The DRD4 Gene and Inattentive ADHD

Geneticists have been looking at the genes that are thought to play a role in ADHD and have discovered about 20 genes that seem to be associated with the diagnosis. Some researcher have proposed that ADHD arises from the combination of specific genes and that, in the future, subtypes will be categorized based on the combinations of genes that are causing the most problematic symptoms in a particular person.

Many studies have concluded that the DRD4-7 repeat allele, a dopamine neuro-transmitter regulating gene, is associated with ADHD. A recent study did a meta-analysis of all the ADHD genetics studies and discovered something interesting. The more Inattentive ADHD (ADHD-PI) cases in a study, the less the association of DRD4-7 and ADHD.

When there are fewer people with Inattentive ADHD in the study, the association of the gene with ADHD is greater. The implication here is that the DRD4-7 gene is related to the Combined type of ADHD but not to the Inattentive subtype of ADHD.  This particular dopamine transporter regulator gene does not seem to be one of the problems in people with Inattentive ADHD

In order for Inattentive ADHD to be classified as a different disorder from the Combined type and Hyperactive/Impulsive type of ADHD in the manual that psychiatrist use to diagnose ADHD (the DSM); there will have to be compelling evidence that the process as work in these subtypes is different. The DSM-IV is currently being revised and the question of whether Inattentive ADHD needs to be a separate disorder is being debated.

There are some psychologists who argue that all the ADHD subtypes are more alike than different. Behavioral studies have shown that on tests of executive function, the subtypes are similar but personality test and temperament studies have shown great differences in the subtypes.

Finding clear genetic differences in the subtypes would be a compelling reason to see the Inattentive subtypes as a different developmental problem. The combination of genes at play in inattentive ADHD will likely be different from the genes at play in ADHD with Oppositional Defiance Disorder, Hyperactive/Impulsive ADHD, ADHD with Major Depression, Combined type ADHD, ADHD with Sluggish Cognitive Tempo, etc.  Perhaps we need DSM categories for all these subtypes as well.

The expeditious diagnosis of the different subtypes of ADHD will allow for better, and more specialized treatment. The current ability to recognize and rapidly treat people with ADHD-PI is problematic and Inattentive ADHD is the most neglected, most 'silent' and most undiagnosed subtype of ADHD.

Research is extremely important but the amount of research dollars targeted for the study of Inattentive ADHD is currently non-existent. Research dollars are unlikely to increase unless Inattentive ADHD is separated from the other subtypes of ADHD. The discovery of a genetic profile that characterizes the genes involved in this subtype may be our best hope for being placed in a DSM-V category all our own.

Am J Med Genet B Neuropsychiatr Genet. 2010 Apr 28. [Epub ahead of print]
Meta-analysis of the heterogeneity in association of DRD4 7-repeat allele and AD/HD: Stronger association with AD/HD combined type.

Smith TF.

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