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Gene variant is associated with brain anatomy, clinical course of ADHD

A variant of the dopamine receptor gene may be associated with attention-deficit/hyperactivity disorder (ADHD) and with thinner tissue in areas of the brain that handle attention, but also appears associated with better clinical outcomes among individuals with the disorder, according to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

ADHD is among the most heritable of neuropsychiatric disorders, according to background information in the article. Several genes have been identified as possibly associated with the condition. One of the most frequently cited is a polymorphism or different type of the dopamine D4 receptor gene (DRD4) known as the 7-repeat form. Previous studies have suggested that carriers of the risk allele [alternate form of a gene] may also have a unique neuropsychological, clinical and pharmacological profile, although there remains considerable debate over the exact nature of this phenotype [characteristic], the authors write.

Philip Shaw, M.D., Ph.D., of the National Institute of Mental Health, Bethesda, Md., and colleagues compared 105 children with ADHD (average age 10.1) to 103 healthy controls, using both magnetic resonance imaging (MRI) and DNA testing. Sixty-seven (64 percent) of the children with ADHD also had a follow-up clinical evaluation an average of six years later.

Among all participants, both with and without ADHD, having the 7-repeat form of DRD4 was associated with thinner tissue in areas of the brain known to control attentionthe right orbitofrontal/inferior prefrontal and posterior parietal cortex. Similar regions were also generally thinner in participants with ADHD than those without. As a result of the overlapping main effects of genotype and diagnosis, there was a stepwise increment in cortical thickness in these regions, with subjects with ADHD with the DRD4 7-repeat allele having the thinnest cortex, followed by subjects with ADHD lacking
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Contact: Jules Asher
301-443-4536
JAMA and Archives Journals
6-Aug-2007


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