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   Author  Topic: CH history, genetic link and nicotine  (Read 14130 times)
Annette
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CH history, genetic link and nicotine
« on: May 5th, 2008, 9:09pm »
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It is interesting to note that CH is a relatively new disease. Considering the amount of pain and the unusual physical manifestation one would speculate that had CH existed for a very long time, there should some description of it early in the medical history of man. However, the very first description of a head pain that matches CH was in 1641. The first text book report of CH was in 1745. The name cluster headache was not coined until 1952 when the cyclical nature of the condition was first noted.
 
http://www.springerlink.com/content/8g039438847x6x05/
 
 
Since a very high percentage of CHers smoke, lets look at the history of tobacco. Although tobacco was smoked by the Mayans thousands of years ago, it was only used in high quantity to produce psychedelic effects in shamans and high priests. Native American Indian men smoked tobacco only during special ceremonies. Christopher Columbo discovered tobacco on his famous trip in 1498. Tobacco was then slowly introduced into Europe, Asia and the Middle East from 1500 to 1600. However, not until 1604 that the first commercialised tobacco plant was formed in America which began to supply England and Europe with large quantities.  
 
The number of smokers ( all men ) increased steadily from 1600. The first description of CH was in 1641. Was it a coincidence?
 
 
Now lets look at CH in women. CH in women was considered rare initially, but the gap is closing.
 
Before 1960s   M: F ratio    6.2 -1
1960s        5.6 -1
1970s        4.3 -1
1980s        3    -1
1990s        2.1 -1
 
 
What about the rate of smoking tobacco in woman ? I couldnt find one for US but found one for Australia, which I would say is quite representative of the industrialised countries.
 

 
 
So as men and women started to smoke and gradually increasing the amount of tobacco consumed, there seem to be a correlation of CH reported. Is it still coincidental ?
 
 
Now lets look at CH and nicotine. So far apart from the observation that most CHers smoke and the above seemingly coincidental ratio, we havent really got an concrete causal correlation between the two. Or have we ?
 
 
The first genetic risk factor for CH has been identified in the Hypocretin Receptor 2 gene. CH appears to be associated with the  G1246A polymorphism of this gene.
 
http://www.neurology.org/cgi/content/abstract/66/12/1917
 
http://www.ncbi.nlm.nih.gov/pubmed/15477554
 
Hypocretin 1 and 2 are two newly identified peptides produced exclusively in the dorsal and lateral hypothalamus. They have widespread neuroexcitatory activies throughout the brain.  
 
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailVie w&TermToSearch=9419374
 
They have a major role in the hypothalamic control of hunger, the circadian clock through sleep-wake mechanisms and pain perception via the brain stem. Starting to sound familiar ?
 
 
Now its interesting to note that nicotine from tobacco binds to the same receptors and mimic the effects of hypocretins.  
 
http://www.jneurosci.org/cgi/content/full/25/21/5225/FIG2
 
http://www.jneurosci.org/cgi/content/abstract/25/21/5225
 
 
What would happen if excessive nicotine intake over the long period of time ( even generations ) causes abnormal reactions in the hypothalamus which starts to derail the circadian clock? This will no doubt lead to an imbalance of melatonin and serotonin. Can this lead to the development of CH ? In theory it can.
 
Prof Goadsby has found an abnormal area in the hypothalamus that is related to CH. Could this have been caused by nicotine exposure? We will need more detailed studies to look at it specifically.  
 
http://news.bbc.co.uk/1/hi/health/380497.stm
 
 
Furthermore Hypocretin has a direct effects on other neurotransmitters such as dopamine, norepinephrine and GABA, all of which are involved in the mechanism of CH.  
 
So what does all this mean ? It means there is a link between nicotine in tobacco and CH. Does one cause the other? We will need more studies to determine.  
 
In the mean time, you are welcome to draw your own conclusion.
 
Thank you for reading and painfree wishes to all  Smiley
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Re: CH history, genetic link and nicotine
« Reply #1 on: May 5th, 2008, 9:20pm »
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Thats pretty interesting stuff, Annette.  Keep in mind I have no idea what the hell a hypocretin is.  My first guess would be a very slow slow person, but I dont think thats right.
 
How could we study the morphing of genes through generations?  Can we inspect this gene to see if we all have this malformed gene thingy?
 
Interesting.
 
 
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Re: CH history, genetic link and nicotine
« Reply #2 on: May 5th, 2008, 9:34pm »
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on May 5th, 2008, 9:09pm, Annette wrote:

 
The first genetic risk factor for CH has been identified in the Hypocretin Receptor 2 gene. CH appears to be associated with the  G1246A polymorphism of this gene.
 
<snip>
 
What would happen if excessive nicotine intake over the long period of time ( even generations ) causes abnormal reactions in the hypothalamus which starts to derail the circadian clock? This will no doubt lead to an imbalance of melatonin and serotonin. Can this lead to the development of CH ?

 
Well...in the case of those who have never smoked who developed CH, (like me--I started with CH long before I began smoking) the bottom line is that we're then talking about inheritance of an acquired characteristic--and that contradicts what I, at least, understand about natural selection.
 
Quote:
The first genetic risk factor for CH has been identified in the Hypocretin Receptor 2 gene. CH appears to be associated with the  G1246A polymorphism of this gene.

 
Unless it can be shown that the G1246A polymorphism of the Hypocretin Receptor 2 gene conferred some other selective advantage that has allowed its spread throughout the population since the advent of smoking...well...I don't see how this gene could have an increased frequency--without invoking Larmarckian inheritance of acquired characteristics.
 
Just my couple of cent's worth for discussion's sake.   Smiley
 
Best wishes,
 
George
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Re: CH history, genetic link and nicotine
« Reply #3 on: May 5th, 2008, 9:38pm »
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Annette,
 
You've obviously gone to a lot of effort researching this topic and developed a very credible treatise.  In my mind... this outstanding work is worthy of publication...  Where can you get an article on this topic published?  I've a feeling you'll have a lot of neurologist in agreement with your hypothesis and willing to weigh in with comments.
 
Please keep us posted...
 
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Re: CH history, genetic link and nicotine
« Reply #4 on: May 5th, 2008, 9:41pm »
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I believe my doctor thinks along the same lines as you Annette about the smoking thing.  She has raised enough hell with me over the years.  If you ever see a group of CHers, looks like a barn fire, or a LA freeway.
 
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Re: CH history, genetic link and nicotine
« Reply #5 on: May 5th, 2008, 9:44pm »
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Annette,
 
You are on quite a roll lately  Cool  Another facinating post.
 
Unfortunately I'm in the same boat as B$ and can't tell how much water all this holds but it's a very interesting theory Annette.  I wonder if there is hope for future generations as we slowly reduce smoking rates across the globe.
 
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Re: CH history, genetic link and nicotine
« Reply #6 on: May 5th, 2008, 10:00pm »
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Very valid point of argument George. However, CH is not a monofacet condition. It has many possible causative mechanisms. The hypocretin hypothesis is just one of many.
 
Abnormal neuronal activites on the Hypocretin receptors have  only been proven to cause abnormality in the sleep wake cycle of the circadian clock controlled by the hypothalamus. There are extensive studies on this for narcolepsy.
 
We actually have 2 circadian clocks. One is run by the hypothalamus which keeps a 22-24 hrs time. This is more like a day clock if you like. This is the one affected by Hypocretins.
 
The other clock is the Pineal gland. This one is controlled by sunlight and the production of serotonin and melatonin. This one changes according to the seasons as the length of day light varies throughout the year. This is more like a year clock.  
 
Both clocks are linked through the activities of neurotransmitters such as serotonin via the hypothalamus. Abnormalities in either of these clocks can lead to abnormal functioning of the hypothalamus which potentially can cause CH.
 
Various things can cause insults to the pineal gland. Head injury, certain drugs and chronic brain chemical imbalances due to chronic allergy, drug use and even diet can potentially affect the pineal gland enough to start causing the 2nd clock to malfunction.
 
Lastly, as hypocretin receptor is only the first to be detected in CH, there may be other alleles to be discovered. Some genes can remain dormant for generations and only become activated in one particular person, often for unknown reason.
 
It would be great if all CHers and their immediate relatives can have a genetic test for this particular receptor. The result of such a study would be a lot more revealing.  
 
Who knows George, maybe because your CH was purely genetically caused that you have always experienced strictly cyclical patterns of CH. May be it was why you didnt experience the " jumping all over the place" CH like some others? Just out of interest, did you notice any change in the pattern, intensity, or characteristic of your CH before and after you started to smoke ?  
 
 
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Re: CH history, genetic link and nicotine
« Reply #7 on: May 5th, 2008, 10:08pm »
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This is a really interesting topic and the historical aspect is fascinating.  
 
I too have heard that there's a higher frequency of smoking in the CH population than the general population (I smoke heavily and am a CH sufferer). I also believe that there's no documented evidence linking smoking and CH outside of this statistic.
 
I'm really curious to know if there's any study showing a cessation in CH with cessation of smoking. Anybody heard of such a study?
 
I actually quit smoking once, for 15 months, specifically because I thought it may stop my episodic CH. It did actually, but I started smoking again so don't know if it would have stuck. It could have just been a longer-than-usual remission (which for me is usually closer to 12 months).
 
Comments are appreciated.
 
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Re: CH history, genetic link and nicotine
« Reply #8 on: May 5th, 2008, 10:11pm »
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on May 5th, 2008, 10:00pm, Annette wrote:

 
Who knows George, maybe because your CH was purely genetically caused that you have always experienced strictly cyclical patterns of CH. May be it was why you didnt experience the " jumping all over the place" CH like some others? Just out of interest, did you notice any change in the pattern, intensity, or characteristic of your CH before and after you started to smoke ?  
 
 

 
No, no significant change in the pattern, intensity, or characteristics of my CH after I began smoking.  
 
I started with CH at the age of 13.  Began smoking in college at the age of 18.  
 
Perhaps an oddity in my genetic makeup made smoking abnormally attractive to me--although I do know that the vasoconstrictive effect of nicotine means that I'll invariably smoke when a hit is ended.  It helps.  Won't stop one from starting, won't kill one, but it seems to speed the disappearance of the afterburn.  It's probably one of the reasons I still smoke.
 
Let it never be said that I am a completely rational creature.  
 Wink
 
All the best,
 
George
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Re: CH history, genetic link and nicotine
« Reply #9 on: May 5th, 2008, 10:21pm »
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on May 5th, 2008, 10:08pm, krojo wrote:

 
I'm really curious to know if there's any study showing a cessation in CH with cessation of smoking. Anybody heard of such a study?
 
 
Comments are appreciated.
 
-Rob

 
 
 
So far there isnt any study on cessation of smoking to cessation of CH activity. However, there have been in the last 2 years that I have been here occasional reports from a few individuals who said quitting smoking had helped them, either by reducing the intensity or by lengthening the remission periods.  
 
The difficulty with episodic CHers is the remission time can vary naturally from a few months to a few years so if one is to stop smoking, one will need to stop for at least 3+ years to be able to determine if that was the cessation of smoking that actually helped CH.  
 
Most smokers, CHers or not, find it really difficult to stop and the rate of resuming within the first 12 months is high.
 
Another concern is if long term exposure to nicotine has caused some permanent damage to the neurons then cessation of smoking later in life may not bring the desire effect. Unlike other cells in the body, neurons in the brain dont recover or renew in most instances. Any damage to brain cells is likely to stay, unfortunately.  
 
 
For future generations, it would be interesting to test for this receptor gene in the children of CHers, then follow them up longitudinally through the years to see whether its the smokers that are more likely to develop CH ?  
 
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Re: CH history, genetic link and nicotine
« Reply #10 on: May 5th, 2008, 10:36pm »
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When I went to Nursing school in '86, they taught that there was no genetic link in cancer.  Stuff changes, doesn't it?  My daddy had clusters, and I've got 'em.  If there is no genetic link, think of what the odds are that we'da both had them.  Both of us, of course, heavy smokers.
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Re: CH history, genetic link and nicotine
« Reply #11 on: May 5th, 2008, 11:05pm »
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Quote:
What would happen if excessive nicotine intake over the long period of time ( even generations ) causes abnormal reactions in the hypothalamus which starts to derail the circadian clock? This will no doubt lead to an imbalance of melatonin and serotonin. Can this lead to the development of CH ? In theory it can.

 
Assuming heredity transmission of an acquired trait is pure Lysenkoism.   Roll Eyes
 
 
http://en.wikipedia.org/wiki/Trofim_Lysenko
http://en.wikipedia.org/wiki/Lysenkoism
 
                  smokin
 
 
 
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Re: CH history, genetic link and nicotine
« Reply #12 on: May 5th, 2008, 11:13pm »
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maybe its late or maybe I'm naturally stupid but there are so many words in this thread I never heard of.  Seriously, I hope one of these theories people post will eventually cure my CH.  Lets see, I am 32 years old and I smoke so the odds are pretty certain I'll have these for the rest of my life.  Aren't I positive tonight?
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Re: CH history, genetic link and nicotine
« Reply #13 on: May 5th, 2008, 11:25pm »
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on May 5th, 2008, 11:05pm, AlienSpaceGuy wrote:

 
Assuming heredity transmission of an acquired trait is pure Lysenkoism.   Roll Eyes
 
 

 
 
Pardon me but what exact acquired trait are you talking about here? Are you referring to smoking as an acquired trait ? or are you talking about CH as an acquire trait ? I can't reply properly to your comment without a clear understanding of what it means. Please elaborate further. Thank you.
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Re: CH history, genetic link and nicotine
« Reply #14 on: May 5th, 2008, 11:34pm »
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Interesting.
 
I wonder, though. Is it possible that CH symptoms were just looked at as supernatural events rather than illness prior to 1641?
Seriously. Think of a k10 dance. Kinda looks like a demonic possession in a way.
 
There is a lot I don't understand about this info, but I still have to think the tobacco/CH connection is still a chicken/egg conundrum.
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Re: CH history, genetic link and nicotine
« Reply #15 on: May 5th, 2008, 11:52pm »
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  Quote:

I wonder, though. Is it possible that CH symptoms were just looked at as supernatural events rather than illness prior to 1641?  
Seriously. Think of a k10 dance. Kinda looks like a demonic possession in a way.  
 

 
   Salem witch trials come to mind doesn't it?
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Re: CH history, genetic link and nicotine
« Reply #16 on: May 6th, 2008, 12:02am »
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on May 5th, 2008, 11:34pm, nani wrote:
Interesting.
 
I wonder, though. Is it possible that CH symptoms were just looked at as supernatural events rather than illness prior to 1641?
Seriously. Think of a k10 dance. Kinda looks like a demonic possession in a way.
.

 
 
 
That is entirely possible, but unlikely.  
 
When looking up the history and earlier reports/descriptions of migraine, the closest cousin to CH, there was mention of its typical symptoms thousands of years ago.
 
In fact it was our friend Hippocrates who described it very well with symptoms of aura, head pain and nausea.
 
 
http://www.healthguidance.org/entry/2866/1/A-Brief-History-Of-Migraines. html
 
 
I would say that there must be at least a few doctors prior to the 1960s who would not dismiss classical CH symptoms to demonic dances, if they had seen it.  
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Re: CH history, genetic link and nicotine
« Reply #17 on: May 6th, 2008, 1:45am »
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on May 5th, 2008, 11:34pm, nani wrote:
... but I still have to think the tobacco/CH connection is still a chicken/egg conundrum.

Fair comment, too.  
 
Recent research has put that particular question to bed (the chicken that laid the egg came first) but Annette's hypothesis is just as valid as a point of discussion.
 
Around the same time as tobacco was moving around the world we saw the spread of Indian corn (forgive me if that term's no longer PC), potatoes, opium, tea and spices, the beginnings of the Industrial Revolution and smog, soap, underwear and Women's suffrage.
 
And that's even before the Great Carrot Plague!!
 
Excuse my interruption, Annette, and please continue with your most interesting idea because unless we consider all avenues, there's no point exploring any.
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Re: CH history, genetic link and nicotine
« Reply #18 on: May 6th, 2008, 2:58am »
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on May 6th, 2008, 1:45am, AussieBrian wrote:

 
 
Recent research has put that particular question to bed (the chicken that laid the egg came first) but Annette's hypothesis is just as valid as a point of discussion.
 

 
 
Ah no my dear Brian, it was certainly not the chicken nor the egg that came first, it was the Jungle Fowl ( Gallus ) that came first. This bird that has been around as long as some dinosaurs ( at least 5000 years ago ) came before both the chicken and the egg !   Cool
 
http://en.wikipedia.org/wiki/Red_Junglefowl
 
 
In regard to the other things that were spreading around the world at the same time as tobacco, such as Indian corn or potatoes or even the great carrot, I am sorry but I wont be looking at their possible link to CH. Why ? Because even if I can prove a causal link, there wont be any massively profitable company to stage a class action on. Opium may have some pretty loaded manufacturers and distributors, but I still dont fancy facing an angry God Father in Courts !  Wink
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Re: CH history, genetic link and nicotine
« Reply #19 on: May 6th, 2008, 3:37am »
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This has been very interesting. Smiley
 
I've never smoked, but my father did all through my childhood but he quit smoking few years before his death.
 
My ch begun back in 2001, the same fall I moved to London and begun my uni studies. During my first year, I went to the uni karaoke nights with my friends, but eventually stopped, because the uni bar was always filled with students who smoked like there's no tomorrow and the smoke made me cough in my pre-ch days and sometimes triggered a hit during my early ch days.
 
Unless dad's smoking altered his genes which I got and getting some passive smoke to my system, that's my links to tobacco.  
 
Sanna
 
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Re: CH history, genetic link and nicotine
« Reply #20 on: May 6th, 2008, 7:25am »
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I contend that clusterheads display an addictive personality.  They smoke a lot, drink a lot, hang around message boards, etc.
 
I think that the condition that causes clusters also effects brain chemistry to cause this addictive trait.
 
Therefore clusters cause smoking, not vice versa.  Or more corectly, the brain disformity that causes clusters, causes us to have addictive personalities which leads to smoking.
 
So my philosophy is the hypothalamus is the chicken, ch and smoking are both eggs.
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Re: CH history, genetic link and nicotine
« Reply #21 on: May 6th, 2008, 7:50am »
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on May 6th, 2008, 7:25am, Bob P wrote:
I contend that clusterheads display an addictive personality.  They smoke a lot, drink a lot, hang around message boards, etc.
 
I think that the condition that causes clusters also effects brain chemistry to cause this addictive trait.
 
Therefore clusters cause smoking, not vice versa.  Or more corectly, the brain disformity that causes clusters, causes us to have addictive personalities which leads to smoking.

Ding, ding, ding! Give the man a cigar!
 
This is the theory to which I also subscribe. Not only does it make it a tad easier to justify smoking (not the real reason I think it's correct, but it is a nice salve for my guilty conscience), but I would think that clusters would be far more prevalent amongst smokers if the converse were true - if smoking caused clusters, that is.
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Re: CH history, genetic link and nicotine
« Reply #22 on: May 6th, 2008, 8:38am »
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on May 5th, 2008, 10:00pm, Annette wrote:

 
 
We actually have 2 circadian clocks. One is run by the hypothalamus which keeps a 22-24 hrs time. This is more like a day clock if you like. This is the one affected by Hypocretins.
 
The other clock is the Pineal gland. This one is controlled by sunlight and the production of serotonin and melatonin. This one changes according to the seasons as the length of day light varies throughout the year. This is more like a year clock.  
 
Both clocks are linked through the activities of neurotransmitters such as serotonin via the hypothalamus. Abnormalities in either of these clocks can lead to abnormal functioning of the hypothalamus which potentially can cause CH.
 

 
I wonder if it is possible for the Pineal gland and the Hypothalamus to become chemically "uncoupled" ?  Severe sleep deprivation (5+ days of absolutely no sleep) has been reported to brake a cycle.  Perhaps this resets the clocks.
 
I tend to agree with Bob P. about our condition predisposing us to an "addictive personality"  I had quit smoking for 8 years and some of my worst cycles were during that time.    
 
With respect to CH being a modern ailment, I could see migrain being written about way back in ancient times without observers thinking they were nut jobs but at the same time I could easily see a CH sufferer looked upon as being posessed.  I'm sure headbashing was done back then like some do today.  I have always wondered about trepanning.  Poor ba$$tards!
 
Thought provoking post Annette.
 
-P.
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Re: CH history, genetic link and nicotine
« Reply #23 on: May 6th, 2008, 9:16am »
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on May 6th, 2008, 7:25am, Bob P wrote:
I contend that clusterheads display an addictive personality.  They smoke a lot, drink a lot, hang around message boards, etc.
 
I think that the condition that causes clusters also effects brain chemistry to cause this addictive trait.
 
Therefore clusters cause smoking, not vice versa.  Or more corectly, the brain disformity that causes clusters, causes us to have addictive personalities which leads to smoking.

 
 
I used to think that too, the problem is when I tried to prove that theory, I could not find evidences to sustain it . For that theory to work, one would expect:
 
1- CH was present before tobacco. There was no evidence of that.
 
2- CHers would more likely start smoking AFTER the start of CH. There is no evidence of this, most CHers who smoke, do so years before CH starts. ( In schizophrenics, where it is proven that their abnormal brain function caused them to be more addicted to nicotine, the majority started smoking AFTER becoming symptomatic ).  
 
3- The prevalence of CH in women should stay the same. What caused the steady rate of increase? What is the difference between women of 1990s compared to 1960s that make them more susceptible to CH ? The only noticeable difference is the change in lifestyle.
 
3- It has been proven that nicotine addiction ( and a lot of other addictions ) are related to the dopamine pathway. The higher the dopamine level, the more the person should smoke. Dopamine level in an episodic CHer drops to normal during remission, but there is no reduction in the consumption of nicotine reported. There is no evidence that CHers smoke less during remission. While this has been noted with schizophrenics, who smoke a lot more during periods of psychosis but less when in remission.  
 
4- Niccotine should have some noticeable effect on the condition. When schizophrenics stop smoking, their symptoms temporarily worsen. This does not happen in CHers, there is never any report that stopping smoking causes an increase in CH activities, if anything there has been a few reports that it helped.  
 
5- There have been case reports of schizophrenics stopping smoking when in remission longer than 3 years. There has been no such report in episodic CHers.  
 
 
I started my research on the relationship between nicotine consumption and CH, the evidences I found led me the other way.  
 
I would love it if you Bob or anyone else can find evidences that suggests CH causes smoking.  
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Veni Vidi Velcro

   
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Re: CH history, genetic link and nicotine
« Reply #24 on: May 6th, 2008, 9:28am »
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on May 6th, 2008, 7:50am, Brew wrote:

 
This is the theory to which I also subscribe. Not only does it make it a tad easier to justify smoking (not the real reason I think it's correct, but it is a nice salve for my guilty conscience), but I would think that clusters would be far more prevalent amongst smokers if the converse were true - if smoking caused clusters, that is.

 
 
Clusters would be far more prevalent amongst smokers unless there needs to be also a certain genetic or anatomical brain defect that is required for the symptoms of CH to manifest.  
 
I dont think you need to subscribe to any theory to make the choice to smoke Bill. People continue to smoke despite concrete evidence that smoking causes lung cancers. I have cared for many dying lung cancer patients who continued to smoke until their last breath.  
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