ADHD gene #5: Serotonin transporter gene (5-HTT)

ADHD Genes

ADHD Gene #5: Serotonin Transporter Gene (5-HTT, also referred to as "SLC6A4"): 5-HTTLPR long allele, location 17q11.1-12

This is the fifth gene that is being discussed on our list of ADHD genes. If you are not familiar with some of the terms in this post, here is a section on background information as it pertains to our study on ADHD genes. For a list of the other ADHD genes, please click here. The Serotonin Transporter Gene is found on human chromosome #17 (the q11.1-12 refers to a more specific region on the chromosome, and is not important for the time being). As mentioned in previous posts, genes come in different forms or alleles. One of the forms, or alleles of the Serotonin Transporter (5-HTT) gene has been associated with an increased risk of developing ADHD.

It is important to note that the terms Serotonin Transporter Gene, 5-HTT, and SLC6A4 all refer to the gene as a whole. The term "5-HTTLPR" refers to a specific section or part of the gene that can vary from individual to individual. For more background information on how genes are structured, please click here.

When the results of several family studies was pooled statistically, individuals with the "long" allele of the gene ("long" refers a form of the gene that has slightly longer DNA sequence than the shorter form of the gene), had an increased likelihood of developing ADHD than those with the "short" allele of the gene. Nevertheless, there is still some evidence that the "short" form may be tied to a higher incidence of ADHD as well (however, the trend in evidence typically favors the "long" allele).

Based on three different studies, there is some preliminary evidence suggesting that this "ADHD gene" (5-HTTLPR long allele), may be linked to autism as well, but a number of more recent studies have failed to support this claim. Nevertheless, it is known that individuals with certain forms of ADHD may possess higher levels of the neurochemical serotonin, which is also typically seen at higher levels in autistic individuals. Keep in mind that the gene of discussion in this post, 5-HTTLPR, is responsible for transporting serotonin into cells, with the "long form" (the "ADHD form"), transporting more serotonin than the "short" or "non-ADHD" form.

Based on how the most recent classifications, definitions, and diagnoses of mental disorders are done, individuals that fall anywhere on the autistic spectrum cannot be labeled as "ADHD" or vice versa (i.e., an individual may be diagnosed as being one or the other, but not both). However, a number of individuals with ADHD exhibit a number of symptoms that overlap with autism as well as vice versa. Of potential interest, our gene of topic, 5-HTTLPR, is responsible for shuttling serotonin into immune cells called lymphoblasts. Lymphoblasts are essentially an early, immature form of lymphocytes, which play a major role in an immune reaction such as an invading pathogen or an allergic response. The "long form" or "ADHD form" of this 5-HTTLPR gene shuttles more serotonin into the lymphoblast immune cells than does the short, "non-ADHD" form.

Higher levels of serotonin in these types of immune cells have been tied to an increase in migraine headaches, something that is also seen at higher levels in ADHD individuals. However, at the time, the cause is thought to be due more to an improper serotonin breakdown and disposal in these immune cells than transport mediated by the 5-HTTLPR gene. Nevertheless, it is an observation of potential interest.

Serotonin transporters, such as 5-HTTLPR, are also thought to play a role in seasonal affective disorders and depression. Higher activity levels of serotonin transporter proteins are seen during the fall and winter months (when depression is typically higher) than in the spring and summer. Although this 5-HTTLPR is likely not the primary culprit, the "ADHD form" of this gene does result in an environment similar to the "winter blues". This is due to the fact that the longer "ADHD form" of the gene transports more serotonin into cells and away from the space in between the cells. The net result is lower levels of free serotonin, which is typically seen in patients suffering from depression. Not surprisingly, depression is seen in much higher levels in several types of ADHD when compared to the general population.

One caveat here: some of the comparisons here are meant to simply report on a potential genetic overlap among ADHD and other disorders or diseases (migraines, autism, depression, etc.). At this point, there is not enough information to adequately confirm that the "ADHD version" of the Serotonin Transporter gene being discussed in this post is the primary cause of some of these other disorders. However, keep in mind that some of the underlying mechanisms of action are very similar and should suggest further investigation.

ADHD genes