Iron Deficiency in Indian Children with Attention Deficit Hyperactivity Disorder

From Department of Pediatrics, Maulana Azad Medical College and associated Lok Nayak Hospital; and Department of Biochemistry, GB Pant Hospital, New Delhi 110 002, India.  

Received: October 15, 2009;
Initial review: November 12, 2009;
Accepted: December 18, 2009. 
Published online 2010 March 15.

 PII: S097475590900746-2

A case control study was conducted at the Child Development and Early Intervention Clinic to determine the body iron status of children with ADHD, and study the correlation between the body iron status and ADHD symptoms. Serum ferritin was measured in newly diagnosed cases with ADHD and compared with that of controls. Correlation was studied between serum ferritin levels and the severity of ADHD symptoms as determined by Conners’ Rating Scale. Serum ferritin was found to be significantly lower in children with ADHD (6.04 ± 3.85 ng/mL) as compared to controls (48.96 ± 41.64 ng/mL, P value<0.001). There was a significant negative correlation between serum ferritin levels and oppositional subscore on Conners’ Rating Scale.

Key words: Attention Deficit Hyperactivity Disorder, Children, Ferritin, India, Iron.

Attention deficit hyperactivity disorder (ADHD) is amongst the most common neurobehavioral disorders in children, with prevalence rate as high as 4%-12% in school-aged children(1). It is characterized by three core symptoms of inattention, hyperactivity and impulsivity(2). Multiple theories of ADHD have been proposed, but the dopamine deficit theory is the most widely accepted. Brain imaging and functional studies have shown abnormalities in the dopamine modulated frontal-striatal circuits(3). Molecular genetic studies have also shown an association between ADHD and polymorphisms of dopamine receptor D4 gene, dopamine receptor D5 gene and dopamine transporter gene(3,4). Dopamine syn-thesis is dependent on availability of iron, as it is a coenzyme of tyrosine hydroxylase, which converts tyrosine to L-dopa, which is then decarboxylated to dopamine(5).

Role of iron has also been extensively studied in Restless leg syndrome (RLS), a condition related to ADHD. Iron deficiency has been associated with secondary RLS and aggravates of idiopathic RLS(6,7). It is postulated that iron deficiency affects dopamine levels in substantia niagra and putamen(8). Iron deficiency is also associated with a number of other neurologic disorders including development delay, stroke, pseudotumor cerebri, breath-holding episodes and cranial nerve palsies(9). Recently, its possible involvement as a contributing cause of ADHD has also been reported from some developed countries(10-15). Serum ferritin is a reliable measure of iron stores in body tissues, including brain, and low level can detect an early iron deficiency sufficient to cause neurological or behavioral symptoms. This study was planned to investigate the contribution of iron deficiency to the ADHD symptoms in the Indian setting.

A case control study was conducted in Child Development and Early Intervention Clinic (CDEIC) in the Department of Pediatrics, of a tertiary care hospital in New Delhi, India in the year 2007. All 6-14 years old children who were newly diagnosed as ADHD in the clinic as per DSM IV TR criteria and with hemoglobin of >10 g/dl were included in the study. To confirm the presence of symptoms in two settings, only children with both Conners’ Parents Rating Scale (CPRS) and Conners’ Teachers Rating Scale (CTRS) T-scores of ³65 were included.

TABLE I



Characteristics in the Study Population

TABLE II



Distribution of T- scores of ADHD Patients

In a former similar study, mean serum ferritin levels were also found to be significantly lower in the children with ADHD (23±13 ng/mL) as compared to controls (44±22 ng/mL). The serum ferritin levels correlated with ADHD symptoms severity measured with CPRS. Serum ferritin levels also correlated with the cognitive subscore and tended toward a correlation with the hyperactivity subscore but did not correlate with the oppositional subscore(10). In another study on 52 ADHD children, lower ferritin levels were associated with higher hyperactivity scores on CPRS(11). However, in contrast to these two studies, we found that serum ferritin levels did not correlate significantly with hyperactivity or cognitive sub-score. This could be because there was not much variation in the serum ferritin levels in our cases, as all patients with ADHD had serum ferritin below 15ng/mL. It could also be because of small sample size of our study.

In a previous large study on subjects with ADHD, CPRS and CTRS total scores were negatively correlated with serum ferritin with more prominent negative correlation in the comorbid ADHD subjects. This study concluded that presence of comorbid conditions might increase the effect of lower iron stores on behavioral measures(12). ADHD children with lower serum ferritin levels were also shown to have higher scores on Sleep Disturbance Scale for Children(14).

In contrast to the results of above studies, in the study by Millichap, et al.(15), the mean serum ferritin level in patients with ADHD was not different from that of controls. Also in this study there was no difference in the clinical characteristics of patients with lowest and highest serum ferritin levels. However, the population enrolled in this study was heterogeneous with seizure disorders, neurological deficits and learning difficulties. They did not have any controls in their study but have compared their results with National U.S. data. Failure to find any differences in this study may only signify that low iron levels may not be a universal finding in children with ADHD but needs to be addressed in those with deficiency.

15. Millichap JG, Yee MM, Davidson SI. Serum ferritin in children with attention deficit hyperactivity disorder. Pediatr Neurol 2006; 34: 200-203.