Relation of ferritin levels with symptom ratings and cognitive performance in children with attention deficit-hyperactivity disorder.

Attention deficit – hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood. ADHD consists of two symptom domains, hyperactivity/impulsivity and inattentiveness.1 Although numerous studies conducted with children with ADHD have been published each year, the exact pathophysiology of the symptoms is unclear at the moment. However, many studies using different methodologies have indicated that dopamine is a key element of ADHD pathophysiology. Rats with lesions involving the ventral tegmental area have hyperactivity and problems in focusing on specific stimulus. These animals also have difficulties in shifting behavior. 2 Similarly, cortical DA deficiency causes hyperactivity, problems in inhibition, spatial orientation and temporal organization. The changes in prefrontal cortical areas also lead to reactive changes of the subcortical dopaminergic system.3 These studies indicate that dopamine may have an important role in all of the main symptom domains of ADHD. Some authors suggested that the lack of efficient dopaminergic control in the cortical and limbic striatal areas might result in selective attention and behavioral inhibition. 4,5 Iron is a coenzyme of tyrosine hydroxylase, which is critical in dopamine synthesis. 6 Iron is also related with monoamine oxidase, which is critical for the degradation of dopamine. Iron is colocalized with dopaminergic neurons in the brain, 6 and D2 and D4 receptor and dopamine transporter densities decrease with decreased brain iron levels.7,8 All these results suggest that iron metabolism may have important role in ADHD pathophysiology. However, the relationship of ADHD and iron metabolism has not been thoroughly studied. One study showed that children with ADHD had lower mean ferritin levels when compared with normal controls and that low serum ferritin levels were related to more severe symptoms, as indicated by higher Conners Parent Rating Scale scores. 9 Other studies have focused on the utility of iron supplementation in ADHD, with conflicting results. 10 The published studies have not investigated the possible relationship between iron levels and cognitive functioning of children with ADHD. This is surprising in the light of the previous studies that children with ADHD perform relatively worse than controls in vigilance and sustained attention tasks, executive function tests such as planning and organization, complex problem solving, set shifting, verbal learning, memory tests, motor inhibition and response monitoring. 11–20 Iron deficiency without anemia can cause cognitive problems because brain iron levels decrease before anemia becomes evident.21 Indeed, children with iron deficiency with or without anemia have been shown to have significant cognitive problems including lower IQ, motor problems, spatial memory, and selective attention,22,23 which can last for years. 24 The aim of the present study was to investigate the relationship between ferritin, hemoglobin, mean corpuscular volume (MCV) and red cell distribution width (RDW) and neuropsychological measures obtained by a broad test battery in children and adolescents with ADHD. We selected these variables because iron deficiency is usually defined by low serum ferritin levels, or low MCV and high RDW. Anemia is clearly defined as having low serum hemoglobin values. The neuropsychological test battery was selected to cover executive functions and attentional processes.