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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 15 of 15. This is the beginning of the thread.
Posted by Larry Hoover on February 21, 2007, at 15:38:55
Pretty robust p values.....to 10 ^-7.
http://archpsyc.ama-assn.org/cgi/content/abstract/63/11/1209
Lar
Posted by linkadge on February 21, 2007, at 20:20:49
In reply to MAO-A elevated in major depression, posted by Larry Hoover on February 21, 2007, at 15:38:55
Yeah, I read this study, but I found a few larger studies that showed no major differences of MAO levels in depression.
I find this type of hand-and-glove study a little questionable, since the study designers know what they want to find.
Linkadge
Posted by Phillipa on February 21, 2007, at 23:08:23
In reply to Re: MAO-A elevated in major depression, posted by linkadge on February 21, 2007, at 20:20:49
So what does it mean you need MAO B? I'm not well versed on the subject trying to learn although it's comes slow to me. Love Phillipa
Posted by Larry Hoover on February 22, 2007, at 6:44:48
In reply to Re: MAO-A elevated in major depression, posted by linkadge on February 21, 2007, at 20:20:49
> Yeah, I read this study, but I found a few larger studies that showed no major differences of MAO levels in depression.
I can't find any comparable studies. None I've seen looked at so many regions of the brain, nor employed this state-of-the-art scanning method.
> I find this type of hand-and-glove study a little questionable, since the study designers know what they want to find.
>
> LinkadgeI come to a far different conclusion. They know what they were looking to assess, but not the values that might be observed. The two groups differed by two standard deviations, and with extraordinarily low estimates of chance findings.
I think it would be hard to exclude this study from consideration in the conceptualization of the biochemistry of major depressive disorder.
Lar
Posted by linkadge on February 22, 2007, at 9:34:55
In reply to Re: MAO-A elevated in major depression » linkadge, posted by Larry Hoover on February 22, 2007, at 6:44:48
I would need to see larger studies of this type in order to be convinced.
Linkadge
Posted by bulldog2 on February 22, 2007, at 11:41:32
In reply to Re: MAO-A elevated in major depression, posted by linkadge on February 22, 2007, at 9:34:55
If this study could be replicated that would be a major breakthrough. I know this theory has been proposed in the past but from what I had read it was never scientifically documented. However if this were shown to be true that could explain the efficacy of maois in mdd.
Posted by notfred on February 22, 2007, at 18:07:07
In reply to MAO-A elevated in major depression, posted by Larry Hoover on February 21, 2007, at 15:38:55
So the logical recourse is a MAOI of MAO-A, if I understand this brief extract ? That would exclude Emsam but include nardil and parnate. It might suggest why some MAOI's are more effective AD's than other classes.
Posted by sdb on February 23, 2007, at 1:56:32
In reply to MAO-A elevated in major depression, posted by Larry Hoover on February 21, 2007, at 15:38:55
> Pretty robust p values.....to 10 ^-7.
>
> http://archpsyc.ama-assn.org/cgi/content/abstract/63/11/1209
>
> LarInteresting arcticle, is a robust p value if there's no bias and other things.
sdb
Posted by Larry Hoover on February 23, 2007, at 8:04:54
In reply to Re: MAO-A elevated in major depression }} Lar, posted by sdb on February 23, 2007, at 1:56:32
> > Pretty robust p values.....to 10 ^-7.
> >
> > http://archpsyc.ama-assn.org/cgi/content/abstract/63/11/1209
> >
> > Lar
>
> Interesting arcticle, is a robust p value if there's no bias and other things.
>
> sdbHere's why I think the small sample size is less relevant:
1. They sampled 10 brain regions, and every one was significantly different between the two groups. Not one exception.
2. The smallest chance estimate was p < .001.
3. If you consider each regional assay as an individual experiment, then the chance probability for the entire set is the product of each estimate.....i.e. vanishingly small chance of it being a fluke finding.
4. They published validation studies for their method before they conducted this sampling exercise.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16079787I can't find anything comparable in the literature. If anybody knows of one, please point it out to me.
Now, as a preliminary finding, it most certainly will draw further funding and research. That's all I hope for. Hypoxia also causes MAO elevation in other disorders, in other tissues. How that comes to pass is the real question. Monoamine disturbance is the result of some predicate process, methinks. That's where my curiosity lies.
Lar
Posted by Larry Hoover on February 23, 2007, at 8:11:58
In reply to Re: MAO-A elevated in major depression, posted by notfred on February 22, 2007, at 18:07:07
> So the logical recourse is a MAOI of MAO-A, if I understand this brief extract ? That would exclude Emsam but include nardil and parnate. It might suggest why some MAOI's are more effective AD's than other classes.
I don't think it's wise to exclude drugs with proven efficacy based on an hypothesis alone.
The proven efficacy of MAO inhibition is consistent with these findings, yes. But it is not explained by these findings.
Like any antidepressant class, MAO inhibitors take weeks to become effective, despite the fact that the enzyme inhibition is nearly instantaneous (literally, on contact). So, the MAO-mediated mechanism is secondary to something else. Something we don't yet grasp. MAOIs are still analogous to duct tape. They're "fixing" something that isn't really fixed at all.
Lar
Posted by notfred on February 23, 2007, at 9:25:42
In reply to Re: MAO-A elevated in major depression » notfred, posted by Larry Hoover on February 23, 2007, at 8:11:58
>
> The proven efficacy of MAO inhibition is consistent with these findings, yes. But it is not explained by these findings.
>
> Like any antidepressant class, MAO inhibitors take weeks to become effective, despite the fact that the enzyme inhibition is nearly instantaneous (literally, on contact). So, the MAO-mediated mechanism is secondary to something else. Something we don't yet grasp. MAOIs are still analogous to duct tape. They're "fixing" something that isn't really fixed at all.
>
> LarCool thanks, that makes sence.
Posted by linkadge on February 23, 2007, at 11:53:08
In reply to Re: MAO-A elevated in major depression, posted by notfred on February 23, 2007, at 9:25:42
Perhaps an arguement for lower dose MAOI's. Perhapse we don't need 80% inhibition of MAO-A in order to achieve theraputic response.
Also perhaps an argument for some of the documented antisuicide effect of coffee?
Linkadge
Posted by sdb on February 23, 2007, at 13:08:23
In reply to Re: MAO-A elevated in major depression }} Lar » sdb, posted by Larry Hoover on February 23, 2007, at 8:04:54
> > > Pretty robust p values.....to 10 ^-7.
> > >
> > > http://archpsyc.ama-assn.org/cgi/content/abstract/63/11/1209
> > >
> > > Lar
> >
> > Interesting arcticle, is a robust p value if there's no bias and other things.
> >
> > sdb
>
> Here's why I think the small sample size is less relevant:
> 1. They sampled 10 brain regions, and every one was significantly different between the two groups. Not one exception.
> 2. The smallest chance estimate was p < .001.
> 3. If you consider each regional assay as an individual experiment, then the chance probability for the entire set is the product of each estimate.....i.e. vanishingly small chance of it being a fluke finding.
> 4. They published validation studies for their method before they conducted this sampling exercise.
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16079787
>
> I can't find anything comparable in the literature. If anybody knows of one, please point it out to me.
>
> Now, as a preliminary finding, it most certainly will draw further funding and research. That's all I hope for. Hypoxia also causes MAO elevation in other disorders, in other tissues. How that comes to pass is the real question. Monoamine disturbance is the result of some predicate process, methinks. That's where my curiosity lies.
>
> Lar
>
>Hi Lar
You answered exactly to what I wanted to point out.
warm regards
sdb
Posted by psychobot5000 on February 25, 2007, at 11:18:42
In reply to Re: MAO-A elevated in major depression, posted by linkadge on February 23, 2007, at 11:53:08
> Perhaps an arguement for lower dose MAOI's. Perhapse we don't need 80% inhibition of MAO-A in order to achieve theraputic response.
>
Except (I would say) that experienced practicioners with MAOis inevitably find their patients respond better when they push and push the dosages--often well-above the DSM-recommended ranges.That said...tranylcypromine is most useful to me in absurdly low dosages, it seems.
Also, for all the focus on MAO-a, this type of data does not seem to accound for selegiline/Emsam's apparently greater efficacy than Moclobemide--which meta-analyses show is sligtly less effective than SSRIs. Practitioners in European countries have apparently been disappointed with it.
Posted by Larry Hoover on February 25, 2007, at 13:08:02
In reply to Re: MAO-A elevated in major depression, posted by psychobot5000 on February 25, 2007, at 11:18:42
> Also, for all the focus on MAO-a, this type of data does not seem to accound for selegiline/Emsam's apparently greater efficacy than Moclobemide--which meta-analyses show is sligtly less effective than SSRIs. Practitioners in European countries have apparently been disappointed with it.
Moclobemide is alone in this category in being a reversible inhibitor. It's a competitive inhibitor (different Lineweaver-Burk plots), whereas the others do damage to the binding site of the enzyme.
Lar
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