Variant Of Dopamine Receptor Gene Linked To ADHD

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Main Category: ADHD
Also Included In: Psychology / Psychiatry;  Neurology / Neuroscience;  Genetics
Article Date: 10 Aug 2007 - 0:00 PDT

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Scientists believe that a variant of the dopamine receptor gene may be linked to ADHD (attention-deficit/hyperactivity disorder) and with other thinner tissue in parts of the brain that deal with attention. You can read about this in hives of General Psychiatry (JAMA/Archives).

Evidence has shown that ADHD is one of the most inherited neuropsychiatric disorders, say the authors. Many genes have been detected as maybe linked to ADHD. One of which is a polymorphism of the dopamine D4 receptor gene (DRD4), called 7-repeat form.

The authors write "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."

Philip Shaw, M.D., Ph.D., of the National Institute of Mental Health, Bethesda, Md., and team compared 105 children who suffered from ADHD, average age 10.1, to 103 children who did not have ADHD. They used MRI (magnetic resonance imaging) and DNA tests. 64% of the ADHD children were followed up six years later.

The scientists found that those with the 7-repeat form of DRD4 tended to have thinner tissue in the right orbitofrontal/inferior prefrontal and posterior parietal cortex - parts of the brain that deal with attention. This was the case for both the children with ADHD and the controls.

They also found that similar areas were also generally thinner among the children with ADHD, compared to the controls.

The authors wrote "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 the 7-repeat allele, healthy 7-repeat allele carriers and finally by healthy non-carriers."

Later follow-up showed that the differences between the brain anatomy of those with and without the DRD4 7-repeat allele were more acute during early development and disappeared by the time the children were in their late teens. Those with ADHD who had the DRD4 7-repeat allele had better clinical outcomes and recouped thickness in their right parietal cortex - an indication previously associated with better outcomes, and that parallels ADHD's characteristic improvement with age.

The authors concluded that "Cross-sectional studies have found regional increases in cortical thickness to correlate with cognitive function, including enhanced verbal declarative and extinction memory, and with 'fluid' intelligence in older, healthy subjects. In children, gains in verbal knowledge are mirrored by change in the cortical thickness of speech areas. While our current study demonstrates changes in cortical thickness and symptoms occurring in tandem, a future goal is to refine further our appreciation of cortical thickness by examining the links between this neuroanatomical variable and putative cognitive endophenotypes (invisible but measurable components on a disease pathway) for ADHD, such as response inhibition and working memory."

"Polymorphisms of the Dopamine D4 Receptor, Clinical Outcome, and Cortical Structure in Attention-Deficit/Hyperactivity Disorder"
Philip Shaw, MD, PhD; Michele Gornick, BS; Jason Lerch, PhD; Anjene Addington, PhD; Jeffrey Seal, BS; Deanna Greenstein, PhD; Wendy Sharp, MSW; Alan Evans, PhD; Jay N. Giedd, MD; F. Xavier Castellanos, MD; Judith L. Rapoport, MD
Arch Gen Psychiatry. 2007;64:921-931.
Click here to see abstract online

Written by: Christian Nordqvist
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