Monday, January 07, 2008

Depression, Dreaming and Rehearsal learning

We all know that depression is marked by an increase in REM Sleep or dreaming and their are various theories of why this increased dreaming may be a root cause of depression itself. One theory posits that having too much dreams or emotional negativity even while sleeping (most dreams have negative content) may lead to maintenance of downward spiral of depressive cognitive and emotional style. Another theory posits that having too much negative dreams may lead us to get exhausted and the morning weariness found in depression is due to this fact.

I'll not comment regarding the purported mechanism and causal direction of link between depression and dreaming. Suffice it to note few pertinent facts:

  • Depressives dream 3 -4 times more than normal people.
  • Most Anti-depressants cause REM sleep to be suppressed and this may underlie their therapeutic action or may just be a side-effect.
  • There is mixed evidence as to whether REM sleep is also altered in Mania (although a decrease in REM sleep is not mentioned in literature- if anything REM increases just like in depression)

Now I'll like to highlight an important experiment conducted by Wisconsin Madison scientists. They deprived rats of REM sleep and found that such rats became idiots in terms of survival sense and failed all standard test of survival. I'll first describe the procedure and their results and then theorize:

What happens when a rat stops dreaming? In 2004, researchers at the University of Wisconsin at Madison decided to find out. Their method was simple, if a bit devilish. Step 1: Strand a rat in a tub of water. In the center of this tiny sea, allot the creature its own little desert island in the form of an inverted flowerpot. The rat can swim around as much as it pleases, but come nightfall, if it wants any sleep, it has to clamber up and stretch itself across the flowerpot, its belly sagging over the drainage hole.

In this uncomfortable position, the rat is able to rest and eventually fall asleep. But as soon as the animal hits REM sleep, the muscular paralysis that accompanies this stage of vivid dreaming causes its body to slacken. The rat slips through the hole and gets dunked in the water. The surprised rat is then free to crawl back onto the pot, lick the drops off its paws, and go back to sleep—but it won't get any REM sleep.

Step 2: After several mostly dreamless nights, the creature is subjected to a virtual decathlon of physical ordeals designed to test its survival behaviors. Every rat is born with a set of instinctive reactions to threatening situations. These behaviors don't have to be learned; they're natural defenses—useful responses accrued over millennia of rat society.

The dream-deprived rats flubbed each of the tasks. When plopped down in a wide-open field, they did not scurry to the safety of a more sheltered area; instead, they recklessly wandered around exposed areas. When shocked, they paused briefly and then went about their business, rather than freezing in their tracks the way normal rats do. When confronted with a foreign object in their burrow, they did not bury it; instead, they groomed themselves. Had the animals been out in the wild, they would have made easy prey.

The surprise came during Step 3. Each rat was given amphetamines and tested again; nothing changed. If failure to be an effective rat were due to mere sleep deprivation, amphetamines would have reversed the effect. But that didn't happen. These rats weren't floundering because they were sleepy. Something else was going on—but what?

To me it seems that what is happening in these dream-deprived rats is an unlearning of learned helplessness paradigm. In learned helplessness, one stops exploring the environment and becomes extremely cautious. Learned helplessness is an extremely influential theory of depression and I have blogged about it previously. In the dream-deprived rats something exactly the opposite is happening - they are becoming more exploratory and sort of unlearning the basic survival instincts .

To me all this seems to nicely fit together. Dreams may be instrumental in rehearsal learning and when the rat (or human) has been repeatedly exposed to inescapable shocks (unavoidable stress), then it may lose the desire to explore not only in the real world, but also in the dream world - the primary purpose of which is to generate alternative strategies to previously un-encountered negative situations. When one loses or fails to find creative solutions to the inescapable situations, one falls in a negative dream loop whereby one fails to explore adequately new strategies or to reassess the environment in light of new evidences. Instead as one has failed to find creative solutions earlier, one;s dreams become pre-occupied with failure- and with each failure prompts more vigorous search for answers in the dream -thus leading to more REM sleep. Also, as REM sleep is required for thus maintaining the new (unhealthy) associations hence as long as adequate REM sleep is available one stays stuck with the learned negative associations and the learned helplessness.

SSRIs and other anti-depressants , by blocking the REM sleep , may be providing one additional step whereby dreaming stops for some duration and the synapses that underlie negative associations (that were constantly strengthened during dreams) are given time to naturally become weak. Thus events no longer have automatic negative connotations, but can be appraised afresh with a new outlook. This may be one putative mechanism of how anti-depressants work. This may also explain why anti-depressants take so much time to become effective. When dreaming stops, the unlearning doesn't happen in a day- the weakening of associations would take weeks and months to materialize and have an effect.

Cognitive - behavioral theory may also be working on the level of dreams and it would be interesting to note how much dreaming is reduced and brought to normal levels as CBT starts showing effects.

The behavior of the dream deprived rat seems almost manic- unconcerned with survival and unnecessarily risk-taking. One experiment that can be conducted is to first induce learned helplessness in rats (by exposing them to unavoidable shocks) and then dream-deprive them as per the above methodology. If dream-deprivation restores the normalcy in rats and removes the depressive symptomatology we have a new theory of how depression works. This is not a difficult experiment to do and can be easily performed. I'm sure it will lead to positive results. I look forward to hearing from some readers of this blog as to how the experiment actually went (I myself am in no position to conduct such experiments). Do let me know via comments the experimental results- even if they are negative.

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Colin said...

"The surprise came during Step 3. Each rat was given amphetamines and tested again; nothing changed. If failure to be an effective rat were due to mere sleep deprivation, amphetamines would have reversed the effect."

Considering the behavioral effects of amphetamines can be increased by sleep deprivation, I won't be so sure that amphetamines would reverse the effect. It would be interesting to test these same factors using a test that somehow allowed REM but interrupted Slow Wave Sleep.

Found one resource on SD increasing the addictive nature of amphetamines. Not exactly related, but it does show how amphetamines do not just simply cancel out SD. I know there are also other studies out there showing overconfidence in one's performance.:
Paradoxical sleep deprivation potentiates amphetamine-induced behavioural sensitization by increasing its conditioned component

Sandy G said...

Hi Colin,

Amphetamines generally do have the arousal or stimulant effect and thus are good at reversing the SD. The fact that amphetamine addiction becomes stronger on SD, points in this direction only - that mice find amphetamine more rewarding when Sleep Deprived, as they probably need it to feel normal and non-sleepy.

I know that life is not simple and there would be no simple relation between SD and amphetamine and there would always be nuances; but it is safe to conclude that, in general, amphetamine can be considered to reduce the symptoms of SD.

Alas, the experiment you suggest (SD without REM disruption in control mice) may not be possible, although that would have definitively settled the issue.

Jean-Baptiste said...

You've got an really interesting article here. I had never thought about a possible connection between dreams and depression.

As an editor for The Issue, I've decided to feature it in the Science and Health Section today. Check it out at


Sandy G said...

Hi Jean-baptiste,

Thanks . I am honored that my article got featured in The Issue and would thus have a broader readership. Many thanks.

Ellin said...

Antidepressants are 9 out of 10 times misused or abused due to their tranquilizing property. This very tranquilizing trait of the antidepressants makes them vulnerable to misuse. The fact of the matter is that antidepressants are to be used as tranquilizers but only on prescription. On having them otherwise one not only runs the risk of suffering the side effects but also the prospect of dependence on the drug. Antidepressants like xanax are sold online nowadays for the convenience of the people; one should not try to meddle with them or try to get them by foul means.

Anthony said...

Hi Sandy:

"...but it is safe to conclude that, in general, amphetamine can be considered to reduce the symptoms of SD."

Yes, amphetamines do reduce symptoms of sleep deprivation. But that means absolutely nothing!

That is like saying "heroin can be considered to reduce the symptoms of hypersomnia."

Yeah, it sure can. So should we conclude that hypersomnia is closely releated to opiate deficiency?

The thing is - amphetamine affects so many parts of the brain so strongly that any apparent relationship between sleep and depression would be absolutely swamped by the direct effects of the amphetamine. I don't think one could reach any reasonable conclusion with a very carefully controlled experiment.

I can tell you from personal experience as a (legitimate, but sometimes abusive, and trying to get off it) Adderall user, that amphetamines counter only a tiny subset of the symptoms of sleep deprivation. From times that I've taken Adderall (foolishly) while sleep deprived, I can tell you that while amphetamines technically keep you awake, every other part of your brain "goes on the blink."

The sleep deprived "floundering" behavior is all too familiar to me - but I can tell you, while amphetamines keep you wide, wide awake, they sure as heck don't reverse SD symptoms in general.

Here's a typical late-night kitchen scenario for me:

"...why did I come in here? I was going to... to.... hmmm. ...

... right, I AM in here... ...



...oh, right, I need... ah.. ok. Hmmm. How odd.



Sandy G said...

Hi Anthony,

the meat of my argument is not that amphetamine is related to depression. I don't consider this possibility even remotely. the argument is that REM SD or dream deprivation is related to depression. To bolster my argument, I just need to establish that the cognitive features found in such dream deprived rats are not due to normal SD as normal SD effects would have been overturned by amphetamine usage. Even if the above is not correct, it is not central to my thesis.