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Depression, SSRIs and neurogenesis


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#1 tjcbs

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Posted 21 December 2007 - 08:44 AM


A lot of people who take nootropics assume, or at least they used to, I don't know if people still believe this, that depression is caused by a small hippocampus, which is caused by decreased neurogenesis of unknown cause (perhaps excessive free-radical burden), which anti-depressants uniquely reverse, through some extraordinarily complex downstream mechanism. Therefore why not take anti-depressants if you aren't depressed, since it is in their nature to induce neurogenesis. Sure, people quibble about the neurogenesis effect to be shown only in depressed paitients, but what makes depressed people so special?

Why isn't it much, much, more natural and obvious to conclude that the anti-depressants lift the depression, and that depression in its nature is characterized by low neurogenesis? If you take the core nature of depression to be a withdrawl from the world into a self-reflective state, whether the mood which characterises this self-reflective state is melancholy or anxious or just plain flat, it seems clear that the less the brain is stimulated by the outside world, the less it is stimulated to grow new neurons. This effect has been shown in young brains, in the correlation between brain weight and enviornmental richness in rat pups. It seems likely that the same mechanism of neurogenesis persists into adulthood. As an aside, perhaps vanity, also a withdrawl into the self, is a disorder fundamentally similar to depression.

My own opinion of how anti-depressants work is that they upset the balance of the intricately interrelated mood-related neurotransmitters, which activates the brain's homeostatic mechanisms, moving the configuration of the brain into a different state, hopefully a good one, but . So they work on a principal similar to homeopathy. But it is not the homeostatic mechanisms which cause an increase in neurogenesis, rather it is depression in its functional nature which causes a decrease.

#2 Rags847

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Posted 21 December 2007 - 02:13 PM

Interesting post - I'll give it more thought.
A quick reaction: why wouldn't an intensely inward, "self-reflective" state as you describe produce much intense thinking and therefore neurogenesis (neuroplasticity)? Stendall's amazing "On Love" was created in such a state. The depressed, withdrawn person trying to work-through it all is learning life-lessons and gaining insights that they will benefit from down the road.

Edited by Rags847, 21 December 2007 - 02:13 PM.


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#3 tjcbs

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Posted 21 December 2007 - 06:50 PM

Interesting post - I'll give it more thought.
A quick reaction: why wouldn't an intensely inward, "self-reflective" state as you describe produce much intense thinking and therefore neurogenesis (neuroplasticity)? Stendall's amazing "On Love" was created in such a state. The depressed, withdrawn person trying to work-through it all is learning life-lessons and gaining insights that they will benefit from down the road.


I'm not familiar with Stendall, but I am not saying that self-reflection is inherently bad. It is certainly possible for rich cognition to take place where the object of contemplation is one's own mind. I guess that "self-reflective" was not quite what i had in mind, I was thinking more of a stance rather than a particular mental activity, a stance where the external world fades from view, and one's own thoughts, worries, issues etc. become the predominant features in one's mental landscape. Even then I think greatness and insight are possible, but for the vast majority of people this is not the case. I think that depression is the word for when this stance becomes involuntary, and when the mind itself is not a rich enough substrate to support strong healthy thought, a decline in neurogenesis results.

#4 ikaros

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Posted 21 December 2007 - 11:12 PM

A lot of people who take nootropics assume, or at least they used to, I don't know if people still believe this, that depression is caused by a small hippocampus, which is caused by decreased neurogenesis of unknown cause (perhaps excessive free-radical burden), which anti-depressants uniquely reverse, through some extraordinarily complex downstream mechanism. Therefore why not take anti-depressants if you aren't depressed, since it is in their nature to induce neurogenesis. Sure, people quibble about the neurogenesis effect to be shown only in depressed paitients, but what makes depressed people so special?

Why isn't it much, much, more natural and obvious to conclude that the anti-depressants lift the depression, and that depression in its nature is characterized by low neurogenesis? If you take the core nature of depression to be a withdrawl from the world into a self-reflective state, whether the mood which characterises this self-reflective state is melancholy or anxious or just plain flat, it seems clear that the less the brain is stimulated by the outside world, the less it is stimulated to grow new neurons. This effect has been shown in young brains, in the correlation between brain weight and enviornmental richness in rat pups. It seems likely that the same mechanism of neurogenesis persists into adulthood. As an aside, perhaps vanity, also a withdrawl into the self, is a disorder fundamentally similar to depression.

My own opinion of how anti-depressants work is that they upset the balance of the intricately interrelated mood-related neurotransmitters, which activates the brain's homeostatic mechanisms, moving the configuration of the brain into a different state, hopefully a good one, but . So they work on a principal similar to homeopathy. But it is not the homeostatic mechanisms which cause an increase in neurogenesis, rather it is depression in its functional nature which causes a decrease.


I think you've misunderstood some key concepts about depression. Small hippocampus does not cause depression, but it is depression itself that causes reduction in the volume of the hippocampus. Depression is characterized by elevated stress hormones which damage and interfere with neurogenesis. The mechanism is complex, but if you're healthy and have a positive outlook on life, SSRIs will not boost neurogenesis, because their therapeutic effect lies in part in blocking the overflow of glucocorticoids in the brain, and in the normal brain there is nothing to fix, so to say. Also people who have a rich inner life don't necessarily have to be depressed or have a smaller brain, it all depends on their interpretation of their existential situation - i.e. if you think your life sucks, then the body reacts to this by releasing more "mobilizing" chemicals (hormones) and this in short-term is useful, in long-term destructive. In fact stimulation is, yes, brain boosting, but it does not matter if it arrives from outside or inside. You although might be right about the fact that anti-depressants upset the neurotransmitter systems, which can be almost illustrated as kicking an old malfunctioning apparatus which sometimes just needs that little extra kick to make it work again. This fact would explain the SSRI/SSRE (tianeptine) controversy (why medication with opposite mechanisms of action alleviate the same core symptoms).

#5 abolitionist

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Posted 24 February 2008 - 09:25 PM

tianeptine can enhance neurogenesis by lowering stress hormones even lower than normal and providing a buffer against acute stress

i think corticotrophin releasing hormone blockers are in the pipeline;

http://www.neurotran...t/newdrugs.html

"Pexacerfont, BMS-562086 CRF1 antagonist Bristol-Myers Squibb Depression, anxiety Phase III"

Edited by abolitionist, 24 February 2008 - 09:27 PM.


#6 StrangeAeons

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Posted 28 February 2008 - 06:28 AM

all in all I'd say you're initial premise is a fallacy only the euthymic could make. Depression isn't some meditative, inward-driven state. It's a dampening of one's motivation and enjoyment from life, and tends to correlate (I'd say there's definitely a vicious cycle as far as causality) with very negative outlooks on life. As far as a euthymic person taking SSRI's, keep in mind there are side effects, and they can in fact make some people feel mentally cloudy or emotionally "blunted".

#7 yoyo

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Posted 28 February 2008 - 04:31 PM

It also involve congnitive inflexability ie ruminating thoughts.

#8 Stim1234

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Posted 29 February 2008 - 01:09 AM

Serotonin neurogenesis

Serotonin 5-HT1 receptors are implicated in anxiety and depression. These receptors belong to the family A of G-protein-coupled receptors and couple to inhibitory G-proteins. Recent studies show that chronic activation of 5-HT1A receptors leads to proliferation of hippocampal neurons suggesting that neurogenesis contributes to the effects of antidepressants.

Activation of the 5-ht1a receptor in the hippocampus increases neurogenesis.

#9 Jacovis

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Posted 26 June 2008 - 09:43 AM

So is the neurogenesis that some of these SSRIs cause when used for a while like a permanent alteration?

A friend's sister apparently took some SSRI and apparently was 'cured' of her depression so that even months after she stopped taking the drug, she wasn't depressed anymore. I haven't met the sister personally but it sounds unlikely to me. Is this possible? - if so would it not be worth the hassle of actually trying an SSRI despite all the negatives associated with their use (or perhaps Tianeptine would be a safer option)...

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#10 Yearningforyears

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Posted 27 June 2008 - 06:51 PM

A lot of people who take nootropics assume, or at least they used to, I don't know if people still believe this, that depression is caused by a small hippocampus, which is caused by decreased neurogenesis of unknown cause (perhaps excessive free-radical burden), which anti-depressants uniquely reverse, through some extraordinarily complex downstream mechanism. Therefore why not take anti-depressants if you aren't depressed, since it is in their nature to induce neurogenesis. Sure, people quibble about the neurogenesis effect to be shown only in depressed paitients, but what makes depressed people so special?

Why isn't it much, much, more natural and obvious to conclude that the anti-depressants lift the depression, and that depression in its nature is characterized by low neurogenesis? If you take the core nature of depression to be a withdrawl from the world into a self-reflective state, whether the mood which characterises this self-reflective state is melancholy or anxious or just plain flat, it seems clear that the less the brain is stimulated by the outside world, the less it is stimulated to grow new neurons. This effect has been shown in young brains, in the correlation between brain weight and enviornmental richness in rat pups. It seems likely that the same mechanism of neurogenesis persists into adulthood. As an aside, perhaps vanity, also a withdrawl into the self, is a disorder fundamentally similar to depression.

My own opinion of how anti-depressants work is that they upset the balance of the intricately interrelated mood-related neurotransmitters, which activates the brain's homeostatic mechanisms, moving the configuration of the brain into a different state, hopefully a good one, but . So they work on a principal similar to homeopathy. But it is not the homeostatic mechanisms which cause an increase in neurogenesis, rather it is depression in its functional nature which causes a decrease.


I noticed a huge improvement in memory recall and a general strengthening of the self, after taking 25 mg of sertaline (plus rhodiola) for a couple of days. I have been off sertralin for ten days, but the effects are still there.
I can definitely see this working as a nootropic.




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