Tuesday, May 5, 2009

ADHD, IQ and Gene Combinations

How combinations of 2 "ADHD genes" increase the risk of verbal IQ deficiency and behavioral disorders:

We have spoken at length on the matter of genes and their effects on the disorder of ADHD. The vast majority of the numerous ADHD gene studies we have previously discussed have looked at these genes in an isolated manner. However, it begs the question as to what the implications are of having more than one "ADHD gene". For example, does having 2 genes of the "ADHD form" double the risk of having the disorder? Quadruple it? What about having 3 or more of the "at risk" genes? Do certain specific ADHD genes have a dominating influence in the likelihood of inheriting the disorder?

A recent publication came out in the past few days examining the inter-relationship between ADHD, genetics, IQ and behavioral symptoms. It is worth noting that the two genes implicated in the study and their association with ADHD are ones we have previously discussed, the Dopamine Receptor 4 gene, (DRD4) and the Dopamine Transporter 1 gene (DAT1).

ADHD gene #1: DRD4: This gene, called the DRD4 (short for dopamine Receptor gene 4) is located on human chromosome #11. In addition to its association with Attention Deficit Hyperactivity Disorder, this gene is also believed to be associated with schizophrenia, alcoholism and drug abuse, Parkinson's (namely a resistance to this disorder, associated with a specific form of the gene), mood disorders, and novelty-seeking behaviors (which have obvious implications to the impulsive nature of ADHD). Additionally, the proteins coded for by this specific genetic region appear to be major targets for the antipsychotic drug clozapine.

ADHD gene #2: DAT1: This gene, called DAT1 (short for Dopamine Transporter gene 1) is located on human chromosome #5 (in the p15.3 region of the chromosome to be specific, if you are not familiar with this terminology, this is simply a more specific location on the 5th human chromosome). This gene also goes by the name SLC6A3 or simply DAT (without the "1"). Like the DRD4 gene mentioned above, the DAT1 gene has also been implicated in ADHD as well as a number of other disorders. These include (but are not limited to): Tourette Syndrome, cigarette smoking (interestingly, this includes a form of the gene which apparently offers "genetic protection" against the risk of nicotine dependence), bipolar disorders, substance abuse and Tourette Syndrome.

**Blogger's note: The fact that so many psychological and behavioral disorders are also believed to be connected to genes associated with ADHD is simply not a matter of coincidence, especially in this blogger's personal opinion. The majority of the disorders listed above are frequently seen alongside ADHD as comorbid disorders. While no one can deny that environmental factors do play a critical role in the development of these disorders, it is worth repeating the fact that certain individuals, because of the forms of these two (as well as several other "ADHD genes") inherently have at least some degree of genetic predisposition to these inter-related disorders.

Childhood externalizing behaviors:

Childhood externalizing behaviors cover a wide spectrum of behavioral disorders. These include behaviors such as excessive aggression, antisocial behaviors towards peers or authorities, defiant behaviors (in excess of the typical range of expected age-dependent behavior range), excessive hyperactivity, conduct disorders, etc. These should not be confused with the more "internalizing" behaviors, such as anxiety and related disorders. With regards to ADHD subtypes, the externalizing behaviors such as conduct disorders are often more likely to be seen with the hyperactive-impulsive and combined ADHD subtypes, while the internalizing childhood behaviors such as anxiety are more frequently affiliated with the inattentive subtype of ADHD.

IQ: Although IQ is often thought of as one specific number which hovers around 100 for the majority of the population (i.e. 110, 97, etc.), it is actually comprised of multiple subcategories. Generally, the scores in each of these subcategories also generally centralize around 100 and most individuals scores show slight to moderate differences between the subcategory scores. However, in the case of most learning disabilities, this is not the case. Typically, children and adults with learning disabilities have average or above average scores in many of the IQ subtypes, but often have glaring deficits in one or more areas, in which the IQ for that particular area is significantly lower than the rest. In the case of this study relating IQ, externalizing behaviors and the DAT1 and DRD4 genes, the particular IQ subtype most in question is the verbal IQ.

The study found some interesting points with regards to IQ, externalizing behaviors, and the 2 "ADHD genes" (keep in mind that when we are talking about these genes, we are only talking about specific forms, or alleles, of these genes, which are seen only in a fraction of the population. For reference sake, the "at risk" forms of the two genes are referred to as the 7-repeat allele for the DRD4 gene and the 10-repeat allele for the DAT1 gene. Don't get caught up too much in the specifics, these "repeat" describe specific DNA patterns that are seen in these "at risk" forms of the DRD4 and DAT1 genes). The results can be summarized in the following points below:

  • For ADHD children who had only the "at risk" DRD4 (but not the DAT1) gene form, there was no significant increase in the likelihood of having a low IQ or behavioral disorders.

  • Likewise, for the children who only had the "at risk" DAT1 (but not the DRD4) gene form, there was no significant reduction in IQ or increased risk of behavioral disorders.

  • Additionally, the actual correlation between low IQ and increased risk of deviant behaviors (which is often seen in multiple other studies, especially with regards to the IQ and criminal behavior link), was not observed if the child only had one of the two "at risk gene forms" either for the DRD4 or DAT1 genes.

  • However, for ADHD children who had both the "at risk" forms of DRD4 and DAT1 (please note that this study investigated children who had inherited these gene forms from both parents, i.e. they had 2 copies of each "at risk" gene) showed a significant level of association between low verbal IQ scores and increased likelihood of having increased expression of externalizing behaviors.

  • It is also worth mentioning that the IQ/behavior connection was only seen in the verbal IQ subcategory and "externalizing" behavioral subcategory. In other words, other forms of IQ (such as more "performance" ones such as motor coordination and kinesthetic types of intelligence) and "internal" behavioral disorders (such as anxiety-related disorders), were apparently not factors affiliated with either of these gene forms.

These findings potentially highlight the complexities of disorders such as ADHD, behavioral disorders and personal characteristics such as genetics, and may also explain some of the incongruities between studies. For example, if one particular genetic study finds a specific form of a certain gene to be associated with ADHD, another one will typically find there to be no genetic linkage (even if the studies are conducted in the same manner with similar study numbers, subjects, and experimental methods).

This may be due to the fact that most of these psychological, behavioral, and functional connections are associated with multiple genes and do not pop out unless more than one "at risk" gene forms are in place. In other words, multi-gene analysis studies (although much more difficult to conduct and analyze) may be our best bet for finding the real genetic basis for ADHD occurrence and related behaviors. This may stress the fact that gene-gene interactions may be as powerful as gene-environment interactions for assessing the risk of an individual acquiring attentional and behavioral disorders such as ADHD.

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So, I don't really believe it may have success.

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