A facebook reader asks," Could you explain that in layman's terms?" (Dopamine transporter changes and stimulant medication use)
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FYI

A facebook reader asks," Could you explain that in layman's terms?" (Dopamine transporter changes and stimulant medication use)

I recently tweeted a link to an article in the American Journal of Psychiatry suggesting there are specific brain changes in individuals with ADHD who have history of stimulant medication use. 

The tweet bounced to my Facebook page where a reader (hi, Lindsey!) asked:

Okay David, I took a look at the article... I'm wondering if you could explain what was said in layman's terms?

Sure - quite simply:  It's an exciting time to be doing this work!  Now, a somewhat longer explanation follows...here we go:

Dopamine transporters (DAT) are proteins which terminate the action of dopamine at the synapse.  They basically "clean up" the synapse so it's ready for the next firing.  Stimulant medications work in one of two ways:
  • They either increase the dopamine in the intracellular fluid of vesicles in the presynaptic neuron (that's the bulbous thing in the image below).   That's chiefly the mechanism of action of meds like lisdexamfetamine, amphetamine salts preparations, and the brand name mentioned in the R.E.M. song "What's the Frequency, Kenneth?"
  • And/or they prevent reuptake of dopamine from the synapse (the area marked "synaptic cleft" in the illustration below) by binding to the dopamine transporters (DAT)
















The effect of either mechanism of action is to increase the availability of dopamine, which is the neurotransmitter associated with motivation and reward.

A question which often comes up at my ADHD workshops is this:  if an individual takes prescription stimulant medications, will the synapse adapt and change in response to this new level of dopamine?  This is a really good question, because we know that there are such changes (sometimes called "downregulatio") with some medication use.  But until I read this article in AJP (that's the one I tweeted), I'd not read anything to help me respond to this question as it pertains to stimulant meds.

So, what the authors of this article report is that brain imaging (PET and SPECT) of individuals with and without ADHD showed some interesting differences.  In a cluster of brain regions called the striatum, the ADHD brains had higher DAT density.  And the density appeared to be associated with history of stimulant medication use.  That is, subjects with history of stimulant use had higher DAT density than ADHD subjects without stimulant medication use.  

Now it is not entirely clear whether DAT density is desired or problematic, and it has not been easy to identify changes in DAT in the various disorders (parkinson's, schizophrenia, substance abuse) in which dopamine plays an important role.  But the relationship in this study between stimulant use and DAT density raises interesting questions.  As the authors point out, this study is correlational:  it tells us there is a relationship but doesn't tell us whether one thing caused the other thing.  

One possibility is that stimulant medication use does, in fact, change brain structure at the level dopamine transporter proteins.  Another possibility is that this study identifies an important way in which ADHD brains might be different from non-ADHD brains:  they may have this higher DAT density.  And it may be that, in this study, the ADHD subjects who had used meds were more symptomatic (and more impaired) than the ADHD subjects who had not used stimulants.

Lindsey (and anyone else who's still reading at this point) - there's good news and bad news here.  The bad news is that we'll have to wait for additional research to answer the questions raised by this study.  The good news is that those of us currently taking an interest in attention and executive functioning - and attempting to identify and treat adults and students with distractibility and organizational challenges - are at the scientific "front end" of all of this.  There's a lot we know about how to help these folks reach their highest potential, but sooo much more to learn.

It's an exciting time to be doing this work!




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