The Gene Behind the Overwhelm

Your body isn’t overreacting. It’s just working overtime.

By Lori Finlay, NP, CNS

I’m writing part of this to you from the middle of a home remodel. Sawdust in rooms I didn’t think dust could reach. A schedule that changes daily. Noise, disruption, and unpredictability, for weeks on end.

For most people, that’s stressful. For me, it’s been something else entirely.

Have you ever come out of a hard season, a move, a renovation, a family crisis, a demanding stretch at work, and felt like your body never quite came back down? Like your sleep stayed light, your patience stayed short, your hot flashes got worse instead of better, long after the actual chaos ended?

Have you been told your labs look normal, when nothing about how you feel is normal?

If you read last week’s post, you already know part of why. You’re likely an HSP, a Highly Sensitive Person, one of roughly 1 in 5 of us whose nervous system takes in and processes more of the world than most. That’s not the whole story, though. There’s a piece underneath it, written into your genes, that I want to walk through with you today, gently, and in a way that actually matters for your body.

I’ll come back to the remodel. First, let me show you what’s happening underneath.

The Gate That Won’t Quite Close

You have an enzyme in your body called COMT, short for catechol-O-methyltransferase. Its job is to clean up. It clears out stress hormones like adrenaline once they’ve done their work, and it clears out used estrogen, too. Same enzyme, two jobs.

For roughly a quarter of us, that enzyme runs slow, 25 to 40 percent slower than average, because of a common genetic variant. If you’ve had genetic testing, you may have seen this labeled as heterozygous (one copy of the slow variant) or homozygous (two copies, and the stronger effect). If that’s you, stress hormones and estrogen both linger longer than they should. That lingering is a huge piece of why you feel things so intensely, why your mind won’t quiet down at night, why perimenopause can hit you so much harder than it hits your friends.

I believe there’s real overlap between HSP women and this slower-clearing gene. I don’t have research proving that link outright yet, that’s still an open question I’m chasing, but I see it constantly in my own practice, and I’ve lived it in my own body.

The Other Piece: Detox That’s Already Behind

COMT isn’t the only clean-up crew your body relies on. Glutathione is one of your body’s primary detox molecules, and a family of enzymes called GSTs, glutathione S-transferases, use it to package up used estrogen and everyday toxins so your body can safely remove them. Some of us are born missing a functional copy of the genes that make these enzymes work, called GSTM1 and GSTT1. I’m one of them. Magnesium plays a role here too, it’s a required cofactor for COMT to function at all, which is part of why so many of us are chronically low in it without realizing how much that one mineral is being asked to do.

What that means in plain terms: my detox pathway had almost nothing to work with, even before life added anything extra on top.

Why the Remodel Matters Here

Now back to the sawdust.

Noise, disruption, and unpredictability are potent triggers for a sensitive nervous system, and sustained triggers mean sustained cortisol. Cortisol doesn’t stay quietly in its own lane. When it runs high for weeks, it competes with progesterone for the same raw material your body uses to make both hormones. It also slows the very enzymes I just walked you through, the ones responsible for clearing out excess estrogen and stress hormones.

In other words, the exact wiring that makes me so aware of this remodel is the same wiring the remodel is now taxing. That’s not a coincidence. That’s a feedback loop.

So this season, I haven’t treated my sleep, my early bedtime, or the morning meditation, scripture / prayer time, as indulgences.  I’ve treated them as medicine, because for a body like mine, they are. I’ll be honest, the afternoon “napitation” hasn’t happened in weeks. Some seasons, protecting what you can, and practicing “floors”, is enough.

What This Can Mean for Breast Health and Mood

When estrogen isn’t cleared efficiently, whether the holdup is COMT, glutathione, or both, two things tend to happen.

First, that matters for long-term breast health. The pathway your body uses to clear estrogen is a real, documented piece of estrogen-related risk. Second, and often more immediately, lingering estrogen and stress hormones together tend to show up as mood, more anxiety, more irritability, more of that wired-but-exhausted feeling that never fully lifts.

I’m not telling you this to frighten you. I’m telling you because I don’t want you spending years, the way I did, wondering what’s wrong with you when the honest answer is simply: your body needs a different kind of support than the standard advice accounts for.

What I Want You to Take From This

Being told to calm your nervous system with a breathing app or an herbal anxiolytic  (anti-anxiety Rx) isn’t wrong. It’s just incomplete.

If your COMT gene runs slow, if your glutathione pathway isn’t clearing what it needs to clear, no amount of breathwork alone will fully resolve what your body is carrying. Regulation and biochemistry have to be addressed together, not as competing ideas, but as two halves of the same picture.

This is exactly why I don’t recommend guessing your way through supplements or detox protocols. Knowing your actual genotype, not just your symptoms, changes how confidently you and your provider can move, and what kind of support truly fits your body.

Consider This

A remodel is temporary. My nervous system’s response to it is not a flaw to manage away. It’s information. The same is true for whatever high-stimulation season you’re in right now.

Your body is telling you something real about what it’s processing and what it needs to clear. I’ve learned to listen to that instead of pushing through it.

I want that for you too.

For the women who refuse to let their lifespan outrun their vitality span,

Lori Finlay, NP, CNS