Ferritin and hyperactivity ratings in attention deficit hyperactivity disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common psychiatric disorders of childhood and adolescence. There are currently three subtypes of ADHD: combined, inattentive and hyperactive-impulsive, as defined by the DSM-IV-TR criteria1. The exact pathophysiology of ADHD symptoms remains unclear, although several converging lines of investigation suggest that both genetic and environmental factors, and their interactions, are important. An emerging interest of research in recent years has been the investigation of a possible association of iron metabolism as a risk factor for ADHD. To date, although a number of studies have shown that children with ADHD have lower mean ferritin levels when compared with normal controls, and that low serum ferritin levels are related with more severe ADHD ratings, as reported by teachers and/or parents 1–5, other studies have also reported negative findings6–7 . Understandably, a number of studies have also focused on the utility of iron supplementation in ADHD; these studies have yielded conflicting results8–9. It has also been shown that iron deficiency during infancy might lead to learning and memory problems, which might also have enduring effects in grade-school period10. In a relatively small sample, we previously reported that there were no significant correlations between ferritin level and performance in vigilance and sustained attention tasks, executive function tests like planning and organization, complex problem solving, set shifting, and response monitoring3. In another distinct sample, we also showed that presence of comorbid conditions might also increase the effect of lower iron stores on behavioral measures11. However, the sample size of this latter study did not allow us to control for the effects of ADHD subtype as well as different comorbid conditions on parent and teacher ratings. In this study, our aim was to investigate the relationship between age, gender, ferritin level, hemoglobin, mean corpuscular volume (MCV), reticulosite distribution width (RDW) with parent and teacher reports and cognitive measures in a large sample of children and adolescents with ADHD. The control of ADHD subtype and specific comorbid condition categories is important since it has been shown that both are associated with symptom ratings12–13. We therefore also controlled for confounders including ADHD subtype (combined, inattentive, hyperactive-impulsive), presence of comorbid conditions (grouped into four: anxiety disorders, oppositional defiant/conduct disorder, learning disabilities and other conditions including tic disorders, elimination disorders, and mood disorders). We selected the hematological variables since iron deficiency is usually defined by low serum ferritin levels, or low MCV and high RDW values. We also selected Digit Span, Digit Symbol and Trail Making Test Part A as attentional indices. Based on our prior findings, we predicted that after controlling for the above mentioned variables, parent and teacher reported hyperactivity ratings would be negatively associated with ferritin level. We also predicted that ferritin level would not be significantly associated with attention problems ratings and cognitive measures.