Because I don't believe that  I had ever thought about the question that 
Michael Britt posed, I really appreciated the question itself and most 
certainly the thoughtful responses by David and Mike.  I probably can say the 
same thing just about every week but being that Thanksgiving has just passed 
... well ... yeah ... thank you, TIPS. 



Miguel  



----- Original Message -----


From: "Mike Palij" <[email protected]> 
To: "Teaching in the Psychological Sciences (TIPS)" 
<[email protected]> 
Cc: "Michael Palij" <[email protected]> 
Sent: Monday, November 26, 2012 11:34:06 AM 
Subject: Re: [tips] Questions about Serotonin and Depression 

To add to what David says below, the journal "Philosophical Transactions 
of the Royal Society-B (Biological Sciences) recently had a special issue on 
the "serotonin hypothesis" (NOTE:  it is important to note that it is a 
hypothesis 
and not just a description) which can be accessed here: 
http://rstb.royalsocietypublishing.org/content/367/1601.toc 

There is an introductory article that provides a brief overview of the 
research: 

Paul R. Albert, Chawki Benkelfat, and Laurent Descarries (September 5, 
2012 ) 
Introduction: The neurobiology of depression-revisiting the serotonin 
hypothesis. I. 
Cellular and molecular mechanisms Phil. Trans. R. Soc. B, 367, 1601 
2378-2381; doi:10.1098/rstb.2012.0190 1471-2970 

|Abstract 
|The serotonin (5-HT) hypothesis of depression dates from the 1960s. It 
|originally postulated that a deficit in brain serotonin, corrected by 
antidepressant 
|drugs, was the origin of the illness. Nowadays, it is generally accepted 
that 
|recurring mood disorders are brain diseases resulting from the combination, 
|to various degrees, of genetic and other biological as well as 
environmental 
|factors, evolving through the lifespan. All areas of neuroscience, from 
genes 
|to behaviour, molecules to mind, and experimental to clinical, are actively 
|engaged in attempts at elucidating the pathophysiology of depression and 
|the mechanisms underlying the efficacy of antidepressant treatments. This 
|first of two special issues of Philosophical Transactions B seeks to 
provide 
|an overview of current developments in the field, with an emphasis on 
cellular 
|and molecular mechanisms, and how their unravelling opens new perspectives 
|for future research. 

There are 10 other articles in this issue that are relevant. 

-Mike Palij 
New York University 
[email protected] 

P.S.  It would be a mistake to claim that it is a "lack" of serotonin that 
is the 
problem in depression because the drug tianeptine is a "Selective Serotonin 
Reuptake ENHANCER" (SSRE), that is, it increases the amount of serotonin. 
For one source, see the Wikipedia entry but a PubMed search may be 
warranted: 
http://en.wikipedia.org/wiki/Tianeptine 
I think it is fairer to say that depression is a dysreguation of the normal 
levels of 
various neurotransmitters and other neurochemicals. 

On Mon, 26 Nov 2012 07:45:12 -0800 , David Epstein  wrote: 
>On Mon, 26 Nov 2012, Michael Britt went: 
>>I recently received a couple questions about the effect of SSRIs on 
>>depression and I'm not quite sure of the answer.  Would anyone care 
>>to edify us on these questions? 
>> 
>>Do people with depression produce enough serotonin, but it just 
>>isn?t getting absorbed? In other words, it gets released and then 
>>just hangs out in the synapse area? Or do they not produce enough 
>>serotonin to begin with and what doesn?t get absorbed creates a 
>>"deficiency"? 
>> 
>>As I understand it, SSRIs prevent serotonin from going back into the 
>>originating neuron and MAOs destroy the serotonin left in the 
>>synapse and that medication stops this destruction from 
>>happening. Both of these are designed to keep the serotonin levels 
>>high. Why not just increase the amount of serotonin in the body say 
>>with 5-HTP supplement?  Would more serotonin in the synapse allow 
>>more to be absorbed? 
> 
>My shortest, easiest answer--forgive me for doing it without giving 
>cites--is that you can't think in global terms about there being "too 
>much serotonin" or "too little serotonin."  Serotonin is released 
>along distinct pathways within the brain onto specific target regions, 
>and it does different things in different regions. 
> 
>This is partly explained by (and partly just complicated by) the fact 
>that there are at least 14 different subtypes of receptor for 
>serotonin.  The receptors aren't like the serotonin transporter that 
>SSRIs block.  They don't "absorb" serotonin; they're activated by it, 
>the way a key on your computer keyboard is activated by your finger 
>(without absorbing your finger!). 
> 
>What's more, the different types of receptor can change in number or 
>sensitivity over the course of minutes, hours, days, weeks, or months. 
>(The words to look up here and upregulation, downregulation, 
>sensitization, and desensitization.)  Those changes, which happen in 
>slow and complicated ways in response to SSRIs and other 
>antidepressants, are probably part of what makes the antidepressants 
>work. 
> 
>OK? 


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