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.

Treating ADHD with....Mirrors?

Using mirrors may help ADHD kids retain focus in school-related tasks:

One of the major goals of this blog is to examine as many different treatment methods as possible for ADHD, with the hopes of informing individuals with the disorder and parents and teachers of ADHD children to allow them to make the best possible decision for them and their child. This search has brought me to some interesting treatment methods, including the one described below. We will be examining the theory and potential effectiveness for the use of mirrors in treating ADHD. The majority of this information comes from a 1998 study done by Zentall, Hall and Lee, entitled Attentional Focus of Students with Hyperactivity During a Word-Search Task.

Please note: Psychology and behavioral modification strategies are not my personal forte, this blogger's strengths typically lie in the chemical, genetic and physiological aspects of ADHD and treatment of the disorder. Nevertheless, I was so intrigued by this paper, I have decided to give my best stab at reviewing the study and explaining the effects and overall practicality of its findings.

Some major highlights of the study are as follows:

  • Earlier studies suggest attempts to regulate ADHD behaviors using self-control methods often fail. This is likely due to a number of factors, such as the relative differences in ADHD children to be motivated by delayed rewards or gratification (although I personally have seen several cases to the contrary. At my school, we offer a special ski trip which must be earned by behavior, and a number of kids, including those with ADHD are able to modify their behavior to remarkable degrees to earn a trip five weeks away. Nevertheless, rewards of less magnitude, especially ones further down the road have often been largely ineffective, at least based on my personal experiences). However, physiological studies do suggest some sort of absence or difference in the intrinsic reward system and motivation in ADHD children.

  • Instead, ADHD children typically respond better to external stimuli, either good or bad. In other words, a child with ADHD will often show an improvement in response if he or she can see his or her behaviors or actions partly regulated from an outside source.

  • The use of mirrors is geared towards this externally-driven stimulus method, by allowing the ADHD child to observe or see themselves from a third-person perspective. They are essentially taking cues from an external source in lieu of self-regulating their behaviors. In other words, they may perceive reinforcements better from the "child in the mirror" than internal reinforcements from themselves.

  • The study even hints that children with ADHD may have a type of delay in the development of self-awareness. While this blogger's opinion is currently neutral on the validity of this assertion, the fact that neuro-developmental and cognitive delays are so prevalent in children diagnosed with ADHD, it is entirely possible that the rewiring and brain maturation processes responsible for developing a mature sense of "self" may also be behind the curve age-wise in ADHD children. If this is the case, then we would expect the mirror trick to lose effectiveness as the child ages and finally develops this sense of "self".

  • Boosting states of arousal, including through the use of emotional states has been shown to increase a child's attentional focus. Several theories for hyperactivity, such as those by Zentall, support this assertion, claiming that excessive activity (beyond the perceived age and gender-appropriate amounts) may be a way for the child to achieve these heightened levels of arousal necessary for the performance of cognitive tasks, including school work.

    If this is the case, attempting to merely calm this hyperactivity via behavioral or pharmaceutical treatment may, in essence, be detrimental to the ADHD child, as it robs him or her from achieving a state of arousal necessary to achieve the desired state of focus. This may even play a significant role as to why a number of children with ADHD are predominantly kinesthetic learners (as opposed to the more "passive" auditory of visual learning styles). **Please not that the previous two italicized statements are simply personal opinions and musings of the blogger at the moment, however, note the potential effects that medication may have on this mirror treatment at the bottom of this post.

  • Numerous adult studies confirm what may seem intrinsically obvious (but relevant to our current discussion): the presence of external "observers", including an audience, cameras, or even mirrors, significantly increase attentional focus (and subsequent self-control) in the individual being observed. However, limited study has been done on this phenomena in children. Nevertheless, it appears to make inherent sense that a child who is under the "watchful eye" of someone (even if that someone is their personal reflection in a mirror), may exhibit higher levels of attentional behaviors.

  • The study highlights a work by Carver and Scheier called Attention and Self-regulation: A control therapy approach to regulating human behavior (1981) in which the use of mirrors increased the effectiveness of academic-related methods such as copying letters (which has practical uses in note-taking), persistence in problem-solving tasks (which has direct uses in academic areas such as math and science), and the extent of response generation exercises (which have direct implications in brainstorming activities and subjects such as creative writing assignments). Thus, the possible benefits of mirror usage are far reaching for the ADHD child.

  • The experiment comprised of giving both ADHD and non-ADHD children a word puzzle (which was unsolvable, as a handful of the words the child was instructed to find did not exist in the puzzle. The children were notified of this fact, but were not notified on the number of words that were missing. When the child believe that he/she had found all of the words in the word search, he/she notified the experimenter and stopped the task. In other words, this study was tailored to track attention and persistence for a particular task). Both the ADHD and non-ADHD children worked on the puzzle in either one of two conditions: in front of a mirror (approximately 2 feet by 3 feet in size, on a wall in front of the table where the child was performing the word-finding task), or without a mirror.

  • ADHD children showed noticeable improvements when working in front of the mirrors (i.e. finding more words). In contrast, the non-ADHD children who worked in front of mirrors were either unaffected or showed decreased levels of performance on the word finding task.

  • Additionally, the study examined when a child looked up at the mirror or ignored it. It appears that looking up at the mirror improved the performance of the ADHD group but either did not effect or decreased the effectiveness of the non-ADHD'ers. Therefore perception of being "watched" appeared to improve the focus of the ADHD group, but may have overwhelmed the non-ADHD group. Interestingly, several of the ADHD children who were placed in front of the mirror but did not look up at it had significantly lower levels of performance than those that did look at the mirror. The study suggested that these children may have already developed strong "internalizing" behaviors of self-focus, such as vivid daydreaming.

  • These findings may be interesting, due to a number of reasons. In previous posts, we have recently alluded to the fact that a particular region of the brain called the basal ganglia, which essentially governs how fast an individual "idles" (i.e. a "type A personality" such as a workaholic, obsessive-compulsive individual typically has higher basal ganglia activity, while individuals with ADHD often have lower levels of activity in this brain region).

    The basal ganglia activity is also increased when there's a sudden change in external stimuli, especially when the sudden change is perceived as dangerous or harmful. Under conditions such as these, the basal ganglia can become so overwhelmed, that the individual temporarily "freezes". Under a highly unpredictable or stressful situation (such as witnessing a traffic accident, crime or heart attack), ADHD individuals are often the first ones to react to the situation. It is believed that this is due to the fact that they have lower baseline levels of activity than their non-ADHD counterparts, and therefore have more capacity to accommodate to this new-found stress before either freezing up or becoming overwhelmed.

    Tying this in with our mirror discussion, the difference in response to the feeling of being "observed" by the mirror, may be due, at least in part, to heightened basal ganglia activity, which may begin to overwhelm the non-ADHD group but help optimized the basal ganglia activity in the ADHD group of children. This assertion remains the blogger's personal hypothesis, and was not mentioned in the study, however, I believe that there is sufficient groundwork to warrant a mention of this possibility.

  • Finally, there was a small side-study involving children who did not fit into either the ADHD or non-ADHD group (often due to medication). It appears that for the medicated group, the presence of the mirror was actually detrimental to performing the word finding task at hand. Therefore, the combination of mirror and medication for ADHD, especially in the academic or classroom setting, needs to be further investigated.