ADHD Genes
ADHD Gene #3: Dopamine Transporter Gene (DAT, SLC6A3), Human Chromosome #5
There have been a number of recent postings on genes thought to be connected with ADHD. Previous ones discussed include the ADHD form of the Dopamine D4 receptor Gene (DRD4), the ADHD form of the Dopamine D5 Receptor Gene (DRD5), and, to a lesser degree, the DRD2 ADHD gene. However, one of the most intriguing ADHD genes is a gene called the Dopamine Transporter Gene, abbreviated as DAT. An ADHD form (also called allele), of this gene, which is located on the 5th chromosome in humans, has been tabbed. The ADHD gene DAT has been discussed in another recent post, where it has been tied to a mutated form of a protein called the dopamine transporter protein that "shuttles" an important brain chemical, called dopamine, in and out of neuron cells. While the regular form of this protein functions, normally, the mutated form causes it to run in the opposite direction at high speed, significantly changing the distribution of the dopamine chemical throughout the brain. This balance can result in extreme ADHD symptoms, and has also been seen in bipolar individuals.
Statistically speaking, there is a weaker correlation between the above form of the gene and ADHD behavior than the previous two genes. Nevertheless, this gene serves as an important target for stimulant medications (such as Ritalin) for both rats and humans. A number of studies have been done on an analogous gene in mice has shown that altering this gene function resulted in a noticeable increase in hyperactivity and decrease in behavioral inhibition and control.
Remember, two ADHD genes mentioned in previous posts, the DRD4 ADHD gene, and the DRD5 ADHD gene are both thought to be more affiliated with the inattentive component of ADHD. In contrast, individuals with the DAT gene mentioned in this posting, above are more prone to hyperactivity and behavioral inhibition problems associated with ADHD. We will soon discuss the various components and subtypes of ADD and ADHD in later posts, but for now, please keep in mind that a number of different genes may be at work within and ADHD individual.
There is still a fair amount of research to be done on this gene, but for now, we can cautiously assume that there is a correlation between forms of this DAT gene, located on the 5th human chromosome, and ADHD.
ADHD genes
Friday, September 5, 2008
Thursday, September 4, 2008
ADHD Genes: DRD2
ADHD Genes
Dopamine D2 Receptor Gene (DRD2): TaqI A1 allele, chromosome 11 q22-q23
Based on the same overview study (Faraone and Khan, J Clin Psychiatry 2006; 67 (sup 8), 13-20) as the other seven ADHD genes, there has been some association between a gene on the 11th human chromosome and likelihood of developing ADHD. The form (also called "allele") of this gene associated with ADHD is called the Dopamine D2 Receptor Gene (DRD2) TaqI A1 allele. The findings from the main study on this gene were not replicated, but one study found that individuals possessing the above form of the gene showed an increased likelihood of having ADHD.
Interestingly, this form of the gene is also associated with at least two other disorders that are known to frequently occur alongside of ADD and ADHD. Individuals carrying the TaqI A1 form of the gene also showed a significant increased likelihood of having Tourette’s disorder. Tourette’s is a relatively common comorbid (meaning “occurring along with” or “occurring along side of”) disorder of ADD or ADHD. For those not familiar with the disorder, Tourette’s is a disorder that can result in involuntary behaviors such as “tics”, involuntary twitching, and, in some cases, outbursts of inappropriate speech and profanity. Along with ADD and ADHD, Tourette’s is also seen alongside of other disorders such as Obsessive Compulsive Disorder (OCD) at relatively high frequencies.
In addition to Tourette’s, there is evidence has linked the TaqI A1 form of DRD2 to Parkinson’s Disease (Grevle, et. al, Allelic association between the DRD2 TaqI A Polymorphism and Parkinson’s disease, Movement Disorders 2001, Volume 15, Issue 6, 1070-74). Several findings have pegged ADD and ADHD individuals to having a higher likelihood of developing Parkinson’s later in life. There is a distinct possibility that this form of the gene may be a significant underlying factor between the two disorders.
ADHD genes
Dopamine D2 Receptor Gene (DRD2): TaqI A1 allele, chromosome 11 q22-q23
Based on the same overview study (Faraone and Khan, J Clin Psychiatry 2006; 67 (sup 8), 13-20) as the other seven ADHD genes, there has been some association between a gene on the 11th human chromosome and likelihood of developing ADHD. The form (also called "allele") of this gene associated with ADHD is called the Dopamine D2 Receptor Gene (DRD2) TaqI A1 allele. The findings from the main study on this gene were not replicated, but one study found that individuals possessing the above form of the gene showed an increased likelihood of having ADHD.
Interestingly, this form of the gene is also associated with at least two other disorders that are known to frequently occur alongside of ADD and ADHD. Individuals carrying the TaqI A1 form of the gene also showed a significant increased likelihood of having Tourette’s disorder. Tourette’s is a relatively common comorbid (meaning “occurring along with” or “occurring along side of”) disorder of ADD or ADHD. For those not familiar with the disorder, Tourette’s is a disorder that can result in involuntary behaviors such as “tics”, involuntary twitching, and, in some cases, outbursts of inappropriate speech and profanity. Along with ADD and ADHD, Tourette’s is also seen alongside of other disorders such as Obsessive Compulsive Disorder (OCD) at relatively high frequencies.
In addition to Tourette’s, there is evidence has linked the TaqI A1 form of DRD2 to Parkinson’s Disease (Grevle, et. al, Allelic association between the DRD2 TaqI A Polymorphism and Parkinson’s disease, Movement Disorders 2001, Volume 15, Issue 6, 1070-74). Several findings have pegged ADD and ADHD individuals to having a higher likelihood of developing Parkinson’s later in life. There is a distinct possibility that this form of the gene may be a significant underlying factor between the two disorders.
ADHD genes
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ADHD genes
ADHD Gene #2 DRD5
In another post, I described that there were at least 7 well-known genes that are associated with ADHD. In fact, since the publication of this paper, additional ones have been identified. Within the past couple of months, another key study on ADHD genes has been discussed.
ADHD Gene #2: Dopamine D5 receptor gene (DRD5): CA repeat, 148 bp
In a previous posting, we discussed an ADHD gene found on the 11th chromosome in humans, called the DRD4. One of the forms (also called alleles) of this gene was associated with the disorder of ADHD, in particular the inattentive component of ADHD.
A second ADHD gene called the "Dopamine D5 receptor gene", or DRD5, is also thought to have strong familial ties to the disorder. Like the DRD4 gene listed above, DRD5 has multiple forms (or alleles). This is located on chromosome number 4 for humans. The "ADHD allele" which is referred to as "CA repeat, 148 bp" (this notation is commonly used by geneticists and refers to the length and DNA makeup of the "ADHD form" of the gene, the exact details aren't entirely important) is slightly greater in length than the non-ADHD form(s). While different studies on this allele have produced different results, it appears that this form of the gene, like the form of the DRD4 ADHD gene listed above, is tied more towards the inattentive than hyperactive component of ADHD. Statistically, however, there appears to be a weaker association between the DRD5 gene and ADHD than the DRD4 gene.
ADHD Gene #2: Dopamine D5 receptor gene (DRD5): CA repeat, 148 bp
In a previous posting, we discussed an ADHD gene found on the 11th chromosome in humans, called the DRD4. One of the forms (also called alleles) of this gene was associated with the disorder of ADHD, in particular the inattentive component of ADHD.
A second ADHD gene called the "Dopamine D5 receptor gene", or DRD5, is also thought to have strong familial ties to the disorder. Like the DRD4 gene listed above, DRD5 has multiple forms (or alleles). This is located on chromosome number 4 for humans. The "ADHD allele" which is referred to as "CA repeat, 148 bp" (this notation is commonly used by geneticists and refers to the length and DNA makeup of the "ADHD form" of the gene, the exact details aren't entirely important) is slightly greater in length than the non-ADHD form(s). While different studies on this allele have produced different results, it appears that this form of the gene, like the form of the DRD4 ADHD gene listed above, is tied more towards the inattentive than hyperactive component of ADHD. Statistically, however, there appears to be a weaker association between the DRD5 gene and ADHD than the DRD4 gene.
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ADHD genes
Sunday, August 31, 2008
ADHD Protein on "Speed"?
ADHD treatment options and resources
New mutation found on an "ADHD gene"
I was going to post some more information on the second ADHD gene on the list, but I recently came across a very interesting article on genetic mutations and ADHD, which can be found here.
The original study was recently published in the July 9, 2008 issue of the Journal of Neuroscience by the groups of Aurelio Galli and Randy Blakely. Several subtypes of ADHD are thought to be caused by an imbalance in the levels of of dopamine, an extremely important chemical found in the brain and nervous system that regulates proper neural functioning. There is an ideal balance between the amount of dopamine that is stored in neurons and the amount that is present in the "gaps" between different neuron cells.
It is here, that a critical protein comes into play. A special protein called the Dopamine Transporter (DAT) protein acts as a type of "shuttle" or "ferry" that helps balance dopamine levels inside and outside of the neuronal cells by aiding in the transport of dopamine in and out of the cells. This protein is actually "coded" for by the third ADHD gene on the list of a recent post.
It is strongly suggested that individuals diagnosed with ADHD have lower than normal levels of this dopamine in the gaps between neuron cells. As a result, a number of ADHD drugs focus on this DAT "shuttle" in an attempt to manipulate its ability to clear dopamine to the cells (think of the analogy of building a dam to trap and collect a stream of water in a region where it is scarce). In essence, this helps "fix" the problem of the low dopamine levels in this space, which is associated with ADHD.
Here is where it gets interesting. A rare mutation causes this shuttling DAT protein to essentially run in reverse at high speeds. Instead of "mopping up" dopamine and carrying it into the surrounding neurons, this mutated form of the protein essentially "squeezes" dopamine out of the cells and into the open space. This mutant protein actually functions in a very similar way to amphetamines such as the popular ADHD drug Adderall (which, incidentally, is chemically similar and has a similar, but much more benign, mode of function as the drug "Speed"). Here lies the paradox-- we would think that this mutated transporter protein, which behaves like a drug used to treat ADHD would be beneficial for ADHD individuals. However, the opposite is true. Individuals which possessed this mutation exhibited noticeable ADHD behavior.
Further complicating the issue is the fact that Adderall, while behaving much like this mutation by making the DAT shuttle run backwards, actually blocks some of the key negative effects of the mutation. Think of it as an almost homeopathic-like solution, treating "like" with "like". Ritalin, another ADHD medication which, in turn, can counteract the ability of Adderall to make this shuttle protein move backwards. For sake of brevity, I will save this discussion for a later post in the near future!
Finally, it is also interesting to note that this DAT mutation is very rare. Outside of this study, only one other case had been seen by the researchers, that of a bipolar girl. I found this interesting because it is sometimes difficult to distinguish differences between ADHD and pediatric bipolar disorders. The overlap of this mutation between the two disorders may lend some credence to underlying genetic mechanisms that both disorders seem to share.
ADHD treatment options and resources
New mutation found on an "ADHD gene"
I was going to post some more information on the second ADHD gene on the list, but I recently came across a very interesting article on genetic mutations and ADHD, which can be found here.
The original study was recently published in the July 9, 2008 issue of the Journal of Neuroscience by the groups of Aurelio Galli and Randy Blakely. Several subtypes of ADHD are thought to be caused by an imbalance in the levels of of dopamine, an extremely important chemical found in the brain and nervous system that regulates proper neural functioning. There is an ideal balance between the amount of dopamine that is stored in neurons and the amount that is present in the "gaps" between different neuron cells.
It is here, that a critical protein comes into play. A special protein called the Dopamine Transporter (DAT) protein acts as a type of "shuttle" or "ferry" that helps balance dopamine levels inside and outside of the neuronal cells by aiding in the transport of dopamine in and out of the cells. This protein is actually "coded" for by the third ADHD gene on the list of a recent post.
It is strongly suggested that individuals diagnosed with ADHD have lower than normal levels of this dopamine in the gaps between neuron cells. As a result, a number of ADHD drugs focus on this DAT "shuttle" in an attempt to manipulate its ability to clear dopamine to the cells (think of the analogy of building a dam to trap and collect a stream of water in a region where it is scarce). In essence, this helps "fix" the problem of the low dopamine levels in this space, which is associated with ADHD.
Here is where it gets interesting. A rare mutation causes this shuttling DAT protein to essentially run in reverse at high speeds. Instead of "mopping up" dopamine and carrying it into the surrounding neurons, this mutated form of the protein essentially "squeezes" dopamine out of the cells and into the open space. This mutant protein actually functions in a very similar way to amphetamines such as the popular ADHD drug Adderall (which, incidentally, is chemically similar and has a similar, but much more benign, mode of function as the drug "Speed"). Here lies the paradox-- we would think that this mutated transporter protein, which behaves like a drug used to treat ADHD would be beneficial for ADHD individuals. However, the opposite is true. Individuals which possessed this mutation exhibited noticeable ADHD behavior.
Further complicating the issue is the fact that Adderall, while behaving much like this mutation by making the DAT shuttle run backwards, actually blocks some of the key negative effects of the mutation. Think of it as an almost homeopathic-like solution, treating "like" with "like". Ritalin, another ADHD medication which, in turn, can counteract the ability of Adderall to make this shuttle protein move backwards. For sake of brevity, I will save this discussion for a later post in the near future!
Finally, it is also interesting to note that this DAT mutation is very rare. Outside of this study, only one other case had been seen by the researchers, that of a bipolar girl. I found this interesting because it is sometimes difficult to distinguish differences between ADHD and pediatric bipolar disorders. The overlap of this mutation between the two disorders may lend some credence to underlying genetic mechanisms that both disorders seem to share.
ADHD treatment options and resources
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ADHD genes,
DAT,
Dopamine Transporters
ADHD gene #1 (DRD4)
The ADHD genes
ADHD treatment options
On my last post on ADHD treatment options I listed 7 different genes that have been found to be affiliated with ADHD. We will be focusing on the first listed ADHD gene in this post, the Dopamine D4 receptor gene (DRD4).
ADHD Gene #1: Dopamine D4 receptor gene (DRD4): exon III VNTR, 7-repeat
* A quick note: The"exon III VNTR, 7-repeat" bit listed above is a type of nomenclature used by geneticists to describe where on the gene the "ADHD allele" is found. Since genes can be fairly long (the "average" gene for humans is thought to be over 10,000 blocks of DNA strung together), this nomenclature is used to pinpoint both the location and what type of DNA the "ADHD form" of this gene contains. Genetic screeners will look to see if this form is present to assess your "genetic risk" for ADHD. For those of you who are interested or are familiar with genetics, I will include this information for these 7 ADHD genes, otherwise, feel free to ignore this extra info!
This gene is located on the 11th chromosome of the human genome. It is perhaps the gene most commonly affiliated with ADHD, and some studies suggest that the "ADHD allele" mentioned above is tied to nearly doubling the likelihood of an individual having ADHD. Based on research up to this point, the DRD4 gene has, potentially, the strongest correlation to ADHD for the aforementioned ADHD genes. This gene is highly associated with the frontal region of the brain (frontal subcortex), and is more affiliated with the inattentive component of ADHD than the hyperactive one, which suggests that this gene may be more tied to ADD than most of the other 6 ADHD genes listed previously.
ADHD genes and treatments
ADHD treatment options
On my last post on ADHD treatment options I listed 7 different genes that have been found to be affiliated with ADHD. We will be focusing on the first listed ADHD gene in this post, the Dopamine D4 receptor gene (DRD4).
ADHD Gene #1: Dopamine D4 receptor gene (DRD4): exon III VNTR, 7-repeat
* A quick note: The"exon III VNTR, 7-repeat" bit listed above is a type of nomenclature used by geneticists to describe where on the gene the "ADHD allele" is found. Since genes can be fairly long (the "average" gene for humans is thought to be over 10,000 blocks of DNA strung together), this nomenclature is used to pinpoint both the location and what type of DNA the "ADHD form" of this gene contains. Genetic screeners will look to see if this form is present to assess your "genetic risk" for ADHD. For those of you who are interested or are familiar with genetics, I will include this information for these 7 ADHD genes, otherwise, feel free to ignore this extra info!
This gene is located on the 11th chromosome of the human genome. It is perhaps the gene most commonly affiliated with ADHD, and some studies suggest that the "ADHD allele" mentioned above is tied to nearly doubling the likelihood of an individual having ADHD. Based on research up to this point, the DRD4 gene has, potentially, the strongest correlation to ADHD for the aforementioned ADHD genes. This gene is highly associated with the frontal region of the brain (frontal subcortex), and is more affiliated with the inattentive component of ADHD than the hyperactive one, which suggests that this gene may be more tied to ADD than most of the other 6 ADHD genes listed previously.
ADHD genes and treatments
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ADHD genes
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