Researchers Try to Bust Depression by Unravelling Sleep Cycles

If you’ve spent time within the bleak doldrums of major depression, you almost certainly have some understanding of the unique relationship that one suffering from major depressive disorder (MDD) has with his or her bed. It’s best described as persistent antagonism; one’s bed becomes one's enemy, a locality of failure.

Manifested as an inability to sleep, an inability to not sleep, or both, the circadian effects of MDD are highly shitty and, as of right now, it is a symptom that remains in large part unaddressed by depression medications. The various drugs available, likely some combination of them, might well be life-saving/life-enabling, but sleep usually remains a problem.

At various points in my life, one in the morning and one in the afternoon have become alternatively known as fuck you o’clock (fuck you AM and fuck you PM, that is). You know what I'm talking about: There's a point during the day where I’m theoretically tired as hell, yet my body and brain are conspiring in every imaginable way to make me unable to sleep, no matter that I’ve been up since five in the morning and have four more hours to accomplish sleeping.

What follows is perhaps several more hours of thrashing around punctuated by fits of rage. The PM version of fuck you o'clock is basically the inverse: waking up at one in the afternoon and feeling like I haven’t slept more than an hour while also feeling like a totally worthless human being for sleeping so late. “Normal” is somewhere in between (a long distance from either pole) and I have never in my adult or semi-adult life experienced it.

Exercise helps, medication helps a bit, supplements (melatonin, valerian) help for approximately 30 minutes. Sleeping outside in a tent outside helps quite a bit in the right conditions, but still not as much as good ol’ Benadryl, which helps at fuck you AM, but necessitates fuck you AM, by virtue of having a long 12 hour half-life. This means that after my usual double dose is metabolized, there’s still a normal adult dose in my bloodstream. That’s a hell of a hangover.

The proper term for a Benadryl hangover (or hangover from some other sleeping med or hypnotic, like Xanax) is “daytime sedation.” It’s considered a serious and widespread problem. Obviously, the entire problem doesn’t trace to depression—insomnia happens for other reasons—but it is a highly motivating factor in the hunt for better depression treatments.

It’s a difficult hunt: researchers have, until now, been unable to physiologically link depression and sleep disorders, obviously making it difficult to target a depression-specific drug at them. A study out Monday in the Proceedings of the National Academy of Sciences offers a bit of hope, for the first time physically linking circadian cycles to MDD.

The idea is that during the body’s circadian cycles, genes in the body express more or less at different times of the day. Gene expression is simply the times during which information contained in genes is actually used to create a physical product, like proteins or RNA. This is one of the most fundamental processes shared by all life and one that, when disturbed, is also a big-deal cause of cancer.

In any case, this cyclic gene expression gives way to cyclic circadian cycles and, we (you, more accurately), get normal sleep out of the whole thing. The authors of the PNAS paper, led by University of Michigan geneticist Jun Z. Li, found that in patients with MDD, those expression cycles are weaker.

Here’s why this important for depressives looking to finally get some goddamn good sleep. Identifying a physical process for something is the first step for identifying a physical solution. (This is obviously assuming a physical solution is necessary.)

If researchers are able to pin down a depression drug that can take on circadian cycles, this might well also be a better depression drug generally—if not other mood disorders--to say nothing of being able to understand mental illness better. This is not coming tomorrow, obviously, but it's a start. In the meantime, I’ll be sleeping in some woods (ideally) with my little pink diphenhydramine friends.

Reach this writer at michaelb@motherboard.tv.