Tuesday, January 25, 2011

Appetite, Sleep, and Mood - The Connection

Whew.  Between making up for my holiday vacation and the snow days (we might get yet another storm, up to 18 inches, tomorrow, and there is still 2&1/2 feet on the ground!!), work has been incredibly busy.  At the same time, my children have decided to run sleep deprivation experiments on me.  The problem with being sleep-deprived is that when you try to read rather clunky textbooks on the basic and clinical science of sleep and mental illness, you tend to nod off rather quickly.  (the reference for this post is the aforementioned clunky textbook)

That's a rather verbose introduction to the fact that I need a perky song or two to blog by today.  Let's start with Ra Ra Riot's Boy. (right click in new tab if you want to keep reading).

So - appetite, sleep, and mood.  We psychiatrist types ask about such things all the time, because we know they are inexorably related.  In fact, problematic appetite, sleep and energy levels have a clinical nickname - "neurovegetative symptoms."  Well, that's not much of a nickname.  We call it "neuroveg" for short.  We also call ending a relationship with a patient "termination."  And emotions "affects."  We aren't particularly fun people, really.  (Kidding!  Sort of.)

So let's talk neurotransmitters.  Wakefulness in general is supported by several excitatory neurotransmitter pathways, among them acetylcholine and norepinephrine.  These brain chemicals send wakey wakey signals to the forebrain, and when this happens, our brain EEG signals go from large sleepy floppy slow wave sleep to the brisk jagged beta waves of being awake.  If we lack acetylcholine and norepinephrine signals to the forebrain, we get all drowsy and fall into non-REM sleep (all our restorative sleep).   If you are into the whole neurochemistry/electricity thing, the excitatory neurotransmitters lead to rapid firing and depolarization of the wakeful brain neurons.  The lack of that signal leads to a relative hyperpolarization and long, slow lazy signal of the sleeping brain.

To get into even more nitty gritty, remember that the basic energy currency of the cells is ATP.  That's short for adenosine triphosphate.  In order to lend power to chemical reactions, the ATP gives up its three phosphates one by one until it becomes plain old adenosine again.  And in the brain, the more adenosine, the more difficult it becomes to send signal to the wakey wakey neurons.  That makes sense - you've spent your energy reserves and have a bunch of waste adenosine around?  Chill out, cool down, and rest, so the nighttime healing and restoration of reserves can commence.

(Time for another song?  I really like this one by The Black Keys.  It's overplayed but, some songs are never really overplayed.)

To recap - the neurotransmitter monoamines, norepinephrine and acetylcholine, promote wakefulness.  Non-REM sleep (stage 1-4) is the opposite of wakefulness, and lack of monoamine input leads to progressively more slow wave sleep.  BUT, remember that during polysomography, it is difficult to tell the difference between someone waking up and someone in REM sleep.  The EEG waves of REM sleep are impossible to tell from being awake - only the rapid eye movements and the paralyzing of our major large muscle groups can let the sleep researcher know that the subject is in REM sleep and hasn't woken up. 

Turns out REM sleep neurons turn on when there is almost NO input from the monoamines, while sleepy-inducing neurotransmitters like GABA (GABA receptors are activated by GABA (duh), benzos like valium, alcohol, and sleep medicines like lunesta or ambien.) seem to activate both non-REM and REM sleep.

So - in major depressive disorder, we seem to have a lack of monoamines in the right places at the right time in the brain.  GABA is more or less okay.  Therefore, you get a classic sleep hypnogram for major depression - lots of REM sleep that starts way too early in the night, lots of wakefulness, and almost no restorative slow wave sleep.  All clinically effective medicinal treatments for major depressive disorder will improve your hypnogram by increasing the amount of time it takes you to get to REM sleep 10 DAYS EARLIER than you notice any improvement in mood. 

(If your depressive disorder has a lot of anxiety symptoms too, your GABA is probably lacking, so then the sleep gets really messed up.)  

Now, let's bring in appetite.  The Nurses' Health Study and some other studies show that chronic short duration of sleep and chronic long duration of sleep are associated with type II diabetes.  Laboratory subjects who are studied in sleep restriction and sleep deprivation have impaired glucose tolerance and increased appetite.  In the majority of serious psychiatric disorders, disruption of the circadian rhythm and sleep occurs, and major psychiatric disorders are also associated with an increase in appetite and risk of diabetes.  Some of this increase is medication-driven, but there also appears to be an increase in risk of diabetes and weight gain independent of medications.

The center of appetite and mental problems appears to be the hormone orexin.  As we learned earlier, orexin is a hormone that makes you hungry.  Serotonin seems to suppress orexin.  Folks with schizophrenia and atypical depression seem to be pretty low on serotonin, and they will be hungrier and have more central obesity than folks without those disorders.

Putting it all together, disturbances in the sleep-wake cycle reported in psychosis and in atypical depression seem to disrupt the feedback mechanisms of energy and metabolism in a way that decreases glucose tolerance and reduces sleep efficiency and effectiveness.  All the usual neurotransmitter suspects are implicated. 

Another song?  Sure, why not.  How about The Cave by Mumford and Sons.

Or if you want a nice modern classical romantic song, try this little piece from the newest Pride and Prejudice movie.  Good date movie - not too many tears.


  1. Ooo another hormone related to hunger. Orexin? I need to read up more on this.

  2. Hey amily
    If I am depressed and I start going sleep earlier....sleep phase advance. Did the improvent will last or the body has tolerance. What about hgh and mood by the way?

  3. David - orexin is one of the master appetite regulatory hormones, works at the level of the hypothalamus. Definitely worth a looksee.

    Shay - sleep phase advance can lift mood, can bring on mania if one is vulnerable to bipolar disorder, and the body/brain can develop tolerance to it.

  4. Not sure if my comment went through before. I think a common denominator for sleep problems, appetite (physiological, depression, anxiety and a host of other problems is the over production of the fat growth hormone, insulin. I have been healing some of these problems with the diet, The Metabolism Miracle, by Diane Kress RD, CDE. It's been a lifesaver on many levels for me.

  5. I am loving this sleep series, although I'm a total addict to this blog already. Out of the dozens I subscribe to it's one of 3 or 4 I look out for every day. Thanks Emily, it's brilliant to be able to read a biochemical view of human stuff in a humourous and common sense style. I'm a big paleo follower too, so that helps :-)

    One thought that occurred to me here is that if I remember correctly, serotonin production is suspended during REM sleep.

    And on this whole issue, I thought you might be interested in another take on the Dream-REM-Depression connection - one which explains the link from psychology to psychological depressive symptoms. We find it very useful and effective in treating depression with psychological approaches:

    In the interests of openness, I used to work with the writer of this article and the subsequent book.

  6. Lynn - thanks for the book - looks interesting.

    Roger - it is intriguing that the dream state seems to be very similar to psychosis, though obviously dreaming is not pathologic, while psychosis is.

  7. @David, orexin is the new and trendy hormone on the scene, whispers of it being the master controller of leptin.

    @Emily, any practical ideas on how to reduce REM sleep? I slept 9 hours most nights and I'd say I dream for what feels like 7 of them, I then wake up exhausted each and every morning. No other health problems besides that.

  8. SamAbroad - typically we remember dreams if we have too much awakening during the night, and wake up unrefreshed if we don't get enough slow wave sleep. There could be many possible causes - for example, sleep apnea, depression, poor sleep hygiene, stress, medicines, etc. So improving too much wakefulness can really depend on the cause. If you snore or wake up with a headache, sleep apnea could be a likely scenario.

  9. I'm inclined to think stress, more phospholipids then! Runs off to eat some mackerel.

  10. SamAbroad,

    From what I've read neurotensin and orexin are downstream of leptin in the hormone system.

  11. "Roger - it is intriguing that the dream state seems to be very similar to psychosis, though obviously dreaming is not pathologic, while psychosis is."

    Fascinating, and the description Joe gives of psychosis being 'open eyed dreaming' is compelling, as is his description of hearing voices as being an 'awake' left hemisphere listening to right hemisphere generated dialogue.

  12. Hi Emily,

    I came across your blog while Googling info on Orexin. I have a sleep disorder with a cause undermined and with no successful treatment. I've had three overnight sleep studies which have determined that I don't get into deep restorative sleep/SWS. The treatment I've been given is Xyrem (which is for narcoleptics - which I'm not), which I take in a low dose because I just can't tolerate the higher dose, plus a C-Pap. None of which works to make me feel "refreshed" in the am.

    I've also had some minor depression. Its nothing that keeps me from functioning at work or at home but have been prescribed Celexa. Plus I've always battled weight issues - If I exercise and keep to a 1800 Cal diet I'm ok other wise I can pack on the lbs pretty quickly.

    My Sleep Neurologist really doesn't have any answers or ideas beyond the Xyrem or stimulants. I just came across an article about Orexin - it sounds promising. I wanted to get your thoughts on it and anything else that comes to mind that could work.


  13. You present a conundrum. A lack of acetylcholine would seem to cause drowsiness and slower mental processes. However, an increase in acetylcholine would cause less restorative sleep and less restorative sleep would cause "drowsiness." How would you explain this conundrum?


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