Anonymous says, "Why is early morning waking a characteristic symptom of depression and
what other conditions have imbalances of early waking as a symptom?"
Carrie: I know this answer.
Do you know the answer?
Chris: I might, but I'm not going to guess your answer.
I want to hear your answer.
Carrie: The early morning waking, where you wake up in the morning and you just start
there, it's called the cortisol awakening response.
We shorten it to CAR, cortisol awakening response.
It's historically a non-stress-driven natural rise in cortisol.
Researchers aren't 100% sure other than maybe for survival.
When you wake up in the morning, you want to be alert.
You need to be conscious.
You need to be ready to go just in case there are bad things around you and you've been
asleep.
We do know the cortisol awakening response, it happens in about the first 30 to 60 minutes
of your day.
Literally, from the time your eyes open, your cortisol should shoot up to a point and then
gradually come down for the rest of the day.
Now, with depression, it's heavily studied if you have an elevated or excessive cortisol
awakening response, meaning you go higher, your spike is higher and more dramatic than
the average bear, then your risk for morning depression is much higher.
The reason for that as we've already touched upon with estrogen and the serotonin versus
kynurenine pathway because high excessive glucocorticoids or cortisol can also upregulate
the pathway away from serotonin and down towards kynurenine.
If you wake up with excessive amounts of cortisol, for whatever reason, you're stressed out,
you're anticipating your day, you wake up in pain, you wake up with inflammation, something
startled you awake, your kid is throwing up, it can increase your risk for morning depression
because it pushes all that excessive cortisol, pushes your tryptophan away from serotonin
and down towards kynurenine.
Then as Chris said, if you are going down the kynurenine pathway and you already have
issues with that, you can make that quinolinate which is a neurotoxin as well.
So now you have less serotonin and more quinolinic acid, which is a neurotoxin, and now you've
got potentially this double whammy if not a single whammy against you.
When they do the research on morning depression, it's one of the big things they're studying
is the excessiveness of your cortisol awakening response in the morning.
Are you a hyper person?
Are you normal or are you flat-lined?
Do you go down?
Then if you go down, that's a whole different thing that does all sorts of other stuff.
Were you going to say something different?
Chris: No, I didn't know that.
I'll throw out a couple other things that I think could theoretically be an issue.
In addition to the glucocorticoids influencing where tryptophan goes, I have a sneaking suspicion.
I don't have good data supporting this, but it just makes sense to me and it seems to
make sense with some people's anecdotal stories.
The half-life of melatonin is really short.
You have to produce it all night long basically.
Carrie: You mean pineal, not gut in this context you're talking right now.
Chris: Yeah, yeah.
It can definitely be a limiting factor in onset insomnia not to have enough melatonin.
One of the things that can limit that is getting tryptophan into the brain.
Tryptophan gets into the brain mainly as a result of the ratio between tryptophan and
competing amino acids in the blood.
The best ways to increase that are to either take tryptophan in an empty stomach or to
eat a meal with high glycemic carbs or to exercise.
If not having enough tryptophan entering to the brain can be a limiting factor for onset
insomnia, it just seems logical to me that if you didn't get enough tryptophan into the
brain to make enough melatonin precursor to keep synthesizing melatonin through the night
for eight hours basically, that it could also be a factor in how long you stay asleep.
I think this is true for some people because I know people that can't sleep through the
night unless they take ten milligrams of melatonin before they go to bed.
Then what makes them fall asleep if they do wake up and they don't take the melatonin
is eating, especially carbs.
Carrie: Especially carbs, yeah.
Chris: That lines up very nicely with they're getting melatonin precursor stored in their
brain, but just maybe only four hours worth and then they need to get another four-hour
dose of it.
Whereas if they take ten milligrams of melatonin, for some reason, the absorption from the gut
slows a lot when we have a higher dose.
I guess the absorption must be saturated or something because the curve in the blood,
like the half-life in the blood, I don't know if it's the half-life of the individual molecule.
If you take a really large dose of melatonin, you can stretch out the peak curve and how
long it last across the whole night basically, even if it's not time-release.
Yeah, I think that lines up there.
I also think that there are some people, particularly people who do a lot of high-intensity exercise
and don't eat enough carbohydrate who are repleting their hepatic glycogen before they
go to bed.
Your liver has generally stored about 90 grams of glycogen for the purpose of maintaining
your blood sugar between meals.
The longest time that you ever go without a meal is overnight, and so that's when your
liver has the biggest task ahead of it.
It has even more of a task if you're practicing any kind of time-restricted feeding.
Quite often, people who are practicing time-restricted feeding are also practicing high-intensity
exercise and are also practicing carbohydrate restriction.
You might have a CrossFitter who eats 60 grams of carbs a day, is deliberately winding back
the length of their evening meal to 4:00 p.m. and they don't know why they're waking up
at 3:00 a.m. with the heart pounding every day.
I think that's because they are getting an adrenaline and cortisol response.
Carrie: And they're irritable.
Chris: Yeah, irritable.
Carrie: Probably is angry and irritable and snippy.
Chris: I think that can be a big issue for people who are early wakening as well.
I think in both those conditions, if you're not eating enough carbohydrates to keep your
liver glycogen full, you're probably not getting enough to get tryptophan in your brain.
If you're not getting enough tryptophan in your brain to make melatonin all night, you're
probably not getting enough tryptophan in your brain to make serotonin either.
All of those could kind of feed into the same mechanism that you were describing of the
glucocorticoid suppression of serotonin levels.
I think that's a couple more things to add.
Carrie: Yeah, for sure.
Chris: Cool.
Thank you for your question, Anonymous.