Blue Morning

Recently, I wrote about diurnal mood variation: the way in which depression often waxes and wanes over the course of the day. Mornings are generally the worst.

A related phenomenon is late insomnia, or "early morning waking".

But this phrase is rather an understatement. Everyone's woken up early. Maybe you had a flight to catch. Or you were drunk and threw up. Or you just needed a pee. That's early morning waking, but not the depressive kind. When you're depressed, the waking up is the least of your problems.

Suddenly, you are awake, more awake than you've ever been. And you know something terrible has happened, or is about to happen, or that you've done something terribly wrong. It feels like a Eureka moment. You can be a level-headed person, not given to jumping to conclusions, but you will be convinced of this.

In a panic attack, you think you're going to die. Your heart is beating too fast, your breathing's too deep: your body is exploding, you can feel it too closely. With this, With this, you think you should die or even, in some sense, already have. It feels cold: you can no longer feel the warmth of your own body.

The moment passes; the terrible truth that you were so certain of five minutes ago becomes a little doubtful. Maybe it's not quite so bad. At this point, the wakefulness goes too, and you become, well, as tired as you ought to be at 3 am. You try to go back to sleep. If you're lucky, you succeed. If not, you lie awake until morning in a state of miserable contemplation.

While it's happening, you think that you're going to feel this way forever; bizarrely, you think you always have felt this way. In fact, this is the darkest hour.


Why does this happen? There has been almost no research on early morning waking. Presumably, because it's so hard to study. To observe it, you would have to get your depressed patients to spend all night in your brain scanner (or, if you prefer, on your analyst's couch), and even then, it doesn't happen every night.

But here's my theory: the key is the biology of sleep. There are many stages of sleep; at a very rough approximation there's dreaming REM, and dreamless slow-wave. Now, REM sleep tends to happen during the second half of the night - the early morning.

During REM sleep, the brain is, in many respects, awake. This is presumably what allows us to have concious dreams. Whereas in slow wave sleep, the brain really is offline; slow waves are also seen in the brain of people in comas, or under deep anaesthesia.

When we're awake, the brain is awash with modulatory neurotransmitters, such as serotonin, norepinephrine, and acetylcholine. During REM, acetylcholine is present, while in slow-wave sleep it's not; indeed acetylcholine may well be what stops slow waves and "wakes up" the cortex.

But unlike during waking, serotonin and norepinephrine neurons are entirely inactive during REM sleep - and only during REM sleep. This fact is surprisingly little-known, but it seems to me that it explains an awful lot.

For one thing, it explains why drugs which increase serotonin levels, such as SSRI antidepressants, inhibit REM sleep. Indeed, high doses of MAOi antidepressants prevent REM entirely (without any noticeable ill-effects, suggesting REM is dispensable). SSRIs only partially suppress it.

Ironically, SSRIs can make dreams more vivid and colourful. I've been told by sleep scientists that this is because they delay the onset of REM so the dreams are "shifted" later into the night making you more likely to remember them when you wake up. But there could be more to it than that.

The fact that REM is a serotonin-free zone also explains wet dreams. Serotonin is well known to suppresses ejaculation; that's why SSRIs delay orgasm, one of their least popular side effects, although it's useful to treat premature ejaculation: every cloud has a silver lining.

So, having said all that: could this also explain the terror of early-morning waking? Suppose that, for whatever reason, you woke up during REM sleep, but your serotonin cells didn't wake up quick enough, leaving you awake, but with no serotonin (a situation which never normally occurs, remember). How would that feel?

Using a technique called acute tryptophan depletion (ATD), you can lower someone's serotonin levels. In most people, this doesn't do very much, but in some people with a history of depression, it causes them to relapse. Here's what happened to one patient after ATD:
[her] previous episodes of clinical depression were associated with the loss of important friendships had, while depressed, been preoccupied with fears that she would never be able to sustain a relationship. She had not had such fears since then.

She had been fully recovered and had not taken any medication for over a year. About 2 h after drinking the tryptophan-free mixture she experienced a sudden onset of sadness, despair, and uncontrollable crying. She feared that a current important relationship would end.
We don't know why tryptophan depletion does this to some people, or why it doesn't affect everyone the same way, and it's pure speculation that early morning waking has anything to do with this. But having said that, the pieces do seem to fit.

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