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David Baxter

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Depression gene discovered
Tuesday, 11 July 2006

a significant break-through, researchers identify P2RX7 as the gene responsible for major depressive disorders and, surprisingly, find it has no link with serotonin.

It has been known for many years that genetic factors are at the base of depression and bipolar disorder, but the complex molecular networks involved remain unknown.

"The actual gene, known as P2RX7, is found in humans and animals and is responsible for depression. It has taken many years to find," said neuroscientist, Professor Barden from CHUL Research Centre in Quebec, speaking at the Forum of European Neuroscience. Finding it is highly significant in uncovering the molecular pathways involved in depression.

The results were published in June edition of the American Journal of Medical Genetics.

During their lifetime, about 5-12 per cent of men and 10-25 pre cent of women will experience at least one episode of major depression. People with bipolar disorder - also known as manic depression - experience extreme mood swings.

Depression has until now often been associated with the serotonin system in the brain, a system that can influence mood and emotion. "What is particularly exciting is that P2RX7 has nothing to do with serotonin," said Professor Barden. Drugs that boost the flow of serotonin can be effective anti-depressants, but take weeks to take effect. The fact that P2RX7 that has nothing to do with serotonin could partly explain why.

Animal studies have shown that this gene is expressed in brain areas known to be involved in depression, and depressive-like behaviour in mice could be reversed by treatment with drugs that stimulate P2RX7.

P2RX7 also plays an important role in the brain's response to inflammation, which is known to be part of many neuropsychiatric disorders. Additionally, stress hormones decrease the activity of this gene, suggesting a mechanism for the onset of depression following severe stress.

"A person may have the mutated gene, but its 'default setting' means that they may not develop depression. We don't yet know how P2RX7 works and we still believe that a multitude of genes feed into the same pathway that may induce depression," said Professor Barden.

The identification of the gene means that anti-depressants in the future could target the gene directly. With anti-depressants currently targeting the serotonin system, P2RX7 is bypassed to an extent.

In animal studies, activators of P2RX7 have an immediate anti-depressant action, giving hope that new anti-depressant medication, with a new mechanism of action, can be developed.

Source: Barden N, Harvey M, Gagne B, Shink E, Tremblay M, Raymond C, Labbe M, Villeneuve A, Rochette D, Bordeleau L, Stadler H, Holsboer F, Muller-Myhsok B.
Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder. Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141(4):374-82. [Abstract]
 

ThatLady

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Wow! That reallY IS a breakthrough. It's exciting to think that there may soon be a new way to treat depression, and that it may actually target one of the genetic factors directly. :)
 

Halo

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I too was thrilled when I read this post. Thanks Dr. B. for it. I think that finally there will be some serious medical breakthroughs with respect to depression and mental illness. Although I have to admit that I still wish there was some blood test or brain scan that could be done to show what exactly a person is diagnosed with and can relieve me from the feeling of it all being "in my head". Now that would be a great breakthrough but until then, I am happy to see that this genetic link has been made.
 

Retired

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If a gene is identified as the source of depressive illness, does it mean that eventually a blood test could identify people at risk or even serve as a diagnostic tool? Pharmaceutical companies develop designer drugs where the molecule is designed to fit a specific function.

It will be interesting to see the developments in research based on these findings.
 

foghlaim

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I think this is really exciting news also, but as usual it will prob take a decade for the drugs to be available to the populos. sorry to put a dampner on things folks, but isn't that the way things usually go in the science and research field.??

but eventually hopefully there will be a way to find out if a person has this particular gene defect?? and the meds will be available to fix it.

makes me wonder tho about the serotoinin inhibitors.. given that they seem to bypass this gene..hmmm.. i now i should have a question here but it ain't coming to me right now.

still tho all in all it is exciting news!!

nsa
 

^^Phoenix^^

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David Baxter said:
Depression gene discovered
Tuesday, 11 July 2006

a significant break-through, researchers identify P2RX7 as the gene responsible for major depressive disorders and, surprisingly, find it has no link with serotonin.

"The actual gene, known as P2RX7, is found in humans and animals and is responsible for depression. It has taken many years to find,"

NO link with serotonin? that is really interesting
and animals?? thats pretty cool, they can get depressed... (not cool that they get depressed, but cool that there is scientific basis for it)
 
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i've always believed animals have the same feelings as we do (mammals mainly for some reason). interesting to have scientific confirmation.

nsa i am stuck on the question that we're supposed to have too. it's on the tip of my brain. something to do with us trying to cure depression in a roundabout way by targeting serotonin? it's like we're using a detour when we could have a more direct fix. in 15 years time people will be amazed at how we treat depression today.
 

David Baxter

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There was a time when the only treatment was electroconvulsive shock therapy. And we still don't know why that worked - but it did.
 

just mary

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David Baxter said:
There was a time when the only treatment was electroconvulsive shock therapy. And we still don't know why that worked - but it did.

But did it work for everyone? Or is shock therapy just so intense? What I mean is that ECT must be pretty hardcore, I can imagine that it would provoke a change in anyone, not just someone with a depressive disorder.

I also think it's interesting that the gene they found has nothing to do with serotonin. It might make sense now why antidepressants don't work for everyone. Maybe depression is a result of many different factors.

But I'm sure whatever gene therapy they develop will help some people, but not all. This article seems a little over the top for me. It reminds me of when they found the gene for breast cancer but it turned out it was only for a specific type of breast cancer, in other words, you could still get breast cancer even without the breast cancer gene. From what I remember, only 10 to 20 per cent of breast cancer patients had the gene, the rest didn't.

There is no perfect solution, we take what we can get. Human beings are all pretty much the same but we differ in some very tiny ways but these ways can make all the difference.

Take care,
 

David Baxter

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It sometimes took a series of ECT treatments but I think it was pretty effective in relieving severe depression - and still is for depression that doesn't respond to other treatments. There are some undesirable side-effects, of course, so it's certainly not the treatment of choice.

My point wasn't to make a case for using ECT more... it was jjst to point out that there are treatments for many conditions, physical and psychological, that work even though we don't fully understand why they work. The nervous system is highly integrated and very complex - it may well turn out that when medications reduce the uptake of serotonin there is a domino effect that changes several other things in a sequence of events and that one of those other things is the critical event in decreasing depression.
 

just mary

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David Baxter said:
It sometimes took a series of ECT treatments but I think it was pretty effective in relieving severe depression - and still is for depression that doesn't respond to other treatments. There are some undesirable side-effects, of course, so it's certainly not the treatment of choice.

My point wasn't to make a case for using ECT more... it was jjst to point out that there are treatments for many conditions, physical and psychological, that work even though we don't fully understand why they work. The nervous system is highly integrated and very complex - it may well turn out that when medications reduce the uptake of serotonin there is a domino effect that changes several other things in a sequence of events and that one of those other things is the critical event in decreasing depression.

I completely agree Dr. Baxter, the human body is pretty complex - how it all interacts etc. Thanks for the reply, it was interesting.
 

David Baxter

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One of the interesting (to me anyway) research findings some years ago was that following ECT (or insulin shock therapy) or prolonged sleep deprivation, both of which produce at least temporary reduction in deprssion, there was a sharp increase in the hromone prolactin. Given that there is tight integration between neurochemistry and the endocrine system, as well as the links between hromonal variations and mood (e.g., post-partum depression, PMS) I found that fascinating.
 

David Baxter

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No, I don't think it's that simple. It really is all interconnected - it's like a domino effect - when one thing changes, it ripples all through the system and other things change up or down as well.
 

just mary

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I'm not sure how this fits in but I just wanted to post it. I was just listening to "Quirks and Quarks" on CBC radio - it's a science show. A geneticist was being interviewed and she explained that "genetic determinism" no longer exists in genetics - their (geneticists) studies focus more on how the gene interacts with the environment. I guess this relates to how everything is interconnected and just because you have the gene for depression - it does not mean you will develop it - other factors have to be present.
 

David Baxter

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Exactly, JM!

What seems to be inherited is a vulnerability or increased predisposition to developing certain conditions or illnesses like depression, anxiety, or even possibly schizophrenia.
 

Kanadiana

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This article gets a WOW from me too! Perked my attention even more at the mention of depression and inflammation??? Never heard inflammation to be involved in depression before. Am I reading that correctly? ;)
 

Kanadiana

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Like rheumatoid arthritis predisposition being activated by (they think) a virus or something in the environment. Until activated the predisposition is simply a dormant potential waiting for a trigger that may, or may not, happen in a lifetime.

Once activated, other autoimmune disorders seem to have the doors opened for them as well... our systems and the environment are so complexly interactive ... I like your description of "dominoes effect" David. Cuz that's sure how things seem to go.
 
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i think that's how it works too. you've got a predisposition and if the "right" conditions are met you get depression. i think that women are especially vulnerable right after having given birth because hormone levels are completely different. they should study the baby blues more, it might give us some more insight. i remember how tearful and horrible i felt a few days after each baby, and it was so obvious to me that my emotions were out of place and that i was crying over things that didn't need crying about. it was as if my body was just doing this to me and i had no control over it. hormone levels are all over the place right after a baby. this really might give us a clue. i wonder if anyone has done any studies focusing on the baby blues (where it doesn't develop into post partum) - measure the mother's hormone levels and document how blue she is feeling.
 
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kanadiana i have read about inflammation playing a role depression as well. see http://www.instincttoheal.org/ i have the book by this dr and it talks, amongst other things, about inflammation. this book is excellent and i recommend it to anyone. there are a lot of excerpts on this website. i have looked into this guy and he seems to be legitimate (not one of those, buy my book and it will solve all your problems kind of guy). i saw an interview with him as well and he came across as a reliable doctor and researcher. mind you i wasn't able to get over my depression with all of his techniques but i think the problem is that i went beyond mild depression. this book focuses on mild depression and things you can do to get better. it also explains how your brain works, and that there are two parts to it, the emotional brain and the rational brain. i could write pages about everything he touches on but i'll stop here. it is all incredibly fascinating. take a look at his website, i am sure you will be interested in what he has to say.

i think he is also the one that developed emdr, this is something that has caused a lot of skepticism in the field of psychology but it does seem to work and is becoming more accepted. i wish i had access to it where i live, i think it would speed up my recovery.
 

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