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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 32. This is the beginning of the thread.
Posted by Ame Sans Vie on June 15, 2003, at 23:06:39
http://story.news.yahoo.com/news?tmpl=story&u=/ap/manic_depression_gene
Posted by avid abulia on June 15, 2003, at 23:16:35
In reply to Scientists Say they ID the Depression Gene, posted by Ame Sans Vie on June 15, 2003, at 23:06:39
yeah, and some dude was just by looking for you. he said something about... what was it? ... ah yes, i believe lakeside property?
~AA
Posted by cubbybear on June 16, 2003, at 2:21:00
In reply to Scientists Say they ID the Depression Gene, posted by Ame Sans Vie on June 15, 2003, at 23:06:39
Whoever wrote the headline evidently didn't bother to read the story, or doesn't understand the difference between depression (Major) and bi-polar disorder. It's another example of lack of accuracy in the media.
Posted by Questionmark on June 16, 2003, at 5:25:03
In reply to Re: Scientists Say they ID the Depression Gene, posted by cubbybear on June 16, 2003, at 2:21:00
i dont know if i'm more annoyed with the scientists or the journalist(s) here, but probably the latter.
"Depression gene." Balogni! Yeah i just identified the arrogant scientist and idiot journalist genes. One gene responsible for all the exaggerating idiotic media-types' personality. or maybe it was the scien... ah who cares.
Posted by Larry Hoover on June 16, 2003, at 10:53:37
In reply to Scientists Say they ID the Depression Gene, posted by Ame Sans Vie on June 15, 2003, at 23:06:39
> http://story.news.yahoo.com/news?tmpl=story&u=/ap/manic_depression_gene
"A particular variant of the gene was associated with only about 3 percent of cases in a study"
Wooh! I'm totally underwhelmed!
"It's likely only one of many genes involved in the disease," Kelsoe said. "Who knows how many such genes there are? It's likely in the dozens."
I wish that headline writers had a clue. The text is completely inconsistent with the headline.
:-/
Lar
Posted by jrbecker on June 16, 2003, at 12:44:54
In reply to Re: Scientists Say they ID the Depression Gene » Ame Sans Vie, posted by Larry Hoover on June 16, 2003, at 10:53:37
There's no doubt that the genetic underpinnings of bipolar disorder are multidimensional, so the news of this discovery should be taken with a grain of salt. However, I do think the GRK link does have some clout to it. G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity. GRK-3 dysfunction might partially explain why cycling causes such drastic mood changes, and furthermore, why many bipolars are much more sensitive to dopaminergic meds than their unipolar counterparts. Other kinases have been theorized to play a similar role in BPD, including glycogen-synthase kinase-3 (GSK-3beta) -- also implicated in Alzheimer's and diabetes; as well as protein kinase C (PKC).
By the way, John Kelsoe's BPD genetic research is very highly respected in the field, so it's not like this info's coming out of left field. THe GRK-3 research has been building for a while now...
http://www.psycheducation.org/depression/fitness.htm
Posted by avid abulia on June 16, 2003, at 13:16:49
In reply to Re: BPD, GRK, and dopamine, posted by jrbecker on June 16, 2003, at 12:44:54
there are so many different variations of illnesses that can be labelled bipolar disorder, one must wonder *which bipolar patients he is looking at* and *which chromosomes* as well... due to isolation and inbreeding, there are several amish communities in which a phenomenally high number of people have BD, but in each case, the gene has been narrowed down to one chromosome--and it is a different chromosome in each community. it is likely to be a number of genes more than in the dozens.
~AA
Posted by jrbecker on June 16, 2003, at 14:11:05
In reply to Re: BPD, GRK, and dopamine, posted by jrbecker on June 16, 2003, at 12:44:54
Must have powerpoint to view presentation...
Posted by jemma on June 16, 2003, at 14:12:48
In reply to Re: BPD, GRK, and dopamine, posted by jrbecker on June 16, 2003, at 12:44:54
>GRK-3 dysfunction might partially explain why cycling causes such drastic mood changes, and furthermore, why many bipolars are much more sensitive to dopaminergic meds than their unipolar counterparts.
Hi there - I was intrigued by this statement and I wonder how it fits with my experience of dopamine. I've been diagnosed with bipolar disorder, yet dopamine seems to have a sedative effective on me. Wellbutrin makes me sluggish, and ritalin puts me to sleep. When you say sensitive, do mean that bipolars find dopamine induces mania? I'm trying to find a balance that works for me and counteracts my bipolar depression, and I'd appreciate whatever insight you could offer.
By the way, I always enjoy your posts. You are one of the people on this forum that I've learned a lot from.
- Jemma
Posted by jrbecker on June 16, 2003, at 15:04:16
In reply to Re: BPD, GRK, and dopamine » jrbecker, posted by jemma on June 16, 2003, at 14:12:48
Drugs or supplements that modulate dopamine (Requip, Stimulants, caffeine, NADH, tyrosine, wellbutrin [sometimes], even strattera [which affects DA]) make me tired too. At first, they rev me up, but then a rebound effect kicks in and makes me just shut down. I attribute this partly to the wicked feedback mechanisms in place that help to regulate dopamine's output. Secondly, dopamine plays contrasting roles for arousal in different parts of the brain. So because BPs are more sensitive to DA to begin with, it also means that screwing with its output will have more drastic effects.
I'm sorry that I don't have any real suggestion for you. My main strategy is to avoid most dopaminergic meds to begin with since they do more harm than good. For instance, if I take a stimulant, I really only get 2 good hours of focus and energy before I crash, and then become tired, irritable and anxious the rest of the day. I'm hopeful and confident that future drugs will be less adverse to this problem.
Research like this is definitely a step in the right direction.
JB
Posted by SLS on June 16, 2003, at 15:58:44
In reply to Re: BPD, GRK, and dopamine » jemma, posted by jrbecker on June 16, 2003, at 15:04:16
> For instance, if I take a stimulant, I really only get 2 good hours of focus and energy before I crash, and then become tired, irritable and anxious the rest of the day.
Hi JB.That is pretty much how amphetamine affects me. I receive a mild improvement for a few hours. If I continue to take it beyond the first day, I don't receive any benefit at all. I then need to d/c it for awhile so as to get the positive effect again.
- Scott
Posted by Ritch on June 17, 2003, at 9:53:26
In reply to Re: BPD, GRK, and dopamine, posted by jrbecker on June 16, 2003, at 12:44:54
> There's no doubt that the genetic underpinnings of bipolar disorder are multidimensional, so the news of this discovery should be taken with a grain of salt. However, I do think the GRK link does have some clout to it. G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity. GRK-3 dysfunction might partially explain why cycling causes such drastic mood changes, and furthermore, why many bipolars are much more sensitive to dopaminergic meds than their unipolar counterparts. Other kinases have been theorized to play a similar role in BPD, including glycogen-synthase kinase-3 (GSK-3beta) -- also implicated in Alzheimer's and diabetes; as well as protein kinase C (PKC).
>
> By the way, John Kelsoe's BPD genetic research is very highly respected in the field, so it's not like this info's coming out of left field. THe GRK-3 research has been building for a while now...
>
> http://www.psycheducation.org/depression/fitness.htm
>
>
Hey, I never noticed that on the site before. Thanks. A therapist that I was seeing in the '80's showed me something that I thought was interesting-except it was focused on the psycho-social elements of why it (bipolar disorder) exists. Basically, the gist of it was that people with bipolar perform a *social role* as inventors, story-tellers, preachers/shamans. I remember a picture of an aboriginal campfire scene on the front of the document with the priest (or shaman) raising his hands and telling a story-while everyone was carefully listening. Freaky stuff.
Posted by Simcha on June 18, 2003, at 2:21:27
In reply to Re: BPD, GRK, and dopamine » jrbecker, posted by Ritch on June 17, 2003, at 9:53:26
Hey Ritch,
Could that be why I'm getting a Masters in Counseling Psychology with a Specialization in Transpersonal Psychology? It's like mixing Shamanism with Psychotherapy. I'm not Bipolar, yet, I have Major Depressive Disorder and many of my relatives are Bipolar, and some with psychotic tendancies.
Also, it's interesting to note that in many Shamanic traditions they use medicines to heighten awareness of the other realms. We are using medicines in order to be balanced in this realm. I wonder sometimes if my sensitivity to this life is because I'm able to "pierce the veil," so to speak, into the other realms. No, I'm not psychotic. I just believe in many things that cannot be explained by science.
I would never give up my medication and go back to life like it was when I was severely depressed. Yet I wonder if the medication might be blocking a natural ability to commune with other realities than this physical realm. Anyway, it's food for thought...
Simcha
> > There's no doubt that the genetic underpinnings of bipolar disorder are multidimensional, so the news of this discovery should be taken with a grain of salt. However, I do think the GRK link does have some clout to it. G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity. GRK-3 dysfunction might partially explain why cycling causes such drastic mood changes, and furthermore, why many bipolars are much more sensitive to dopaminergic meds than their unipolar counterparts. Other kinases have been theorized to play a similar role in BPD, including glycogen-synthase kinase-3 (GSK-3beta) -- also implicated in Alzheimer's and diabetes; as well as protein kinase C (PKC).
> >
> > By the way, John Kelsoe's BPD genetic research is very highly respected in the field, so it's not like this info's coming out of left field. THe GRK-3 research has been building for a while now...
> >
> > http://www.psycheducation.org/depression/fitness.htm
> >
> >
>
>
> Hey, I never noticed that on the site before. Thanks. A therapist that I was seeing in the '80's showed me something that I thought was interesting-except it was focused on the psycho-social elements of why it (bipolar disorder) exists. Basically, the gist of it was that people with bipolar perform a *social role* as inventors, story-tellers, preachers/shamans. I remember a picture of an aboriginal campfire scene on the front of the document with the priest (or shaman) raising his hands and telling a story-while everyone was carefully listening. Freaky stuff.
>
Posted by Ritch on June 18, 2003, at 9:57:24
In reply to Re: BPD, GRK, and dopamine » Ritch, posted by Simcha on June 18, 2003, at 2:21:27
Hi Simcha,
I certainly don't have any plans to quit my Depakote to see if the "magic" will return, that's for sure. When I get really high (not the irritable mixed dysphoric junk), *magic* is what it feels like. Everything glows with signficance. It almost reaches a point where EVERYTHING is like everything else. Everything seems perfectly interconnected. I start becoming very superstitious. No event appears to be coincidental or happenstance. Unfortunately, these experiences make it tough to work and navigate Home Depot :) I never get much "insight" when I'm depressed though. It is like turning off all of the magic and getting in a suspended animation pod for a long trip to Mars or something. Shut-down or standy mode. System suspended. It would be nice to truly feel a functional stable/wellness for say three months in a row. That isn't going to happen without meds.
> Hey Ritch,
>
> Could that be why I'm getting a Masters in Counseling Psychology with a Specialization in Transpersonal Psychology? It's like mixing Shamanism with Psychotherapy. I'm not Bipolar, yet, I have Major Depressive Disorder and many of my relatives are Bipolar, and some with psychotic tendancies.
>
> Also, it's interesting to note that in many Shamanic traditions they use medicines to heighten awareness of the other realms. We are using medicines in order to be balanced in this realm. I wonder sometimes if my sensitivity to this life is because I'm able to "pierce the veil," so to speak, into the other realms. No, I'm not psychotic. I just believe in many things that cannot be explained by science.
>
> I would never give up my medication and go back to life like it was when I was severely depressed. Yet I wonder if the medication might be blocking a natural ability to commune with other realities than this physical realm. Anyway, it's food for thought...
>
> Simcha
>
> > > There's no doubt that the genetic underpinnings of bipolar disorder are multidimensional, so the news of this discovery should be taken with a grain of salt. However, I do think the GRK link does have some clout to it. G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity. GRK-3 dysfunction might partially explain why cycling causes such drastic mood changes, and furthermore, why many bipolars are much more sensitive to dopaminergic meds than their unipolar counterparts. Other kinases have been theorized to play a similar role in BPD, including glycogen-synthase kinase-3 (GSK-3beta) -- also implicated in Alzheimer's and diabetes; as well as protein kinase C (PKC).
> > >
> > > By the way, John Kelsoe's BPD genetic research is very highly respected in the field, so it's not like this info's coming out of left field. THe GRK-3 research has been building for a while now...
> > >
> > > http://www.psycheducation.org/depression/fitness.htm
> > >
> > >
> >
> >
> > Hey, I never noticed that on the site before. Thanks. A therapist that I was seeing in the '80's showed me something that I thought was interesting-except it was focused on the psycho-social elements of why it (bipolar disorder) exists. Basically, the gist of it was that people with bipolar perform a *social role* as inventors, story-tellers, preachers/shamans. I remember a picture of an aboriginal campfire scene on the front of the document with the priest (or shaman) raising his hands and telling a story-while everyone was carefully listening. Freaky stuff.
> >
>
>
Posted by jemma on June 18, 2003, at 10:14:21
In reply to Re: BPD, GRK, and dopamine » jemma, posted by jrbecker on June 16, 2003, at 15:04:16
Posted by SLS on June 18, 2003, at 12:10:17
In reply to Re: BPD, GRK, and dopamine, posted by jrbecker on June 16, 2003, at 12:44:54
Hi JRB
> G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity.
Do you know in which direction the excitability of DA neurons is modulated by GRK-3? In other words, if the activity of GRK-3 is increased, how is DA neurotransmission influenced? Is the sensitivity or experession of DA receptors changed? Second messengers?
Thanks.
- Scott
Posted by jrbecker on June 18, 2003, at 23:33:10
In reply to Re: BPD, GRK, and dopamine » jrbecker, posted by SLS on June 18, 2003, at 12:10:17
Scott,
GRK-3 activation is largely there as a control mechanism against dopamine overactivty. In one article about the recent discovery, Kelsoe made the analogy of "like being born on cocaine" when GRK-3 is not working correctly. So this speaks more to manic symptoms than it does symotoms of the depressive cycle. However, Kelsoe theorized that the likely dysfunctional GRK-3 gentic location is called the promotor region, which is responsible for turning the kinase on and off. And just like in some people, it might be more of an issue of turining it off as it is as turning it on. Thus, thsi might explain variances of individuals who are more prone to atypical-featured bipolar depression vs. classic bipolar I or frequent cycling. But I think the overall dysfunction refers to variances in consistent modulation of GRK-3. See article for more...
http://www.sciencedaily.com/releases/2003/06/030617080403.htm
I posted a link to Kelsoe's presentation in an above link (it's powerpoint) and I'll provide it again here below. There's really some great points he makes about genetic research. Most importantly, he states that there's anywhere from 20-200 major genetic defects that might predispose someone to bipolarity, so the idea of GRK-3 as the "single" defect is not at all likely. Secondly, and more interesting, he states that any genetic test can only explain 50-70% of an illness. Meaning there is still a lot of room for phenotypic (environmental) expression as well as other unknown factors. So it seems Kelsoe silences most of his doubters about this new discovery by somewhat agreeing with them in the notion that this is really only one small piece of the puzzle -- but an integral piece perhaps.A few of the slides actually go through the different chromosomes they have flagged as possibly implicated in the disease. One slide mentions all of the possible genetic links that come out of this meta-analysis, including one for brain-derived neurotrpic factor (BDNF) and another for regulation of the circadian clock (that one's definitely part of my issue!!).
http://ethics.ucsd.edu/seminars/2003/kelsoe.ppt
I"ll try to figure out if there's some way to convert the presentation from powerpoint so that everybody can view it, but I would definitely recommend trying to find a way to print this out if you can. It's fairly interesting stuff.
JB
> Hi JRB
>
> > G-protein coupled receptor kinase (GRK-3) is largely responsible for modulation of dopamine activity.
>
> Do you know in which direction the excitability of DA neurons is modulated by GRK-3? In other words, if the activity of GRK-3 is increased, how is DA neurotransmission influenced? Is the sensitivity or experession of DA receptors changed? Second messengers?
>
> Thanks.
>
>
> - Scott
Posted by SLS on June 19, 2003, at 8:38:14
In reply to Re: BPD, GRK, and dopamine » SLS, posted by jrbecker on June 18, 2003, at 23:33:10
Hi JB.
I don't know how many copyright laws this breaks, but I converted the powerpoint file to webpage.
http://sl.schofield3.home.att.net/medicine/GRK-3_Kelsoe.htm
- Scott
Posted by Ritch on June 19, 2003, at 11:12:28
In reply to Re: BPD, GRK, and dopamine, posted by SLS on June 19, 2003, at 8:38:14
> Hi JB.
>
> I don't know how many copyright laws this breaks, but I converted the powerpoint file to webpage.
>
> http://sl.schofield3.home.att.net/medicine/GRK-3_Kelsoe.htm
>
>
> - Scott
>
Scott, you did a great job converting that. It was easy to read, and wasn't data heavy switching slides. Very interesting.
Posted by jrbecker on June 20, 2003, at 14:52:47
In reply to Re: BPD, GRK, and dopamine » SLS, posted by Ritch on June 19, 2003, at 11:12:28
very interesting. extremely up-to-date on the specific biochemistry of depression/bipolar illness and its implications for treatment.
best to view with a high-speed connection:
http://www.bipolargrandrounds.com/archived.html
click on Dr. Manji's webcast originally presented on Tuesday, February 11, 2003
If anything, you should watch it for the simple reassurance you'll get from knowing just how dedicated some people currently are to solving all this stuff.
Secondly, it will erase any impulse you might have about wanting to quit your mood stabilizer.
Posted by Ritch on June 21, 2003, at 0:04:57
In reply to advanced biochemistry models of BP disorder, posted by jrbecker on June 20, 2003, at 14:52:47
> very interesting. extremely up-to-date on the specific biochemistry of depression/bipolar illness and its implications for treatment.
>
> best to view with a high-speed connection:
>
> http://www.bipolargrandrounds.com/archived.html
>
> click on Dr. Manji's webcast originally presented on Tuesday, February 11, 2003
>
> If anything, you should watch it for the simple reassurance you'll get from knowing just how dedicated some people currently are to solving all this stuff.
>
> Secondly, it will erase any impulse you might have about wanting to quit your mood stabilizer.
Thanks for that link-it looks very comprehensive and thought out. I bookmarked it and will check into some of the stuff later next week when I've got more patience for my slopoke connection. I only quit antimanic meds once (lithium), and it was a big disaster-I know better after that experience!
Posted by Ron Hill on June 21, 2003, at 11:32:18
In reply to advanced biochemistry models of BP disorder, posted by jrbecker on June 20, 2003, at 14:52:47
Posted by jrbecker on June 21, 2003, at 11:56:37
In reply to Re: BPD, GRK, and dopamine, posted by SLS on June 16, 2003, at 15:58:44
Scott,
a little more info on your original questions about GRK-3. First, GRK-3 is a g-coupled protein receptor kinase (I failed to answer this question the first time round). And secondly, as I mentioned before, in instances of bipolar I, it is theorized that there is a lack of GRK-3, and thus, a susceptibility to excess dopamine and other neurotransmitter activity. Where as in Bipolar II, contrastingly, there might be somehow an inability to turn GRK-3 off -- or perhaps more of the dyfunctional psyhogenes for BP II lie altogether elsewhere. This is echoed in Kelsoe's subject findings: "in four human subjects, reduced GRK3 expression corresponded with bipolar I, while the other two subjects not showing a GRK3 decrease had bipolar II."
By the way, this link goes a little further into some of the other gene locations they thought were suspect as well.
http://www.mcmanweb.com/article-89.htm
Give thanks to John McManamy for being there to do first-hand reporting for all of us.
Posted by McPac on June 21, 2003, at 14:25:12
In reply to Re: advanced biochemistry models of BP disorder » jrbecker, posted by Ritch on June 21, 2003, at 0:04:57
"I only quit antimanic meds once (lithium), and it was a big disaster"
>>>>>>>>> Ritch, how did you get after quitting the lith.?
Any rage/anger after quitting it?
Thanks!!
Posted by Ritch on June 21, 2003, at 18:13:03
In reply to Ritch, Re: advanced biochemistry models of BP, posted by McPac on June 21, 2003, at 14:25:12
> "I only quit antimanic meds once (lithium), and it was a big disaster"
>
> >>>>>>>>> Ritch, how did you get after quitting the lith.?
> Any rage/anger after quitting it?
> Thanks!!Actually, I didn't consciously plan to stop it cold and do without it. I was going to college (the 2nd time out of 3 times), and I was reducing my dose because of severe diarrhea from it (it was making attending classes difficult and nothing but an opioid would stop it). Anyhow, I found that I could keep my mania reasonably manageable by taking 300mg every 36 hrs. More than that and I couldn't tolerate it-less than that and I got too wired. Then, the mania went away with the season and I just stopped it and it didn't seem to make any difference. But, I very, very, slowly, got more depressed. I just didn't make the connection-felt like it wasn't any worse than it ever was (with or without meds). But it WAS a LOT worse. So much so, that I dropped out of school. Then in the Spring I got manic (bubbly-not angry). When I got depressed again-it was a humdinger and I got fired because I couldn't keep up with the workload and show up at jobsites on time and finish up my work. Then I really crashed hard. I finally went back to my doctor and I got on 600mg/day of Li again and I was a completely different person in about two weeks. Honestly, I don't *think* that NOT taking the mood stabilizers brought on mixed states (dysphoria-rage). I think that TAKING the wrong antidepressants or the wrong dosage of AD's is what *caused* the mixed episodes. My rage episodes have been the worst when I was taking doxepin, Remeron, Wellbutrin, etc. It would be more accurate to say that quitting antimanics, makes me scatter-brained and silly, taking the wrong AD's triggers the mixed stuff.
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