![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 24 of 24. This is the beginning of the thread.
Posted by saturn on July 21, 2006, at 19:44:53
I can't understand why a single 50 mg dose of Zoloft would cause 9/10 chest pain in a healthy twenty something. Or the same w/ 10 mg ritalin or why taking 5 mg dex/adderall for 3 days would send me to the er with my heart beating out of my chest at over 140 beats per minute. And yet I pass all echos and stress tests w/ flying colors (except for an asymptomatic "right bundle branch block") and run and lift weights like an olympian--zero heart issues off of meds.
So I don't take anything. I'm afraid to even try. Something clearly must be wrong for me to experience absolutely crushing...i mean drop to your knees chest pain on a single 50 mg dose of zoloft. This is clearly physiologic and not "panic". Docs say it's all good. Probably seen 8 cardiologists. So now I'm a hypochondriac which in combination w/ my untreated adhd is causing some depression...but of course I can't take an SSRI. So I exercise and try fish oils and everything that doesn't work and study pharmacology and experiences on PB and still can't figure out what is wrong with me. Do I have coronary vasospasm? Where can I possibly go from here? Apologies for posting on this topic ad nauseaum. Happy Friday.
Posted by Phillipa on July 21, 2006, at 20:48:48
In reply to what is my problem, posted by saturn on July 21, 2006, at 19:44:53
A paradoxical reaction to zoloft? Love Phillipa
Posted by linkadge on July 21, 2006, at 21:08:49
In reply to Re: what is my problem » saturn, posted by Phillipa on July 21, 2006, at 20:48:48
Strange. The response to the stimulants is more understanable in the sence that these meds effect norepinephrine to some extent.
Why zoloft would do so, I don't know.
Cardiovascular responses to the SSRI's are not unheard of. Though, I don't know if the mechanism is fully understood.
It would be interesting what a Serotonin Transporter Allele testing would reveal. Perhaps you poses the SS varient of the serotonin tranporter. Do SSRI's give you noticable GI disturbances?
Serotonin is involved in cardiac function. There is a theory that too much serotonin may adversly affect the heart.
Perhaps too, it may be due to an acute or "start up" anxiety effect that some people experience on the SSRI's.
Linkadge
Posted by rvanson on July 21, 2006, at 21:26:57
In reply to what is my problem, posted by saturn on July 21, 2006, at 19:44:53
Have you tried any other SSRI before Zoloft?
How about any other A/D?
>
> I can't understand why a single 50 mg dose of Zoloft would cause 9/10 chest pain in a healthy twenty something. Or the same w/ 10 mg ritalin or why taking 5 mg dex/adderall for 3 days would send me to the er with my heart beating out of my chest at over 140 beats per minute. And yet I pass all echos and stress tests w/ flying colors (except for an asymptomatic "right bundle branch block") and run and lift weights like an olympian--zero heart issues off of meds.
>
> So I don't take anything. I'm afraid to even try. Something clearly must be wrong for me to experience absolutely crushing...i mean drop to your knees chest pain on a single 50 mg dose of zoloft. This is clearly physiologic and not "panic". Docs say it's all good. Probably seen 8 cardiologists. So now I'm a hypochondriac which in combination w/ my untreated adhd is causing some depression...but of course I can't take an SSRI. So I exercise and try fish oils and everything that doesn't work and study pharmacology and experiences on PB and still can't figure out what is wrong with me. Do I have coronary vasospasm? Where can I possibly go from here? Apologies for posting on this topic ad nauseaum. Happy Friday.
Posted by james K on July 22, 2006, at 3:26:39
In reply to what is my problem, posted by saturn on July 21, 2006, at 19:44:53
I can't say your particular exact problem, but I would urge to continue trusting your instincts and symptoms. My wife has experienced intense and scary side-effects from many things such as non-aspirin NSAIDs (now acknowledged to cause death in some), Buspar (I don't know if it's been acknowledged to cause anything), Statins (now acknowledged to cause muscle pain and damage), and had mini-strokes diagnosed as migraines. Our perceptions may be years ahead of the "acknowledgements"
Posted by bassman on July 22, 2006, at 8:01:23
In reply to what is my problem, posted by saturn on July 21, 2006, at 19:44:53
Maybe you are just really, really sensitive to meds...like I am. I have to start at very low doses to let my body get used to any psychotropic drug. I would have probably started at 5 mg Zoloft for a few days just to have confidence nothing too odd was going to happen. I do think you were really smart to have what happened checked out-what if it had just been a coincidence that the chest pain came after taking the Zoloft and the two events were unrelated and there really was a heart problem? I hope you have better luck with meds in the future-once you get over the trauma of that event!
Posted by saturn on July 22, 2006, at 10:09:58
In reply to Re: what is my problem » saturn, posted by Phillipa on July 21, 2006, at 20:48:48
> A paradoxical reaction to zoloft? Love Phillipa
wish i knew :)
Posted by saturn on July 22, 2006, at 10:27:51
In reply to Re: what is my problem, posted by linkadge on July 21, 2006, at 21:08:49
> >
> It would be interesting what a Serotonin Transporter Allele testing would reveal. Perhaps you poses the SS varient of the serotonin tranporter. Do SSRI's give you noticable GI disturbances?Hi Link. I've never heard of this variant. I'll have to look into it...thanks for the suggestion. Is this variant involved in any psychiatric pathology? I don't recall having any GI disturbances. Admittedly, however, this occured a few years ago and it could be possible that the chest pain could have overshadowed any concurrent GI problems.
I had taken prozac approximately two years prior to the zoloft and don't recall any GI problems then either. I do recall it made my heart race a bit...I specifically recall mentioning this to my doc but it was nothing like my reaction to zoloft or stims...it may have caused some chest discomfort also but again nothing on par w/ zoloft or stims.
>
> Serotonin is involved in cardiac function. There is a theory that too much serotonin may adversly affect the heart.
>
> Perhaps too, it may be due to an acute or "start up" anxiety effect that some people experience on the SSRI's.Unfortunately, this was way beyond that :(
Posted by saturn on July 22, 2006, at 10:39:27
In reply to Re: what is my problem, posted by rvanson on July 21, 2006, at 21:26:57
> Have you tried any other SSRI before Zoloft?
>
> How about any other A/D?I had taken Prozac for several months approximately two years before trying Zoloft. I do recall it made my heart race a bit--but I was also a smoker at this time and think I wrote it off to the smoking. I would probably have also written off minor chest discomfort to smoking as well and this was ten years ago so it's really hard to say. But, as far as I can recall I generally tolerated it fairly well at 20-30 mg for nearly a year. I stopped mainly due to sexual side effects.
I have tried Remeron on few very brief occassions with no problems (except sedation).
Posted by saturn on July 22, 2006, at 10:57:24
In reply to Re: what is my problem » saturn, posted by james K on July 22, 2006, at 3:26:39
> I can't say your particular exact problem, but I would urge to continue trusting your instincts and symptoms. My wife has experienced intense and scary side-effects from many things such as non-aspirin NSAIDs (now acknowledged to cause death in some), Buspar (I don't know if it's been acknowledged to cause anything), Statins (now acknowledged to cause muscle pain and damage), and had mini-strokes diagnosed as migraines. Our perceptions may be years ahead of the "acknowledgements"
Thanks james. I hope your wife is OK. I know absolutely 100% that your suggestion to follow my instincts and symptoms is correct. Chest pain is nothing to play around with. I'd rather be depressed and walk into walls all day w/ my ADHD than have a heart attack or something from these meds. Many people including docs likely think I'm blowing this out of proportion (I can almost guarantee 99% of pdocs would not believe the side effects I've had from Zoloft and miniscule stims--they simply would say it's panic. I know the difference), but they've probably never experienced multiple episodes of truly excruciating chest pain--even if it lasts only a few seconds. Or going to the ER with a heart rate around 150. I would never forgive myself if I ignored these symptoms and something bad happened.
The frustrating thing is seeing others tolerate and do so well on meds. One of my best friends' life has been completely transformed for the better w/ Adderall. That said, I will not ignore my symptoms as you suggest. Thanks for reaffirming the validity of this for me. Saturn.
Posted by saturn on July 22, 2006, at 11:06:02
In reply to Re: what is my problem, posted by bassman on July 22, 2006, at 8:01:23
> Maybe you are just really, really sensitive to meds...like I am. I have to start at very low doses to let my body get used to any psychotropic drug. I would have probably started at 5 mg Zoloft for a few days just to have confidence nothing too odd was going to happen.
Excellent suggestion. However I did try this approach with Dexedrine--1.25 mg every 4 hours up up to a total of 5 mg in a day. I did this for 3 days with zero problems. My confidence was up that I could slowly begin to increase the dose. However on the day I intended to do so I woke up with my heart beating out of my chest at 150 beats/min and wound up in the ER.
I do think you were really smart to have what happened checked out-what if it had just been a coincidence that the chest pain came after taking the Zoloft and the two events were unrelated and there really was a heart problem? I hope you have better luck with meds in the future-once you get over the trauma of that event!
Thanks bassman. This Zoloft experience happened about 4 years ago and unfortunately I've had a few similiar such episodes from several stimulants since. I feel like a cat that's used up most of my nine lives--I don't want to push my luck! Peace...Saturn.
Posted by saturn on July 22, 2006, at 11:08:21
In reply to Re: what is my problem, posted by linkadge on July 21, 2006, at 21:08:49
> >
> It would be interesting what a Serotonin Transporter Allele testing would reveal. Perhaps you poses the SS varient of the serotonin tranporter. Do SSRI's give you noticable GI disturbances?Hi Link. I've never heard of this variant. I'll have to look into it...thanks for the suggestion. Is this variant involved in any psychiatric pathology? I don't recall having any GI disturbances. Admittedly, however, this occured a few years ago and it could be possible that the chest pain could have overshadowed any concurrent GI problems.
I had taken prozac approximately two years prior to the zoloft and don't recall any GI problems then either. I do recall it made my heart race a bit...I specifically recall mentioning this to my doc but it was nothing like my reaction to zoloft or stims...it may have caused some chest discomfort also but again nothing on par w/ zoloft or stims.
>
> Serotonin is involved in cardiac function. There is a theory that too much serotonin may adversly affect the heart.
>
> Perhaps too, it may be due to an acute or "start up" anxiety effect that some people experience on the SSRI's.Unfortunately, this was way beyond that :(
Posted by saturn on July 22, 2006, at 11:13:48
In reply to Re: what is my problem, posted by bassman on July 22, 2006, at 8:01:23
>>Maybe you are just really, really sensitive to meds...like I am. I have to start at very low doses to let my body get used to any psychotropic drug. I would have probably started at 5 mg Zoloft for a few days just to have confidence nothing too odd was going to happen.
Excellent suggestion. However I did try this approach with Dexedrine--1.25 mg every 4 hours up up to a total of 5 mg in a day. I did this for 3 days with zero problems. My confidence was up that I could slowly begin to increase the dose. However on the day I intended to do so I woke up with my heart beating out of my chest at 150 beats/min and wound up in the ER.
>>I do think you were really smart to have what happened checked out-what if it had just been a coincidence that the chest pain came after taking the Zoloft and the two events were unrelated and there really was a heart problem? I hope you have better luck with meds in the future-once you get over the trauma of that event!
Thanks bassman. This Zoloft experience happened about 4 years ago and unfortunately I've had a few similiar such episodes from several stimulants since. I feel like a cat that's used up most of my nine lives--I don't want to push my luck! I don't feel particurly traumatized by the event, just extremlely cautious because of it/them. Thank...Peace...Saturn.
Posted by linkadge on July 22, 2006, at 19:45:02
In reply to Re: what is my problem » linkadge, posted by saturn on July 22, 2006, at 11:08:21
Strange.
There are a few different varients of the serotonin transporter gene. Each code for a different level of baseline activity. People with the SS varient (which seems to code for a lower baseline uptake of serotonin) seem to experience more side effects during SSRI treatment.
Linkadge
Posted by SLS on July 23, 2006, at 12:14:18
In reply to Re: what is my problem » saturn, posted by linkadge on July 22, 2006, at 19:45:02
> Strange.
>
> There are a few different varients of the serotonin transporter gene. Each code for a different level of baseline activity. People with the SS varient (which seems to code for a lower baseline uptake of serotonin) seem to experience more side effects during SSRI treatment.Do the initial intensities of these side effects diminish with time to approach those seen with LL and LS, or do they remain elevated by comparison?
Maybe these are the people who should be taking very small dosages of these drugs; dosages that would be considered "subtherapeutic" or even homeopathic by conventional standards. Perhaps the autoreceptors refuse to downregulate, never having been exposed to normal ranges of serotonin during critical periods of development. Pindolol might help.
- Scott
Posted by SLS on July 23, 2006, at 12:33:22
In reply to Re: what is my problem » saturn, posted by linkadge on July 22, 2006, at 19:45:02
> Strange.
>
> There are a few different varients of the serotonin transporter gene. Each code for a different level of baseline activity. People with the SS varient (which seems to code for a lower baseline uptake of serotonin) seem to experience more side effects during SSRI treatment.Just musing...
I would guess that the postsynaptic membrane would have a greater density of receptors at baseline in the SS condition. This would explain the more pronounced serotonergic side effects. If they do not downregulate in the presence of an SRI and the attendant increased concentration of serotonin, the side-effects would persist and there would be a reduced chance of obtaining a robust antidepressant response as the synaptic dynamics are not restructured to enhance transmission efficiency. Again, the resistence against downregulation might be an artifact of the lack of appropriate synaptic serotonin during critical phases of development. Again, pindolol might help.
- Scott
Posted by SLS on July 23, 2006, at 12:40:16
In reply to Re: what is my problem, posted by SLS on July 23, 2006, at 12:33:22
I'm exactly backwards on this stuff.
Oh, well.
I'll try to figure it out later...
- Scott
> > Strange.
> >
> > There are a few different varients of the serotonin transporter gene. Each code for a different level of baseline activity. People with the SS varient (which seems to code for a lower baseline uptake of serotonin) seem to experience more side effects during SSRI treatment.
>
> Just musing...
>
> I would guess that the postsynaptic membrane would have a greater density of receptors at baseline in the SS condition. This would explain the more pronounced serotonergic side effects. If they do not downregulate in the presence of an SRI and the attendant increased concentration of serotonin, the side-effects would persist and there would be a reduced chance of obtaining a robust antidepressant response as the synaptic dynamics are not restructured to enhance transmission efficiency. Again, the resistence against downregulation might be an artifact of the lack of appropriate synaptic serotonin during critical phases of development. Again, pindolol might help.
Posted by SLS on July 23, 2006, at 13:00:14
In reply to Re: what is my problem » saturn, posted by linkadge on July 22, 2006, at 19:45:02
While I'm trying to uncover the secrets of synaptic dynamics, why don't I just throw out a much simpler idea.
How about just giving SS people tianeptine (Stablon)?
- Scott
Posted by linkadge on July 23, 2006, at 16:38:01
In reply to Re: what is my problem » linkadge, posted by SLS on July 23, 2006, at 12:14:18
People with low SS verisons of the serotonin tranporter seem to fair poorly on SSRI's as a whole. They seem to have less thereaputic effect, create more severe and intollerable side effects in these individuals.
It is possable that these people are depressed for other reasons altogether.
It'd be nice to see if tianeptine was any more tollerable in this group.
Linkadge
Posted by SLS on July 23, 2006, at 20:15:30
In reply to Re: what is my problem, posted by linkadge on July 23, 2006, at 16:38:01
> People with low SS verisons of the serotonin tranporter seem to fair poorly on SSRI's as a whole. They seem to have less thereaputic effect, create more severe and intollerable side effects in these individuals.
>
> It is possable that these people are depressed for other reasons altogether.
>
> It'd be nice to see if tianeptine was any more tollerable in this group.I did a quick search on Medline. I wanted to get an idea as to if there were any differences in baseline receptor densities in the SS SERT gene promotor variant. One study reported a global decrease in the number of 5-HT1a receptors in vivo brain of SS and LS, but not LL humans as assayed using PET scan.
I guess I really was backwards afterall.
Would you happen to know if any studies exist comparing 5-HTTLPR genotypes with levels of brain serotonin (post-mortem or otherwise)?
Another study of interest found that 5-HT1a binding was reduced in depression, but remained reduced after treatment with an SSRI. I guess my question would be whether binding was reduced further after treatment. The abstract didn't say.
Taken together, one might wonder if certain depressions result from reduced 5-HT1a binding secondary to SS and LS reduced SERT expression; the heterozygous being more common and amenable to treatment with SSRIs, while the homozygous being infrequent and less amenable to treatment with SSRIs and more susceptible to side effects with these drugs.
- Scott
Posted by linkadge on July 24, 2006, at 21:28:30
In reply to Re: what is my problem, posted by SLS on July 23, 2006, at 20:15:30
Its difficult to say. It is necesarry to to consider too whether the study is talking about 5-ht1a post synaptic receptors or presynaptic autoreceptors.
Sometimes serotonergic receptor alterations are used as justification for SSRI or MAOI treatment, without considering that the problem may lie elsewhere.
For instance, I was under the impression that post synaptic 5-ht1a recptors were upregulated in the frontal cortex suicide brain, as well as in schizophrenic patients. This may or may not have anything to do with the regulation of serotonin uptake. Serotonin 5-ht1a agonists like buspar, and clozapine have the ability to downregulate postsynaptic 5-ht1a receptors.
I think that upregulated 5-ht1a could be a result of some deficinacy of an endogenius serotonergic modulators like anandamide.
Anandamide potentiats 5-ht1a receptors and antagonizes 5-ht2a receptor responses (kind of like clozapine). Deficinacies in such agents could reusult in the abberent receptor binding found in some of these illnesses.
The below study says that presynaptic 5-ht1a autoreceptors are enriched in suicide victomes. I think this is referring to an enrichment of presynaptic autorecptors, which would resut in more inhibition of serotonin firing.
In this case, SSRI's work to downregulate autoreceptors. (At lest thats how I see it), resulting in more serotonin release. But, I have also seen that agents like buspar are able to achieve the same thing. So who knows how the autoreceptor became so overactive.
http://www.futurepundit.com/archives/001768.html
The below study suggests that 5-ht1a autoreceptors are upregulated in depression, which result in less serotonin release. Using buspar as a probe.
http://bjp.rcpsych.org/cgi/content/abstract/164/3/372
This study says the same thing.
I think that potent and selective 5-ht1a and 5-ht1b autoreceptor antagonists would result in immediate reduction in depression, since then you would not have to wait for any autorecptor downregulation to occur.
Lithium can have immediate antidepressant effects (through 5-ht1b autoreceptor antagonism). I'd like to see the effects of a lithium + pindolol combination. Lithium affects other things too. So, I think that immediate antidepressant effect can wane due to all the other stuff it does.
Pindolol kindof sucks because its not too strong an autoreceptor agtagonist, and it has post syntaptic antagonist properties too.
The body actually has an "endogenious" 5-ht1b autorecptor antagonist call the 5-ht moduline.
This is another potential target for psychiatry.
5-ht moduline works at nanomolecular concentrations to increase 5-ht release in certain areas of the brain.http://www.medscape.com/medline/abstract/12728412
ECT too, works to downregulate serotonin autoreceptors without effecting serotonin uptake at all. RTMs does the same thing.
I personally think that SERT has little to do with the origins of depression at all. I think its serotonin release that is the problem not serotonin uptake. SS may have more episodes of depression for different reasons altogether. Perhaps the extra serotonin in the amygdala makes them more sensitive to stress and depression.
Linkadge
Posted by SLS on July 24, 2006, at 23:20:03
In reply to Re: what is my problem, posted by linkadge on July 24, 2006, at 21:28:30
Hi Linkadge.
> Its difficult to say. It is necesarry to to consider too whether the study is talking about 5-ht1a post synaptic receptors or presynaptic autoreceptors.
I agree. I don't think the assay used allowed for that distinction to be made. The thing is, both receptor populations would tend to be downregulated in the presence of excess neurotransmitter. Such has been observed in SERT knockout mice.
Don't forget about those tricky somato-dendritic autoreceptors.
> Sometimes serotonergic receptor alterations are used as justification for SSRI or MAOI treatment, without considering that the problem may lie elsewhere.Again, I agree. It is a bit childish to treat the brain with such a simplistic approach. My lack of knowledge renders me childish most of the time.
> For instance, I was under the impression that post synaptic 5-ht1a recptors were upregulated in the frontal cortex suicide brain, as well as in schizophrenic patients. This may or may not have anything to do with the regulation of serotonin uptake. Serotonin 5-ht1a agonists like buspar, and clozapine have the ability to downregulate postsynaptic 5-ht1a receptors.I wasn't aware that clozapine had that property. I think one could make the argument that the increased number of 5-HT1a receptors in this region is indeed the result of reduced 5-HT activity. This might be secondary to another pathology, however.
> I think that upregulated 5-ht1a could be a result of some deficinacy of an endogenius serotonergic modulators like anandamide.
You might be right. I haven't looked much into the cannabinoid system. My guess, though, is that it depends upon how vulnerable this system is to becoming dysregulated after being exposed to stress. Whatever it is that goes wrong in depression, I feel that it must be triggerable by psychosocial stress and reside in systems that remain plastic and do not maintain homeostasis under such conditions.
> Anandamide potentiats 5-ht1a receptors and antagonizes 5-ht2a receptor responses (kind of like clozapine). Deficinacies in such agents could reusult in the abberent receptor binding found in some of these illnesses.
>
> The below study says that presynaptic 5-ht1a autoreceptors are enriched in suicide victomes. I think this is referring to an enrichment of presynaptic autorecptors, which would resut in more inhibition of serotonin firing.> In this case, SSRI's work to downregulate autoreceptors. (At lest thats how I see it), resulting in more serotonin release.
I think there is a re-calibration of the entire homeostatic feedback system. In the presence of increased synaptic neurotransmitter, presynaptic autoreceptors are downregulated as are the postsynaptic excitatory receptors. There is a change in the signal-to-noise ratio that must occur if neural signals are to be transduced efficiently. Reuptake inhibitors create a lot of noise when they are first applied. The first neuron gets muted and the second neuron doesn't know when to send a true signal. Only after a period of a few weeks do the two neurons shake hands and settle on a standard volume setting to communicate at. Well, that's kind of a weak analogy, but I'm too lazy to come up with a better one. For years, my focus had been on the presynaptic neuron and its autoreceptors. It would explain deficiencies in both the synthesis and release of neurotransmitters. It was an attractive idea to a child. :-)
> But, I have also seen that agents like buspar are able to achieve the same thing. So who knows how the autoreceptor became so overactive.
Buspar is a full agonist at presynaptic autoreceptors, but only a partial agonist at postsynaptic receptors. I guess they mean excitatory receptors when they say that. They never mention somato-dendritic autoreceptors.
> The below study suggests that 5-ht1a autoreceptors are upregulated in depression, which result in less serotonin release. Using buspar as a probe.> http://bjp.rcpsych.org/cgi/content/abstract/164/3/372
If something doesn't act as a braking system, it becomes a positive feedback loop. So, what exactly is this braking system? Is this the primary site of pathology?
less 5-HT -> upregulated 5-HT1a -> less 5-HT -> upregulated 5-HT1a -> less 5-HT -> upregulated 5-HT1a...
The presynaptic machinery is still attractive to me. It certainly looks easier to deal with than the second messenger cascades and gene regulation and transcription of the postsynaptic neuron. Maybe things aren't that easy. (Just being childish again).
> I think that potent and selective 5-ht1a and 5-ht1b autoreceptor antagonists would result in immediate reduction in depression, since then you would not have to wait for any autorecptor downregulation to occur.
That's why I had thought to use pindolol. The thing with pindolol, though, is that it acts only at somato-dendritic autoreceptors. Although debated, pindolol has been reported to accelerate the response to SSRI antidepressants. This would make sense in that it would perhaps prevent accomodation of the postsynaptic neuron due to its constant stimulation by serotonin. It would allow for repolarization to occur and provide for the induction of appropriate action potentials. This probably would not happen in the absence of pindolol for two or more weeks until the postsynaptic receptors downregulate and no longer chronically depolarize the cell.
> Lithium can have immediate antidepressant effects (through 5-ht1b autoreceptor antagonism). I'd like to see the effects of a lithium + pindolol combination. Lithium affects other things too. So, I think that immediate antidepressant effect can wane due to all the other stuff it does.
> Pindolol kindof sucks because its not too strong an autoreceptor agtagonist, and it has post syntaptic antagonist properties too.
What would be of interest are presynaptic 5-HT1a and 5-HT1b antagonists. I haven't looked into them.
> I personally think that SERT has little to do with the origins of depression at all.
I personally think that I have no idea what the hell is going on!
> I think its serotonin release that is the problem not serotonin uptake.
I doubt it is the reuptake that is the primary site of pathology, but is perhaps an added vulnerability factor. There are probably several things that have to go wrong for one to develop MDD.
> SS may have more episodes of depression for different reasons altogether. Perhaps the extra serotonin in the amygdala makes them more sensitive to stress and depression.
I think you would have to look at the distribution of receptor subtypes located there to be sure. SERT knockout mice did not show even downregulation of 5-HT receptors among subtypes or in all brain regions. However, I would say that if intense anxiety were one of the side effects of SS people who are placed on SSRIs, then you probably hit the nail on the head.
I'm sorry, Linkadge. This is a pretty crappy post. It rambles. I'm not going to bother to proofread this thing. It's getting late, but I wanted to respond to the wealth of information and brilliant thought that you always bring to this forum.
- Scott
Posted by linkadge on July 25, 2006, at 17:06:15
In reply to Re: what is my problem » linkadge, posted by SLS on July 24, 2006, at 23:20:03
The thing that interested me about 5-ht1b autoreceptor antagonists, is that they are able to increase serotonin in selective areas of the brain, like the hippocampus. The reason I think that serotonin uptake is not involved is because in order to get a downregulation of serotonin autoreceptors, you need to take enough to completely wipe out sexual behavior.
You take an SSRI, you will get some increase in hippocampal serotonin, but at the expense of serotonin in the amygdala, and serotonin in the part of the brain regulating sexual behaviors.
The 5-ht moduline, is an endogenious 5-ht1b autoreceptor antagoinsts. Suppose, that the acitivity of this agent was out of whack for some reason. This would result in low levels of serotonin in certain areas of the brain.
Take a look at this agent.http://biopsychiatry.com/sb-236057.htm
Its a 5-ht1b autoreceptor invere agonist. It seems to selectivly increase seronin in the dentate gyrus in a similar manner to paroxetine.
The 5-ht moduline, and lithium essentially do the same thing. They block the 5-ht1b autoreceptors and increase serotonin release in the hippocampus.
That is very significant. This is where we want the serotonin to promote neurogenesis.
Linkadge
Posted by SLS on July 25, 2006, at 18:08:25
In reply to Re: what is my problem » SLS, posted by linkadge on July 25, 2006, at 17:06:15
Nice stuff. Thanks.
- Scott
This is the end of the thread.
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