Abstract
Background & Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders in childhood. The exact etiology of this disease is unknown, but it is believed to be related to the disorder of catecholaminergic and serotonergic systems. Also, serum vitamin D levels in patients with ADHD is lower. Several studies have also shown the effect of vitamin D on the synthesis pathways of dopamine, serotonin, and a number of neurotrophic factors. Therefore, this study aimed to investigate the effect of vitamin D3 supplementation on serum levels of Brain-Derived Neurotrophic Factor (BDNF), dopamine, and serotonin in school-aged children with ADHD.
Methods: Eighty-six children with ADHD were divided into two groups, based on randomized permuted blocks. Patients received 2000 IU vitamin D/day or a placebo for 12 weeks. Serum levels of BDNF, dopamine, serotonin, and 25-hydroxyvitamin D [25(OH)D] were measured at baseline and at the end of the study. Results: Serum levels of 25(OH)D and dopamine significantly increased in the vitamin D group, compared to the placebo group (p < 0.05). However, serum BDNF and serotonin levels did not change significantly. Conclusion: Vitamin D3 supplementation in children with ADHD can increase serum dopamine levels, but further studies are needed to determine the effects of vitamin D on neurotrophic factors and serotonin.Keywords: Attention-deficit/hyperactivity disorder, vitamin D, supplementation, brain-derived neurotrophic factor, dopamine, serotonin.
Graphical Abstract
[1]
Li Z, Chang SH, Zhang LY, Gao L, Wang J. Molecular genetic studies of ADHD and its candidate genes: A review. Psychiatry Res 2014; 219(1): 10-24.
[2]
Skounti M, Philalithis A, Galanakis E. Variations in prevalence of attention deficit hyperactivity disorder worldwide. Eur J Pediatr 2007; 166(2): 117-23.
[3]
Hodgkins P, Setyawan J, Mitra D, et al. Management of ADHD in children across Europe: Patient demographics, physician characteristics and treatment patterns. Eur J Pediatr 2013; 172(7): 895-906.
[4]
Barkley RA, Poillion MJ. Attention deficit hyperactivity disorder: A handbook for diagnosis and treatment. Behav Disord 1994; 19(2): 150-2.
[5]
Hirayama S, Terasawa K, Rabeler R, et al. The effect of phosphatidylserine administration on memory and symptoms of attention-deficit hyperactivity disorder: A randomised, double-blind, placebo-controlled clinical trial. J Hum Nutr Diet 2014; 27(Suppl. 2): 284-91.
[6]
Wolraich ML, Wibbelsman CJ, Brown TE, et al. Attention-deficit/hyperactivity disorder among adolescents: A review of the diagnosis, treatment, and clinical implications. Pediatrics 2005; 115(6): 1734-46.
[7]
Biederman J, Faraone SV, Spencer TJ, Mick E, Monuteaux MC, Aleardi M. Functional impairments in adults with self-reports of diagnosed ADHD: A controlled study of 1001 adults in the community. J Clin Psychiatry 2006; 67(4): 524-40.
[8]
Sharma A, Couture J. A review of the pathophysiology, etiology, and treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Ann Pharmacother 2014; 48(2): 209-25.
[9]
Cantwell DP. Attention deficit disorder: A review of the past 10 years. J Am Acad Child Adolesc Psychiatry 1996; 35(8): 978-87.
[10]
Russell VA. Overview of animal models of Attention Deficit Hyperactivity Disorder (ADHD). Curr Protoc Neurosci 2011; 54(1): 9-35.
[11]
Tarver J, Daley D, Sayal K. Attention-Deficit Hyperactivity Disorder (ADHD): An updated review of the essential facts. Child Care Health Dev 2014; 40(6): 762-74.
[12]
Doggett AM. ADHD and drug therapy: Is it still a valid treatment? J Child Health Care 2004; 8(1): 69-81.
[13]
Widenhorn-Müller K, Schwanda S, Scholz E, Spitzer M, Bode H. Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with Attention Deficit/Hyperactivity Disorder (ADHD): A randomized placebo-controlled intervention trial. Prostaglandins Leukot Essent Fatty Acids 2014; 91(1-2): 49-60.
[14]
Liu DY, Shen XM, Yuan FF, et al. The physiology of BDNF and its relationship with ADHD. Mol Neurobiol 2015; 52(3): 1467-76.
[15]
Tsai SJ. Attention-deficit hyperactivity disorder may be associated with decreased central brain-derived neurotrophic factor activity: Clinical and therapeutic implications. Med Hypotheses 2007; 68(4): 896-9.
[16]
Lesch KP, Waider J. Serotonin in the modulation of neural plasticity and networks: Implications for neurodevelopmental disorders. Neuron 2012; 76(1): 175-91.
[17]
Bala KA, Doğan M, Kaba S, Mutluer T, Aslan O, Doğan SZ. Hormone disorder and vitamin deficiency in Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASDs). J Pediatr Endocrinol Metab 2016; 29(9): 1077-82.
[18]
Goksugur SB, Tufan AE, Semiz M, et al. Vitamin D status in children with attention-deficit-hyperactivity disorder. Pediatr Int 2014; 56(4): 515-9.
[19]
Shang-Guan LL, Zhao YR. Serum levels of 25-hydroxyvitamin D in children with attention deficit hyperactivity disorder. Zhongguo Dang Dai Er Ke Za Zhi 2015; 17(8): 837-40.
[20]
Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 α-hydroxylase in human brain. J Chem Neuroanat 2005; 29(1): 21-30.
[21]
Brion F, Dupuis Y. Calcium and monoamine regulation: Role of vitamin D nutrition. Can J Physiol Pharmacol 1980; 58(12): 1431-4.
[22]
Hajiluian G, Nameni G, Shahabi P, Mesgari-Abbasi M, Sadigh-Eteghad S, Farhangi MA. Vitamin D administration, cognitive function, BBB permeability and neuroinflammatory factors in high-fat diet-induced obese rats. Int J Obes 2017; 41(4): 639-44.
[23]
Patrick RP, Ames BN. Vitamin D hormone regulates serotonin synthesis. Part 1: Relevance for autism. FASEB J 2014; 28(6): 2398-413.
[24]
Saedisomeolia A, Samadi M, Gholami F, et al. Vitamin D’s molecular action mechanism in attention-deficit/ hyperactivity disorder: A review of evidence. CNS Neurol Disord Drug Targets 2018; 17(4): 280-90.
[25]
Smith MP, Fletcher-Turner A, Yurek DM, Cass WA. Calcitriol protection against dopamine loss induced by intracerebroventricular administration of 6-hydroxydopamine. Neurochem Res 2006; 31(4): 533-9.
[26]
Corominas-Roso M, Ramos-Quiroga JA, Ribases M, et al. Decreased serum levels of brain-derived neurotrophic factor in adults with attention-deficit hyperactivity disorder. Int J Neuropsychopharmacol 2013; 16(6): 1267-75.
[27]
Swanson JM, Flodman P, Kennedy J, et al. Dopamine genes and ADHD. Neurosci Biobehav Rev 2000; 24(1): 21-5.
[28]
Baek DJ, Lee CB, Baek SS. Effect of treadmill exercise on social interaction and tyrosine hydroxylase expression in the attention-deficit/hyperactivity disorder rats. J Exerc Rehabil 2014; 10(5): 252-7.
[29]
Kopecková M, Paclt I, Goetz P. Polymorphisms and low plasma activity of dopamine-beta-hydroxylase in ADHD children. Neuroendocrinol Lett 2006; 27(6): 748-54.
[30]
Puchacz E, Stumpf WE, Stachowiak EK, Stachowiak MK. Vitamin D increases expression of the tyrosine hydroxylase gene in adrenal medullary cells. Brain Res Mol Brain Res 1996; 36(1): 193-6.
[31]
Sanchez B, Relova JL, Gallego R, Ben-Batalla I, Perez-Fernandez R. 1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats increases glial cell line-derived neurotrophic factor and partially restores tyrosine hydroxylase expression in substantia nigra and striatum. J Neurosci Res 2009; 87(3): 723-32.
[32]
Baksi SN, Hughes MJ. Alteration of adrenal catecholamine levels in the rat after dietary calcium and vitamin D deficiencies. J Auton Nerv Syst 1984; 11(4): 393-6.
[33]
Shirazi HA, Rasouli J, Ciric B, Rostami A, Zhang GX. 1,25-Dihydroxyvitamin D3 enhances neural stem cell proliferation and oligodendrocyte differentiation. Exp Mol Pathol 2015; 98(2): 240-5.
[34]
Pirotta S, Kidgell DJ, Daly RM. Effects of vitamin D supplementation on neuroplasticity in older adults: A double-blinded, placebo-controlled randomised trial. Osteoporos Int 2015; 26(1): 131-40.
[35]
Li H, Liu L, Tang Y, et al. Sex-specific association of Brain-Derived Neurotrophic Factor (BDNF) Val66Met polymorphism and plasma BDNF with attention-deficit/hyperactivity disorder in a drug-naïve Han Chinese sample. Psychiatry Res 2014; 217(3): 191-7.
[36]
Shim SH, Hwangbo Y, Kwon YJ, et al. Increased levels of plasma Brain-Derived Neurotrophic Factor (BDNF) in children with Attention Deficit-Hyperactivity Disorder (ADHD). Prog Neuropsychopharmacol Biol Psychiatry 2008; 32(8): 1824-8.
[37]
Banerjee E, Nandagopal K. Does serotonin deficit mediate susceptibility to ADHD? Neurochem Int 2015; 82: 52-68.
[38]
Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: Relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J 2015; 29(6): 2207-22.
[39]
Mann JJ, McBride PA, Anderson GM, Mieczkowski TA. Platelet and whole blood serotonin content in depressed inpatients: Correlations with acute and life-time psychopathology. Biol Psychiatry 1992; 32(3): 243-57.
[40]
Moffitt TE, Brammer GL, Caspi A, et al. Whole blood serotonin relates to violence in an epidemiological study. Biol Psychiatry 1998; 43(6): 446-57.
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