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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 20 of 20. This is the beginning of the thread.
Posted by SLS on September 12, 2006, at 13:07:32
Lithium and valproate (Depakote) reduce glutamate receptors in hippocampus. These drugs are predominantly anti-manic.
Lamotrigine (Lamictal) and riluzole (Rilutek) increase glutamate receptors in hippocampus. These drugs are predominantly anti-depressant. Imipramine, an antidepressant, produces similar results.
It seems that the more we know, the less we understand. Of course, we are getting closer and closer to the point where all of this data will fit into their appropriate places in the puzzle, and all will be understood. Well, maybe not all. What would the brain be without mystery?
------------------------------------------The Anticonvulsants Lamotrigine, Riluzole, and Valproate Differentially Regulate AMPA Receptor Membrane Localization: Relationship to Clinical Effects in Mood Disorders
http://www.nature.com/npp/journal/vaop/ncurrent/abs/1301178a.html
-------------------------------------------
So much for Prozac and serotonin-deficiency theory.
- Scott
Posted by Meri-Tuuli on September 13, 2006, at 6:11:32
In reply to Glutamatergic neurotransmission and mood disorders, posted by SLS on September 12, 2006, at 13:07:32
I guess the brain scientists are trying to understand something that is beyond their comprehension really, I mean, basically they are walking brains trying to study other brains..and I suppose that is really hard! If you know what I mean.
I don't think too much of mood disorder theories really. Its sooo complicated, and everyone is so unique that its impossible really - I mean there must be a hunderd million factors to take into account.. But then, what do I know?
Posted by TENMAN on September 13, 2006, at 6:41:35
In reply to Glutamatergic neurotransmission and mood disorders, posted by SLS on September 12, 2006, at 13:07:32
Hey Scott, thought you might find this study interesting.
TenMan
Posted by SLS on September 13, 2006, at 7:30:31
In reply to Re: Glutamatergic neurotransmission and mood disorders, posted by TENMAN on September 13, 2006, at 6:41:35
> Hey Scott, thought you might find this study interesting.
>
> TenMan
>
> http://www.grinnell.edu/academic/neuroscience/pn-v3/includes/41-44_PN3.pdf#search=%22hyperforin%20glutamate%22That's quite a revelation.
I hope someone tries to repeat the experiment.
- Scott
Posted by Phillipa on September 13, 2006, at 13:24:43
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by SLS on September 13, 2006, at 7:30:31
So are you saying the SSRI's are a hoot. If you are I believe it. Love Phillipa
Posted by notfred on September 13, 2006, at 18:27:43
In reply to Glutamatergic neurotransmission and mood disorders, posted by SLS on September 12, 2006, at 13:07:32
> -------------------------------------------
>
> So much for Prozac and serotonin-deficiency theory.
>
It never was a valid theory; only mentioned in the popular press.
Posted by linkadge on September 13, 2006, at 19:00:31
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by notfred on September 13, 2006, at 18:27:43
One aspect of the monoamine theory which I never understood was the following:
Evidence for a serotonin deficiancy was based on the idea that serotonin metabolite levels 5-htaa were low in the brains of suicide victoms.
Though, I was under the impression that reuptake inhibitors and MAOI's actually *decrease* the level of these metabolites?
Linkadge
Posted by notfred on September 13, 2006, at 20:08:19
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by linkadge on September 13, 2006, at 19:00:31
If depression was caused by a simple difficency
RI's would fix that. BLAM ! no depression. Too bad
it does not work that way.The science of measuring NT's in places other than
blood and CSF, ie in the places it is thought to count in the context of MI, is expermental."Evidence for a serotonin deficiancy was based on the idea that serotonin metabolite levels 5-htaa were low in the brains of suicide victoms."
I suspect they were looking at CSF. Do post mortum
levels corralate in any way to levels when someone is alive ?
Posted by SLS on September 13, 2006, at 23:35:30
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by linkadge on September 13, 2006, at 19:00:31
> One aspect of the monoamine theory which I never understood was the following:
>
> Evidence for a serotonin deficiancy was based on the idea that serotonin metabolite levels 5-htaa were low in the brains of suicide victoms.Review for the audience:
serotonin = 5-HT = neurotransmitter
MAO = monoamine oxidase = catabolic (breakdown) enzyme
5-HT <MAO> -> 5-HIAA
5-HT is broken down by MAO into 5-HIAA.
I know the amount of 5-HIAA found in urine and CSF is thought to reflect the rate of 5-HT turnover in the brain. I imagine the same is true of the amount that is found in the post-mortem brain. Turnover is usually interpreted as being indicative of neurotransmitter amounts or brain activity. The higher the level of 5-HIAA, the greater the activity of serotonergic neurons.
> Though, I was under the impression that reuptake inhibitors and MAOI's actually *decrease* the level of these metabolites?When physiological conditions are changed by medication, the consequence is a reduced 5-HT catabolism as either the MAO enzyme is directly inhibited (MAOI) or 5-HT is prevented from reaching it due to its sequestration in the synaptic cleft (reuptake inhibitor). The result of reduced catabolism of 5-HT is reduced 5-HIAA.
- Scott
Posted by SLS on September 13, 2006, at 23:53:22
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by notfred on September 13, 2006, at 18:27:43
> > -------------------------------------------
> >
> > So much for Prozac and serotonin-deficiency theory.
> >
>
>
> It never was a valid theory; only mentioned in the popular press.
I don't know about the valid part, but I do think it has played a significant role in scientific thought over the years. Even scientists are allowed to think simplistically. Things are simple from time to time.
- Scott
Posted by notfred on September 14, 2006, at 0:24:54
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by SLS on September 13, 2006, at 23:53:22
Even scientists are allowed to think simplistically. Things are simple from time to time.
>
>
> - Scott
But not here. There is no way neurochemistry is simple. If the causes of MI are simple, why no cure or treatment that is very effective ?
Posted by SLS on September 14, 2006, at 0:39:35
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by notfred on September 14, 2006, at 0:24:54
> Even scientists are allowed to think simplistically. Things are simple from time to time.
> >
> >
> > - Scott
>
>
> But not here. There is no way neurochemistry is simple. If the causes of MI are simple, why no cure or treatment that is very effective ?Simply because we haven't made bootstraps long enough yet.
:-)
- Scott
Posted by linkadge on September 14, 2006, at 8:41:40
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by SLS on September 14, 2006, at 0:39:35
I think that certain aspects of the monamine theory are usefull. For instance, while a direct monoamine imballance may not be evident, that is not to say that current antidepressants can't ameliorate certain aspects of certain mood disorders.
For instance, in many mood disorders, metabolism in the prefrontal cortex is diminished. Certain antidepressants can improve that. Activity in the lower brainstem too, may be overactive or underactive, and certain drugs can change that.
It is important to look at other parts of the brain, and not only the hippocampus.
Can, for instance, will targetting *just* the hippocampus change other symtoms like psychomotor retardation etc?
Linkadge
Posted by SLS on September 14, 2006, at 9:00:40
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by linkadge on September 14, 2006, at 8:41:40
> I think that certain aspects of the monamine theory are usefull. For instance, while a direct monoamine imballance may not be evident, that is not to say that current antidepressants can't ameliorate certain aspects of certain mood disorders.
I agree.Perhaps hitting targets upstream can produce a cascade of events that alter pathologies downstream. Symptom clusters might be ameliorated by hitting targets downstream. Who knows if there even is a single target between the upstream and downstream to aim at. In my case, I think there is. Mood shifts are so rapid and complete, it is difficult to believe that multiple systems containing second-messenger system-mediated events could possibly contribute. 'Tis a puzzlement.
- Scott
Posted by linkadge on September 14, 2006, at 11:39:36
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by SLS on September 14, 2006, at 9:00:40
Another thing to consider is this. Persons with a family history of unipolar depression often show atrophy in the prefrontal cortex. So even under the most ideal conditions, the frontal cortex might be in a state of hypofunction. In this case, you've got certain drugs that can boost activity there. While they are not curing the atrophy, they may restore some ballance that may not be otherwise achievable.
So perhaps the hippocampus is hypfunctioning as a result of prefrontal hypofunction. In which case directly targeting the hippocampus may
not completely restore normal behavior.
Linkadge
Posted by SLS on September 14, 2006, at 12:11:09
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by linkadge on September 14, 2006, at 11:39:36
> Another thing to consider is this. Persons with a family history of unipolar depression often show atrophy in the prefrontal cortex. So even under the most ideal conditions, the frontal cortex might be in a state of hypofunction. In this case, you've got certain drugs that can boost activity there. While they are not curing the atrophy, they may restore some ballance that may not be otherwise achievable.
> So perhaps the hippocampus is hypfunctioning as a result of prefrontal hypofunction. In which case directly targeting the hippocampus may
> not completely restore normal behavior.I tend to agree with this scenario. There is a positive feedback loop between the cortex and the hippocampus for which the frontal cortex must remain functional in order for the whole system to operate properate properly. I have, in the past, considered hippocampal hypofunction and atrophy to be secondary to the primary pathology of mood illness - whatever that is. I can now see how it becomes a contributor towards a worsening course of illness once it is initiated.
http://bjp.rcpsych.org/cgi/content/full/177/5/402/FIG1
- Scott
Posted by notfred on September 14, 2006, at 13:14:31
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by SLS on September 14, 2006, at 12:11:09
I would agree, too, with the last few posts by SLS and Linkage. It is a complex process & depression may have different causes and processes amoung different people.
I never go into full remission on a "clean" RI.
Only dirty polypharmacology yields full remission, for me.
Posted by Phillipa on September 14, 2006, at 18:07:53
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by linkadge on September 14, 2006, at 11:39:36
So Link if all my family has unipolar depression which they do what drugs target the hypocampus? And restore a normal mood? Any? Or is it still trial and error? Love Phillipa
Posted by Phillipa on September 14, 2006, at 18:13:38
In reply to Re: Glutamatergic neurotransmission and mood disor, posted by notfred on September 14, 2006, at 13:14:31
Never in l0 years have I had any type of remission. Love Phillipa
Posted by linkadge on September 15, 2006, at 6:51:09
In reply to Re: Glutamatergic neurotransmission and mood disor » linkadge, posted by Phillipa on September 14, 2006, at 18:07:53
I'm just saying that in persons with a family history of unipolar or bipolar depression, there seems to be a trait marker of atropy to the frontal cortex region.
Linkadge
This is the end of the thread.
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