Hyperserotonemia and Autism
Charlie has taken Zoloft—a selective serotonin reuptake inhibitor (SSRI), which works by inhibiting the uptake of serotonin, and thereby allows for more serotonin to be available to be taken up by other nerves—-for some years. He was prescribed it by his pediatric neurologist for anxiety that we linked to his head-banging and aggressive outbursts. Charlie is on a very low dose; an attempt to take him off the Zoloft led to immediate reports of increased nervousness and obsessiveness from his teachers. So I was curious about a recently reported study about “hyperserotonemia”—elevated levels of serotonin in the blood—in children with autism, from researchers at Vanderbilt University. From a press release:
[Researchers report that] a well-known protein found in blood platelets, integrin beta3, physically associates with and regulates the serotonin transporter (SERT), a protein that controls serotonin availability.
……. Serotonin has long been suspected to play a role in autism since elevated blood serotonin and genetic variations in the SERT have been linked to autism.
Alterations in brain serotonin have also been associated with anxiety, depression and alcoholism; antidepressants that block SERT (known as SSRIs, or selective serotonin reuptake inhibitors) block SERT’s ability to sweep synapses clean of serotonin.
Working in the lab of Randy Blakely, Ph.D., [Ana] Carneiro [Ph.D.] was searching for proteins that interact with SERT that might contribute to disorders where serotonin signaling is altered.
“Levels of SERT in the brain are actually quite low, so we decided to see what progress we could make with peripheral cells that have much higher quantities,” said Blakely, the Allan D. Bass Professor of Pharmacology and director of the Vanderbilt Center for Molecular Neuroscience. “This took us to platelets.”
In platelets, SERTs accumulate serotonin produced in the gut. SSRIs or genetic deletion of SERT in animals prevents serotonin uptake in the platelet.
“Prior research had fingered the integrin beta3 gene as a determinant of blood serotonin levels and, independently, as a risk factor for autism,” Blakely said.
In the current study, Carneiro identified a large set of proteins that “stick” to SERT, presuming they might control SERT activity. One of these turned out to be integrin beta3.
Once they confirmed a physical relationship between the two proteins, Blakely’s team investigated whether the interaction can change SERT activity. They found that cells lacking integrin beta3 exhibit reduced serotonin uptake and that integrin beta3 activation or a human integrin beta3 mutation greatly enhances serotonin uptake.
Researchers note that they don’t think it is the platelet itself that contributes to autism, but are looking at how integrin proteins (like integrin beta3) might control the brain’s serotonin transporter. Researchers also think that too much SERT activity—too much activity in the brain’s serotonin transmitter—imposed by the kind of abnormal integrin interactions noted above could restrict the availability of serotonin in the brain during a child’s development, as well as in that of an adult.
The study is published online in the Journal of Clinical Investigation by Ana Carneiro, Ph.D., and colleagues; its findings may have implications for treating cardiovascular disorders, hyperserotonemia, autism, and depression.
Tags: asd, asperger, autism, brain, medication, Neuroscience, Parenting, pdd-nos, ssri, zoloftRelated Stories
POSTED IN: Medicine, Neuroscience
11 opinions for Hyperserotonemia and Autism
CS
Mar 4, 2008 at 8:55 pm
Kristina, can you make this a little more layman friendly. Are they saying that it could be detrimental to use SSRI’s?
Kristina Chew, PhD
Mar 4, 2008 at 9:21 pm
That wasn’t what I took from reading the study: I could be wrong, but my sense was that the fact that SSRI’s are beneficial for some autistic persons suggests serotonin uptake is “abnormal” in some autistic persons. Similarly, this study also seems to be pointing to the same notion, that serotonin uptake occurs differently in the brains of autistic persons, and this affects the function of brain synapses, and therefore the workings of the brain.
This is the closing comment from Carneiro in the press release:
So this study might possibly point to the development of a new kind of medication or other treatment to affect serotonin uptake and brain function.
Marla
Mar 4, 2008 at 9:46 pm
Very very interesting. We too have noticed M is better with similar medication. Less aggressive and she often would say,”My brain feels better.” and then when we tried to wean she would say, “I want my medicine back.”
I hope they continue to make developments in this area. I think this is pretty exciting information. Thank you for sharing it.
Kristina Chew, PhD
Mar 4, 2008 at 10:33 pm
That is really interesting, too—-we kept thinking we could take Charlie off the Zoloft but it does something, however subtle. He’s been on the same low low dose for years.
Eleanor
Mar 5, 2008 at 12:04 pm
I found the article too dense to understand really(perhaps I better rephrase that: I found myself too dense…) but I printed out a copy and will take it to my son’s psychiatrist, who has mentioned in passing that at some point she might want to try him on an SSRI. I hope she can interpret the article for me.
madam ovary
Mar 5, 2008 at 1:35 pm
translatingautism.com to the rescue?
Deb K
Mar 5, 2008 at 11:40 pm
Sounds like its a gut issue first, then it effects the brain? What came first the chicken or the egg?
Kristina Chew, PhD
Mar 6, 2008 at 12:14 am
I’ve always had trouble getting my mind around SSRIs and how they work. The main thing that stands out to me is that this study points to the role of the function of synapses in the brain and how those have effects on autistic persons, behaviors, cognitive functioning—-I’m checking Translating Autism for a translation, too!
I noted the gut part, too, Deb K…..
Ettina
Mar 6, 2008 at 1:53 pm
SSRIs are supposed to increase serotonin, so if serotonin levels are too high in autistics, it should make things worse.
I wonder if maybe autistics actually *need* higher serotonin levels? In which case, even with abnormally high serotonin, they may be helped by increasing it?
passionlessDrone
Mar 6, 2008 at 3:17 pm
Hello friends -
SSRIs don’t exactly increase serotonin, so much as reduce the frequency with which serotonin is removed from the synapses (I think).
If I am not mistaken (?) serotonin attaches to a neuron, and gives it some message. Something else comes along and clears it up; i.e., the re-uptake. SSRI’s inhibit that re-uptake (thus, the name, selective serotonin reuptake inhibitor) so the serotonin is available longer. You don’t make more serotonin while on SSRI’s, but rather, what you make is more effective at attaching to the neurons; because it is not being removed as efficiently. Very clever stuff.
Just having serotonin isn’t enough; it has to be transported to the right location. I believe the primary finding in this study was a particular protein has been found to be integral to this transportation; and mutations in the genes responsible for creating this protein have been found in the autistic population more than the undiagnosed population. Thus, again, it isn’t too much serotonin, so much as it being in the wrong place, it cannot get transported to where it is needed. Assuming the same thing is occuring in the brain, SSRIs would help because what does get transported winds up sticking around for longer, and having more of an impact.
HTH!
Take care!
- pD
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