|Year : 2019 | Volume
| Issue : 1 | Page : 41
Relationship between antioxidant status and attention deficit hyperactivity disorder among children
Sorraya Nasim1, Amirmansour Alavi Naeini1, Mostafa Najafi2, Mohammadreza Ghazvini3, Akbar Hassanzadeh4
1 Department of Community Nutrition, School of Nutrition and Food Science and Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Psychiatry, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3 Isfahan Center of Health Research, National Institute of Health Research, Isfahan, Iran
4 Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Submission||13-Feb-2018|
|Date of Acceptance||31-Jan-2019|
|Date of Web Publication||03-Apr-2019|
Amirmansour Alavi Naeini
Department of Community Nutrition, School of Nutrition and Food Sciences, Isfahan University of Medical Sciences, HezarJerib St., P.O. Box: 81746-73461, Isfahan
Source of Support: None, Conflict of Interest: None
Background: Attention deficit hyperactivity disorder (ADHD) is one of the prevalent neuropsychiatric disorders in childhood. In general, diagnoses of ADHD include inattention, hyperactivity, and impulsivity. Recent studies have reported increased oxidative stress in psychiatric disorders such as ADHD, but the results are conflicting. This research aimed to study the relationship between antioxidant status and ADHD in children of 6–13 years old. Methods: From schools, 32 ADHD students whose diseases were diagnosed by child and adolescence psychiatrist based on Diagnostic and Statistical Manual of Mental Disorders-IV index were recruited; moreover, 32 healthy subjects, which according to the medical history questionnaire of psychiatric disorder had not had chronic disease, were selected. Total antioxidant capacity (TAC), catalase (CAT), glutathione (GSH), and malondiadehyde (MDA) were measured. General information, health history, and medication history were collected. All participants completed a 168-item food frequency questionnaire. Dietary intakes of antioxidants were obtained through this questionnaire. Results: There was no significant difference between mean of energy intake and Zn, Se, vitamin E, C, and β-carotene as antioxidants between the two groups. The mean of serum TAC, GSH level, and CAT level in the patients were significantly lower than the healthy group (P < 0.001), but the mean of MDA was not significantly different between the two groups (P = 0.18). Conclusions: The result of this study indicates that, in ADHD, the serum levels of GSH, CAT, and TAC decrease; the level of antioxidant in the serum has been compromised to fight oxidative stress. More perspective studies with large sample sizes are essential to confirm these findings.
Keywords: Antioxidant, attention deficit hyperactivity disorder, children, oxidative stress
|How to cite this article:|
Nasim S, Naeini AA, Najafi M, Ghazvini M, Hassanzadeh A. Relationship between antioxidant status and attention deficit hyperactivity disorder among children. Int J Prev Med 2019;10:41
|How to cite this URL:|
Nasim S, Naeini AA, Najafi M, Ghazvini M, Hassanzadeh A. Relationship between antioxidant status and attention deficit hyperactivity disorder among children. Int J Prev Med [serial online] 2019 [cited 2019 Apr 22];10:41. Available from: http://www.ijpvmjournal.net/text.asp?2019/10/1/41/255418
| Introduction|| |
Attention deficit hyperactivity disorder (ADHD) is the most common behavioral disorder and one of the prevalent neuropsychiatric disorders in childhood.,, ADHD is diagnosed almost in all patients before the age of 16, and this disease continues to adolescence in about 60% of patients and improves between the ages of 12 and 20.,,
ADHD is a general problem worldwide and in children has led to an increase in public health concerns., The global prevalence of ADHD in children and adolescents has been reported from 5% to 10% and that in Iranian school-age children is 9.7%., ADHD is more common in boys, and the proportion of this disorder varies from 2 to 9 times in boys to girls., The main symptoms of ADHD based on Diagnostic and Statistical Manual of Mental Disorders-IV criteria include a sustained pattern: (1) attention deficit, (2) hyperactivity, and (3) impulsivity (incidence of sudden behaviors without thinking) is disproportionate to age.,, Children with ADHD may also experience more negative social events and have less social skills. These patients have symptoms of motor function, disturbance in family relationships, and peers. Educational failure, weakness of self-esteem, depression, aggression, anxiety, learning disability, antisocial behavior, and occupational problems are the symptoms of this disorder.,,, The cause of ADHD is still unclear although biochemical, genetic, psychological, environmental factors, neurochemical, and neuroanatomical disorders are involved in the etiology of ADHD., Certain areas of the brain that are connected with attention have a defect in neuronal transmission. Researchers believe that biomedical factors such as changes in the catecholamine's signal, deficiency, imbalance, or inefficiency of neurotransmitters, which includes dopamine, serotonin, and noradrenaline, and the slowness of the inhibitory activity of the brain play a role in the development of ADHD.,, Dietary factors such as lack of micronutrients (zinc, copper, and omega-3) and nutritional behaviors may contribute to the development of ADHD.,
More research on ADHD focused on genetic factors and less concentrated on mechanisms and other factors involved in it. One of these factors is oxidative metabolism. Several studies have shown that neuronal damage by oxidants plays an important role in the pathophysiology of mental disorders. In various studies, the relationship between ADHD and oxidative stress has been investigated., Free radicals such as superoxide and radical hydroxyl ions (OH−), which are called reactive oxygen species (ROSs), may be produced excessively during the natural processes of metabolism. Despite the very short half-life, these compounds have a strong tendency to combine with fats, proteins, and DNA in nervous and non-neuronal cells., ROS reacted with the proteins in the membranes to prevent the normal intake of enzymes and neurotransmitters. Furthermore, it is associated with the death of neurons in many neurological disorders such as psychiatric disorders., Cells and biological fluid contain enzymes and nonenzymatic antioxidants that act together to protect cells from oxidative damage and prevent the formation of radicals. After the adipose tissue, the organ that has the highest fat content is the brain. This tissue has the most sensitivity to oxidative stress than other tissues due to its high content of peroxidizable long-chain fatty acid, high mitochondrial activity, relatively low antioxidant content, and high glucose uptake, which is a process with high free radical production.[31–33]
Few studies have been conducted on relation between ADHD and antioxidants. Based on the results of previous studies on the theory of oxidative stress and its destructive role in the nervous system, the present study compares the possible changes in oxidative and antioxidant parameters in ADHD children with healthy individuals.
| Methods|| |
This case–control study, which was conducted in Isfahan province, Iran, was carried out from October 2016 to January 2017.
The exclusion criteria in this study for the subjects include the use of antioxidant supplements, multivitamins, minerals, and omega-3s over the past 1 year, and smoking and lack of co-operation of the participants in the study or their families with project executive. In addition, patients who had taken another medicine apart from Ritalin were excluded from the study. Written consent was obtained from all subjects, and the stages of the plan were explained to all the subjects. After at least 8 h of fasting and physical inactivity, all participants were taken venous blood samples. Antioxidant parameters including total antioxidant capacity (TAC), catalase (CAT), glutathione (GSH), and malondiadehyde (MDA) were measured in this study. The venous blood samples were then centrifuged for about 10 min with 3000 rpm. The serum was isolated at 80°C until the time of analysis. General information, health history, and medication history were collected using demographic questionnaire. Height in standing position without shoes with the precision of 0.5 cm and weight with light clothing without shoes were measured at a precision of 100 g. Information about physical activity was obtained through Baecke physical activity questionnaire. Validity and reliability of this questionnaire have already been validated. To evaluate the dietary intakes of antioxidants (Vitamin E, C, Se, Zn, and β-carotene), all participants completed a 168-item food frequency questionnaire (FFQ) whose validity and reliability were confirmed. The subjects were asked to indicate the frequency of their intake of any food in relation to its amount over the past year. The quantities listed for each food product were converted to gram per day according to the household measures. Analysis of FFQ data was performed using N4 nutritional software. Serum levels of MDA were measured by the spectrophotometric method using reagent thiobarbituric acid. The CAT activity was measured by the spectrophotometric method based on the rate of reduction of optical absorption of hydrogen peroxide (H2O2). Ellman (DTNB) was used as a reagent to measure GSH. The TAC of the serum was measured by Rise et al.'s method.
Data were analyzed by independent t-test and Pearson's correlation coefficient. The level of significance in all tests is considered 0.05. SPSS v. 22 software was used to analyze the statistical measurements. Descriptive analysis was used to describe the demographic data and clinical data of the research samples.
| Result|| |
In this study, 36 patients and 32 healthy people were selected. Demographical values of patients and control groups are shown in [Table 1]. In the patient group, 35 patients (97.2%) used Ritalin, but in the healthy group, no one had a history of Ritalin intake. Independent t-test showed that there was no significant difference between the two groups in mean of age, weight, height, BMI, leisure time points, and sports score.
As shown in [Table 2], the mean of TAC, GSH, and CAT levels in the patients was significantly lower than the healthy group (P < 0.001), but the mean of MDA was not significantly different between the two groups (P = 0.18).
|Table 2: Comparison of the oxidative stress parameters among ADHD and control groups|
Click here to view
[Table 3] shows that there was no statistically significant difference in Zn, Se, vitamin E, vitamin C, β-carotene, and energy, which includes carbohydrate (CHO), fat, and protein (Pro) intake, between the two groups.
|Table 3: Comparison of dietary antioxidants and energy intake in ADHD and control groups|
Click here to view
Pearson's correlation coefficient showed that there was no significant relationship between dietary antioxidant levels (vitamin E, C, Se, Zn, and β-carotene) with serum antioxidants and MDA in the healthy and patient groups (P > 0.05) [Table 4].
|Table 4: Pearson correlation coefficients between dietary antioxidants level with the oxidative stress parameters in the patient and healthy groups|
Click here to view
GSH level and TAC were not significantly correlated with any dietary antioxidants (P > 0.05) [Table 4].
| Discussion|| |
The aim of this study was to measure the levels of serum and dietary antioxidants intake, and MDA is used as an oxidant marker in ADHD patients in comparison with healthy people. The results showed that in the case group the serum levels of GSH, CAT, and TAC decrease, but the mean of MDA was not significantly different between the two groups. In addition, there was no statistically significant differences in Zn, Se, vitamin E, vitamin C, β-carotene, and energy, which includes carbohydrate (CHO), fat, and protein (Pro) intake, between the two groups. In the study of Karababa et al., the relationship between total antioxidant status and ADHD was not observed. In Karababa et al.'s study, however, the measurement of oxidation parameters and age group was different from this study. The findings of Hatice Sezen, regarding the overall antioxidant status, was consistent with this study results. TAC is one of the important indicators of oxidative stress, as it determines the synergistic effect of different antioxidant compounds in the sample. However, TAC does not evaluate all the antioxidant components and the important role of enzymes such as SOD, CAT, and GPX; consequently, the data should be interpreted with caution. In this study, reducing the antioxidant capacity in the patient group is likely to contribute to the progression of ADHD by strengthening the mechanism that increases the levels of oxidant. Another finding of this study is that CAT levels were significantly lower in children with ADHD than in the control group. On the other hand, V. Kanak Celik et al. did not see the relationship between CAT levels and ADHD. The study included children who had ADHD recently diagnosed. Probably, at the beginning of the disease, antioxidant enzymes against oxidative stress have created a high potential protection.
The serum GSH level in this study was significantly lower in the patients than in the control group; any human study for GSH levels in children with ADHD was not found. The results of Douglas Teixeira Leffa et al.'s study indicate that the brain GSH is not different from those of ADHD and healthy mice. The findings of this study show that although the mean antioxidant markers in ADHD patients were significantly lower than the healthy group, there was no significant difference in serum MDA between the two groups. A study by Dimem Oztop reported a decrease in the MDA level in ADHD patients; in this study, oxidative stress may be reduced due to hypodopaminergic conditions.
On the other hand, the reason for this contradiction with his study may be due to the geographical locations and the gender groups. On the other hand, recent studies have reported an increase in oxidative stress in adults with ADHD. However, a similar increase in children in this study was not observed in children. In the study of Muhmut Bulut et al., which was conducted on adults with ADHD, the results showed that the serum levels of MDA were higher in patients than in healthy subjects. Differences in the findings may be due to the fact that children are less exposed to environmental risk factors that increase oxidative stress such as toxin, psychological stress, smoking, and alcohol., In addition, when only one oxidant parameter such as MDA is measured, it may be possible that the reduction or not change of the parameters is observed. Despite the actual increase in the oxidation state. On the other hand, the lack of difference in this oxidant parameter may be related to the consumption of Ritalin by patients. Previous studies have shown that methylphenidate treatment in children with ADHD may have protective effect on oxidative stress. Long-term exposure to oxidative toxin in adults, measuring only one oxidative stress marker or the protective effect of Ritalin are some of the important factors that can cause this difference in these findings. The most important limitation of our study is the small sample size, and few oxidative stress markers were detected.
| Conclusions|| |
The result of this study indicates that, in ADHD, the serum levels of GSH, CAT, and TAC decrease; and the level of antioxidant in the serum has been compromised to fight oxidative stress. Although this study aims to identify the antioxidant agents with ADHD, the findings may help to prevent or treat ADHD. However, more perspective studies with large sample sizes are essential to confirm these findings.
Financial support and sponsorship
Conflict of interest
There are no conflicts of interest.
| References|| |
Joshi K, Lad S, Kale M, Patwardhan B, Mahadik SP, Patni B, et al
. Supplementation with flax oil and vitamin C improves the outcome of Attention Deficit Hyperactivity Disorder (ADHD). Prostaglandins Leukot Essent Fatty Acids 2006;74:17-21.
Rucklidge JJ, Frampton CM, Gorman B, Boggis A. Vitamin-mineral treatment of attention-deficit hyperactivity disorder in adults: Double-blind randomized placebo-controlled trial. Br J Psychiatry 2014;204:306-15.
Aarts E, Ederveen THA, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, et al
. Gut microbiome in ADHD and its relation to neural reward anticipation. PLoS One 2017;12:e0183509.
Najib J, Wimer D, Zeng J, Lam KW, Romanyak N, Paige Morgan E, et al
. Review of lisdexamfetamine dimesylate in adults with attention-deficit/hyperactivity disorder. J Cent Nerv Syst Dis 2017;9:1-11.
Shafaat A, Tirgari-Seraj A, Daneshpoor SMM, Hajian M, Khademloo M. Prevalence of attention deficit hyper activity disorder in high-school students of Sari, Iran. J Mazandaran Univ Med Sci 2013;23:12-8.
Stoltz N, Farm B. The presence of B-m-Hydroxyphenylhydracrylic Acid in the Urine of Patients with ADHD and Other Neurodegenerative Metabolic Disorders. Doctoral dissertation. North-West University; 2004.
Daneshparvar M, Mostafavi SA, Zare Jeddi M, Yunesian M, Mesdaghinia A, Mahvi AH, et al
. The role of lead exposure on attention-deficit/hyperactivity disorder in children: A systematic review. Iran J Psychiatry 2016;11:1-14.
Zhou F, Wu F, Zou S, Chen Y, Feng C, Fan G. Dietary, nutrient patterns and blood essential elements in Chinese children with ADHD. Nutrients 2016;8:1-14.
Kul M, Unal F, Kandemir H, Sarkarati B, Kilinc K, Kandemir SB. Evaluation of oxidative metabolism in child and adolescent patients with attention deficit hyperactivity disorder. Psychiatry Investig 2015;12:361-6.
Woo HD, Kim DW, Hong YS, Kim YM, Seo JH, Choe BM, et al
. Dietary patterns in children with attention deficit/hyperactivity disorder (ADHD). Nutrients 2014;6:1539-53.
Abdollahian E, Shakeri M, Vosough E. The prevalence of attention deficit and hyperactivity disorderin preschool-age children in Mashhad, north-east of Iran. Med J Mashhad Univ Med Sci 2004;47:275-80.
Sarkhel S. Kaplan and Sadock's Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry, 10th ed. Indian J Psychiatry 2009;51:331. [Full text]
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th
ed. Arlington: American Psychiatric Publishing; 2013.
Mowinckel AM, Alnæs D, Pedersen ML, Ziegler S, Fredriksen M, Kaufmann T, et al
. Increased default-mode variability is related to reduce task-performance and is evident in adults with ADHD. Neuroimage Clin 2017;16:369-82.
Kita Y, Inoue Y. The direct/indirect association of ADHD/ODD symptoms with self-esteem, self-perception, and depression in early adolescents. Front Psychiatry 2017;31;8:137.
Anney RJ, Lasky-Su J, O'Dúshláine C, Kenny E, Neale BM, Mulligan A, et al
. Conduct disorder and ADHD: Evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study. Am J Med Genet B Neuropsychiatr Genet 2008;147B:1369-78.
Kim SM, Hyun GJ, Jung TW, Son YD, Cho IH, Kee BS, et al
. Balance deficit and brain connectivity in children with attention-deficit/hyperactivity disorder. Psychiatry Investig 2017;14:452-7.
Guney E, Cetin FH, Alisik M, Tunca H, Tas Torun Y, Iseri E, et al
. Attention deficit hyperactivity disorder and oxidative stress: A short term follow up study. Psychiatry Res 2015;229:310-7.
Oades RD. Dopamine may be 'hyper'with respect to noradrenaline metabolism, but 'hypo' with respect to serotonin metabolism in children with attention-deficit hyperactivity disorder. Behav Brain Res 2002;130:97-102.
Cherkasova MV, Faridi N, Casey KF, Larcher K, O'Driscoll GA, Hechtman L, et al
. Differential associations between cortical thickness and striatal dopamine in treatment-naïve adults with ADHD vs. healthy controls. Front Hum Neurosci 2017;11:421.
Villagomez A, Ramtekkar U. Iron, magnesium, vitamin D, and zinc deficiencies in children presenting with symptoms of attention-deficit/hyperactivity disorder. Children 2014;1:261-79.
Ceylan MF, Sener S, Bayraktar AC, Kavutcu M. Changes in oxidative stress and cellular immunity serum markers in attention-deficit/hyperactivity disorder. Psychiatry Clin Neurosci 2012;66:220-6.
Karababa İF, Savas SN, Selek S, Cicek E, Cicek EI, Asoglu M, et al
. Homocysteine levels and oxidative stress parameters in patients with adult ADHD. J Atten Disord 2017;21:487-93.
Lee JY, Hwang IW, Lim MH, Kwon HJ, Jin HJ. Association of glutathione S-transferases M1, T1 and P1 gene polymorphisms with attention deficit and hyperactivity disorder in Korean children. Gene 2016;586:228-33.
Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD. Free radicals and antioxidants in human health: Current status and future prospects. J Assoc Physicians India 2004;52:794-804.
Oztop D, Altun H, Baskol G, Ozsoy S. Oxidative stress in children with attention deficit hyperactivity disorder. Clin Biochem 2012;45:745-8.
Selek S, Ceylan MF. A relationship between oxidative status and attention deficit hyperactivity disorder. InStudies on Psychiatric Disorders. New York: Humana Press; 2015. p. 143-50.
Çelik VK, Erşan E, Erşan S, Bakır S, Dogan O. Plasma catalase, glutathione-s-transferase and total antioxidant activity levels of children with attention deficit and hyperactivity disorder. Adv Biosci Biotechnol 2013;4:183-7.
Farhud D, Shalileh M. Relation between omega 3 fatty acid, iron, zinc and treatment of ADHD. Zahedan J Res Med Sci 2014;16:1-5.
Simsek S, Gencoglan S, Ozaner S, Kaplan I, Kaya MC. Antioxidant status and DNA damage in children with attention deficit hyperactivity disorder with or without comorbid disruptive behavioral disorders. Bull Clin Psychopharmacol 2016;26:119-25.
Cavalca V, Veglia F, Squellerio I, Marenzi G, Minardi F, De Metrio M, et al
. Glutathione, vitamin E and oxidative stress in coronary artery disease: Relevance of age and gender. Eur J Clin Invest 2009;39:267-72.
Gumpricht E, Rockway S. Can ω-3 fatty acids and tocotrienol-rich vitamin E reduce symptoms of neurodevelopmental disorders? Nutrition 2014;30:733-8.
Florindo AA, Latorre Mdo R, Santos EC, Negrão CE, Azevedo LF, Segurado AA. Validity and reliability of the Baecke questionnaire for the evaluation of habitual physical activity among people living with HIV/AIDS. Cad Saude Publica 2006;22:535-41.
Hosseini-Esfahani F, Asghari G, Mirmiran P, Jalali Farahani S, Azizi F. Reproducibility and relative validity of food group intake in a food frequency questionnaire developed for the Tehran lipid and glucose study. RJMS 2010;17:41-55.
Rajaei Z, Hadjzadeh MA, Nemati H, Hosseini M, Ahmadi M, Shafiee S. Antihyperglycemic and antioxidant activity of crocin in streptozotocin-induced diabetic rats. J Med Food 2013;16:206-10.
Aebi H. Catalase in vitro
. Methods Enzymol 1984;105:121-6.
Costa CM, dos Santos RC, Lima ES. A simple automated procedure for thiol measurement in human serum samples. J Bras Patol Med Lab 2006;42:345-50.
Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: The FRAP assay. Anal Biochem 1996;239:70-6.
Sezen H, Kandemir H, Savik E, Basmacı Kandemir S, Kilicaslan F, Bilinc H, et al
. Increased oxidative stress in children with attention deficit hyperactivity disorder. Redox Rep 2016;21:248-53.
Costa JO, Vásquez CM, Santana GD, Silva ND, Braz JD, Jesus AM, et al
. Plasma total antioxidant capacity and cardiometabolic risk in non-obese and clinically healthy young adults. Arq Bras Cardiol 2017. doi: 10.5935/abc. 20170095.
Rubio CP, Hernández-Ruiz J, Martinez-Subiela S, Tvarijonaviciute A, Ceron JJ. Spectrophotometric assays for total antioxidant capacity (TAC) in dog serum: An update. BMC Vet Res 2016;12:166.
Leffa DT, Bellaver B, de Oliveira C, de Macedo IC, de Freitas JS, Grevet EH, et al
. Increased oxidative parameters and decreased cytokine levels in an animal model of attention-deficit/hyperactivity disorder. Neurochem Res 2017;42:3084-92.
Bulut M, Selek S, Bez Y, Cemal Kaya M, Gunes M, Karababa F, et al
. Lipid peroxidation markers in adult attention deficit hyperactivity disorder: New findings for oxidative stress. Psychiatry Res 2013;209:638-42.
Tsaluchidu S, Cocchi M, Tonello L, Puri BK. Fatty acids and oxidative stress in psychiatric disorders. BMC Psychiatry 2008;8:S5.
[Table 1], [Table 2], [Table 3], [Table 4]