To date, however, all of the research linking antidepressants and neurogenesis has involved animals. It was generally assumed that if drugs altered neurogenesis in mice, the same thing happened in humans – but this was an assumption, and clearly a pretty big one. Now a new report from a New York-based team claims that antidepressants do enhance neurogenesis in people - Antidepressants increase neural progenitor cells in the human hippocampus.
The authors took post-mortem brain samples from three groups of people – those with no history of depression, those with depression who were not on antidepressants when they died, and depressed people who were on antidepressants. They counted the number of neural progenitor cells (NPCs) in the hippocampus using a stain which specifically marks these cells (anti-nestin).
Although like all post-mortem studies the sample size was small (n=19 total), depressed people taking antidepressants when they died had much higher NPC numbers, indicating greater neurogenesis, compared to the other two groups. (Control: 360±246; untreated: 1119±752; treated: 17229±3443).
The picture above illustrates this; the brown cells are NPCs, and there are evidently more of them in the antidepressant-taking person on the right compared to the control on the left. The authors presumably picked these images because they look different, so, pinch of salt. But still, as an antidepressant user myself, it's nice to see what might well be going on inside my skull at this moment.The dentate gyrus of the hippocampus, the area where neurogenesis happens, was also larger in the antidepressant-treated group.
Is this evidence for the neurogenesis theory? Not exactly. It’s fairly good evidence that some antidepressants do boost hippocampal neurogenesis in humans, in accordance with the animal data. But we really don’t know what that means. It could just be a side effect, and nothing to do with how they work. I’ve previously written about some recent animal experiments finding that antidepressants have effects on behaviour even when neurogenesis is completely blocked. And notably, five of the seven antidepressant-treated patients in this study died from suicide. So, to put it bluntly, the drugs didn’t work very well, despite sending neurogenesis through the roof...
Boldrini, M., Underwood, M., Hen, R., Rosoklija, G., Dwork, A., John Mann, J., & Arango, V. (2009). Antidepressants increase neural progenitor cells in the human hippocampus Neuropsychopharmacology DOI: 10.1038/npp.2009.75
17 comments:
How is this supposed to work?
Controls (not depressed) have way way less of this cell (360).
Those that are depressed have more of the cell type (1119).
Then, those treated have the most of the cell type (17229).
So having either a lot of not a lot of the cells seems to be good? I can't view the full article if this is explained there.
Jeff
should be "either a lot or not a lot"
An excellent question. the authors don't even try to explain the finding that depressed people have more NPCs than controls.
Which is the opposite of what you'd expect if you think "depression = low neurogenesis".
To be honest it's almost certainly just a random finding because there is so much variation in these cell numbers.
But that in itself is not good news for the neurogenesis theory - if some people can get by with much lower rates of neurogenesis than others, is it really that important?
Survival of the differentiated progenitor cells might just as, or more, important than the proliferation. I guess it's pretty hard to do a human study on that atm though.
For a psychiatrist, I'm frighted by how dull I find this sort of thing - it's not necessary to know much about it for membership exams, or clinical practice, so I guess I'm just running scared.
What I am interested in is whether antidepressants work or not. Whilst I do think that they work for some people, I think that they're massively over prescribed and that some of this is explained by social inequality. Also, I'm not confident I can tell you what 'depression' is. If you ever ask a few people what it means to them when they say they have it they will tell you something different - so the notion of an 'antidepressant' is nonsense. Moncrieff's symptom based approach appears sensible to me.
More on that some other time. I think that this article is interesting, if rather flabby. Be interested to know what you think FP
"it's not necessary to know much about it for membership exams, or clinical practice, so I guess I'm just running scared."
I seem to recall seeing the most bizarrely specific neuroanatomy questions about Purkinje cells. But rumour is that MRCPsych standards have got so bad they're dropping the pass marks.
With regards to Moncreiff's view - is it really that novel - I've been involved in psychiatric research for years, and clinical practice more recently, and the claim that:
"Drugs for psychiatric problems are prescribed on the assumption that they mostly act against neurochemical substrates of disorders or symptoms...antidepressants are believed to reverse biochemical pathways that give rise to symptoms of depression and antipsychotics are thought to act on mechanisms that produce psychotic symptoms."
does not ring true for me at all. I would say that a very small minority of researchers, and a larger minority of clinicians (psychiatrists - non-psychiatrists believe all sorts of nonsense) subscribe to naive monoamine or dopamine theories of depression or schizophrenia (respectively) and the majority believe that their drugs cause symptomatic relief only.
It's an interesting one. As pj says there are few serious people who believe in naive monoamine theories any more (if they ever did).
But they are not lining up to debunk them - only people like Moncrieff are.
The weakness of monoamine theories is an elephant in the room. No-one points it out mainly because despite being flawed they are probably not totally wrong and they are better than any rival biological theory.
Basically people live in the hope that someone (preferably them) will come up with a refined monoamine theory which will answer all of the outstanding questions.
Until then the monoamine theory is worth more alive than dead, as it were.
Maybe it's an epiphenomenon!
Molecular Psychiatry (2009) 14, 764–773
"The mood-improving actions of antidepressants do not depend on neurogenesis but are associated with neuronal remodeling"
Could well be: in fact I wrote about that very paper previously.
I'm a layman with a fortunate (light at present) case of bipolar disorder. I like the idea of anti depressants being a fountain of youth of sorts by stimulating neurogenesis, as it is an optimistic theory, basically implying that healing is possible in damaged brain cells?
But I wonder if that neurogenesis takes place while we are asleep? If so, then the ADs might really be helping the patient to have closer to normal sleep (REM states and/or what not,) in addition to shoring up shortages and surpluses of brain chemistry. Perhaps the wacked out brain chemistry prevents proper REM (or whatever -- speaking as a layman, again) from taking place. In which case neurogensis would be a side effect of restoring proper sleep functions.
Googling after my post above, I did find a study that suggests REM affects neurogensis:
R. Guzman-Marin et al. (2008). Rapid eye movement sleep deprivation contributes to reduction of neurogenesis in the hippocampal dentate gyrus of the adult rat. Sleep, 31(2):167-175.
(From this web page article: http://cem5445.wordpress.com/ )
Oops:
"All major antidepressant drugs, except trimipramine and mirtazapine, suppress REM sleep, and it has been proposed that the clinical efficacy of these drugs largely derives from their suppressant effects on REM sleep. The three major classes of antidepressant drugs, monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), profoundly suppress REM sleep.[114] Mirtazapine either has no effect on REM sleep or increases it slightly.[115] The MAOIs almost completely suppress REM sleep, while the TCAs and SSRIs have been shown to produce immediate (40-85%) and sustained (30-50%) reductions in REM sleep. This effect often causes increased fatigue in patients who take large doses of antidepressants for extended periods of time. Such fatigue can occasionally interfere with a patient's everyday activities. Abrupt discontinuation of MAOIs can cause a temporary phenomenon known as "REM rebound" in which the patient experiences extremely vivid dreams and nightmares."
But I don't think they are mentioning the newer anti depressants. I take Wellbutrin XL, and that alone, as my only Rx. So perhaps the ADs that boost dopamine and norapenephrine support REM sleep, while their predecessors do not?
I'll stop here as 3 posts is probably too many. But two last links, googling dopamine / REM and norapenephrine / REM in turn:
http://www.neurology.org/cgi/content/citation/61/10/1328 .
http://books.google.com/books?id=3bTz0ifs5cQC&pg=RA1-PA173&lpg=RA1-PA173&dq=norepinephrine+REM&source=bl&ots=T_qqWYKygR&sig=D5DGljf7cTY_ktXPXide2ATX0NA&hl=en&ei=DMn5SrCBOoPuswOgldnHCQ&sa=X&oi=book_result&ct=result&resnum=10&ved=0CCQQ6AEwCTgK#v=onepage&q=norepinephrine%20REM&f=false
So after googling norapenephrine and REM, I must admit I am totally confused and must await the professionals here to comment, hopefully, to make any sense out of my layman's theory that antidepressants provide closer to normal sleep functionality in addition to their multiple other benefits/affects.
(The dopamine and REM URL didn't publish in it's entirety above, so here's the title at least:)
"REM sleep behavior disorder: A dopaminergic deficiency disorder?
Jean K. Matheson and Clifford B. Saper "
I want to commend you, for questioning the findings on this topic here. I think it is time, the US and UK and scientists who train here and start labs in developing countries, stop and think for a minute , what science are they doing in studies like these.As a former researcher in India and here in the US in neuroscience and now out of science, I am glad I am not contributing to these. Neuroscience research is difficult and as technology advances , it will become easier. But that doesnot give us the right to do something , just to publish and get grants.
The economic crisis the world in general is facing is a wake up call to all of us. It is time to stop spending hundreds of millions of dollars(and other currencies) , on studies like these which are totally wasteful.I recommend that everyone view WWW.storyofstuff.com, to see how destructive we are to our world. It is time to stop adding to this waste from the scientific community as well and start being responsible to the world around you.
do people die from anti depressants because im 20 and i have anxsety and depression what is the best medication for that?
I realize this is an older post, but it's still quite important as this "neurogenesis" trope gets spread all over as a justification for prescribing antidepressants.
(And its corollary -- that antidepressant-induced neurogenesis is necessary because depression causes neurological deterioration -- is heinous.)
Anyway, there's been a 20-year uncontrolled field study of antidepressants with millions of subjects. We already know the value of the putative neurogenesis. Despite it, there is doubt antidepressants work better than placebo.
A common side effect is sexual dysfunction -- clearly antidepressant-induced neurogenesis (if it exists) is not an unmixed blessing.
And finally, emotional anesthesia is a common outcome of lengthy antidepressant usage. I question whether you can call this a victory over depression.
So if antidepressants "work" by inducing neurogenesis, we have yet to see a functional benefit from it.
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