutathione, superoxide dismutase (SOD), and catalase play a crucial role in neutralizing reactive oxygen species (ROS) and protecting cells from oxidative damage. Reduced levels or impaired activity of these antioxidants may result in increased oxidative stress and cellular dysfunction ( 16 ). Also, Mitochondria, the cellular powerhouses responsible for energy production, are vulnerable to oxidative damage. Oxidative stress can disrupt mitochondrial function, leading to decreased energy production, impaired cellular metabolism, and increased ROS production. Mitochondrial dysfunction has been implicated in the pathophysiology of schizophrenia and may contribute to symptoms such as fatigue, cognitive impairment, and negative symptoms. More importantly Oxidative stress can induce DNA damage through the formation of DNA adducts and strand breaks. DNA damage can lead to genetic and epigenetic alterations that affect neuronal development, synaptic plasticity, and neurotransmitter signaling, potentially contributing to the emergence of schizophrenia symptoms ( 17 ). Diets low in anti-inflammatory nutrients or high in pro-inflammatory ones (omega-6 fatty acids are pro-inflammatory, whereas omega-3 fatty acids are anti-inflammatory) can activate and exacerbate neuroinflammation, which, if left unchecked, can lead to pathological changes in schizophrenia and worsen its symptoms ( 18 ). Previous studies reporting redox and oxidant parameters have reported changes which have been heterogenous with less emphasis on its relationship with the psychopathy of the disorders. Therefore, this study is aimed at investigating the influence of redox activity, lipid peroxidation and micronutrient antioxidants in the expression of clinical phenotypes of schizophrenia. Materials and Methods Study Population and Design This is a case control study matched for gender and age, with no family history of mental illness in controls. A total number of 220 consented drug naïve volunteers including 120 participants with Schizophrenia and 100 apparently healthy controls were recruited. The study participants were clients visiting the assessment unit of Neuropsychiatric Hospital, Aro, Abeokuta, Ogun State, Nigeria. The Positive and Negative Symptom Scale (PANSS) was applied to evaluate psychotic symptoms. The study was approved by the Health Research Ethics Committee of Neuropsychiatric Hospital, Aro Abeokuta, Ogun State, Nigeria (PR003/19). Biochemical Assessment Lipid peroxidation was quantified as Malondialdehyde (MDA) via the development of thiobarbituric acid reacting substance (TBARS) ( 19 ). Catalase activity was determined as previously described ( 20 ), Superoxide dismutase was determined by its ability to inhibit auto oxidation of epinephrine ( 21 ), Total antioxidants capacity was estimated by phosphomolybdenum method ( 22 ), Zinc and Selenium were analysed by Flame Atomic Absorption Spectrophotometry (FAAS) ( 23 ). Vitamin E and C were measured as previously described ( 24 ). Statistical analysis Statistical analysis was performed using IBM statistical package for social sciences (SPSS v. 25). Continuous variable were evaluated using the student’s T-test. Pearson Correlation was used to determine association of psychopathy with biochemical parameters. Logistic regression analyses were performed to explore which characteristics were related to the risk of schizophrenia. Significance was set at p < 0.05. Results The mean score for the Positive, Negative and General Psychopathology score in the case are 19.76 ± 7.1, 20.14 ± 7.7 and 35.54 ± 12.1, respectively (Fig. 1 ). The serum levels of both enzymatic and non-enzymatic antioxidants in Schizophrenia and Controls were presented in Table 1 . There was a significant increase in enzymatic antioxidant levels in individuals with schizophrenia compared to the controls. Specifically, levels of superoxide dismutase (SOD) and catalase (CAT) were elevated in schizophrenia cases (SOD: 19.58 ± 0.80 vs. 10.12 ± 0.045 µmol/ml/min; CAT: 41.73 ± 1.8 vs. 21.33 ± 0.98 µmol/ml/min; p < 0.05). In contrast, non-enzymatic antioxidants were significantly reduced in schizophrenia patients compared to controls. A reduction in glutathione (GSH) levels was observed in schizophrenia (GSH: 145.15 ± 0.28 vs. 159.07 ± 1.59 µmol/L). Similarly micronutrients non-enzymatic antioxidants; zinc (0.18 ± 0.01 vs. 0.27 ± 0.02 ppm), selenium (0.08 ± 0.01 vs. 0.10 ± 0.01 ppm), vitamin C (12.98 ± 0.49 vs. 15.08 ± 0.37 mg/dl), and total antioxidant capacity (TAC: 65.49 ± 1.51 vs. 81.64 ± 1.48 ng/dl), ( p 0.05. In addition, MDA, a product of lipid peroxidation was significantly higher in patients with schizophrenia compared to control (2.32 ± 0.19 and 1.17 ± 0.10 umol/ml) p < 0.05, Table 2 showed logistic regression predictors of schizophrenia. The regression model showed that an increase in MDA levels was associated with higher odds of schizophrenia (OR = 2.017). Reductions in GSH, TAC, zinc, selenium, and vitamin C levels were also associated with increased odds of schizophrenia. Pearson Correlation of MDA with antioxidants parameters reveal. that MDA were correlated with certain antioxidant parameters (0.281, 0.179, -0.247 and − 0.221) (P 0.05). Table 1 Serum Levels of Antioxidants in Schizophrenia and Controls. Variables Schizophrenia (Mean ± SEM) Control (Mean ± SEM) t-value p-value Zinc (ppm) 0.18 ± 0.01 0.27 ± 0.02 -3.548 0.001* Selenium (ppm) 0.08 ± 0.01 0.10 ± 0.01 -2.296 0.024* Vitamin C (mg/100g) 12.98 ± 0.49 15.08 ± 0.37 -3.225 0.002* Vitamin E (mg/100g) 1.74 ± 0.15 1.91 ± 0.12 -0.875 0.383 TAC (mg/100g) 65.49 ± 1.57 81.64 ± 1.48 -7.274 < 0.001* MDA (µmol/ml) GSH (µmol/ml) CAT (µmol/ml/min) SOD (µmol/ml/min) 2.32 ± 0.19 145.15 ± 0.28 41.73 ± 1.81 19.58 ± 0.80 1.17 ± 0.10 159.07 ± 1.59 21.23 ± 0.98 10.12 ± 0.45 4.878 -8.647 9.915 9.439 < 0.001* < 0.001* < 0.001* < 0.001* *Significant at p < 0.05. Table 2 Logistic regression showing predictors of schizophrenia Variables Odd Ratio 95% CI P-value MDA 2.017 1.466–3.027 < 0.001 TAC SOD 0.904 1.593 0.871–0.939 1.347–1.886 < 0.001 < 0.001 CAT 1.190 1.124–1.259 < 0.001 GSH 0.553 0.439–0.696 < 0.001 Zn 0.016 0.001–0.189 0.001 Se 0.369 0.166–0.822 0.015 Vit C Vit E 0.861 0.880 0.781–0.949 0.661–1.771 0.003 0.380 *Significant at p < 0.05. Table 4 Pearson Correlation of MDA with antioxidants parameters Variables MDA SOD r = 0.281, p = 0.001 CAT r = 0.179, p = 0.034 GSH r=-0.247, p = 0.003 TAC r=-0.221, p = 0.009 Zn r=-0.101, p = 0.235 Se r=-0.139, p = 0.156 Vit C r=-0.660, p = 0.483 Vit E r=-0.045, p = 0.594 *Significant correlation, p < 0.05, r = Pearson correlation The mean score for the Positive, Negative and General Psychopathology score in the case is 19.76 ± 7.1, 20.14 ± 7.7 and 35.54 ± 12.1, respectively (Fig. 1 ). Table 3 presents the correlation analysis between oxidative stress parameters and the three symptom domains of the PANSS scale. Figure 2 shows a negative correlation between GSH and positive symptoms (r=-0.285, p = 0.013 No correlation was found for other variables such as CAT, SOD, Vitamin C, Vitamin E, TAC, and GSH. Table 3 Pearson Correlation of Biochemical Parameters with Positive, Negative and General Symptoms in Schizophrenia Population Biochemical Variable Positive Symptoms Negative Symptoms General Symptoms MDA r=-0.095, P = 0.417 r = 0.054, p = 0.648 r = 0.033, p = 0.77 Zinc r=-0.071, p = 0.544 r = 0.152, P = 0.193 r = 0.075, p = 0.521 Selenium r=-0.086, p = 0.923 r = 0.021, p = 0.906 r=-0.017, p = 0.902 Vitamin C r = 0.156, p = 0.183 r = 0.156, p = 0.182 r = 0.037, P = 0.753 Vitamin E r=-0.018, p = 0.874 r=-0.003, p = 0.982 r=-0.100, p = 0.396 CAT SOD r=-0.187, P = 0.473 r=-0.030, P = 0.790 r=-0.008, p = 0.947 r=-0.067, p = 0.569 r=-0.115, p = 0.325 r=-0.177, p = 0.128 GSH r=-0.285, p = 0.013 r = 0.101, P = 0.390 r=-0.029, p = 0.804 TAC r= -0.083, p = 0.458 r = 0.059, p = 0.616 r = 0.151, p = 0.197 *Significant correlation, p < 0.05, r = Pearson correlation Discussion Schizophrenia is a disorder of multiple etiological pathway, which converge into a common pathway and account for the array of clinical symptoms ( 25 ). Free radicals mediated abnormalities have been implicated in the development of such important consequences in schizophrenia ( 17 ). The increase in lipid peroxidation reported in this study might have implication in the pathophysiology of schizophrenia. The increased serum MDA activity in schizophrenia patients observed is consistent with previous findings ( 10 ). This MDA activities observed among this group can be evaluated as a marker of peroxidative damage to the phospholipid membrane, a process which may lead to neuronal membrane instability which can result in disruption of the cell cycle and neurotransmitter release, and uptake ( 7 ). Oxidative stress has been suggested to contribute to the pathophysiology of schizophrenia in particular, the oxidative damage in lipids, proteins and DNA seen in schizophrenia are known to impair cell viability and function, these may contribute to the risk of the disorder ( 26 ). The increased activity of SOD and CAT observed in this study is consistent with previous findings ( 9 ), which may represent a response to elevated oxidative stress resulting from excessive free radical production. Antioxidant enzymes protect cellular components from damage caused by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals ( 27 ). Furthermore, evidence point towards an alteration in the activities of enzymatic and non-enzymatic antioxidant system, this is clearly shown in the low level of non-enzymatic antioxidant enzymes which agrees with previous study ( 31 ). Plasma level of Vitamin C decreases in schizophrenia related to normal controls. The antioxidants function of ascorbic acid may protect against dopamine dysregulation induced neurodegenerative processes ( 32 ). Studies suggest that supplementation with vitamin C may reduce oxidative stress and improve outcomes in schizophrenia, as patients may have higher requirements due to increased redox activity ( 33 ). Although Vitamin E was not found to show any effect in this study but acts synergistically with Vitamin C to achieve their scavenging role. Supplementation in their duct may be advisable as they consume less of these vitamins because of their psychotic state and their poor dietary fiber consumption ( 12 ). Lower levels of Zinc were also demonstrated in this study while previous studies suggest its link with psychosis. Lower zinc levels in participants with schizophrenia may be because of inflammation or genetic dysregulation in molecules that maintain zinc homeostasis and nutritional deficiencies that might leads to NMDA hyperactivity, a possible psychotic symptomatology. Thus, zinc supplements might modulate glutamatergic transmission within the neural networks that converge in the prefrontal cortex thus leading to a reduction in symptomatology. However direct modulation of hyperactive NMDA receptors by Zinc inhibition may target microcirculation that is not accessible to conventional D2 receptor antagonists ( 34 ). Although Selenium and Zinc are essential micronutrients that have important roles in reducing oxidative stress and protect DNA from attack of reactive oxygen species, interestingly, our study showed difference in selenium activity relative to control. Antioxidants micronutrients such as Zn, Se, Vit E, Vit C and TAC have no relationship with positive, negative and general symptoms of schizophrenia in this study. This could be due to the fact that the population presented with mild to moderate symptoms and are drug naïve, the situation might be different if they are chronic cases and this was contradicted by a study conducted by Dadheech et al ., ( 35 ). A significant inverse correlation was found between glutathione levels and positive symptoms of schizophrenia. Glutathione regulates glutamate metabolism and maintains redox balance in the brain. Dysregulation of the glutamate neurotransmitter system, particularly involving the NMDA receptor, has been linked to schizophrenia ( 26 , 28 ). Glutathione depletion may disrupt glutamate neurotransmission, which could contribute to the development of positive symptoms in schizophrenia. This is supported by reduced GSH levels in schizophrenia patients in this study.. Additionally, genetic variations in the glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme involved in GSH synthesis, have been associated with an increased risk of schizophrenia ( 29 ). Inflammation and immune dysregulation have also been implicated in schizophrenia. Glutathione helps modulate inflammation and protect against neuroinflammation. Disturbances in glutathione levels may therefore contribute to neuroinflammatory processes, further influencing positive symptoms ( 30 ). Other antioxidant markers, including CAT, SOD, vitamin C, vitamin E, selenium, and zinc, showed no significant relationship with symptom severity, which may result from variations in redox regulation across different illness phases ( 26 ). Abnormality in glutamatergic neurotransmission mediated by NMDA receptor hypofunction has been linked with the pathophysiology of schizophrenia. The link between the glutamatergic system and glutathione may suggest why positive symptoms correlated negatively with GSH concentration in this study. Previous studies have demonstrated that GSH is significantly associated with positive symptoms of PANSS ( 36 ). However, other studies have found a link between GSH and negative symptoms ( 37 ). Other antioxidants did not correlate with all the symptoms scale of PANSS. Superoxide dismutase (SOD) and catalase (CAT), important antioxidant enzymes correlated positively with MDA concentration while negatively with GSH and TAC levels. This positive correlation suggests that as lipid peroxidation increases, the activity of these antioxidant enzymes also rises which may reflect an adaptive response aimed at neutralizing elevated levels, furthermore antioxidant enzymes involved in neutralising superoxide radicals and in breaking down hydrogen peroxide generated during oxidative stress also tends to increase. In contrast, MDA had a null finding with other antioxidant parameters. These findings buttressed the hypothesis of a compensatory antioxidant response to counteract oxidative stress. It is important to note that the other antioxidant parameters did not exhibit significant positive correlations with MDA; in fact, some showed negative correlations. For example, reduced glutathione (GSH) and total antioxidant capacity (TAC) were negatively correlated with MDA, indicating that higher levels of MDA are associated with lower levels of these antioxidants. Overall, these correlations suggest complex interactions between oxidative stress markers (MDA) and antioxidant parameters in individuals with schizophrenia ( 16 ). Conclusion This study provides evidence that redox and micronutrient imbalance influence the clinical phenotypes of schizophrenia among drug-naïve Nigerian subjects. The findings support the hypothesis that oxidative stress and micronutrient dysregulation play a role in the pathophysiology of schizophrenia. This suggest that antioxidant and micronutrient supplementation may be used as promising adjunct therapeutic strategies. Future longitudinal studies are needed to confirm causal relationships and evaluate the therapeutic efficacy of targeted antioxidant interventions in schizophrenia management. Declarations Ethics approval and consent to participate: Ethics approval was obtained from the Health Research Ethics Committee of Neuropsychiatric Hospital, Aro Abeokuta, Ogun State, Nigeria (PR003/19), and written informed consent to participate was obtained from all participants prior to their enrollment. Consent for publication All participants provided written informed consent for the publication of anonymized data derived from this study Availability of data and materials All data generated and gathered during this study are available with the corresponding author on reasonable request. Funding: The authors did not receive any funding for this study. Competing interests: The authors declare no competing interest. Clinical trial number: Not Applicable Author Contributions Conceptualization: OA and JDA Methodology: TAO, BMS, ASJ, WBG and OAO Formal Analysis: OJO, BMS, WBG, OAO and ASJ Sampling and Investigation: TAO, OJO, and OAO Resources: OA, TAO, BMS, WBG, OAO, and ASJ Data Curation: TAO, OA, JDA Writing – Original Draft: TAO, OA Writing–Review & Editing: OA and JDA Supervision: OA and JDA Project Administration: OA, JDA and TAO Funding Acquisition: OA and TAO Acknowledgements We acknowledge the invaluable support received from the staff of the Neuropsychiatric Hospital, Aro, and the University of Lagos throughout the course of this project. Special appreciation is extended to the Centre for Genomics of Non-Communicable Diseases and Personalized Healthcare, University of Lagos, Akoka, Lagos, Nigeria, for their technical guidance, resources, and collaborative efforts that significantly contributed to the success of this work. References Dziwota E, Stepulak M, Włoszczak-Szubzda A, Olajossy M. Social functioning and the quality of life of patients diagnosed with schizophrenia. Ann Agric Environ Med [Internet]. 2018;25(1):50–5. Available from: http://www.journalssystem.com/aaem/Social-functioning-and-the-quality-of-life-of-patients-diagnosed-with-schizophrenia,72507,0,2.html De Hert M, Correll CU, Cetkovich-Bakmas M, Cohen D, Asai I, Detraux J et al. Physical illness in patients with severe mental disorders. World Psychiatry. 2011. Lerner PP, Sharony L, Miodownik C. Association between mental disorders, cognitive disturbances and vitamin D serum level: Current state. Clin Nutr ESPEN [Internet]. 2017; Available from: https://doi.org/10.1016/j.clnesp.2017.11.011 Oso TA, Akpan RM, Ogunwale O, Akinloye O. Pattern of Mental Disorder in a Neuropsychiatric Hospital in NIgeria: A Decade Retrospective Review. Niger J Psychiatry. 2022;20:2–13. Doǧan Bulut S, Bulut S, G�riz O. The relationship between sex hormone profiles and symptoms of schizophrenia in men. Compr Psychiatry. 2016;69:186–92. Choudhury A, Sahu T, Ramanujam PL, Banerjee AK, Chakraborty I, Kumar A, et al. Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases. Neuropsychiatry (London). 2018;8(1):395–424. Sitarz R. Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Naïve. Patients. 2022;1–10. Rukmini MS, D’Souza B, D’Souza V. Superoxide dismutase and catalase activities and their correlation with malondialdehyde in schizophrenic patients. Indian J Clin Biochem [Internet]. 2004;19(2):114–8. Available from: http://link.springer.com/ 10.1007/BF02894268 Schiavone S, Trabace L, Inflammation. Stress Response, and Redox Dysregulation Biomarkers: Clinical Outcomes and Pharmacological Implications for Psychosis. 2017;8(October):1–10. Hurşİtoğlu O, Orhan FÖ, Kurutaş EB, Doğaner A. Diagnostic Performance of Increased Malondialdehyde Level and Oxidative Stress in Patients with Schizophrenia Diagnostic Performance of Increased Malondialdehyde Level and Oxidative Stress in Patients with Schizophrenia. 2021;(May). Madireddy S, Madireddy S. Regulation of reactive oxygen species-mediated damage in the pathogenesis of schizophrenia. Brain Sci. 2020;10(10):1–24. Brown HE, Roffman JL. Vitamin Supplementation in the Treatment of Schizophrenia. CNS Drugs [Internet]. 2014;28(7):611–22. Available from: http://link.springer.com/ 10.1007/s40263-014-0172-4 Asiedu B, Anang Y, Nyarko A, Doku DA, Amoah BY, Santa S et al. The role of sex steroid hormones in benign prostatic hyperplasia. Aging Male [Internet]. 2017;20(1):17–22. Available from: https://www.tandfonline.com/doi/full/ 10.1080/13685538.2016.1272101 Onaolapo OJ, Onaolapo AY. Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment. World J Clin Cases [Internet]. 2021;9(28):8295–311. Available from: https://www.wjgnet.com/2307-8960/full/v9/i28/8295.htm Dudzińska E, Szymona K, Bogucki J, Koch W, Cholewińska E, Sitarz R et al. Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Naïve Patients. J Clin Med [Internet]. 2022;11(9):2551. Available from: https://www.mdpi.com/2077-0383/11/9/2551 Uddin SMN, Sultana F, Uddin MG, Dewan SMR, Hossain MK, Islam MS. Effect of antioxidant, malondialdehyde, macro-mineral, and trace element serum concentrations in Bangladeshi patients with schizophrenia: A case‐control study. Heal Sci Reports [Internet]. 2021;4(2). Available from: https://onlinelibrary.wiley.com/doi/ 10.1002/hsr2.291 Grabnar I, Vovk T, Kores Plesnicar B, Boskovic M. Oxidative Stress in Schizophrenia. Curr Neuropharmacol. 2011. Jahrami H, Faris MA, Ghazzawi HA, Saif Z, Habib L, Shivappa NHJ. Increased Dietary Inflammatory Index Is Associated with Schizophrenia: Results of a Case-Control Study from Bahrain. Nutrients. 2019;11. 2019. De Leon AD, Borges J. CR. Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay. J Vis Exp [Internet]. 2020;(159). Available from: https://app.jove.com/t/61122 Akinloye O, Adaramoye O, Kareem O. Changes in antioxidant status and lipid peroxidation in Nigerian patients with prostate carcinoma. Polish Arch Intern Med [Internet]. 2009;119(9):526–32. Available from: http://pamw.pl/en/node/759 Misra HP, Fridovich I. The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. J Biol Chem [Internet]. 1972;247(10):3170–5. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0021925819452289 Phytochemical screening and evaluation of antioxidant and antibacterial activities of seeds and pods extracts of Calycotome villosa subsp. Intermedia. J Appl Pharm Sci [Internet]. 2017; Available from: http://www.japsonline.com/abstract.php?article_id=2242 Aydinoglu S. Iron and Zinc Determination in Dietary Supplements by Flame Atomic Absorption Spectrophotometry. Brazilian J Pharm Sci [Internet]. 2022;58. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502022000100863&tlng=en Nojavan S, Khalilian F, Kiaie FM, Rahimi A, Arabanian A, Chalavi S. Extraction and quantitative determination of ascorbic acid during different maturity stages of Rosa canina L. fruit. J Food Compos Anal [Internet]. 2008;21(4):300–5. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0889157508000045 Ripke S, Neale BM, Corvin A, Walters JTR, Farh KH, Holmans PA et al. Schizophrenia Working Group of the Psychiatric Genomics Consortium: Biological Insights From 108 Schizophrenia-Associated Genetic Loci. Nature [Internet]. 2014;511(7510):421–7. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112379/%0 Ahttp://dx.doi.org/10.1038/nature13595 Murray AJ, Rogers JC, Katshu MZUH, Liddle PF, Upthegrove R. Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders. Front Psychiatry [Internet]. 2021;12. Available from: https://www.frontiersin.org/articles/ 10.3389/fpsyt.2021.703452/full Chen P, Wang D, Xiu M, Chen D, Lackey B, Wu HE et al. Polymorphism of Transferrin Gene Impacts the Mediating Effects of Psychotic Symptoms on the Relationship between Oxidative Stress and Cognition in Patients with Chronic Schizophrenia. Antioxidants [Internet]. 2022;11(1):125. Available from: https://www.mdpi.com/2076-3921/11/1/125 McCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry [Internet]. 2020;19(1):15–33. Available from: https://onlinelibrary.wiley.com/doi/ 10.1002/wps.20693 Iwata Y, Nakajima S, Plitman E, Truong P, Bani-Fatemi A, Caravaggio F et al. Glutathione Levels and Glutathione-Glutamate Correlation in Patients With Treatment-Resistant Schizophrenia. Schizophr Bull Open [Internet]. 2021;2(1). Available from: https://academic.oup.com/schizbullopen/article/doi/ 10.1093/schizbullopen/sgab006/6162602 Vallée A. Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway. Int J Mol Sci [Internet]. 2022;23(5):2810. Available from: https://www.mdpi.com/1422-0067/23/5/2810 Lu Z, Wen T, Wang Y, Kan W, Xun G. Peripheral non-enzymatic antioxidants in patients with schizophrenia: a case-control study. BMC Psychiatry [Internet]. 2020;20(1):241. Available from: https://bmcpsychiatry.biomedcentral.com/articles/ 10.1186/s12888-020-02635-8 De Simone G, Mazza B, Vellucci L, Barone A, Ciccarelli M, de Bartolomeis A. Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment. Antioxidants [Internet]. 2023;12(4):975. Available from: https://www.mdpi.com/2076-3921/12/4/975 Bitanihirwe BKY, Woo TUW. Oxidative stress in schizophrenia: An integrated approach. Neurosci Biobehav Rev [Internet]. 2011;35(3):878–93. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0149763410001727 Paz RD, Tardito S, Atzori M, Tseng KY. Glutamatergic dysfunction in schizophrenia: From basic neuroscience to clinical psychopharmacology. Eur Neuropsychopharmacol [Internet]. 2008;18(11):773–86. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0924977X08001673 Dadheech G, Mishra S, Gautam S, Sharma P. Oxidative stress, α-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian J Clin Biochem [Internet]. 2006;21(2):34–8. Available from: http://link.springer.com/ 10.1007/BF02912908 Tsai MC, Liou CW, Lin TK, Lin IM, Huang TL. Changes in oxidative stress markers in patients with schizophrenia: The effect of antipsychotic drugs. Psychiatry Res [Internet]. 2013;209(3):284–90. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0165178113000449 Ballesteros A, Summerfelt A, Du X, Jiang P, Chiappelli J, Tagamets M et al. Electrophysiological intermediate biomarkers for oxidative stress in schizophrenia. Clin Neurophysiol [Internet]. 2013;124(11):2209–15. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1388245713006950 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6646822","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":459903250,"identity":"e02f4bf4-3275-4595-b3f8-2e8dd68b54d3","order_by":0,"name":"Tolutope Adebimpe Oso","email":"","orcid":"","institution":"Centre for Genomics of Non-Communicable Diseases and Personalized Healthcare, University of Lagos, Akoka","correspondingAuthor":false,"prefix":"","firstName":"Tolutope","middleName":"Adebimpe","lastName":"Oso","suffix":""},{"id":459903251,"identity":"6e53eda6-a107-4630-a66d-d32341e12f57","order_by":1,"name":"Adeleye Sunday Joshua","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Adeleye","middleName":"Sunday","lastName":"Joshua","suffix":""},{"id":459903252,"identity":"d1a534cc-a450-4b42-b862-637d20f11d48","order_by":2,"name":"Bamidele Musa Sikiru","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Bamidele","middleName":"Musa","lastName":"Sikiru","suffix":""},{"id":459903253,"identity":"03a4f246-525b-4e01-b286-48fa92177e2e","order_by":3,"name":"Wasiu Babatunde Ganiyu","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Wasiu","middleName":"Babatunde","lastName":"Ganiyu","suffix":""},{"id":459903254,"identity":"a39dbece-1ee4-4ee8-915b-4c03a40cf9d9","order_by":4,"name":"Olarotimi Alexander Owolagba","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Olarotimi","middleName":"Alexander","lastName":"Owolagba","suffix":""},{"id":459903255,"identity":"968e17c9-a9d5-4471-a535-1e1fce9fe474","order_by":5,"name":"Olalekan John Okesanya","email":"","orcid":"","institution":"Neuropsychiatric Hospital","correspondingAuthor":false,"prefix":"","firstName":"Olalekan","middleName":"John","lastName":"Okesanya","suffix":""},{"id":459903256,"identity":"804f3f23-a52b-4c9b-abd2-72d650bd45b1","order_by":6,"name":"Adegboyega Ogunwale","email":"","orcid":"","institution":"Neuropsychiatric Hospital","correspondingAuthor":false,"prefix":"","firstName":"Adegboyega","middleName":"","lastName":"Ogunwale","suffix":""},{"id":459903257,"identity":"ef0f2522-b769-4cb6-b635-364acf3f37c0","order_by":7,"name":"Joseph Dada Adeyemi","email":"","orcid":"","institution":"University of Lagos","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"Dada","lastName":"Adeyemi","suffix":""},{"id":459903258,"identity":"1fbe4afe-1873-4fc8-ada6-446412756f98","order_by":8,"name":"Oluyemi Akinloye","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAUlEQVRIiWNgGAWjYFACNoYDDAVAmr2BgSGhACxkQIQWkBqeA0AtBkRqgaiRSIArxq+Fn/1Y4uECA5vEfsk3Zg8eGNjZNbA3b5Ng3FGLU4tkT9qBwzMM0hJnzs4xN0gwSE5u4DlWJsF45jhOLQYH0hsO8xgcTtxwO8dMIsGAOZlBAshgbDuGW8v55xAt+2+eAWmpT2aQf0NAyw2gw8C2SPCAtBy2YwAxGNtqcPtlxrMEoJY04xln0sqAWo4nsPGkFVskth3AqYWfP834M0+FjWx/++Ftkj8qqu352Q9vvPGxrQ6nFhhwbIAyEttAZALDYYJa7NEZhG0ZBaNgFIyCEQMAj1NSvPgXG2IAAAAASUVORK5CYII=","orcid":"","institution":"Centre for Genomics of Non-Communicable Diseases and Personalized Healthcare, University of Lagos, Akoka","correspondingAuthor":true,"prefix":"","firstName":"Oluyemi","middleName":"","lastName":"Akinloye","suffix":""}],"badges":[],"createdAt":"2025-05-12 12:53:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6646822/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6646822/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83439575,"identity":"da6d8d78-1b73-4023-8b6a-30a3000c48ac","added_by":"auto","created_at":"2025-05-26 09:13:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":16819,"visible":true,"origin":"","legend":"\u003cp\u003eMean Score of Positive and Negative Symptoms Scale\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6646822/v1/018ff97d838a96b81385dd27.png"},{"id":83439574,"identity":"e98247a7-88e0-4a1e-b50c-a788e02ae58b","added_by":"auto","created_at":"2025-05-26 09:13:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":11917,"visible":true,"origin":"","legend":"\u003cp\u003eShowing the Correlation of Glutathione with positive symptoms\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6646822/v1/4d39633b90f42b4920a07b71.png"},{"id":94163092,"identity":"09ca9274-7dc2-43b5-808a-d0af7f8b07a9","added_by":"auto","created_at":"2025-10-23 05:23:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":882390,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6646822/v1/ff98a333-a93a-4554-9a81-723a5af94ba7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Redox-Oxidative Stress and Micronutrients Interplay in the Clinical Phenotype of Schizophrenia in Nigeria Subjects","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSchizophrenia is a disorder that affects social and emotional function (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is a constellation of features which may be characterized as positive, negative and general psychopathological symptoms (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Positive symptoms include hallucinations, delusions and paranoia, while alogia, anhedonia, avolition, and blunted affect mark the negative domain. General psychopathology tends to refer to impairments such as poor memory and poor executive functioning (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). It is the most common diagnosis resulting in help seeking in Nigeria (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), and affects 1% of the general population worldwide and has been known to contribute significantly to years lost to disability (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Schizophrenia is a disorder with widespread structural and functional alterations, which are not completely understood. However, studies have shown numerous biochemical pathways in the neurobiology of the disorder. Some of which are not directly causative but act as risk factors for the disorder (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIn the past, much focus and emphasis had been placed on the dopamine system alterations based on indirect evidence from the role most antipsychotics medications play by acting on the dopamine receptor and specifically the D\u003csub\u003e2\u003c/sub\u003e sub-type (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, efforts have been made to identify other biological processes that may contribute to the process and symptomatology in schizophrenia. One of such is the redox-oxidative stress and micronutrients antioxidants in schizophrenia (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Redox dysregulation as a potential pathway in symptomatology manifestation rises when there is increased oxidative damage and decreased capacity of intracellular antioxidant defense system. This give rise to oxidative stress which results from the disequilibrium between pro-oxidant processes and the antioxidant defense system in favor of the former (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are several consequences of oxidative stress due to increased free radical production and inefficient antioxidant systems which lead to lipid peroxidation (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Oxidative stress has been linked to low levels of antioxidant vitamins such as C, E, and beta carotene (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). People with schizophrenia have also been found to have altered antioxidant levels in the blood and brain and altered antioxidant enzyme activity. Additionally, oxidative stress has been suggested as a potential connection between schizophrenia and vitamin deficiency. Studies have also shown that antioxidant vitamins such as C and E offer protection against cellular damage due to either inflammation or highly reactive oxygen species (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Redox dysregulation is linked to reduction of parvalbumin, containing GABA interneurons and volumes of their perineuronal nets, white matter abnormalities and microglia activation. Activity of transcription factors, kinases and phosphatases regulating diverse aspect of neurodevelopment and synaptic pathway vary according to cellular redox state (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, the mechanism through which nutrition and nutritional deficiencies induce schizophrenia or exacerbate its symptoms is not completely understood but several modalities have been suggested. These include poor diet, bad eating habits, and nutritional deficiencies that have been connected to the onset of hyperhomocysteinemia, oxidant-antioxidant status derangement, immunological dysregulation, and changes in the levels of pro-inflammatory markers. The neuroprogressive hypothesis, which regarded abnormalities in oxidative stress and immune-inflammatory indicators as potential pathways in the pathophysiology of schizophrenia has previously discussed the significance of inflammation and oxidative stress in schizophrenia (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). According to current theories, the connection between nutrition and schizophrenia may involve the stimulation of neuro-inflammation and modification of the gut microbiota, both of which have been linked in some instances to the exacerbation of schizophrenia symptoms (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOxidative stress and redox imbalance can disrupt the normal functioning of neurotransmitter systems in the brain, particularly the glutamate system. Glutamate is an excitatory neurotransmitter that plays a crucial role in synaptic transmission and cognitive processes. Imbalances in glutamate levels or receptor functioning have been implicated in the pathophysiology of schizophrenia and may contribute to symptoms such as cognitive impairments, hallucinations, and disorganized thinking (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). In addition, increased oxidative stress can lead to damage to neuronal structures, including lipid peroxidation and protein oxidation. This can disrupt neuronal membrane integrity and impair cellular functions. Oxidative stress can also trigger inflammatory processes in the brain, leading to neuroinflammation. Neuroinflammation has been associated with the development and progression of schizophrenia and may contribute to the positive symptoms of the disorder (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Furthermore, redox imbalance in schizophrenia may involve a deficiency in the antioxidant defense system. Antioxidants such as glutathione, superoxide dismutase (SOD), and catalase play a crucial role in neutralizing reactive oxygen species (ROS) and protecting cells from oxidative damage. Reduced levels or impaired activity of these antioxidants may result in increased oxidative stress and cellular dysfunction (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Also, Mitochondria, the cellular powerhouses responsible for energy production, are vulnerable to oxidative damage. Oxidative stress can disrupt mitochondrial function, leading to decreased energy production, impaired cellular metabolism, and increased ROS production. Mitochondrial dysfunction has been implicated in the pathophysiology of schizophrenia and may contribute to symptoms such as fatigue, cognitive impairment, and negative symptoms. More importantly Oxidative stress can induce DNA damage through the formation of DNA adducts and strand breaks. DNA damage can lead to genetic and epigenetic alterations that affect neuronal development, synaptic plasticity, and neurotransmitter signaling, potentially contributing to the emergence of schizophrenia symptoms (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Diets low in anti-inflammatory nutrients or high in pro-inflammatory ones (omega-6 fatty acids are pro-inflammatory, whereas omega-3 fatty acids are anti-inflammatory) can activate and exacerbate neuroinflammation, which, if left unchecked, can lead to pathological changes in schizophrenia and worsen its symptoms (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Previous studies reporting redox and oxidant parameters have reported changes which have been heterogenous with less emphasis on its relationship with the psychopathy of the disorders. Therefore, this study is aimed at investigating the influence of redox activity, lipid peroxidation and micronutrient antioxidants in the expression of clinical phenotypes of schizophrenia.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population and Design\u003c/h2\u003e \u003cp\u003eThis is a case control study matched for gender and age, with no family history of mental illness in controls. A total number of 220 consented drug na\u0026iuml;ve volunteers including 120 participants with Schizophrenia and 100 apparently healthy controls were recruited. The study participants were clients visiting the assessment unit of Neuropsychiatric Hospital, Aro, Abeokuta, Ogun State, Nigeria. The Positive and Negative Symptom Scale (PANSS) was applied to evaluate psychotic symptoms. The study was approved by the Health Research Ethics Committee of Neuropsychiatric Hospital, Aro Abeokuta, Ogun State, Nigeria (PR003/19).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eBiochemical Assessment\u003c/h3\u003e\n\u003cp\u003eLipid peroxidation was quantified as Malondialdehyde (MDA) via the development of thiobarbituric acid reacting substance (TBARS) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Catalase activity was determined as previously described (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), Superoxide dismutase was determined by its ability to inhibit auto oxidation of epinephrine (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e), Total antioxidants capacity was estimated by phosphomolybdenum method (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), Zinc and Selenium were analysed by Flame Atomic Absorption Spectrophotometry (FAAS) (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). Vitamin E and C were measured as previously described (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using IBM statistical package for social sciences (SPSS v. 25). Continuous variable were evaluated using the student\u0026rsquo;s T-test. Pearson Correlation was used to determine association of psychopathy with biochemical parameters. Logistic regression analyses were performed to explore which characteristics were related to the risk of schizophrenia. Significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe mean score for the Positive, Negative and General Psychopathology score in the case are 19.76\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1, 20.14\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 and 35.54\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The serum levels of both enzymatic and non-enzymatic antioxidants in Schizophrenia and Controls were presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was a significant increase in enzymatic antioxidant levels in individuals with schizophrenia compared to the controls. Specifically, levels of superoxide dismutase (SOD) and catalase (CAT) were elevated in schizophrenia cases (SOD: 19.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80 vs. 10.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.045 \u0026micro;mol/ml/min; CAT: 41.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 vs. 21.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98 \u0026micro;mol/ml/min; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In contrast, non-enzymatic antioxidants were significantly reduced in schizophrenia patients compared to controls. A reduction in glutathione (GSH) levels was observed in schizophrenia (GSH: 145.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28 vs. 159.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.59 \u0026micro;mol/L). Similarly micronutrients non-enzymatic antioxidants; zinc (0.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 vs. 0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 ppm), selenium (0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 vs. 0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 ppm), vitamin C (12.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49 vs. 15.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37 mg/dl), and total antioxidant capacity (TAC: 65.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.51 vs. 81.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48 ng/dl), (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were lower in cases compared to controls. However, Vitamin E showed no significant difference between test and control (1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15 and 1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12) p\u0026thinsp;\u0026gt;\u0026thinsp;0.05. In addition, MDA, a product of lipid peroxidation was significantly higher in patients with schizophrenia compared to control (2.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19 and 1.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10 umol/ml) p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e showed logistic regression predictors of schizophrenia. The regression model showed that an increase in MDA levels was associated with higher odds of schizophrenia (OR\u0026thinsp;=\u0026thinsp;2.017). Reductions in GSH, TAC, zinc, selenium, and vitamin C levels were also associated with increased odds of schizophrenia. Pearson Correlation of MDA with antioxidants parameters reveal. that MDA were correlated with certain antioxidant parameters (0.281, 0.179, -0.247 and \u0026minus;\u0026thinsp;0.221) (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). On the other hand, Zinc, Selenium, Vitamin C and Vitamin E did not show any significant correlation (-0.101, -0.139, -0.060 and \u0026minus;\u0026thinsp;0.045) (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSerum Levels of Antioxidants in Schizophrenia and Controls.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSchizophrenia\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003cp\u003e(Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SEM)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc (ppm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.548\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium (ppm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-2.296\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.024*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin C (mg/100g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e12.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e15.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-3.225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.002*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E (mg/100g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.875\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.383\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC (mg/100g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e65.49\u0026thinsp;\u0026plusmn;\u0026thinsp;1.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e81.64\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-7.274\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDA (\u0026micro;mol/ml)\u003c/p\u003e \u003cp\u003eGSH (\u0026micro;mol/ml)\u003c/p\u003e \u003cp\u003eCAT (\u0026micro;mol/ml/min)\u003c/p\u003e \u003cp\u003eSOD (\u0026micro;mol/ml/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.32\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e \u003cp\u003e145.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e \u003cp\u003e41.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.81\u003c/p\u003e \u003cp\u003e19.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003c/p\u003e \u003cp\u003e159.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.59\u003c/p\u003e \u003cp\u003e21.23\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003cp\u003e10.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4.878\u003c/p\u003e \u003cp\u003e-8.647\u003c/p\u003e \u003cp\u003e9.915\u003c/p\u003e \u003cp\u003e9.439\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003e*Significant at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regression showing predictors of schizophrenia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOdd Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e2.017\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.466\u0026ndash;3.027\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u003c/p\u003e \u003cp\u003eSOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.904\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e1.593\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.871\u0026ndash;0.939\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e1.347\u0026ndash;1.886\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e1.190\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e1.124\u0026ndash;1.259\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.553\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.439\u0026ndash;0.696\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.016\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.001\u0026ndash;0.189\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSe\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.369\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.166\u0026ndash;0.822\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.015\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVit C\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eVit E\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003e0.861\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.880\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.781\u0026ndash;0.949\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.661\u0026ndash;1.771\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003e0.380\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003e*Significant at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePearson Correlation of MDA with antioxidants parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMDA\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003er\u0026thinsp;=\u0026thinsp;0.281, p\u0026thinsp;=\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003er\u0026thinsp;=\u0026thinsp;0.179, p\u0026thinsp;=\u0026thinsp;0.034\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003er=-0.247, p\u0026thinsp;=\u0026thinsp;0.003\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003er=-0.221, p\u0026thinsp;=\u0026thinsp;0.009\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZn\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.101, p\u0026thinsp;=\u0026thinsp;0.235\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSe\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.139, p\u0026thinsp;=\u0026thinsp;0.156\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVit C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.660, p\u0026thinsp;=\u0026thinsp;0.483\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVit E\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.045, p\u0026thinsp;=\u0026thinsp;0.594\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003e*Significant correlation, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, r\u0026thinsp;=\u0026thinsp;Pearson correlation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe mean score for the Positive, Negative and General Psychopathology score in the case is 19.76\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1, 20.14\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7 and 35.54\u0026thinsp;\u0026plusmn;\u0026thinsp;12.1, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e presents the correlation analysis between oxidative stress parameters and the three symptom domains of the PANSS scale. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows a negative correlation between GSH and positive symptoms (r=-0.285, p\u0026thinsp;=\u0026thinsp;0.013 No correlation was found for other variables such as CAT, SOD, Vitamin C, Vitamin E, TAC, and GSH.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePearson Correlation of Biochemical Parameters with Positive, Negative and General Symptoms in Schizophrenia Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiochemical Variable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePositive\u003c/p\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative\u003c/p\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGeneral\u003c/p\u003e \u003cp\u003eSymptoms\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMDA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.095, P\u0026thinsp;=\u0026thinsp;0.417\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.054, p\u0026thinsp;=\u0026thinsp;0.648\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.033, p\u0026thinsp;=\u0026thinsp;0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eZinc\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.071, p\u0026thinsp;=\u0026thinsp;0.544\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.152, P\u0026thinsp;=\u0026thinsp;0.193\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.075, p\u0026thinsp;=\u0026thinsp;0.521\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSelenium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.086, p\u0026thinsp;=\u0026thinsp;0.923\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.021, p\u0026thinsp;=\u0026thinsp;0.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er=-0.017, p\u0026thinsp;=\u0026thinsp;0.902\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.156, p\u0026thinsp;=\u0026thinsp;0.183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.156, p\u0026thinsp;=\u0026thinsp;0.182\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.037, P\u0026thinsp;=\u0026thinsp;0.753\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitamin E\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.018, p\u0026thinsp;=\u0026thinsp;0.874\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er=-0.003, p\u0026thinsp;=\u0026thinsp;0.982\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er=-0.100, p\u0026thinsp;=\u0026thinsp;0.396\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAT\u003c/p\u003e \u003cp\u003eSOD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er=-0.187, P\u0026thinsp;=\u0026thinsp;0.473\u003c/p\u003e \u003cp\u003er=-0.030, P\u0026thinsp;=\u0026thinsp;0.790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er=-0.008, p\u0026thinsp;=\u0026thinsp;0.947\u003c/p\u003e \u003cp\u003er=-0.067, p\u0026thinsp;=\u0026thinsp;0.569\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er=-0.115, p\u0026thinsp;=\u0026thinsp;0.325\u003c/p\u003e \u003cp\u003er=-0.177, p\u0026thinsp;=\u0026thinsp;0.128\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003er=-0.285, p\u0026thinsp;=\u0026thinsp;0.013\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.101, P\u0026thinsp;=\u0026thinsp;0.390\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er=-0.029, p\u0026thinsp;=\u0026thinsp;0.804\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003er= -0.083, p\u0026thinsp;=\u0026thinsp;0.458\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.059, p\u0026thinsp;=\u0026thinsp;0.616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003er\u0026thinsp;=\u0026thinsp;0.151, p\u0026thinsp;=\u0026thinsp;0.197\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*Significant correlation, p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, r\u0026thinsp;=\u0026thinsp;Pearson correlation\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSchizophrenia is a disorder of multiple etiological pathway, which converge into a common pathway and account for the array of clinical symptoms (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Free radicals mediated abnormalities have been implicated in the development of such important consequences in schizophrenia (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The increase in lipid peroxidation reported in this study might have implication in the pathophysiology of schizophrenia. The increased serum MDA activity in schizophrenia patients observed is consistent with previous findings (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This MDA activities observed among this group can be evaluated as a marker of peroxidative damage to the phospholipid membrane, a process which may lead to neuronal membrane instability which can result in disruption of the cell cycle and neurotransmitter release, and uptake (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Oxidative stress has been suggested to contribute to the pathophysiology of schizophrenia in particular, the oxidative damage in lipids, proteins and DNA seen in schizophrenia are known to impair cell viability and function, these may contribute to the risk of the disorder (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The increased activity of SOD and CAT observed in this study is consistent with previous findings (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e), which may represent a response to elevated oxidative stress resulting from excessive free radical production. Antioxidant enzymes protect cellular components from damage caused by reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFurthermore, evidence point towards an alteration in the activities of enzymatic and non-enzymatic antioxidant system, this is clearly shown in the low level of non-enzymatic antioxidant enzymes which agrees with previous study (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e). Plasma level of Vitamin C decreases in schizophrenia related to normal controls. The antioxidants function of ascorbic acid may protect against dopamine dysregulation induced neurodegenerative processes (\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). Studies suggest that supplementation with vitamin C may reduce oxidative stress and improve outcomes in schizophrenia, as patients may have higher requirements due to increased redox activity (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). Although Vitamin E was not found to show any effect in this study but acts synergistically with Vitamin C to achieve their scavenging role. Supplementation in their duct may be advisable as they consume less of these vitamins because of their psychotic state and their poor dietary fiber consumption (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eLower levels of Zinc were also demonstrated in this study while previous studies suggest its link with psychosis. Lower zinc levels in participants with schizophrenia may be because of inflammation or genetic dysregulation in molecules that maintain zinc homeostasis and nutritional deficiencies that might leads to NMDA hyperactivity, a possible psychotic symptomatology. Thus, zinc supplements might modulate glutamatergic transmission within the neural networks that converge in the prefrontal cortex thus leading to a reduction in symptomatology. However direct modulation of hyperactive NMDA receptors by Zinc inhibition may target microcirculation that is not accessible to conventional D2 receptor antagonists (\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e). Although Selenium and Zinc are essential micronutrients that have important roles in reducing oxidative stress and protect DNA from attack of reactive oxygen species, interestingly, our study showed difference in selenium activity relative to control. Antioxidants micronutrients such as Zn, Se, Vit E, Vit C and TAC have no relationship with positive, negative and general symptoms of schizophrenia in this study. This could be due to the fact that the population presented with mild to moderate symptoms and are drug na\u0026iuml;ve, the situation might be different if they are chronic cases and this was contradicted by a study conducted by Dadheech \u003cem\u003eet al\u003c/em\u003e., (\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA significant inverse correlation was found between glutathione levels and positive symptoms of schizophrenia. Glutathione regulates glutamate metabolism and maintains redox balance in the brain. Dysregulation of the glutamate neurotransmitter system, particularly involving the NMDA receptor, has been linked to schizophrenia (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Glutathione depletion may disrupt glutamate neurotransmission, which could contribute to the development of positive symptoms in schizophrenia. This is supported by reduced GSH levels in schizophrenia patients in this study.. Additionally, genetic variations in the glutamate-cysteine ligase catalytic subunit (GCLC), a key enzyme involved in GSH synthesis, have been associated with an increased risk of schizophrenia (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e). Inflammation and immune dysregulation have also been implicated in schizophrenia. Glutathione helps modulate inflammation and protect against neuroinflammation. Disturbances in glutathione levels may therefore contribute to neuroinflammatory processes, further influencing positive symptoms (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). Other antioxidant markers, including CAT, SOD, vitamin C, vitamin E, selenium, and zinc, showed no significant relationship with symptom severity, which may result from variations in redox regulation across different illness phases (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAbnormality in glutamatergic neurotransmission mediated by NMDA receptor hypofunction has been linked with the pathophysiology of schizophrenia. The link between the glutamatergic system and glutathione may suggest why positive symptoms correlated negatively with GSH concentration in this study. Previous studies have demonstrated that GSH is significantly associated with positive symptoms of PANSS (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). However, other studies have found a link between GSH and negative symptoms (\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Other antioxidants did not correlate with all the symptoms scale of PANSS. Superoxide dismutase (SOD) and catalase (CAT), important antioxidant enzymes correlated positively with MDA concentration while negatively with GSH and TAC levels. This positive correlation suggests that as lipid peroxidation increases, the activity of these antioxidant enzymes also rises which may reflect an adaptive response aimed at neutralizing elevated levels, furthermore antioxidant enzymes involved in neutralising superoxide radicals and in breaking down hydrogen peroxide generated during oxidative stress also tends to increase. In contrast, MDA had a null finding with other antioxidant parameters. These findings buttressed the hypothesis of a compensatory antioxidant response to counteract oxidative stress.\u003c/p\u003e \u003cp\u003eIt is important to note that the other antioxidant parameters did not exhibit significant positive correlations with MDA; in fact, some showed negative correlations. For example, reduced glutathione (GSH) and total antioxidant capacity (TAC) were negatively correlated with MDA, indicating that higher levels of MDA are associated with lower levels of these antioxidants. Overall, these correlations suggest complex interactions between oxidative stress markers (MDA) and antioxidant parameters in individuals with schizophrenia (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study provides evidence that redox and micronutrient imbalance influence the clinical phenotypes of schizophrenia among drug-na\u0026iuml;ve Nigerian subjects. The findings support the hypothesis that oxidative stress and micronutrient dysregulation play a role in the pathophysiology of schizophrenia. This suggest that antioxidant and micronutrient supplementation may be used as promising adjunct therapeutic strategies. Future longitudinal studies are needed to confirm causal relationships and evaluate the therapeutic efficacy of targeted antioxidant interventions in schizophrenia management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was obtained from the Health Research Ethics Committee of Neuropsychiatric Hospital, Aro Abeokuta, Ogun State, Nigeria (PR003/19), and written informed consent to participate was obtained from all participants prior to their enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided written informed consent for the publication of anonymized data derived from this study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll data generated and gathered during this study are available with the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not receive any funding for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: OA and JDA\u003c/p\u003e\n\u003cp\u003eMethodology: TAO, BMS, ASJ, WBG and OAO\u003c/p\u003e\n\u003cp\u003eFormal Analysis: OJO, BMS, WBG, OAO and ASJ \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSampling and Investigation: TAO, OJO, and OAO\u003c/p\u003e\n\u003cp\u003eResources: OA, TAO, BMS, WBG, OAO, and ASJ\u003c/p\u003e\n\u003cp\u003eData Curation: TAO, OA, JDA\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; Original Draft: TAO, OA\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWriting\u0026ndash;Review \u0026amp; Editing: OA and JDA\u003c/p\u003e\n\u003cp\u003eSupervision: OA and JDA\u003c/p\u003e\n\u003cp\u003eProject Administration: OA, JDA and TAO\u003c/p\u003e\n\u003cp\u003eFunding Acquisition: OA and TAO\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the invaluable support received from the staff of the Neuropsychiatric Hospital, Aro, and the University of Lagos throughout the course of this project. Special appreciation is extended to the Centre for Genomics of Non-Communicable Diseases and Personalized Healthcare, University of Lagos, Akoka, Lagos, Nigeria, for their technical guidance, resources, and collaborative efforts that significantly contributed to the success of this work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDziwota E, Stepulak M, Włoszczak-Szubzda A, Olajossy M. Social functioning and the quality of life of patients diagnosed with schizophrenia. Ann Agric Environ Med [Internet]. 2018;25(1):50\u0026ndash;5. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.journalssystem.com/aaem/Social-functioning-and-the-quality-of-life-of-patients-diagnosed-with-schizophrenia,72507,0,2.html\u003c/span\u003e\u003cspan address=\"http://www.journalssystem.com/aaem/Social-functioning-and-the-quality-of-life-of-patients-diagnosed-with-schizophrenia,72507,0,2.html\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Hert M, Correll CU, Cetkovich-Bakmas M, Cohen D, Asai I, Detraux J et al. Physical illness in patients with severe mental disorders. World Psychiatry. 2011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLerner PP, Sharony L, Miodownik C. Association between mental disorders, cognitive disturbances and vitamin D serum level: Current state. Clin Nutr ESPEN [Internet]. 2017; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.clnesp.2017.11.011\u003c/span\u003e\u003cspan address=\"10.1016/j.clnesp.2017.11.011\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOso TA, Akpan RM, Ogunwale O, Akinloye O. Pattern of Mental Disorder in a Neuropsychiatric Hospital in NIgeria: A Decade Retrospective Review. Niger J Psychiatry. 2022;20:2\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDoǧan Bulut S, Bulut S, G\u0026iuml;\u0026iquest;\u0026frac12;riz O. The relationship between sex hormone profiles and symptoms of schizophrenia in men. Compr Psychiatry. 2016;69:186\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoudhury A, Sahu T, Ramanujam PL, Banerjee AK, Chakraborty I, Kumar A, et al. Neurochemicals, Behaviours and Psychiatric Perspectives of Neurological Diseases. Neuropsychiatry (London). 2018;8(1):395\u0026ndash;424.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSitarz R. Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Na\u0026iuml;ve. Patients. 2022;1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRukmini MS, D\u0026rsquo;Souza B, D\u0026rsquo;Souza V. Superoxide dismutase and catalase activities and their correlation with malondialdehyde in schizophrenic patients. Indian J Clin Biochem [Internet]. 2004;19(2):114\u0026ndash;8. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://link.springer.com/\u003c/span\u003e\u003cspan address=\"http://link.springer.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF02894268\u003c/span\u003e\u003cspan address=\"10.1007/BF02894268\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchiavone S, Trabace L, Inflammation. Stress Response, and Redox Dysregulation Biomarkers: Clinical Outcomes and Pharmacological Implications for Psychosis. 2017;8(October):1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHurşİtoğlu O, Orhan F\u0026Ouml;, Kurutaş EB, Doğaner A. Diagnostic Performance of Increased Malondialdehyde Level and Oxidative Stress in Patients with Schizophrenia Diagnostic Performance of Increased Malondialdehyde Level and Oxidative Stress in Patients with Schizophrenia. 2021;(May).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadireddy S, Madireddy S. Regulation of reactive oxygen species-mediated damage in the pathogenesis of schizophrenia. Brain Sci. 2020;10(10):1\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown HE, Roffman JL. Vitamin Supplementation in the Treatment of Schizophrenia. CNS Drugs [Internet]. 2014;28(7):611\u0026ndash;22. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://link.springer.com/\u003c/span\u003e\u003cspan address=\"http://link.springer.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40263-014-0172-4\u003c/span\u003e\u003cspan address=\"10.1007/s40263-014-0172-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsiedu B, Anang Y, Nyarko A, Doku DA, Amoah BY, Santa S et al. The role of sex steroid hormones in benign prostatic hyperplasia. Aging Male [Internet]. 2017;20(1):17\u0026ndash;22. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.tandfonline.com/doi/full/\u003c/span\u003e\u003cspan address=\"https://www.tandfonline.com/doi/full/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/13685538.2016.1272101\u003c/span\u003e\u003cspan address=\"10.1080/13685538.2016.1272101\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOnaolapo OJ, Onaolapo AY. Nutrition, nutritional deficiencies, and schizophrenia: An association worthy of constant reassessment. World J Clin Cases [Internet]. 2021;9(28):8295\u0026ndash;311. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.wjgnet.com/2307-8960/full/v9/i28/8295.htm\u003c/span\u003e\u003cspan address=\"https://www.wjgnet.com/2307-8960/full/v9/i28/8295.htm\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDudzińska E, Szymona K, Bogucki J, Koch W, Cholewińska E, Sitarz R et al. Increased Markers of Oxidative Stress and Positive Correlation Low-Grade Inflammation with Positive Symptoms in the First Episode of Schizophrenia in Drug-Na\u0026iuml;ve Patients. J Clin Med [Internet]. 2022;11(9):2551. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/2077-0383/11/9/2551\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/2077-0383/11/9/2551\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUddin SMN, Sultana F, Uddin MG, Dewan SMR, Hossain MK, Islam MS. Effect of antioxidant, malondialdehyde, macro-mineral, and trace element serum concentrations in Bangladeshi patients with schizophrenia: A case‐control study. Heal Sci Reports [Internet]. 2021;4(2). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://onlinelibrary.wiley.com/doi/\u003c/span\u003e\u003cspan address=\"https://onlinelibrary.wiley.com/doi/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/hsr2.291\u003c/span\u003e\u003cspan address=\"10.1002/hsr2.291\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrabnar I, Vovk T, Kores Plesnicar B, Boskovic M. Oxidative Stress in Schizophrenia. Curr Neuropharmacol. 2011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJahrami H, Faris MA, Ghazzawi HA, Saif Z, Habib L, Shivappa NHJ. Increased Dietary Inflammatory Index Is Associated with Schizophrenia: Results of a Case-Control Study from Bahrain. Nutrients. 2019;11. 2019.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Leon AD, Borges J. CR. Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay. J Vis Exp [Internet]. 2020;(159). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://app.jove.com/t/61122\u003c/span\u003e\u003cspan address=\"https://app.jove.com/t/61122\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkinloye O, Adaramoye O, Kareem O. Changes in antioxidant status and lipid peroxidation in Nigerian patients with prostate carcinoma. Polish Arch Intern Med [Internet]. 2009;119(9):526\u0026ndash;32. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://pamw.pl/en/node/759\u003c/span\u003e\u003cspan address=\"http://pamw.pl/en/node/759\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMisra HP, Fridovich I. The Role of Superoxide Anion in the Autoxidation of Epinephrine and a Simple Assay for Superoxide Dismutase. J Biol Chem [Internet]. 1972;247(10):3170\u0026ndash;5. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://linkinghub.elsevier.com/retrieve/pii/S0021925819452289\u003c/span\u003e\u003cspan address=\"https://linkinghub.elsevier.com/retrieve/pii/S0021925819452289\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePhytochemical screening and evaluation of antioxidant and antibacterial activities of seeds and pods extracts of Calycotome villosa subsp. Intermedia. J Appl Pharm Sci [Internet]. 2017; Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.japsonline.com/abstract.php?article_id=2242\u003c/span\u003e\u003cspan address=\"http://www.japsonline.com/abstract.php?article_id=2242\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAydinoglu S. Iron and Zinc Determination in Dietary Supplements by Flame Atomic Absorption Spectrophotometry. Brazilian J Pharm Sci [Internet]. 2022;58. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.scielo.br/scielo.php?script=sci_arttext\u0026amp;pid=S1984-82502022000100863\u0026amp;tlng=en\u003c/span\u003e\u003cspan address=\"http://www.scielo.br/scielo.php?script=sci_arttext\u0026amp;pid=S1984-82502022000100863\u0026amp;tlng=en\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNojavan S, Khalilian F, Kiaie FM, Rahimi A, Arabanian A, Chalavi S. Extraction and quantitative determination of ascorbic acid during different maturity stages of Rosa canina L. fruit. J Food Compos Anal [Internet]. 2008;21(4):300\u0026ndash;5. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://linkinghub.elsevier.com/retrieve/pii/S0889157508000045\u003c/span\u003e\u003cspan address=\"https://linkinghub.elsevier.com/retrieve/pii/S0889157508000045\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRipke S, Neale BM, Corvin A, Walters JTR, Farh KH, Holmans PA et al. Schizophrenia Working Group of the Psychiatric Genomics Consortium: Biological Insights From 108 Schizophrenia-Associated Genetic Loci. Nature [Internet]. 2014;511(7510):421\u0026ndash;7. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112379/%0\u003c/span\u003e\u003cspan address=\"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112379/%0\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003eAhttp://dx.doi.org/10.1038/nature13595\u003c/span\u003e\u003cspan address=\"A10.1038/nature13595\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMurray AJ, Rogers JC, Katshu MZUH, Liddle PF, Upthegrove R. Oxidative Stress and the Pathophysiology and Symptom Profile of Schizophrenia Spectrum Disorders. Front Psychiatry [Internet]. 2021;12. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.frontiersin.org/articles/\u003c/span\u003e\u003cspan address=\"https://www.frontiersin.org/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fpsyt.2021.703452/full\u003c/span\u003e\u003cspan address=\"10.3389/fpsyt.2021.703452/full\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen P, Wang D, Xiu M, Chen D, Lackey B, Wu HE et al. Polymorphism of Transferrin Gene Impacts the Mediating Effects of Psychotic Symptoms on the Relationship between Oxidative Stress and Cognition in Patients with Chronic Schizophrenia. Antioxidants [Internet]. 2022;11(1):125. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/2076-3921/11/1/125\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/2076-3921/11/1/125\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCutcheon RA, Krystal JH, Howes OD. Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry [Internet]. 2020;19(1):15\u0026ndash;33. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://onlinelibrary.wiley.com/doi/\u003c/span\u003e\u003cspan address=\"https://onlinelibrary.wiley.com/doi/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/wps.20693\u003c/span\u003e\u003cspan address=\"10.1002/wps.20693\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIwata Y, Nakajima S, Plitman E, Truong P, Bani-Fatemi A, Caravaggio F et al. Glutathione Levels and Glutathione-Glutamate Correlation in Patients With Treatment-Resistant Schizophrenia. Schizophr Bull Open [Internet]. 2021;2(1). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://academic.oup.com/schizbullopen/article/doi/\u003c/span\u003e\u003cspan address=\"https://academic.oup.com/schizbullopen/article/doi/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/schizbullopen/sgab006/6162602\u003c/span\u003e\u003cspan address=\"10.1093/schizbullopen/sgab006/6162602\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVall\u0026eacute;e A. Neuroinflammation in Schizophrenia: The Key Role of the WNT/β-Catenin Pathway. Int J Mol Sci [Internet]. 2022;23(5):2810. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/1422-0067/23/5/2810\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/1422-0067/23/5/2810\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Z, Wen T, Wang Y, Kan W, Xun G. Peripheral non-enzymatic antioxidants in patients with schizophrenia: a case-control study. BMC Psychiatry [Internet]. 2020;20(1):241. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://bmcpsychiatry.biomedcentral.com/articles/\u003c/span\u003e\u003cspan address=\"https://bmcpsychiatry.biomedcentral.com/articles/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12888-020-02635-8\u003c/span\u003e\u003cspan address=\"10.1186/s12888-020-02635-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Simone G, Mazza B, Vellucci L, Barone A, Ciccarelli M, de Bartolomeis A. Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment. Antioxidants [Internet]. 2023;12(4):975. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.mdpi.com/2076-3921/12/4/975\u003c/span\u003e\u003cspan address=\"https://www.mdpi.com/2076-3921/12/4/975\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBitanihirwe BKY, Woo TUW. Oxidative stress in schizophrenia: An integrated approach. Neurosci Biobehav Rev [Internet]. 2011;35(3):878\u0026ndash;93. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://linkinghub.elsevier.com/retrieve/pii/S0149763410001727\u003c/span\u003e\u003cspan address=\"https://linkinghub.elsevier.com/retrieve/pii/S0149763410001727\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaz RD, Tardito S, Atzori M, Tseng KY. Glutamatergic dysfunction in schizophrenia: From basic neuroscience to clinical psychopharmacology. Eur Neuropsychopharmacol [Internet]. 2008;18(11):773\u0026ndash;86. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://linkinghub.elsevier.com/retrieve/pii/S0924977X08001673\u003c/span\u003e\u003cspan address=\"https://linkinghub.elsevier.com/retrieve/pii/S0924977X08001673\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDadheech G, Mishra S, Gautam S, Sharma P. Oxidative stress, α-tocopherol, ascorbic acid and reduced glutathione status in schizophrenics. Indian J Clin Biochem [Internet]. 2006;21(2):34\u0026ndash;8. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://link.springer.com/\u003c/span\u003e\u003cspan address=\"http://link.springer.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/BF02912908\u003c/span\u003e\u003cspan address=\"10.1007/BF02912908\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsai MC, Liou CW, Lin TK, Lin IM, Huang TL. Changes in oxidative stress markers in patients with schizophrenia: The effect of antipsychotic drugs. Psychiatry Res [Internet]. 2013;209(3):284\u0026ndash;90. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://linkinghub.elsevier.com/retrieve/pii/S0165178113000449\u003c/span\u003e\u003cspan address=\"https://linkinghub.elsevier.com/retrieve/pii/S0165178113000449\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBallesteros A, Summerfelt A, Du X, Jiang P, Chiappelli J, Tagamets M et al. Electrophysiological intermediate biomarkers for oxidative stress in schizophrenia. Clin Neurophysiol [Internet]. 2013;124(11):2209\u0026ndash;15. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://linkinghub.elsevier.com/retrieve/pii/S1388245713006950\u003c/span\u003e\u003cspan address=\"https://linkinghub.elsevier.com/retrieve/pii/S1388245713006950\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Antioxidants, Clinical Phenotypes, Redox-oxidative Stress, Schizophrenia, Micronutrient, Lipid Peroxidation","lastPublishedDoi":"10.21203/rs.3.rs-6646822/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6646822/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eRedox-oxidative dysregulation is implicated in the aetiology of several diseases including schizophrenia with possible influence on clinical symptoms. This study investigated the influence of redox, lipid peroxidation and micronutrient antioxidants in the expression of clinical phenotypes of schizophrenia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total number of 220 consented drug na\u0026iuml;ve volunteers including 120 participants with Schizophrenia and 100 apparently healthy controls were recruited. Schizophrenia symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS). MDA, glutathione, total antioxidant capacity (TAC), enzymatic antioxidants (SOD, Catalase) and non-enzymatic antioxidants (Vit C, Vit E, Zn, Se) were measured by ELISA and Atomic Absorption spectrophotometry technique, respectively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eEnzymatic antioxidants; SOD (19.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80; 10.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.045\u0026micro;mol/ml/min) and CAT (41.73\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8; 21.33\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98 \u0026micro;mol/ml/min) increased in schizophrenia compared with controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) but decreased non-enzymatic antioxidants; Glutathione (GSH: 145.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28; 159.07\u0026thinsp;\u0026plusmn;\u0026thinsp;1.59, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Furthermore, serum level of Zinc (0.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01; 0.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02 ppm), Selenium (0.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01; 0.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 ppm) and Vitamin C (12.98\u0026thinsp;\u0026plusmn;\u0026thinsp;0.49; 15.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37 mg/dl) were lowered in the schizophrenia compared with controls (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Glutathione had a negative correlation with positive symptoms (r=-0.285, p\u0026thinsp;=\u0026thinsp;0.013) while SOD (r\u0026thinsp;=\u0026thinsp;0.281, p\u0026thinsp;=\u0026thinsp;0.001) and CAT (r\u0026thinsp;=\u0026thinsp;0.179, p\u0026thinsp;=\u0026thinsp;0.034) correlated positively with MDA (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In contrast, GSH (r=-0.247, p\u0026thinsp;=\u0026thinsp;0.003) and TAC (r=-0.221, p\u0026thinsp;=\u0026thinsp;0.009) correlated negatively with MDA (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe study implicates redox and antioxidant imbalance in schizophrenia. There was evidence that natural defense against oxidative damage and antioxidant responses is compromised influencing the clinical phototypes of the disease, A meticulous supplementation of micronutrients and antioxidants may be a useful adjunct treatment in the management of schizophrenia.\u003c/p\u003e","manuscriptTitle":"Redox-Oxidative Stress and Micronutrients Interplay in the Clinical Phenotype of Schizophrenia in Nigeria Subjects","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-26 09:13:11","doi":"10.21203/rs.3.rs-6646822/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"97aee8b0-850e-41de-bd37-46671d7f3b40","owner":[],"postedDate":"May 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-23T05:23:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-26 09:13:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6646822","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6646822","identity":"rs-6646822","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}