Tuesday, January 11, 2011

Serotonin, Dopamine, and Stuttering

As in the previous post, which raised the possibility that viruses cause stuttering, this post again addresses the question as to what might be the root cause of excessive dopaminergic activity.

Reiterating the discussion in the post entitled "Antidepressants May Affect Stuttering," SSRIs inhibit the reuptake of serotonin by presynaptic neurons permitting greater concentrations of serotonin in the synapses. Excessive serotonin concentrations may highjack dopamine active transporters (DATs) prohibiting them from doing their job of dopamine reuptake. Consequently, synaptical concentrations of dopamine may be higher, leading to disfluency.

Now consider the possibility that some stutterers might have excessive levels of naturally occurring synaptical serotonin (i.e., independent of whether or not they take antidepressants). This may be the result of a low density of SERTs to reuptake serotonin or of the brain's overactive production of serotonin. At any rate, such a situation might lead to the highjacking of DATs resulting in less reuptake of dopamine, greater concentrations of dopamine, and greater disfluency. If this were the case, we might consider selective serotonin reuptake enhancers (SSREs) to reduce the levels of serotonin.

Independent of whether or not they take antidepressants, some individuals may have lower densities of DATs in the brain impairing its ability to reuptake dopamine, again leading to higher concentrations of dopamine and, hence, adversely affecting fluency. So we might consider the possibility of a class of drugs which we could call dopamine reuptake enhancers (DREs) that would reduce the levels of dopamine in the synapses by making the DATs more efficient with respect to dopamine reuptake.

Are there drugs that are reuptake enhancers?  With respect to the reuptake of dopamine, I am unaware of the existence of any such drugs. The only known drug that enhances the reuptake of serotonin is tianeptine. Tiapentine has low affinity for SERTs, so its effect on serotonin reuptake appears to be indirect. Newer research seems to indicate that tiapentine acts through some downstream mechanism that is not yet fully understood.

What the discussion above illustrates is that the relationships among neurotransmitters and their effects on the brain are very complex. There are interrelationships among the various neurotransmitters and these connections are currently not fully understood by the research community. Given the relationships among the dopaminergic, GABAergic, and serotonergic systems we have thus far seen, the obvious explanation of excessive dopamine as the root cause of disfluency may be overly simplistic.

Moreover, stutterers may fall into various subgroups, for example, characterized by excessive serotonin production, low SERT densities, insufficient DAT activity, other inadequacies of the dopaminergic or GABAergic systems, etc. And the appropriate therapeutic drug treatments to get at the root source for these different subgroups may not be the same.

In future posts, we will further discuss relationships between the serotonergenic and dopaminergic systems

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