Imaging normal and abnormal brain development: new perspectives for child psychiatry.

Child Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892-1600, USA.
Australian and New Zealand Journal of Psychiatry (Impact Factor: 3.41). 07/2001; 35(3):272-81.
Source: PubMed


The availability of non-invasive brain imaging permits the study of normal and abnormal brain development in childhood and adolescence. This paper summarizes current knowledge of brain abnormalities of two conditions, attention deficit hyperactivity disorder (ADHD) and childhood onset schizophrenia (COS), and illustrates how such findings are bringing clinical and preclinical perspectives closer together.
A selected review is presented of the pattern and temporal characteristics of anatomic brain magnetic resonance imaging (MRI) studies in ADHD and COS. These results are discussed in terms of candidate mechanisms suggested by studies in developmental neuroscience.
There are consistent, diagnostically specific patterns of brain abnormality for ADHD and COS. Attention deficit hyperactivity disorder is characterized by a slightly smaller (4%) total brain volume (both white and grey matter), less-consistent abnormalities of the basal ganglia and a striking (15%) decrease in posterior inferior cerebellar vermal volume. These changes do not progress with age. In contrast, patients with COS have smaller brain volume due to a 10% decrease in cortical grey volume. Moreover, in COS there is a progressive loss of regional grey volume particularly in frontal and temporal regions during adolescence.
In ADHD, the developmental pattern suggests an early non-progressive 'lesion' involving neurotrophic factors controlling overall brain growth and selected dopamine circuits. In contrast, in COS, which shows progressive grey matter loss, various candidate processes influencing later synaptic and dendritic pruning are suggested by human post-mortem and developmental animal studies.

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    • "Finally, it has long been recognized that disorders of brain morphology associated with grossly abnormal gyral folding such as polymicrogyria and pachygyria are associated with the development of abnormal cognitive function and with epilepsy (Barkovich et al. 1995; Jansen et al. 2005). Recently, there has been growing awareness of the fact that more subtle developmental disturbances of gyral folding can also lead to developmental, albeit milder neurological disorders such as dyslexia (Galaburda et al. 1985), schizophrenia (Noga et al. 1996; White et al. 2003; Narr et al. 2004), autism (Levitt et al. 2003), William's syndrome (Galaburda et al. 2003; Van Essen et al. 2006), and Rett syndrome (Joyner et al. 2009), and a number of studies have shown subtle abnormal white matter development in such disorders suggesting altered connectivity (Nowell et al. 1988; Rapoport et al. 2001). It is therefore essential to develop a clear picture of the normal patterns and timing of development of brain pathways and to interpret the role of white matter pathways (e.g., Takahashi et al. 2007, 2008) in order to more accurately diagnose subtle disorders of brain connectivity during development. "
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    • "This does not, of course, imply anything about the right hemisphere norepinephrine system itself, but the fact that the mass of cortical tissue it innervates is smaller suggests the possibility that the motor action and sensory arousal systems of ADHD individuals are unbalanced. Further, the tissue connecting the two hemispheres is smaller in some ADHD individuals than in normals, both at the level of the cerebral cortex (Barkley p. 33) and for the cerebellum as well (Rapoport et al. 2001).[3] This suggests that the two systems may not interact as efficiently as necessary for good performance. "
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    Full-text · Article · Dec 2009 · SSRN Electronic Journal
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    • "Earlier cross-sectional imaging studies showed general agreement on findings of increased lateral ventricular volume, decreased total as well as regional GM volumes, and increased basal ganglia volume.38–44 Later on, prospective longitudinal brain magnetic resonance imaging (MRI) studies of the NIMH COS population showed increasing ventricular volume and decreasing total cortical, frontal, medial temporal, and parietal GM volumes at 2- to 6-year follow-up39,45 during adolescent years. "
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    ABSTRACT: Childhood-onset schizophrenia (COS; defined as onset by age 12 years) is rare, difficult to diagnose, and represents a severe and chronic phenotype of the adult-onset illness. A study of childhood-onset psychoses has been ongoing at the National Institute of Mental Health (NIMH) since 1990, where children with COS and severe atypical psychoses (provisionally labeled "multidimensionally impaired" or MDI by the NIMH team) are studied prospectively along with all first-degree relatives. COS subjects have robust cortical gray matter (GM) loss during adolescence, which appears to be an exaggeration of the normal cortical GM developmental pattern and eventually mimics the pattern seen in adult-onset cases as the children become young adults. These cortical GM changes in COS are diagnostically specific and seemingly unrelated to the effects of medications. Furthermore, the cortical GM loss is also shared by healthy full siblings of COS probands suggesting a genetic influence on the abnormal brain development.
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