# Depression gene discovered?



## David Baxter PhD (Jul 11, 2006)

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]


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## ThatLady (Jul 11, 2006)

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.


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## Halo (Jul 11, 2006)

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.


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## Retired (Jul 11, 2006)

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.


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## foghlaim (Jul 11, 2006)

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


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## ^^Phoenix^^ (Jul 13, 2006)

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.
> ...



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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## Into The Light (Jul 13, 2006)

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.


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## David Baxter PhD (Jul 13, 2006)

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


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## just mary (Jul 14, 2006)

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,


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## David Baxter PhD (Jul 15, 2006)

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.


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## just mary (Jul 15, 2006)

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.


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## David Baxter PhD (Jul 15, 2006)

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.


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## Into The Light (Jul 15, 2006)

so is the prolactin hormone responsible for depression if you have too much of it?


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## David Baxter PhD (Jul 15, 2006)

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.


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## just mary (Jul 15, 2006)

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.


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## David Baxter PhD (Jul 15, 2006)

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.


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## Kanadiana (Jul 15, 2006)

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?


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## Kanadiana (Jul 15, 2006)

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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## Into The Light (Jul 15, 2006)

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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## Into The Light (Jul 15, 2006)

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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## Kanadiana (Jul 15, 2006)

Depression runs in my family too ... Mom struggled with it her whole life. Who's to say how much is genetics and how much is conditioning. I dunno at all, probably 6 of 1 and half a dozen of the other in most cases.

I skipped baby blues and went straight for the post partum depression territories. Guess I'm programmed to do things in a big way LOL


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## Kanadiana (Jul 15, 2006)

baseballcap  said:
			
		

> 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 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.



Thanks a lot BBC ... I'll definately check out this guys site and read what he has to say.

I've heard a lot about EMDR and it seems to work for some and not for others. One thing I recall is that when I was going through intrusive memories and flashbacks that I noticed sometimes that when my eyes were focussed in certain directions I could "remember" certain things with eyes "that way" but not "that other way" ... I was so intrigued I even played with that a bit and went WOW. Interesting! It was long after that, years, when EMDR was being talked about and when I read something about it I figured that i'd figured some of that out years before, through experience ... so I had no problem believing in the validity of eye movements triggering or accessing different parts of the brain and memory, or retrieving previously learned information.

We still have so much to learn about body/mind/environment. Being human sure is fascinating and mysterious still


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## Into The Light (Jul 15, 2006)

kanadiana that is really interesting that you've experienced that yourself. this stuff just blows me away. there is so much to learn. i am surprised at how fascinating all this stuff is to me, and keep thinking there must be something i can do with it, i just don't know what. just keep reading and processing for now, i guess.

i hope the website is useful to you. most of the patient stories listed on the website are in the book as well. i always find patient stories really interesting too.


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## Kanadiana (Jul 15, 2006)

Yeah it is interesting on the one hand, then on another it isn't. I think we're so autopilot in how we do things that we just aren't aware of how we do them ... simple things like when studying or trying to remember something and noticing our eye positions when we're thinking hard, and noticing the positions when we "remember" (how did we DO that anyways? LOL) ... 

An example I think of regards auto-pilot once we've learned how to do something, is like tieing shoe laces. It becomes autopilot and we don't think about how we're doing it, we just do it. It takes a lot to learn how to tie show laces. I once was volunteering with psych outpatients and a lady had been released from a home and didn't know how to tie her shoe laces. Part of my job was to teach her how to do that. I was stunned to realize I didn't know how i accomplished it from the point of learning how to hold and position everything then to tie them. I had to slow down in order to be able to work from her level of knowing nothing to be able to know how i had to show her how. It really was a mind boggling experience for me. In a sense I had to dig my own brain to remember how I learned SLOWLY one step at a time. It was a totally humbling experience for me that I've never forgotten.

Its also interesting losing physical abilities I've had all my life as my arthritis and such does permanant damage.

I'm a bit foggy brained at the moment ... all my meds are just sort of hitting me right now with a brain fog DUH ... so will go now


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## David Baxter PhD (Jul 15, 2006)

They sometimes call that "muscle memory". Playing a musical instrument is like that... or many athletic actions.


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## ^^Phoenix^^ (Jul 17, 2006)

just mary  said:
			
		

> 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.


Good point JM, I always forget it when talking about genetics.


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