Psycho-Babble Medication Thread 1079832

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Indivduals w social phobia have too much serotonin

Posted by PeterMartin on June 18, 2015, at 1:20:21

http://medicalxpress.com/news/2015-06-individuals-social-phobia-serotoninnot.html

6/17/15 article:

Previous studies have led researchers to believe that individuals with social anxiety disorder/ social phobia have too low levels of the neurotransmitter serotonin. A new study carried out at Uppsala University, however, shows that the situation is exactly the opposite. Individuals with social phobia make too much serotonin. The more serotonin they produce, the more anxious they are in social situations.

Many people feel anxious if they have to speak in front of an audience or socialise with others. If the anxiety becomes a disability, it may mean that the person suffers from social phobia which is a psychiatric disorder.

Social phobia is commonly medicated using SSRI compounds. These change the amount of the neurotransmitter serotonin in the brain. Based on previous studies, it was believed that individuals with social phobia had too little serotonin and that SSRIs increased the amount of available serotonin. In a new study published in the scientific journal JAMA Psychiatry, researchers from the Department of Psychology at Uppsala University show that individuals with social phobia make too much serotonin.

The research team, led by professors Mats Fredrikson and Tomas Furmark, used a so-called PET camera and a special tracer to measure chemical signal transmission by serotonin in the brain. They found that patients with social phobia produced too much serotonin in a part of the brain's fear centre, the amygdala. The more serotonin produced, the more anxious the patients were in social situations.

A nerve cell, which sends signals using serotonin, first releases serotonin into the space between the nerve cells. The nerve signal arises when serotonin attaches itself to the receptor cell. The serotonin is then released from the receptor and pumped back to the original cell.
"Not only did individuals with social phobia make more serotonin than people without such a disorder, they also pump back more serotonin. We were able to show this in another group of patients using a different tracer which itself measures the pump mechanism. We believe that this is an attempt to compensate for the excess serotonin active in transmitting signals", says Andreas Frick, a doctoral student at Uppsala University Department of Psychology.

This discovery is a major leap forward when it comes to identifying changes in the brain's chemical messengers in people who suffer from anxiety. Earlier research has shown that nerve activity in the amygdala is higher in people with social phobia and thus that the brain's fear centre is over-sensitive. The new findings indicate that a surplus of serotonin is part of the underlying reason.

"Serotonin can increase anxiety and not decrease it as was previously often assumed", says Andreas Fric

 

Re: Indivduals w social phobia have too much serotonin PeterMartin

Posted by SLS on June 18, 2015, at 10:27:28

In reply to Indivduals w social phobia have too much serotonin, posted by PeterMartin on June 18, 2015, at 1:20:21

It's good to see this in print. To go one step further: excessive serotonin 5-HT2c receptor stimulation (in the amygdala) leads to anxiety. This is probably why some SSRIs produce anxiety as a startup side effect that soon disappears. Things are not so simple when it comes to serotonergic neurotransmission, though. For example, fluoxetine (Prozac) is one of the worst offenders when it comes to startup anxiety, yet acts as a competitive 5-HT2c receptor antagonist. Perhaps the increase in serotonin acts to displace fluoxetine within the first few days, allowing the anxiety to appear. Whatever the reasons, it is not incomprehensible that both too little and too much serotonin in illness can be reregulated by SSRIs and SNRIs. My guess is that, upon chronic exposure to serotonin reuptake inhibitors, the presynaptic negative feedback loops that act as thermostats are recalibrated by the neuron in an effort to accommodate to the new conditions. Of course, postsynaptic receptor downregulation also occurs, which reduces membrane sensitivity. It is as if pushing the system hard enough acts as a reset to a default dynamic, regardless of what the baseline amount of serotonin is. In fact, it may not even matter in which direction the system is pushed. Tianeptine (Stablon) is a drug that acts as the reverse of SSRIs. It causes the presynaptic neuron to increase its rate of reuptake (reuptake enhancer), yet acts as an antidepressant. Again, the system must reregulate itself to accommodate the new conditions. The key is to trigger the system to assume a default dynamic which is probably coded for genetically. It might be epigenetics that screw everything up in the first place.

Who knows? I try to keep an open mind and revise my thinking as new facts and opinions emerge.


- Scott


---------------------------------------------------


> http://medicalxpress.com/news/2015-06-individuals-social-phobia-serotoninnot.html
>
> 6/17/15 article:
>
> Previous studies have led researchers to believe that individuals with social anxiety disorder/ social phobia have too low levels of the neurotransmitter serotonin. A new study carried out at Uppsala University, however, shows that the situation is exactly the opposite. Individuals with social phobia make too much serotonin. The more serotonin they produce, the more anxious they are in social situations.
>
> Many people feel anxious if they have to speak in front of an audience or socialise with others. If the anxiety becomes a disability, it may mean that the person suffers from social phobia which is a psychiatric disorder.
>
> Social phobia is commonly medicated using SSRI compounds. These change the amount of the neurotransmitter serotonin in the brain. Based on previous studies, it was believed that individuals with social phobia had too little serotonin and that SSRIs increased the amount of available serotonin. In a new study published in the scientific journal JAMA Psychiatry, researchers from the Department of Psychology at Uppsala University show that individuals with social phobia make too much serotonin.
>
> The research team, led by professors Mats Fredrikson and Tomas Furmark, used a so-called PET camera and a special tracer to measure chemical signal transmission by serotonin in the brain. They found that patients with social phobia produced too much serotonin in a part of the brain's fear centre, the amygdala. The more serotonin produced, the more anxious the patients were in social situations.
>
> A nerve cell, which sends signals using serotonin, first releases serotonin into the space between the nerve cells. The nerve signal arises when serotonin attaches itself to the receptor cell. The serotonin is then released from the receptor and pumped back to the original cell.
> "Not only did individuals with social phobia make more serotonin than people without such a disorder, they also pump back more serotonin. We were able to show this in another group of patients using a different tracer which itself measures the pump mechanism. We believe that this is an attempt to compensate for the excess serotonin active in transmitting signals", says Andreas Frick, a doctoral student at Uppsala University Department of Psychology.
>
> This discovery is a major leap forward when it comes to identifying changes in the brain's chemical messengers in people who suffer from anxiety. Earlier research has shown that nerve activity in the amygdala is higher in people with social phobia and thus that the brain's fear centre is over-sensitive. The new findings indicate that a surplus of serotonin is part of the underlying reason.
>
> "Serotonin can increase anxiety and not decrease it as was previously often assumed", says Andreas Fric

 

Re: Indivduals w social phobia have too much serotonin

Posted by Phillipa on June 18, 2015, at 10:35:24

In reply to Re: Indivduals w social phobia have too much serotonin PeterMartin, posted by SLS on June 18, 2015, at 10:27:28

No wonder years ago when an SSRI introduced my anxiety has tripled. So now I need to get off these insane small doses of SSRI's the generic luvox at 25mg and the lexapro at 2.5mg. Can I just stop them cold turkey and continue with the valium 10mg and .75mg of xanax? Thanks I want off these SSRI's at age 69. And have to wonder if they took my taste and smell away? Phillipa

 

Re: Indivduals w social phobia have too much serotonin

Posted by linkadge on June 18, 2015, at 19:01:16

In reply to Indivduals w social phobia have too much serotonin, posted by PeterMartin on June 18, 2015, at 1:20:21

Yes. This is why 5-ht2 antagonists are likely better agents for social phobia than SSRIs.

Also, there is some evidence that SSRI's actually decrease serotonin not increase it.

Linkadge

 

Re: Indivduals w social phobia have too much serotonin

Posted by linkadge on June 18, 2015, at 19:03:12

In reply to Re: Indivduals w social phobia have too much serotonin, posted by linkadge on June 18, 2015, at 19:01:16

There was a study (will try to look for) that suggested that long term citalopram actually decreased serotonin (in responders).

Serotonin is a stress hormone of sorts. Serotonin release is enhanced with stress.

 

Re: Indivduals w social phobia have too much serotonin linkadge

Posted by SLS on June 18, 2015, at 19:06:15

In reply to Re: Indivduals w social phobia have too much serotonin, posted by linkadge on June 18, 2015, at 19:01:16

> Yes. This is why 5-ht2 antagonists are likely better agents for social phobia than SSRIs.

How long would it take for a 5-HT2 antagonist to exert its therapeutic anxiolytic effects?


- Scott

 

Re: Indivduals w social phobia have too much serotonin

Posted by linkadge on June 18, 2015, at 19:47:24

In reply to Re: Indivduals w social phobia have too much serotonin linkadge, posted by SLS on June 18, 2015, at 19:06:15

(from my experience) 5-ht2 antagonists as anxiolytics are fairly fast acting, hours or days. High doses, may paradoxically increase anxiety / OCD.

Linkadge

 

Re: Indivduals w social phobia have too much serotonin

Posted by SLS on June 18, 2015, at 22:27:43

In reply to Re: Indivduals w social phobia have too much serotonin, posted by linkadge on June 18, 2015, at 19:47:24

> (from my experience) 5-ht2 antagonists as anxiolytics are fairly fast acting, hours or days. High doses, may paradoxically increase anxiety / OCD.

I don't know if it is at all related, but I have historically described nortriptyline as producing a more "pleasant" feeling than desipramine early in treatment. Perhaps this is explained by the 5-HT2a antagonist property of nortriptyline?


- Scott

 

Re: Indivduals w social phobia have too much serotonin

Posted by Hugh on June 20, 2015, at 9:14:07

In reply to Re: Indivduals w social phobia have too much serotonin, posted by SLS on June 18, 2015, at 22:27:43

Serotonin has certainly never done my anxiety or depression or insomnia any good. Perhaps I have far too much of it already.

 

Re: Indivduals w social phobia have too much serotonin

Posted by SLS on June 20, 2015, at 11:36:52

In reply to Re: Indivduals w social phobia have too much serotonin, posted by Hugh on June 20, 2015, at 9:14:07

> Serotonin has certainly never done my anxiety or depression or insomnia any good. Perhaps I have far too much of it already.

When you say "serotonin", Hugh, do you mean reuptake inhibitors only? Have you tried Paxil?

Are you able to tolerate SSRIs, despite not responding to them? What side effects are most difficult to tolerate?

Not all SSRIs/SNRIs (SRIs) are created equal. If they were, we would only need one of them. They often do other things in addition to transporter inhibition. I just want to make sure you have explored enough SRIs to decide to forever exclude them from your treatment plan. Viibryd is a SRI, but adds 5-HT1a partial agonism. Brintellix is a SRI, but adds 5-HT1a complete agonism with 5-HT7 and 5-HT3 antagonism. Combining a standard SRI with one of these two drugs is not necessarily foolhardy, despite the concerns regarding serotonin syndrome. I have seen people taking multiple SRIs - Effexor and Lexapro for example. I think I prefer Viibryd. Being a partial agonist at 5-HT1a probably works to stabilize the synapse more than a complete agonist.

If you are bipolar, you might do well combining Abilify with Lamictal and possibly Trileptal (oxcarbazepine) or Aptiom (eslicarbazepine). If you are unipolar, you can add reuptake inhibitors - Wellbutrin and Pristiq (or Effexor), perhaps.

I don't remember your history, so you might already have tried all of these.


- Scott

 

Re: Indivduals w social phobia have too much serotonin

Posted by bleauberry on June 20, 2015, at 13:50:58

In reply to Indivduals w social phobia have too much serotonin, posted by PeterMartin on June 18, 2015, at 1:20:21

I think this article is maybe jumping to conclusions. I'm not saying I know the right conclusion, only that the brain is a million miles more complicated than explained here. It is likely a poor or incomplete or misleading conclusion. If it is correct, it does little to help the chronic patient except offer an interesting topic of discussion.

 

Re: Indivduals w social phobia have too much serotonin bleauberry

Posted by Phillipa on June 20, 2015, at 20:47:22

In reply to Re: Indivduals w social phobia have too much serotonin, posted by bleauberry on June 20, 2015, at 13:50:58

Is there an answer to how one would know?

 

Re: Indivduals w social phobia have too much serotonin SLS

Posted by Hugh on June 22, 2015, at 10:48:29

In reply to Re: Indivduals w social phobia have too much serotonin, posted by SLS on June 20, 2015, at 11:36:52

I'm unipolar. Clomipramine made it very difficult for me to concentrate. Trazodone made me groggy. Nefazodone made me very irritable. Buspirone caused suicidal ideation. All of them made my heart race. Mirtazapine helped me sleep, and it lessened my depression and anxiety somewhat. I think this was because it's an antihistamine. Selegiline also lessened my depression somewhat, but I gave it up because it was overly stimulating. I tolerate stimulants very poorly.

Of all the things you mentioned, what interests me the most is 5-HT7 antagonism.

 

Re: Indivduals w social phobia have too much serotonin Phillipa

Posted by Hugh on June 22, 2015, at 11:07:12

In reply to Re: Indivduals w social phobia have too much serotonin bleauberry, posted by Phillipa on June 20, 2015, at 20:47:22

> Is there an answer to how one would know?

Trial and error. The amino acid l-leucine can suppress the production of serotonin. But it can also suppress the production of dopamine. Quinine inhibits the conversion of tryptophan into serotonin. But quinine, at high doses, can have some nasty side effects.

You asked if you should quit your SSRIs cold turkey. Absolutely not. If you decide to quit them, do a gradual taper.

 

Re: Indivduals w social phobia have too much serotonin Hugh

Posted by SLS on June 22, 2015, at 12:30:19

In reply to Re: Indivduals w social phobia have too much serotonin SLS, posted by Hugh on June 22, 2015, at 10:48:29

> I'm unipolar. Clomipramine made it very difficult for me to concentrate. Trazodone made me groggy. Nefazodone made me very irritable. Buspirone caused suicidal ideation. All of them made my heart race. Mirtazapine helped me sleep, and it lessened my depression and anxiety somewhat. I think this was because it's an antihistamine. Selegiline also lessened my depression somewhat, but I gave it up because it was overly stimulating. I tolerate stimulants very poorly.
>
> Of all the things you mentioned, what interests me the most is 5-HT7 antagonism.

The ones that I am aware of are Latuda, Abilify (partial agonist), Brintellix. and Risperdal. What other ones are you looking at?

I don't know how accurate this is:
https://en.wikipedia.org/wiki/5-HT7_receptor#Antagonists

How does 5-HT7 antagonism help with depression?

- Scott

 

Re: Indivduals w social phobia have too much serotonin Hugh

Posted by Phillipa on June 22, 2015, at 21:55:25

In reply to Re: Indivduals w social phobia have too much serotonin Phillipa, posted by Hugh on June 22, 2015, at 11:07:12

Hugh thanks low doses. I wonder if even the low doses cause all the side effects now attributed to them?

 

Re: Indivduals w social phobia have too much serotonin

Posted by Horse on June 22, 2015, at 21:58:33

In reply to Re: Indivduals w social phobia have too much serotonin Hugh, posted by SLS on June 22, 2015, at 12:30:19

Saphris? I can't recall with certainty....

 

Re: Indivduals w social phobia have too much serotonin Horse

Posted by SLS on June 23, 2015, at 0:06:12

In reply to Re: Indivduals w social phobia have too much serotonin, posted by Horse on June 22, 2015, at 21:58:33

> Saphris? I can't recall with certainty....

You are right. I found several papers describing Saphris (asenapine) as being a 5-HT7 antagonist.

Here's a nice article about asenapine:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3539266/

Its side effect profile looks pretty good. I like that it does not increase prolactin secretion and produces minimal metabolic effects.


- Scott

 

Re: Indivduals w social phobia have too much serotonin SLS

Posted by Hugh on June 23, 2015, at 12:42:40

In reply to Re: Indivduals w social phobia have too much serotonin Hugh, posted by SLS on June 22, 2015, at 12:30:19

> How does 5-HT7 antagonism help with depression?

Thanks, Scott. I have a long history of GI problems. I know that they exacerbate my depression. It's even possible that they are the root cause of my depression. (We keep learning more and more about the gut-brain connection.) 5-HT7 antagonism might be an effective treatment for inflammation of the gut.

http://www.ncbi.nlm.nih.gov/pubmed/23554310

 

Re: Indivduals w social phobia have too much serotonin Phillipa

Posted by Hugh on June 23, 2015, at 12:45:11

In reply to Re: Indivduals w social phobia have too much serotonin Hugh, posted by Phillipa on June 22, 2015, at 21:55:25

> Hugh thanks low doses. I wonder if even the low doses cause all the side effects now attributed to them?

You're welcome. When's the last time you weren't on any SSRIs? How did you feel?

 

Re: Indivduals w social phobia have too much serotonin Hugh

Posted by Phillipa on June 23, 2015, at 19:41:58

In reply to Re: Indivduals w social phobia have too much serotonin Phillipa, posted by Hugh on June 23, 2015, at 12:45:11

Still the 2.5mg of lexapro & 25mg of generic luvox. Don't notice a thing. Phillipa

 

Re: Indivduals w social phobia have too much serotonin Phillipa

Posted by SLS on June 23, 2015, at 20:50:02

In reply to Re: Indivduals w social phobia have too much serotonin Hugh, posted by Phillipa on June 23, 2015, at 19:41:58

How many years ago did you try Paxil? What were the results?


- Scott

 

Re: Indivduals w social phobia have too much serotonin linkadge

Posted by TriedEveryMedication on July 9, 2015, at 9:31:26

In reply to Re: Indivduals w social phobia have too much serotonin, posted by linkadge on June 18, 2015, at 19:01:16

> Yes. This is why 5-ht2 antagonists are likely better agents for social phobia than SSRIs.
>
> Also, there is some evidence that SSRI's actually decrease serotonin not increase it.
>
> Linkadge

What are some 5-ht2 antagonists on the market?

Thanks


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