Manganese in Children with Attention-Deficit/Hyperactivity Disorder: Relationship with Methylphenidate Exposure

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder that affects children worldwide. The etiology of ADHD is complex and not fully understood. Earlier studies associated elevated levels of manganese (Mn) with learning problems, attention deficits, and ADHD. Furthermore, it has also been shown that the dopamine (DA) system, the primary site of action of pharmacological ADHD treatments, is influenced by high levels of Mn. Recent studies have suggested that Mn accumulates in dopaminergic neurons via the presynaptic dopamine transporter (DAT). A role for altered functioning of the dopaminergic system in the etiology of ADHD has been well established through neurochemical, neurophysiological, imaging, and genetics studies. Methylphenidate (MPH) is a psychostimulant commonly used to manage ADHD symptoms. The pharmacotherapeutic effect of MPH occurs primarily through its action of inhibiting DAT, and thus increasing dopamine, as well as other catecholamines, at the synapse. We assessed a group of children with ADHD and matched control children without psychopathology attending public schools in a southern Brazilian city and reported elevated serum concentrations of Mn in treatment-naïve children with ADHD compared to normal controls. Interestingly, children with ADHD receiving concurrent MPH showed no difference in Mn serum levels versus controls. We then prospectively assessed the impact of naturalistic treatment with MPH and determined that Mn concentrations were significantly reduced from baseline values following MPH exposure.

The Role of Heavy Metal Pollution in Neurobehavioral Disorders: a Focus on Autism

“…Though Mn cannot be considered an environmental pollutant, numerous evidence suggests the potential association between Mn exposure and intellectual impairment in school-aged children, who showed Prenatal cadmium exposure IQ deficits (4.5 years of age) Tian et al (2009) IQ deficits (5 years of age) Kippler et al (2012a) Postnatal cadmium exposure No significant effects on neurodevelopmental scores (2, 5, and 7 years of age) Cao et al (2009) Learning impairment (6-15 years of age) Ciesielski et al (2012);Yousef et al (2011) Social problems and attention deficits (7-16 years of age) Bao et al (2009) deficits in IQ and verbal domain (Bouchard et al 2007: Claus Henn et al 2010Bouchard et al 2011;Menezes-Filho et al 2011). Manganese exposure is further associated with an increased risk of behavioral disorders, including ADHD (Farias et al 2010;Yousef et al 2011). The neurotoxicity of Mn has been associated with deregulation of dopaminergic and cholinergic neurotransmitter release (Finkelstein et al 2007).…”

Review of current evidence on the impact of pesticides, polychlorinated biphenyls and selected metals on attention deficit / hyperactivity disorder in children

“…Lower levels of exposure may produce neurobe havioral deficits involving motor and cognitive functions, as well as psychological perturbations [61,62]. So far, only two studies have been carried out to exam ine the association between exposure to Mn and ADHD or ADHD-like symptoms and both suggested the presence of such relationship [63,59] (Table 5). A case-control study by Farias et al [63] found that chil dren with ADHD of both the inattentive and ADHDcombined types had higher serum manganese levels com pared with the controls, however the study did not control for potential confounders.…”

“…So far, only two studies have been carried out to exam ine the association between exposure to Mn and ADHD or ADHD-like symptoms and both suggested the presence of such relationship [63,59] (Table 5). A case-control study by Farias et al [63] found that chil dren with ADHD of both the inattentive and ADHDcombined types had higher serum manganese levels com pared with the controls, however the study did not control for potential confounders. Also, the study performed in Quebec reported a significant association between higher manganese levels in hair and drinking water and hyperactive behaviors in school children after controlling for sex, age and income [59].…”

Eating habits and psychopathology: translation, adaptation, reliability of the Nutrition Behavior Inventory to Portuguese and relation to psychopathology

“…The present investigation was part of an ongoing longitudinal clinical assessment of behavioral, mood, and learning disorders conducted in our research institute. The assessment and diagnostic methods employed are described in detailed elsewhere 21,22 . The study included only children/ adolescents between 9 and 12 years of age, of both sexes, who were students in schools belonging to the Municipal Education system of Curitiba, a southern city in Brazil, and who were sent for evaluation by a multi-professional team during the period between March 2007 and November 2009.…”

“…First, our sample was made up mainly of male participants. This gender imbalance was related to the characteristics of our center's line of research, as the students were referred to us from local schools 21,22 . In this population, teachers tend to recommend or refer students with externalizing symptoms, rather than those with internalizing symptoms, and research has shown 30 that boys tend to have more externalizing problems than girls.…”