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 diagnoses, are based exclusively on symptoms, they can result from a wide range of causes and susceptibilities. Thus, diagnostic categories do not provide an optimal basis for neurobiological investigations, although they are a necessary Inhibitors,research,lifescience,medical starting point.5 In the case of ADHD, they have been the basis for an increasing number of structural as well as functional neuroimaging

studies. Functional imaging studies have used a wide variety of approaches, and none of the findings reported to date have been convincingly replicated. 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 Inhibitors,research,lifescience,medical ADHD.) ADHD as a disorder cannot be considered without taking into account developmental factors, and an examination of the brain anatomy of ADHD must, be referenced to healthy brain development.

The most influential early work on brain development, was based on postmortem specimens from over 200 autopsy brains obtained from Inhibitors,research,lifescience,medical midprcgnancy through the first year of life, and a large collection of adult brains, but Inhibitors,research,lifescience,medical very few specimens (about 12) in the age range extending from childhood through adolescence. Yakovlev and Lecours demonstrated that myelination continued well beyond the first, year of life,6 but. they were circumspect about their more speculative findings, which they explicitly acknowledged were based on “a crude method of staining myelin sheath” of undetermined

reliability. Nevertheless, they tentatively concluded that. myelination proceeds along a caudal-rostral gradient. Because of the lack of postmortem tissue for children and adolescents, this finding has not been Inhibitors,research,lifescience,medical directly examined. In vivo magnetic resonance imaging The quantitative study of brain development in vivo during childhood and adolescence began in the late 1980s.7,8 Subsequent cross-sectional1,9-11 and mixed longitudinal/ Adenosine cross-sectional studies12 have CI-1033 in vivo confirmed that although total brain volume changes negligibly between ages 5 and 18, this masks robust and complex changes in white and gray matter compartments. White matter volume and signal intensity increase linearly during this age range, presumably reflecting increasing myelination,11,13 and gray matter volume increases until early to mid-adolescence before decreasing during late adolescence,12 apparently representing synaptic pruning and reduction in neuropil, which has been documented during these developmental periods.