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Gene predicts better outcome as cortex normalizes in teens with ADHD

Brain areas that control attention were thinnest in children with attention deficit hyperactivity disorder (ADHD) who carried a particular version of a gene in a study by the National Institutes of Healths (NIH) National Institute of Mental Health (NIMH). However, the areas, on the right side of the brains outer mantle, or cortex, normalized in thickness during the teen years in these children, coinciding with clinical improvement. Although this particular gene version increased risk for ADHD, it also predicted better clinical outcomes and higher IQ than two other common versions of the same gene in youth with ADHD.

Since this gene version had similar structural effects in healthy children as in children with the disorder, our findings suggest that ADHD is at the far end of a continuum of normal traits, said Philip Shaw, M.D., NIMH Child Psychiatry Branch, who led the research. ADHD likely stems from interactions between several such genes and non-genetic factors.

Shaw, Judith Rapoport M.D., and colleagues report on their magnetic resonance imaging (MRI) study in the August 2007 Archives of General Psychiatry.

This study provides us with a first glimpse of how variation in a specific gene influences both brain development and clinical prognosis in ADHD, said NIMH Director Thomas R. Insel, M.D.

When the NIMH researchers first reported last year that normalization of right cortex thickening was associated with better clinical outcomes in ADHD, there were few hints of a genetic connection. Yet evidence from several previous studies led them to suspect involvement of an ADHD-implicated version of a gene that codes for a receptor protein that binds to the brain chemical messenger dopamine.

This version of the dopamine D4 receptor gene, called the 7-repeat variant, accounts for about 30 percent of the genetic risk for ADHD, making it by far the strongest candidate gene implicated in the disorder. Its called the 7-rep
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Contact: Jules Asher
NIMHpress@nih.gov
301-443-4536
NIH/National Institute of Mental Health
6-Aug-2007


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