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Assessment of Biometal Profile in Children with Autism Spectrum Disorder, with Attention Deficit Hyperactivity Disorder, Or With Research Article iMedPub Journals ACTA PSYCHOPATHOLOGICA 2018 www.imedpub.com ISSN 2469-6676 Vol.4 No.1:6 DOI: 10.4172/2469-6676.100162 Assessment of Biometal Profile in Children Murat Pakyurek1*, Atoosa Azarang2, with Autism Spectrum Disorder, with Ana-Maria Iosif3 and Attention Deficit Hyperactivity Disorder, Thomas E Nordahl1 or with Other Psychiatric Diagnoses: A 1 Department of Psychiatry and Behavioral Comparative Outpatient Study Sciences, University of California-Davis, School of Medicine, Sacramento, USA 2 M.I.N.D. Institute, University of California-Davis Medical Center, Sacramento, USA Abstract 3 Department of Public Health Sciences, Background: In recent years, the impact of various micronutrients on the University of California-Davis, School of symptoms of ADHD and ASD has been studied. Our study was aimed at evaluating Medicine, USA the association between the level of serum magnesium, zinc and ferritin in children diagnosed with ADHD and/or ASD. Methods: This case-control pilot study consisted of 32 children who met DSM-V *Corresponding author: Murat Pakyurek criteria for ADHD, 15 children who met DSM-V criteria for ASD and 12 age-matched control children from Electronic Medical Record database. Serum magnesium, [email protected] zinc and ferritin values were com-pared with ANOVA. Clinical Professor of Psychiatry and Results: Blood ferritin level was found to be significantly lower in affected groups Behavioral Sciences, University of California, (F=5.9, p=0.0056). A trend towards decreased values of plasma zinc level was Davis Medical Center, 2230 Stockton Blvd. also found in affected children (F=2.25, p=0.12); whereas no suggestion of any School of Medicine, Sacramento, CA 95817, difference in blood magnesium levels between three groups was significant. USA. Non-parametric analyses were also run and the p value for ferritin 0.08, showed weaker evidence of significance. Tel: +1 916 734-3574 Conclusions: Results of this study indicated that low level of blood ferritin may be Fax: +916 734-0849 a risk factor for development of ASD and ADHD. Future investigations with larger controlled trials are needed and correlational studies would also be helpful. Keywords: ADHD; Autism; Magnesium; Zinc; Ferritin Citation: Pakyurek M, Azarang A, Iosif AM, Nordahl TE (2018) Assessment of Biometal Profile in Children with Autism Received: February 01, 2018; Accepted: February 12, 2018; Published: February Spectrum Disorder, with Attention Deficit 26, 2018 Hyperactivity Disorder, or with Other Psychiatric Diagnoses: A Comparative Outpatient Study. Acta Psychopathol Vol.4 No.1:6 Introduction in the cortical and limbic striatal areas might result in selective Attention Deficit Hyperactivity Disorder (ADHD) is one of the attention and behavioural inhibitions [2,8,9]. most common neuropsychiatric disorders that affects 8-12% of children worldwide [1,2]. ADHD is characterized by consistent Recent investigations on the neurobiology and treatment of and age-inappropriate levels of inattention, impulsivity and/ ADHD have suggested that possible deficiencies of nutrients such or hyperactivity [3]. Although the pathophysiology of ADHD is as iron, zinc, magnesium and polyunsaturated fatty acids could be complex and not clearly understood [4,5], several lines of evidence involved in the etiology of the disorder [10-12]. suggest a relevance of the dopaminergic and noradrenergic Iron plays multiple roles in the brain. It is implicated in proper systems in the cause of ADHD [6,7]. myelination and it serves as a co-factor for several enzymes Many studies using different methodologies have indicated that involved in monoamine neurotransmitter function including dopamine is a key element of ADHD pathophysiology. Some tyrosine hydroxylase which is critical in dopamine synthesis [13]. authors suggested that the lack of efficient dopaminergic control Iron is also related with monoamine oxidase, which is important © Under License of Creative Commons Attribution 3.0 License | This article is available from: www.psychopathology.imedpub.com 1 ACTA PSYCHOPATHOLOGICA 2018 ISSN 2469-6676 Vol.4 No.1:6 for the degradation of dopamine [14]. All of these results suggest to various disease states, including malabsorption and immune that iron metabolism may have important role in ADHD patho- dysregulation syndromes [36]. Changes in the intestinal flora and physiology. Ferritin is a marker of peripheral iron supplies and function are common in autistic patients [37,38]; it is therefore can be used to estimate body-iron stores [15]; however, it is not conceivable that malabsorption due to pathological changes in known if it reflects brain iron levels, but some studies have shown the intestinal mucosa may play an important role as one of the lower levels of ferritin in children with ADHD, other studies have causes of zinc deficiency in autism. Magnesium plays an essential not found this correlation; therefore, current results are mixed role in brain development and functional well-being, through [16-19]. activation of cop-per–zinc superoxide dismutase (CuZn-SOD) and nitric oxide release from cells [39]. Chronic low blood levels of Dietary deficiencies of zinc and magnesium are also suspected Magnesium might lead to growth retardation and behavioural to be associated with mild to significant changes in neuronal changes [40]. Magnesium in conjunction with vitamin B6, has function, which can lead to poor health and adverse effects on been proposed for many years as a nutritional factor in the behavior and learning [20]. Several researchers reported a link treatment of autism [41,42]. between zinc levels and ADHD symptoms [21]. Although the exact mechanism of how zinc may contribute to symptoms of The aim of the present study was to test whether blood levels ADHD is not known, there is evidence that zinc assists in both the of zinc, magnesium and ferritin are altered in children with production and regulation of melatonin, which is an important ADHD and/or ASD compared to healthy control subjects. We factor in the pathophysiology of ADHD due to its modulation hypothesize that blood levels of ferritin and zinc will be abnormal of dopamine. Zinc also binds to and regulates the dopamine in both ADHD and/or ASD children. transporter, which is a site of action of psychostimulants used to treat ADHD [22]. Methods Magnesium acts as an ionic membrane regulator and modulator Our retrospective chart review study included 32 children of ion transfer through membrane channels. In animal studies, with ADHD (aged 5-18 years, mean:10.53, SD:2.86, 84.37% Magnesium has been shown to interact with the serotonergic, boys, 15.63% girls) and 15 children with ASD (aged 5-18 years, noradrenergic, and dopaminergic systems [23]. Magnesium also mean:13.67, SD: 3.46, 80% boys, 20% girls) were collected through activates tyrosine hydroxylase, the rate-limiting step in dopamine Electronic Medical Record (EMR) database from University of synthesis and it binds serotonin and dopamine to their receptors California, Davis (UCD), medical centre from 2015 to pre-sent [24]. (Figure 1). The diagnoses were made after a series of structured interviews were conducted by a psychologist and one Child Autism Spectrum Disorder (ASD), on the other hand, is a multifactorial disorder characterized by deficit in social communication and interactions as well as restrictive and repetitive patterns of behavior [3]. The pathophysiological etiologies which precipitate autism symptoms remain elusive and controversial in many cases, but both genetic and environmental factors (and their interactions) have been implicated [25]. Previous studies have raised concerns that intake of iron, B vitamins, vitamin D, magnesium, calcium, and zinc may be deficient in up to one-third of children with ASD, and that dietary insufficiency may be more common in children on a restrictive diet [26-29]. Studies show that children with autism are at higher risk for iron deficiency and this condition may increase the severity of psychomotor and behavioural problems [30]. Another important element of cell signalling is zinc, which is involved in glutamatergic transmission [31]. There are also some observations from patients with fragile X syndrome suggesting that interactions between zinc and glutamate may exist [32]. It is conceivable that zinc after being absorbed by the postsynaptic neuron can act as an important trophic factor, i.e. as a nutrient that can later be involved in permanent learning processes [33]. Some studies show that zinc levels in the plasma, hair, and nails of patients with ASD may be abnormal [34,35]. Low intracellular zinc has been associated with DNA damage, which might be due to a combination of oxidative stress, impairment of anti-oxidant defenses and impairment of DNA repair. Zinc deficiency occurs Figure 1 Consort flow diagram. not only as a result of abnormal nutritional intake, but also due 2 This article is available from: www.psychopathology.imedpub.com ACTA PSYCHOPATHOLOGICA 2018 ISSN 2469-6676 Vol.4 No.1:6 and Adolescent psychiatrist at UCD, Child and Adolescent clinic based on the criteria for ADHD and ASD defined in the Diagnostic Distribution of Ferritin_blood_level and Statistical Manual of Mental Disorders [3], 5th Edition. All 200 F 5.90 Prob > F 0.0056 procedures were approved by the Institutional Review Board of UCD (No. 999488-1). 150 Seven cases of ADHD children and eleven cases of ASD children l e had comorbid anxiety disorder, one case of ADHD children and v e l d one case of ASD children had mental retardation. Twenty-five o o l b 100 n ADHD children and two ASD children were treated with psycho i t i r r stimulant medications, fourteen children of both categories had e F 10 27 nutritional supplements within the last six months and twenty- two children had asthma/allergy history. Twenty-one of the ADHD 50 children met the criteria for combined, eight for inattentive, two for hyperactive-impulsive and one for ADHD-NOS subtype. 0 The typically-developing (TD) controls included 12 ages, gender ADHD ASD NC and socioeconomic matched control children (mean: 13.50, group SD: 2.35) recruited from UCD Psychiatry Department.
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