Ever-Happy Mouse Sheds Light on Depression

An anonymous reader writes "Scientists have bred a strain of mouse that's permanently cheerful, in hopes of better understanding and treating depression in people. By breeding mice lacking the TREK-1 gene, which is involved in serotonin transmission, researchers were able create a depression-resistant strain. They say it's the first time depression has been eliminated through genetic alteration of an organism."

Lets call him

Pinky

Brain Candy

Reminds me of the movie Brain Candy.

http://www.imdb.com/title/tt0116768/ [imdb.com]

Today's Philosphical question...

If you're incapable of depression, and you're always happy, how do you know if you really are happy?

Re:Today's Philosphical question...

The same question goes for antidepressant drugs. I have spent long hours debating this with a doped up roomate as he gleefully skipped from psychoactive to psychoactive about the benefits and detriments of mommy's little helpers. I know that they got him through some difficult spots (without the psychotic episodes of his adolescence), but they also stifled his writing ability and effictively stopped his songwriting.

He was successful in college and in work thanks to these drugs, but was he truly happy without poetry and music?

Maybe Winston Smith can shed some light on this.

Re:Today's Philosphical question...

Most people are happy without poetry or music. (the "music" that is promoted with millions of dollars isn't really music, it's more like soft core pornography).

So he can't write songs anymore, he can still be a shoe salemen, CEO or a Senator.

Re:Today's Philosphical question...

I have to argue the reverse, I'm only able to write on the anti-depressants, as depression is complex and arrests my motivation for writing, as well as clearing the wooly cobwebs in my brain that make the process so hard.

Re:Today's Philosphical question...

He was successful in college and in work thanks to these drugs, but was he truly happy without poetry and music?

To quote Trent Reznor: "I don't write a lot when I'm happy."

I have a theory that says that the function of modern art is for the viewer to live vicariously through the artist's insanity. Van Gogh was famous for this. So was Leonard Cohen, Janis Joplin, Kurt Cobain, Alan Ginsberg, Salvador Dali, and Jackson Pollock, to name a few.

Perhaps the question isn't "can he be happy without his poetry", but "can he make good poetry without his sadness".

Re:Today's Philosphical question...

i'd rather be incapable of writing than be depressed. and as for not knowing what happiness is without experiencing depression that is a load of horseshit - i knew the difference between happiness and anxiety before i ever got depressed and now all that shit is out of my system and i'm happy again, i can honestly say my earlier understanding of happiness was perfectly accurate.

Re:Today's Philosphical question...

I dunno.

I was depressed because I sucked as an artist.

Then I quit art, and started fixing computers for a living.

I'm much happier now.

And I'm told my code is sheer poetry. (damn groupies)

Re:Today's Philosphical question...

He was successful in college and in work thanks to these drugs, but was he truly happy without poetry and music?

I'm not a big fan of permanently medicating the mind unless absolutely necessary... but when I had a episode of depression brought on by major illness, I wasn't thinking about poetry and music.

I was thinking pretty much constantly about killing myself. Not little fantasies "God I should just shoot myself." No... we're talking cold, calm, and consistent thoughts. Very frightening in retrospect and even more frightening that it felt so normal at the time.

Thank goodness I had family/friends to point me towards medical care. Lexapro changed that like a light switch, and the depression (and anti-depressants) are just a memory. But for some the depression is chronic and the treatment will probably need to be permanent.

And yes, before that happened I never understood the potential severity and use for anti-depressants either. Anti-depressants aren't just about turning off maudlin thoughts of missing your dead turtle.

Re:Today's Philosphical question...

Thank goodness I had family/friends to point me towards medical care. Lexapro changed that like a light switch, and the depression (and anti-depressants) are just a memory. But for some the depression is chronic and the treatment will probably need to be permanent.

And Lexapro can change your life too! Call 800-678-1605 or visit lexapro.com today!

Lexapro can cause nausea, insomnia, problems with ejaculation, somnolence, increased sweating, fatigue, decreased libido, and anorgasmia. Most of the side effects experienced by patients taking Lexapro are mild to moderate and go away with continued treatment, and usually do not cause patients to stop taking Lexapro.

Re:Today's Philosphical question...

If you'd ever been depressed, you'd know the answer to that.

Re:Today's Philosphical question...

...but they also stifled his writing ability and effictively stopped his songwriting.
 
Well is writing wasn't making him happy, probably good that he stopped. Writing can make you think a lot about your problems, and if this is something you find it hard to handle (or you have some major problems), then it can be a negative event.

Being happy means not thinking too much about the bad things.

Re:Today's Philosphical question...

Well is writing wasn't making him happy, probably good that he stopped.

If your brain chemistry is sufficiently fucked up, nothing makes you happy. That's what depression is - the inability to take joy from anything.

Re:Today's Philosphical question...

>mommy's little helpers

That phrase is about valium abuse in the 60s, not antidepressants which take 4 weeks to begin working. Mental illness is a real illness and youre attitude certainly doesnt help. You have a friend who is sick and takes a drug to normalize his moods and you're mocking him? Calling him doped up? Gee, no wonder he's depressed. With friends like you who needs enemies?

As far as the 'kills creativity' argument goes. Who knows. I think its vastly overplayed. "Art" created by people who are depressed or manic tends to be shit anyway. The people with real talent will always shine through regardless of moods. Tons of creative people have been treated for some kind of mental illness and they remained producive afterwards.

If the normalization effect makes someone say "I'd rather do this now" then more power to them. Not to mention, depression kills, I'd rather have a living friend than a suicide victim songmaker.

Re:Today's Philosphical question...

Have you read Interview with the Fountainhead by Ayn Rice?

Radical capitalist vampires? No, I haven't, but I think I might like to.

KFG

Re:Today's Philosphical question...

Have you read Interview with the Fountainhead by Ayn Rice?

No, but I've read the sequel, "Lestat Shrugged".

Re:Today's Philosphical question...

"If you're incapable of depression, and you're always happy, how do you know if you really are happy?"

You find that you spend less time planning your suicide than you used to.

May not generalize to humans

Deactivate a mouse's TREK-1 and it acts like it's on antidepressants.

Take my Trek away from me and I get depressed.

Makes you not care?

I wonder how closely depression and negative emotions like outrage, regret, etc are tied together? If I'm unable to be depressed, would I be able to care about what seems to be a series of bad things shaping the world? People I've met on anti-depressants can be pretty non-chalant regarding just about everything, so long as they're on their pills.

If you can see where I'm going with this, you're probably a paranoid conspiracy theorist too.

Re:Makes you not care?

If you wonder, find out... The answer is somewhat complex.

To give you at least some help: Part of the reason for the apathy of the anti-depressant crowd is that the most common anti-depressants are serotonin boosters (SSRIs), and serotonin is an inhibitory neurotransmitter. Now, certain other antidepressants (e.g, MAOIs) work by boosting other neurotransmitters, and can handle depression without apparently leading to the kind of apathy/nonchalance you're talking about.

With the usual Slashdot disclaimer: I am not a psychiatrist.

Eivind.

Re:Makes you not care?

Spoken like someone who's never had a problem with depression.

Personally, I think that's a small sacrifice to keep from wanting to KILL YOURSELF!

When someone's clinically depressed, the whole world is in shades of grey to them. Things that would normally bring joy are met at best with indifference and anger at worst. Interest in eating and having sex wanes. Social activities and obligations are ignored, along with housework. They feel listless and sleep more.

Then there's the extreme sadness and suicidal tendencies.

Personally, I wouldn't mind not caring for the 4 months out of the year that I'm depressed.

Re:Makes you not care?

People on anti-depressants are not "non-challant" about everything so long as they take their pills. This statement shows a profound misunderstanding of what modern anti-depressents are like. As someone who been taking anti-depressents for most of my life (very long family history of it, suicides everywhere on my family tree), I would like to point out that these are not happy pills, mothers little helpers that makes you stop caring about the world. This is a common belief and one that is simply not true. I feel a full range of emotions like any other person, and the emotional side effects aside from the alteration of the depression is quite small. In fact, I feel MORE emotion that I would off my medication becuase depression tends to overpower other emotions. This was not as true with older varieties of anti-depressents, but the modern SSRI's http://en.wikipedia.org/wiki/SSRI [wikipedia.org] have a minimal inhibitive effect on the range, duration, and power of my negative emotions aside from depression. Even more, I actually CAN get depressed even with the medications if the circumstances of my life dictate it. The ending of a relationship, loss of a loved one or whatever else might get a normal person depressed have the same effect on me. However, it is now short term and recoverable, that is, normal.

Society should think of modern anti-depressents as you would a prosthetic for a person born without a leg. Although unnatural, it corrects a problem, bringing sufferers closer to "normal". Of course, becuase you cannot SEE my handicap, people assume that it is not there, and my condition is a character flaw or choice. This is not true, I have no control over it just as a schizophrenic has no choice in the perception of their hallucinations. Not everyone who is depressed needs these aids, but for sufferers of long term, chronic depression these medications are lifesavers, quite literally. Research and discoveries like those in the article bolster my confidence that future treatments will bring me even closer to normal.

I am surpremely grateful that I live in the age of modern psychopharmacology, I am quite positive that I would not be here if it did not exist.

Re:Makes you not care?

I am a depression immune person who lives with and dates a bipolar woman. I swear that almost every single friend of mine through my girlfriend has some form of depression or another. The biggest difference between me and them is that I don't get irrationally depressed for long periods of time. Everyone gets sad when their dog dies. Resistance to depression doesn't mean that you don't get frustrated or sad. If you take away these emotions you would probably cease to be a truly functional human. You need a little sadness and regret now and then to keep you functional in society and able to maintain human relationships. The big difference is the duration of the depression, the depth of the depression, and the level of tragedy it takes to invoke it.

A truly depressed person can be provoked into a feeling of uselessness over trivial or simply non-existent events. The depression can result in more then just a little remorse or sadness. They can want to kill themselves or refuse to do anything. Further, such depression can last far longer then is appropriate. If you are depression resistant on the other hand, you keep on pushing forward. You never get the "lay down and die" feeling. You can still be sad, frustrated, or remorseful, but such feelings are not so over powering that you can't do anything else

Personally, I applaud any good research into depression. Despite arguments to the contrary, depression IS an illness that is completely worthy of treatment. While depression can be invoked through events in one's life, some times (if not most of the time) it is a purely physical problem in the brain that deserves treatment like any other disease. That is not to imply that psychotherapy does not have its uses, but the belief that a depressed person can simply be talked out of a depression is utterly insane and down right dangerous for some. If all that is standing between happiness in a depressed person is a flipped chemical switch in the brain, they should have the option of getting that switch flipped. I appreciate the work of tortured artists as much as anyone, but I don't want to see my loved ones suffer or pull a Kurt Cobain just to keep my MP3 player filled.

Modern Antidepressants are not "Happy Pills"

The parent post and a number of other posts in this thread showcase the lack of understanding people have of depression and the medication used to treat it.

Depression is not sadness. It a serious mental illness that has very detrimental effects on a person's well being and livelyhood. There is no relationship between depression or its treatment and ones ability to feel emotions like outrage and regret.

Antidepressants are used to treat clinical depression. They are not "happy pills." I personally suffered from depression combined with panic disorder that set in approximately two years ago. Since then I have been taking Lexapro which effectively treated my depression and continues to treat my panic disorder. I don't run around feeling happy all day and I still very much posess the ability to feel sad, happy, angry, outraged and regretful.

I especially can't believe the parent's comment about people being non-chalant while on antidepressants. People who make the decision to take antidepressants don't just pop them like tylenol. They take antidepressants because of a mental illness. Did you consider that it could be the depression that is making these people non-chalant? When you're consumed by your own depression it's a little bit difficult not to be non-chalant about what's going on around you. You have bigger things to worry about.

Re:Makes you not care?

That's like saying to a person with diabetes "Don't use insulin. Mind over matter." There was a study read about a few days ago where they found out that mice who have a certain active gene will be unable to regulate mind serotonin correctly. In other words, when a person started to become depressed, most people's brains would compensate for the significantly by releasing more serotonin to the right areas. However if this gene is active the brain (as it seems to be in a large percentage of those who have depression) wouldn't react at all and the serotonin would continue to drop and stay low. My medication helps my brain keep a constant, higher amount of serotonin in the synaps (that's spelled wrong).

I'm not scared of the dark side of me... I'm scared of the years of misery and pain (physical as well as mental and emotional) that I had before my depression was treated. I'm not out of the woods yet but I don't feel sad and in pain every second of every day. I dislike some of the side effects of my anti-depressants (apathy towards waking up at a set time, eliminates some of my creativity) but I consider the side effects a small price to pay for what I get in return. Research like this makes me hopeful towards better treatments with fewer side effects and I don't have to give anything or as much up to feel... okay.

I'm not happy all the time (nor would I want to be). I think I have a fuller range of emotions than I did before. I have a heightened empathy because I don't need to focus as much of my energy on my emotions all the time. I like being able to be sad sometimes and happy othertimes which I really couldn't get before.

Re:Makes you not care?

Your sense of "depressed," i.e. not in a good mood , saddened, or discouraged by identifiable events, is confused with clinical depression, which is a horrible, debilitating, illness.

In situational depression, e.g. death of a loved one, there is a clear exogenous cause of the depression. This is normal, and is usually worked out "solo" or through counseling, sans medication, or in some intractable cases with short-term use of medication. However, chronic clinical depression, dysthymic disorder, and their ilk are pathological. Depression is a disease. Your method works for most healthy people, but a clinically depressed patient is in open-loop mode: logic, reasoning and "working it out," as you say, don't work. It is wonderful that you are healthy and have worked out your own problems on your own sans pills, but the lives of countless people--whose brains are wired differently than you--have been saved or extended by antidepressants.

Insightful? Believe it or not, there are people who cannot function or would be dead were it not for antidepressants and counseling. Talk to people who have had the actual disease. Empathy will come to you as you grow up and get outside your own myopic view of the universe.

Chandra

Kill the damn things

Kill the damn things before they escape, learn to talk, and start asking us if "we are having a case of the Mondays"

NO GOOD CAN COME OF THIS

a similar effect in humansth

humans can have very similar experience: just quit work and start smoking pot, eating magic mushrooms and dancing on the streets in the nude.

Is it a good idea to get rid of stress-related (causing) mechansims? A stress free life maybe a very exciting prospect for an individual for about a month or a year, but is this going to be good from point of view of the bigger picture? If humans did not stress about things at all, would they bother doing anything, like bothering to find food, protecting the offspring, basically surviving as a species?

Re:a similar effect in humansth

. . .just quit work and start smoking pot, eating magic mushrooms and dancing on the streets in the nude.

Oh, wow man, you've seen me, huh?

KFG

Don't get excited yet

TREK-1 has an important role in neuroprotection against epilepsy and brain and spinal chord ischemia. So there are some very adverse side effects to this.

The article seems very light. There's lots of interesting stuff to be found if you google for "trek-1 gene".

Exciting Applications!

Hey, maybe the scientists can use this to their advantage. Something like this:

PETA spokesman: You're abusing animals in your lab, you fiend.

Scientist: But they're happy!

PETA spokesman: How can they be happy with you jabbing them with needles every half hour? Among OTHER things.

Scientist: Easy - they're permanently cheerful, no matter what we do to 'em. We engineered 'em that way.

PETA spokesman: >.

It's a start

If they can breed a Goth that's permanently cheerful *then* I'll be impressed.

Re:It's a start

"You don't know many goths, do you?"

You say that like it's a bad thing...

First (mis)read

The first time I read the last line I thought it said They say it's the first time depression has been eliminated through genetic alteration of an orgasm

I thought no shit it's going to be happy. A happy little boinker. Boinky, boinky, boinky.

Miranda anyone?

So these scientists haven't yet seen Serenity?

Wait till they get a look at the mice that end up like the Reavers!

Re:How the hell...

There toning it down for the kids. By "Happy" they mean the mice are randy.

Re:How the hell...

Actually, they are toning it down for the article. By happy depression resistant mice researchers generally mean it takes them longer time to give up and decide to let themselves drown in a forced swim experiment. There are some other measures of depression but this is the one I am most familar with and have seen used most often for depression studies.

Re:How the hell...

One way is the 'forced swim test'. They put the mouse in a water tank from which it can't escape. The animal will normaly swim around trying to find a way out. If it is depressed it will tend to give up on swiming and spend long periods of time without moving. Another way is the 'tail suspension test'. It is prety much the same thing. The mouse is suspended on its tail. If it is depressed it won't give a shit about life and will just hang there. Give it some antidepresenats and it will move and try to escape a lot more actively.

Re:How the hell...

Of course, one could argue with any one model of depression in animals. That is why the article mentions that they tested it in 5 models of animal depression. Even more, they showed increased efficacy of seratonin in their brains (which we know can reduce depression in humans), and in addition showed lower corticosterone levels under duress (a common measure of stress in humans and animals), which is indicative of lack of depression in humans (and a good thing in general).

So, yes, you can argue with any one model, but, precisely because of such arguments, articles (in Nature at least) prepare for them in advance - really, as much as is possible. If someone doesn't agree to results like this, then perhaps he/she just have a problem with the whole model of using animals to test human conditions; but this model has been proven time and again in giving eventual benefit to research on humans.

Of course, this result should be replicated by outside labs before we accept it. But it sounds like good research so far.

Re:How the hell...

Not taking away, just strategically moving it daily.

Re:How the hell...

So, like office workers and deadlines?

Re:People are not Mice

Mice don't feel taunted by the universe, to figure out it's secrets.

42, Dude. 42.

KFG

Re:What about appropriate depression ?

Less loss of work time and more productivity. What else is there to strive for?

It may actually work the other way around.

See, the brain (and not only in humans) is nicely tuned to keep needing the next thing to be happy about. Whenever you have some achievement (even small ones, like getting food when you're hungry) the brain gives itself a "yay, I'm happy" chemical signal, but that's followed immediately by releasing the "antidote" to that signal, to get back to the baseline. So you'll need the next achievement for your next moment of joy.

It's what keeps humans and all animals active. It's why your cat plays and thus trains its reflexes daily, instead of vegetating in a corner, still happy that it played last month.

In human society it's also a very important factor in why, for example, consumerism is alive and kicking, and keeping the capitalist economy going well past the point where just the needs are covered. People keep having these illusions like "man, I would be soo happy if I had that one more gadget/shirt/etc", and they do get happy about it... for a very brief time. Then they need their next achievement. And in turn, getting caught in the consumerism race also keeps them in the rat race at work, and taking shit they otherwise wouldn't put up with.

You can see in "video game addiction" cases what happens when people can stay continuously happy. It's not really physiological addiction, but good games give people small rewards often, which triggers the "yay, I'm happy" signal in the brain. There's always one more quest you finished, one more recipe you learned, one more item that you sold at the auction house (or IRL on eBay), one more boss you defeated, one more equipment piece you found, etc. So some people, which are kept happy enough by that, end up not doing anything else. You can see cases going all the way to playing for a month and then dropping dead.

So my take is that if someone actually produced genetically-engineered humans which are permanently happy, those humans would be even worse. They wouldn't even need video games to stay happy, so they probably wouldn't bother even with that. If you can be perfectly happy sitting on the couch watching the wall, you don't need to do anything else. You don't even need to buy a TV. Nor take shit from a PHB and do overtime to afford a huge plasma TV and a fashionable house in the suburbs. You get the idea.

So let me get this straight

Just keeping track ...

Scientists can now produce singing [slashdot.org], fearless [slashdot.org]
, cancer resistant [slashdot.org], super strong [slashdot.org]
, plague-infected [slashdot.org], mice with human brain cells [slashdot.org]
from artificical sperm [slashdot.org].

On top of that these mice are now happy?!

Re:So let me get this straight

Hmm..And on top of that, they are all features normally associated with overlords... .. I, for one, welcome them..

Re:So let me get this straight

It was on the cirriculum for my english class in high school. And I did read it.

So, did that English course go well? ;)

Re:So let me get this straight

Scientists finally clued into what you're saying and decided they sure as hell didn't want any variety those "super mice" angry. All new "super mouse" models will now be forced to comply to the new industry standard in happiness.

Re:So let me get this straight

It is truly an exciting time to be alive...as a mouse.

Re:So let me get this straight

Scientists can now produce singing, fearless , cancer resistant, super strong , plague-infected, mice with human brain cells from artificical sperm. On top of that these mice are now happy?!

Said mice were last over heard singing Monty Python's,"Always look on the bright side of life."