Psycho-Babble Medication | about biological treatments | Framed
This thread | Show all | Post follow-up | Start new thread | List of forums | Search | FAQ

Re: Hey Linkadge!

Posted by linkadge on July 4, 2008, at 10:57:46

In reply to Re: Hey Linkadge! linkadge, posted by Marty on July 3, 2008, at 14:14:15

>MUCH MORE (70% + ?) results IN THE LAST COUPLES >YEARS point to the theory that most AD drugs >induce/stimule SOME KIND OF BRAIN PLASTICITY >MECHANISM/PHENOMENON and that it would be that >effect which brings *MOST* -ALLIVIATED- >DEPRESSED PATIENT out of their misery.

Again, I don't necessarily think so. I think recovery is probably associated with a recovery of normal hippocampal placticity, but I don't think enhancment of hippocampal placiticity is critical for the theraputic effect. The one study I provided is an example of this (ie prozac still had an antidepressant effect in these mice without affecting neurogenesis). Lamotrigine is another example. It has a robust antidepressant effect in some users but does have any neurotrophic effect that we can detect. There is of course the glutamatergic model of antidepressants (I.e. ketamine can aleviate depression in hours, far too short a timeframe to cause any significant hippocampal growth). I (personally) think the lag more required to produce the long term adaptations in regional NMDA function.

>While this is not quite what I would call a >scientific concensus (!!) it's seems this theory >is already as good as the other !

I think its a good idea, but ketamine seems to demonstrate that neurogenesis is not really critical for alleviation of certain forms of depression. I think that the restoration of placticity is a marker of recovery, but not critical for recovery.

>which he's part of, behaviours/strategies are >badly performing to the point where it become a >viable/acceptable risk, from a evolutionism >point of view, TO FORCE THE ORGANISM TO ADOPT >A "SICKNESS BEHAVIOURS" STRATEGY (WITHDRAWAL AND >AVOIDANCE, ECONOMY OF RESOURCES ETC ETC) TO >PROTECT ITSELF WHILE HE PROGRESSIVELY >*UNBUILD/UNLINK* IN A *BRUTEFORCE* KIND OF WAY >SOME NEUROLOGICAL COMPONENTS (neurons, >intraneuronal Unknows, dentrites, glials etc >etc) IN SOME BRAIN ORGANS (ie. hypotalamus. >hypocampus, amygdala etc) WHICH ARE >SUITABBLE/VIABLE TARGETS FOR POSSIBLY >INHIBITING, IN THIS *BRUTEFORCED* MATTER (some >randomness/luck, some more somehow calculated >moves), THE PROBLEMATIC UNVIABLE >BEHAVIOURS/STRATEGIES.

Some depression is associated with reduced hippocampal volume, but there is the possability that reduced hippocampal volume is a risk factor for depression. I think that stress can cause depression through with a variety of mechanisms: hormonal, immune, monoamine, bloodflow changes, intracellular alteration, HPA axis abormalities etc. Antidepressants may not necessarily need to produce neurotrophic effects in order to quell the pain of depression IMO.

Some studies find reduced hippocampal volume only in *chronic / prolonged* depression.

http://www.jneurosci.org/cgi/content/abstract/19/12/5034

This means that depression can exist without hippocampal atrophy and that the atrophy might be a *result* of prolonged depression, not the cause. Alternatively, those with the lowest hippocampal volume may be the ones that are the least responsive to treatment.

For instance, this study found that those with the smallet hippocampal volumes are the ones that are more likely to relapse:

http://bjp.rcpsych.org/cgi/content/abstract/192/6/472

This would suggest that low hippocampal volume is not necessary for depression, but it is sufficiant to worsen the course of depression.

But even the mechanisms of this are unclear. For instance, the smaller hippocampal volume might not directly cause the depression, but it might do so indirectly. For instance smaller hippocampal volume => poorer memories for coping mechanisms. Ie a person with smaller volume may have fewer relative connections with regards to how to cope with certain stressors etc.

>3
>Now where does the AD fits in this theory ? What >about:
>1- SOME would initially increase mechanism #1
>(sick.Behav) + #2(depres) and somehow after ~2 >weeks forces the brain to promote #3 (Growth)in >order to compensate or something ? (Increased >Turnover Link ?) Prozac and Cie (SSRIs/SNRIs etc)

The SSRI's might also may more provide symptomatic treatment. For instance, many of the SSRI's (fluoxetine included) have some sort of opioid mechanism. Some also have an ability to ehance the function of reward circutry. These effects may produce the behavioral effects independant of neurotrophic effects.

>2- SOME would just promote #3(Growth) and leave >the other alone... but after awhile indirectly
>(by way of recovery) inhibits #2 and so #1 ? >SSRE like Tianeptine ?

I think the neurotropic and neuroprotective effects may enhance recovery and reduce relapse by way of positive cognative restructuring. I.e. increased neruogenesis helps establish memories which are critical for more effective coping strategies. *But* there are many drugs which enhance cognition and promote neurogenesis which are not antidepressants. For instance, nootropics and smart drugs are usually not effective antidepressants, some actually *increase* depression (cholinsterase inhibitors etc).

>3- SOME would JUST kill the pain of the process >and so in 'adjusted relieving' would allow the >organism to NOT be paralized too much by the >sickness behaviour and so find more easily >what's working for him

Depression is a vicious cycle. Sometimes symptomatic improvement is all thats needed. Every brain is built with the capacity for depression. Everybody has the *hell* circutry. Chronic stress in mice causes depression through a number of mechanisms. For instance, reward circutry becomes less active. Cholinergic systems also become supersensitive producing superactive memory for negative events. The stress is simply altering a number of emotional switches which tells the brain which circutry to use. The antidepressant combats these effects and attemts to turn off the switches turned on by stress. In doing so, it tries to restore a more balanced functionality of the pain/pleasure circutry.

I think those with lower hippocampal volume may find general day to day adaptation more difficult. Everyday stressors are harder to cope with. This causes an increase is subjective stress which again turns on the depressive switches. Drugs like Ketamine work so quickly because it is able to more quickly target the hyperactive/hypoactive brain circutry and metabolism. An SSRI may take weeks to dampen and enhance certain regional bloodflow wheras ketamine can do it rather quickly.

Ketamine appears capable of produceing longer lasting (weeks) relief from depression. After its influence wears off though, the effects of life and stress may start to resenstize the 'hell' circutry etc. At this point any agent which can help the patient process life events in a more postive way or help the patient change their life in a way that is that will allow the patient to make their life subjectively more managable, may be what prevents relapse - this may be through neurogenesis,

*but* keep in mind anything that can make the patient more active and capable of interacting with their environment is likely to enhance neurogenesis. Learning, physical activity, decreased iscolation, increased sociability, etc are all capable of promoting neurogenesis. So, even if the drug doesn't directly enhance plactiity, it may do so indirectly by simply reducing depression.

>not-paralyzing-already-okay psychological >pain... (Benzo style? .. which are, of course, >not ADs in the strict sense)

Yes, but benzo's tent to dampen neuronal activity in general. They can also dampen pysical activity too, ie they can abolish more adaptive behaviors. So, the reason they are not antidepressants is not necessarily that they don't produce neurogenesis.

>Anyway this whole theory (which Neurogenesis is >part of and support) makes ALOT of senses from >an engineering/evolutionist point of view.. >don't you think ?

Partially. Again, I think it may be part of the picture, but I don't think it is necessarily the *core* issue.

Again (in summary) mainly for the following reasons:

1) Not all studies show AD's promote neurogenesis
2) Some studies show the AD effect does not require neurogenesis.
3) Many compounds with AD effect have no influence on neurogenesis, ketamine, lamotrigine, etc.
4) Some studies show that only *chronic* depression is assocaited with reduced hippocampal volume.
5) There are many neurotrophic agents which are not antidepressant.


Linkadge


Share
Tweet  

Thread

 

Post a new follow-up

Your message only Include above post


Notify the administrators

They will then review this post with the posting guidelines in mind.

To contact them about something other than this post, please use this form instead.

 

Start a new thread

 
Google
dr-bob.org www
Search options and examples
[amazon] for
in

This thread | Show all | Post follow-up | Start new thread | FAQ
Psycho-Babble Medication | Framed

poster:linkadge thread:836811
URL: http://www.dr-bob.org/babble/20080626/msgs/837983.html