Vol 4 n° 4 - Drug Development
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ttention-deficit/hyperactivity disorder (ADHD) is  characterized  by  the  chronic  presence  of  impairing symptoms of excessive hyperactivity, impulsivity, and/or inattention.1  The   clinical   diagnosis   of   International Statistical Classification of Disease, 10th Revision (ICD-10) hyperkinetic disorder (HKD)2 is a restricted subset of ADHD, with narrower inclusion criteria and more exclu- sions.3 Given the high degree of heterogeneity and comor- bidity in ADHD,4 most neurobiological studies of ADHD have focused on combined type ADHD, which requires the presence of at least 6 symptoms of hyperactivity/impul- sivity and at least 6 symptoms of inattention, and is closer to HKD. Clinical diagnoses such as ADHD or HKD are necessary for the fundamental decision of whether or not to treat. However, since these, like all psychiatric diag- noses, are based exclusively on symptoms, they can result from a wide range of causes and susceptibilities.Thus, diag- nostic categories do not provide an optimal basis for neu- robiological investigations, although they are a necessary starting point.5 In the case of ADHD, they have been the basis for an increasing number of structural as well as func- tional neuroimaging studies. Functional imaging studies have used a wide variety of approaches, and none of the findings reported to date have been convincingly repli- cated. For this reason, and due to limitations of space, this brief review will focus on one simple question: what are the anatomic substrates associated with combined type ADHD? (In the text below,ADHD refers to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]1 combined type ADHD.) Keywords:  attention-deficit/hyperactivity  disorder;  magnetic  resonance  imaging; prefrontal brain; basal ganglia; cerebellum Author  affiliations:  Brooke   and   Daniel   Neidich   Professor   of   Child   and Adolescent  Psychiatry,  Director,  Institute  for  Pediatric  Neuroscience,  NYU Child Study Center, New York, NY, USA Address for correspondence:  F. Xavier Castellanos, MD, Brooke and Daniel Neidich Professor of Child and Adolescent Psychiatry, Director, Institute for Pediatric Neuroscience, NYU Child Study Center, 577 First Avenue, CSC Room 204, New York, NY 10016-6404, USA
(e-mail: castef01@med.nyu.edu) B a s i c   r e s e a r c h 4 4 4 Anatomic magnetic resonance imaging studies of attention-deficit/hyperactivity disorder Francisco Xavier Castellanos, MD Neuroimaging techniques are increasingly being applied to the study of attention-deficit/hyperactivity disorder (ADHD). This review focuses on magnetic resonance imag- ing studies of the brain anatomy of ADHD. Such studies were first conducted over a decade ago, and most focus on frontal-striatal regions and tend to find smaller vol- umes in ADHD children than in controls. Recently pub- lished analyses with the largest sample so far of patients and controls found that ADHD is associated with a statis- tically significant 3% to 4% global reduction in brain vol- ume in both boys and girls, with abnormally small caudate nuclei only being found in younger patients. After adjust- ing for global brain differences, only cerebellar hemi- spheric volumes remained significantly smaller in ADHD, and these differences continued throughout childhood and adolescence. Pathophysiological models of ADHD need take into account cerebellar dysfunction, as well as prefrontal-striatal dysregulation. Dialogues Clin Neurosci. 2002;4:444-448. A