Elsevier

Brain and Development

Volume 27, Issue 4, June 2005, Pages 279-285
Brain and Development

Original article
Regional cerebral blood flow in children with ADHD: changes with age

https://doi.org/10.1016/j.braindev.2004.07.010Get rights and content

Abstract

The aim of this study was to investigate the changes in regional cerebral blood flow (rCBF) with age in patients with attention deficit hyperactivity disorder (ADHD). Twenty-nine drug-naive ADHD subjects (24 boys, 5 girls; age 7–13; mean±SD=age 9.2±2.1) and 12 subjects with epilepsy (all diagnosed as having complex partial seizure, 6 boys, 6 girls; age 7–14; mean±SD=8.5±2.1) were included in the study. All cases of ADHD were diagnosed according to DSM-IV criteria. Cerebral blood flow was evaluated with Tc-99m-hexamethylpropyleneamine oxime (Tc99m HMPAO) brain single photon emission tomography (SPECT) during standard resting condition in all of the cases. Asymmetry indices for each region of interest were calculated. Absolute rCBF values were normalized as the absolute rCBF values divided by the whole brain absolute value. The prefrontal lobe asymmetry indices were significantly negatively correlated with age in ADHD cases (r=−0.408, P=0.025), which indicated the increased prefrontal rCBF lateralization from the right to the left side with age. When ADHD cases older than 7 years of age were compared with those with epilepsy, the ADHD cases had lower right prefrontal and frontal rCBF and higher left parietal rCBF. The epilepsy group showed no significant correlations between age and asymmetry indices and showed a different developmental trajectory for prefrontal asymmetry and right prefrontal rCBF values. The results indicated that the left hemisphere dominance in the prefrontal cortex significantly increases with age in ADHD cases.

Introduction

Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder that affects many children, significantly impacting their potential for development [1]. There is an increasing convergence of results demonstrating both structural and functional characteristics of the brains of patients with ADHD. Structural MRI studies have shown abnormalities of the whole brain, the frontal lobes, the basal ganglia, the corpus callosum, the parietal lobes, and the cerebellar vermis [2], [3], [4], [5], [6], [7]. The results of functional studies, mostly comprised of SPECT and PET, have not been entirely consistent, but indicated reduced brain activity in the prefrontal and the parietal cortices, the anterior cingulate cortex, and the caudate nucleus [8], [9], [10], [11], [12], [13], [14], [15], [16]. Thus, right-sided abnormalities of the prefrontal cortex-basal ganglia circuit have been implicated in pathophysiology of ADHD [17].

There have been a number of MRI studies evaluating structural changes of the brain in normal subjects including children. The findings of those studies are summarized as follows: cerebral volume does not change significantly after 5 years of age [18], [19], [20]; the cortical gray matter volume decreases significantly with age [21]; and the cerebral white matter volume increases throughout childhood [20], [21], [22]: these changes appear to be region specific [23].

PET studies involving children with neurological concerns (e.g. seizures, epilepsy, Sturge–Weber syndrome) indicate that cerebral glucose metabolic rates follow a triphasic evolution characterized by rapid increase after birth, persistent high levels during childhood, possibly a result of increased energy demand resulting from transient synaptic exuberance, and a subsequent decline to reach the adult levels by the end of adolescence [24], [25]. Results of SPECT studies indicated that the activities of the frontal, parietal, left temporal and cingulate cortices were significantly higher in children than in adults [26].

The aim of the present study was to investigate the age-specific changes in regional cerebral blood flow (rCBF) and the degree of asymmetry in rCBF in ADHD subjects. There have been few previous SPECT studies involving ADHD children and none have evaluated the changes in rCBF with age.

Section snippets

Subjects

Subjects were 29 patients with ADHD (24 boys, 5 girls; age 7–13; mean±SD=9.19±2.01). None of the cases were left handed per Pediatric Assessment of Neurological Soft Signs [27] handedness items. All of the cases were Caucasian. All subjects were recruited from the general outpatient clinic at the Child Psychiatry Department, who fulfilled the inclusion criteria. The same group of patients has been the subjects of the two previous studies by the same investigators: the one on the effects of

Correlations with age

Age was not significantly correlated with any of the relative rCBF values (−0.340<r<0.193; 0.07<P<0.91) in the ADHD group. However, with increasing age prefrontal asymmetry indices decreased significantly (r=−0.407, P<0.028) in the ADHD group. In the epilepsy group, there were no significant correlations of rCBF or asymmetry indices with age (−0.100<r<0.430; 0.15<P<0.84). Changes with age in the rCBF values (Fig. 1) and asymmetry indices (Fig. 2) in the prefrontal and frontal cortices in the

Discussion

Our results indicate that the prefrontal cortex rCBF during resting conditions in ADHD cases shows increased lateralization from the right to the left with age and that ADHD cases have lower right prefrontal and frontal and higher parietal relative rCBF values compared with those patients with epilepsies. The differences between the groups are more prominent when subjects older than 7 years of age were compared. The decreased right prefrontal and frontal rCBF is consistent with previous studies

Acknowledgements

Part of this study was supported by the Ankara University, project number: 201-08-09-045. We would also like to thank Kerim M. Munir, the Principle Investigator of the NIMH Fogarty International Mental Health and Developmental Disabilities Research Training Program (D43TW05807) at Children's Hospital Boston, and Verda Tunaligil for their contributions to this article.

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