View Full Version : Physiopathology of TS (Tourettes Syndrome)


neuroangel
06-21-04, 10:47 PM
I've been searching online for "excess dopaminergic secretions" "amphetamine" "dopamine antagonists" "involuntary movements" "tourette's syndrome" etc, and I'm not getting the info I am looking for.

I want to see how ADHD and antidepressent meds effect the brain, that causes the involuntary movements. All that keeps coming up: antipsychotics, schizophrenia, parkinson's, huntington's etc.

I'm not having much luck in my "Neural Principles" text book either. Does anyone have good sites or book recommendations? Thanks.

Cyndi

Energizer_Bunny
06-22-04, 02:12 PM
I attended a TS conference a year ago January. I have the book at home that I receied and it is very detailed Give me time and I can see if there is anything in there.

Sherry

neuroangel
06-23-04, 08:26 PM
How did you hear of the TS conference? Thanks for looking into it, very helpful. :)

I ordered the "Biochemistry of Neuropharmacology" about six days ago, so maybe there will be useful info in there. I'll keep you posted if I find anything interesting.

Cyndi

Energizer_Bunny
08-04-04, 12:53 AM
Cyndi,

I have not forgotten you on this one. However, when you ordered your book, was it of assistance?

Sherry

neuroangel
08-09-04, 10:57 PM
There are some helpful things in the book...I need to open it up again. Lately, words and numbers have been putting me to sleep. :\

Cyndi

Energizer_Bunny
08-10-04, 08:55 PM
LOL


I can understand that. I just finished registering for school. I am going to be retaking the math class I dropped last semester because I was so sick and taking a psychology class, which I look forward too. :p

I hate to admit it, but I have been procrastinating on your question, but have not forgotten you. (Hmmmm now where did I put that book....j/k)

Can you do me one favor and try and rephrase your question so I can understand it a little bit better as to what you are looking for.

Thanks Sherry

neuroangel
09-20-04, 08:42 PM
rephrased: On the molecular level, what do antidepressants and stimulants do, that causes people to tic?

I am trying to figure exactly where these meds are going to, anatomically, what neurotransmitters may causing the tics, etc.

Sorry I took so long to respond. My comp was down, and I didn't bother fixing it until today... we're procrastinators around here, eh? ;)

Cyndi

Energizer_Bunny
09-24-04, 09:50 PM
Well part of the question I can answer in that stimulants increase the level of dopamine in the brain which can increase the tics. Studies have shown that tics are increased with stimulants in individuals with TS by 25%

A person with TS can tic more if placed on a stimulant and a person that does not have TS and is placed on a stimulant can develop tics that may go away once the stimulant is stopped.

I looked for info on serotonin and could not locate anything. Sorry.

I am not sure if this is what you were looking for or not or if you wanted much more detailed information than I have.

charlie
09-26-04, 05:43 PM
Hey neuroangel,
you may be able to get something out of the following, I'm sort of lost but it might help you.

"The precise etiology of Tourette's syndrome is unknown. Tics are believed to result from a tripartite dysfunction in the central nervous system. Imaging techniques have implicated the basal ganglia and frontal cortex in the pathogenesis of Tourette's syndrome.12-14 The second source of abnormality is thought to be inappropriate regulation of neurotransmitters, especially dopamine.15 Strong evidence indicates that dopamine excess or supersensitivity of the postsynaptic dopamine receptors is the underlying pathophysiologic mechanism of Tourette's syndrome.16-19 The third hypothesis of dysfunction is a neurophysiologic deficit secondary to neurotransmitter abnormalities, resulting in failure of inhibition of the frontal-subcortical motor circuits.19-22 This area has prominent interconnections with the basal ganglia. As a result, the tic-related neural circuits for throat clearing, sniffing, eye squinting or facial grimacing may run too frequently and out of synchrony with those for other motor movements. Stress and anxiety may neurochemically intensify this inhibitory deficit
copied from this link http://www.aafp.org/afp/990415ap/2263.html
<HTTP: 2263.html 990415ap afp www.aafp.org>

and then this i HOPE is NOT true

"SSRIs and stimulants work by increasing the firing of neurons. While this often has great benefits in the short term, doctors are now realizing that long term use "fries" brain cells. The body views any neuron that fires excessively over time as damaged, and destroys it.

SSRIs and stimulants, taken over a period of 10 years or so, can lead to a loss of brain cells, causing neurodegenerative disorders. Many doctors have recently seen a sudden increase in patients with neurological symptoms, and most have been on Prozac, or a similar drug, for about 10 years. Cheney is seeing this in his own practice"

What mechanisms are at work causing neurons to be "fried"? SSRIs are often prescribed for depression, which involves a lack of serotonin. Serotonin is a neurotransmitter, a chemical messenger. One neuron releases a burst of it into the intersynaptic cleft, (the gap between neurons). The serotonin is then taken up by special receptors in the adjacent neuron. Thus a message is sent from one neuron to another, with serotonin carrying the message across the gap. Excess serotonin is cleared away before a new message is sent. A "reuptake channel" in one neuron vacuums up the left over serotonin.

SSRIs are designed to address a lack of serotonin by blocking the reuptake channel from vacuuming up excess serotonin. While this allows more serotonin to connect with the receptors, often too much is left floating in the intersynaptic cleft. The only way the body can get rid of this excess serotonin is to oxidize it. Unfortunately, this turns it into a toxic compound that, over time, kills both the sending and receiving neurons. Cheney stated, "What starts out as an attempt to increase serotonin and reduce symptoms ends up with the destruction of the serotonergic system itself. It takes about a decade, more in some, less in others"

copied from this site http://www.cfsresearch.org/cfs/cheney/24nf.htm
<HTTP: 24nf.htm cheney cfs www.cfsresearch.org>

you want pictures, this site has pictures:) http://www.nmhct.nhs.uk/pharmacy/moa-ssri.htm

<HTTP: moa-ssri.htm pharmacy www.nmhct.nhs.uk>
"6. HOW SSRI ANTIDEPRESSANTS PROBABLY WORK
If too little serotonin (or noradrenaline) produces the symptoms of depression then correcting this should help to reduce the symptoms. One way of doing this is to block the reuptake (recycling) of transmitters. This is just what an SSRI antidepressant does. They block the reuptake of serotonin, so the next time an impulse comes along, there is more transmitter, a stronger message is passed, and activity in that part of the brain is increased"

The important thing to remember is that SSRI antidepressants probably mainly work by correcting the effect of having too little transmitter. They are NOT JUST STIMULANTS. They have a much more specific way of working than just stimulating you

In people who have had more than two episodes of "major" depression, and got better with antidepressants, research has now shown that over the next three years;-

Less than 1 in 4 people who carry on taking an antidepressant become depressed again
Nearly 9 out of 10 people who do not take an antidepressant become depressed again
If you stop your antidepressant after you have got better, you are six times as likely to become depressed again within three years

2 out of every 3 people who stop their antidepressant after three years become depressed again within the next two years
Only 1 in 20 people who carry on with an antidepressant become depressed again
We do not know for certain what happens after five years. Many people may be advised to carry on with an antidepressant for longer but that is a decision for you and your doctor to make"

"Antidepressants increase the activity of chemical messengers in the brain. Older antidepressants act on messages sent via norepinephrine; newer antidepressants work on messages sent via serotonin (and some work on multiple message networks). Speeding these messages was supposed to be how the drugs worked...
But the drugs speed up brain messages very soon after the first dose. Yet it takes weeks for the drugs to have an effect on depression. What's going on?



A few years ago, Yale University researcher Ronald Duman, PhD, found that some antidepressants make new brain cells grow in one part of the brain -- the hippocampus. That was interesting because that part of the brain has recently been linked to emotional responses...If antidepressants work by stimulating the production of new [brain cells], there's a built-in delay," Hen says in a news release. "Stem cells must divide, differentiate, migrate, and establish connections ... a process that takes a few weeks."
from this site http://my.webmd.com/content/article/72/81660.htm>

@@@@@@@@@ about ADD & meds
"Attention is a cognitive function mediated in the prefrontal cortex, a dopamine-rich area. Consequently, any medical treatment for ADHD must deal with the fact that dopamine neurons are dysfunctional. What is required is an agonist medication (a drug that mimics or increases the effects of a neurotransmitter (http://www.driesen.com/glossary_m-n.htm#NEUROTRANSMITTER) click here for more details about neurotransmitters). The actions of stimulant medications (the best medications for the specific job) promote release of catecholamines (click here for more information about catecholamines (http://www.driesen.com/glossary_c-d.htm#CATECHOLAMINE)) at the synaptic junction, which includes dopamine (a necessary neurotransmitter for the functioning of the attentional system). Stimulants (e.g., amphetamines and methylphenidate), also block the reuptake of catecholamines, prevents their breakdown by monoamine oxidase (MAOI (http://www.driesen.com/imoas.htm)), and exert a direct effect on noradrenergic receptors (norepinephrine/noradrenaline) receptors, inhibit dopamine transporter protein resulting in potentiation (increased strength) of dopaminergic neurotransmission.
What all of this means is that more dopamine (and other catecholamines) is available at the synaptic cleft. This improves the functioning of the attentional system and allows patients to focus their attention longer on things in the environment"
from this site http://www.driesen.com/how_stimulant_medications_work.htm (http://www.driesen.com/how_stimulant_medications_work.htm)

ok if/when you have time angel please break any of this info down into layman's terms for me

signing off research-mode now

neuroangel
09-27-04, 08:19 PM
Ronald Duman and Cheney contradict one another in their studies...enless the SSRIs are creating new brain cells as the dysfunctional ones are being destroyed...

Interesting stuff! I am super tired right now, but I will check out the links you provided within the next day or two. Once I get a better understanding of the catecholamines and action-potential of the neurons, I'll put what I can into laymens terms ofr you. :)

Thanks a bunch!

Cyndi

paulbf
09-28-04, 02:12 AM
Cool links charlie. Which part didn't make sense? I found the quotes very informative. I've also heard of "neurogenesis" with SSRI's, you might try that term for searching.

Neuroangel, here's a page I stumbled onto:
The Chemistry of TS
http://au.geocities.com/jones_kacm/chem.htm

Also you might find something interesting in the French med amisulpride which increases dopamine action at low doses and decreases it at higher doses. It's used as an antipsychotic in high doses and for depression in low doses. At high doses it has both effects in different ways. Sorry I can't elaborate further off the top of my head. I have more links I can dig up if you like.

Energizer_Bunny
10-02-04, 01:00 PM
Cyndi,

I agree with you on the contradictions, I picked that much up out of it myself on reading it,

And to me it is going to happen naturally that a person who is constantly depressed and on anti-depressants, they feel better and once they come off of the anti-depressants, of course they are going to become depressed again.

Thanks for the hard work Charlie on putting that together and doing the research on it.

neuroangel
10-06-04, 05:03 PM
Hi Paul,

If you'd like, you could PM the other links you have. Thanks for the above link. Everyone has been very helpful! :D

Cyndi