They Keep Pushing Pills for Your Mood. Why?

The chemical imbalance story fell apart years ago. What actually runs your mood is the tiny engines you inherited from your mother.

**Note: This piece draws from my original ideas, research, hooks, and metaphors. For editing and some wording, I’ve used AI tools trained on my own books and style, always blending technology with my hands-on curation and oversight. Thank you for being here—Jade.

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You know the mornings I mean. You wake up and the air feels thick. There is a low dread you cannot pin to anything. Your thoughts move like they are walking through wet sand. Nothing happened. Nobody hurt you. And still, getting out of bed feels like bench-pressing the day.

You have been told, in one way or another, that this is in your head. Fix your mindset. Think positive. Maybe it is a chemical imbalance, here is a pill. And I am not here to wave any of that away, some of it helps. But I want to tell you about a scientist who suspected the whole frame was wrong, and who was willing to lock himself in a sealed room to find out.

His name is Martin Picard. He runs the mitochondrial psychobiology lab at Columbia. And to run his first experiment, he climbed onto a twin bed inside a metabolic chamber, a room barely wider than his shoulders, with a sink, a toilet, and a small port cut into the wall so a research team next door could draw his blood through the barrier, hour after hour, even while he slept. There are only about fifty of these chambers on earth. The room measures every breath you take, the exact oxygen you burn and the carbon dioxide you give back, so it can calculate what it costs, down to the calorie, simply to be you.

He was not measuring fitness. He was trying to measure the price of a mood. And the thing he thinks he found is that your feelings are not floating above your biology like weather over a landscape. They are being shaped, in real time, by the smallest machines inside you. Not where you think. Not by the brain alone, and not determined solely by your genes.

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You were taught a lie in the seventh grade

Say the word mitochondria and a phrase drops into your head like a coin in a slot. The powerhouse of the cell. You memorized it for a test. You eat food, the mitochondria burn it into ATP, the energy currency, end of story. Move on to the Golgi apparatus.

That sentence is not wrong. It is just laughably small, like describing your phone as a thing that gets warm. Over the last fifteen years the job description of the mitochondrion has exploded, and it now reaches straight into the machinery of how you feel.

Start with your hormones. The very first step in building every steroid hormone you have does not happen in some gland downstream. It happens inside the mitochondria. Cholesterol has to physically cross into the inner chamber of the mitochondrion to be cut into pregnenolone, the master molecule that becomes cortisol, estrogen, testosterone, progesterone. So when you remember the deadline and feel that cold flush of stress, the cortisol is not appearing from nowhere. Microscopic factories in your cells are cleaving cholesterol to build the exact molecule that is about to flood you. The feeling has a birthplace, and it is in there.

Now your neurotransmitters. Mitochondria supply the raw materials to make glutamate, which fires your nervous system up, and acetylcholine, which you run your memory and your muscles on. Without them, the neurons cannot speak. They also handle calcium, the switch behind every muscle contraction. They fire off reactive oxygen species, a kind of cellular exhaust that doubles as a flare gun, telling the immune system where the damage is. And when a cell is too far gone to save, the mitochondria sit right at the switch of the tightly controlled process that shuts it down. They help decide whether a cell lives or dies.

So the “battery” is not a battery. It is closer to a smart grid crossed with a city council. It decides who gets power, who gets cut off in the storm, when to send the emergency flares, and, along the way, it is helping build the very chemicals that make you anxious, calm, sharp, or flat. That is the organelle you were told to picture as a bean.

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And it is not your genes either

Here is the other story we have to put down, because it is the one people cling to hardest. That your DNA is the blueprint, and the blueprint is destiny.

We spent billions on the Human Genome Project believing that if we read every letter, we would find the gene for depression, the gene for obesity, the gene for a long life, and cure them one by one. Then the data came back, and it was almost embarrassing. Take how long you live. When researchers went looking for how much of your lifespan is written in your genes, they first got numbers like twenty or thirty percent. Then someone noticed the estimates were inflated by a boring human habit. People marry people like themselves. Correct for that, and the true heritability of your lifespan falls below seven percent.

Now, heritability is a slippery word, and I want to be square about it. It measures how much the differences between people track with their genes, not how much your genes flat-out cause in you. Low heritability does not mean ninety percent of your life is a dial you control. The rest is your environment, your experiences, a large helping of plain chance, and the endless way genes and life bend around each other. Much of that is not in your hands at all. But read carefully or read loosely, the number says the same unglamorous thing. Very little of who you become is written in the blueprint alone. It is the same story for most common disease. We call obesity and diabetes and depression “genetic,” and then the actual variants we find explain a sliver, sometimes a fraction of a single percent.

Yes, there are exceptions, and they matter. Huntington’s disease is one mutation, and if you carry it, you will get it, full stop. But that is a severed wire. A piece of hardware snapped clean, and no amount of power turns that screen back on. Those cases are rare. For the vast majority of you, the wiring is intact. The gene for the thing you fear is sitting in the nucleus like a recipe in a closed book. And a recipe does not cook itself.

So here is the frame I want you to hold. Your genes are the hardware. Beautiful, intricate, and largely inert until something powers them on and tells them when to speak. Your mitochondria are a big part of that power. And a phone at one percent, no matter how good the chip, is a slab of glass. The energy is what brings the hardware to life, helps decide which pages of the book get read tonight and which stay shut, and turns a catalog of possibilities into an actual, living, feeling you.

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How a feeling actually gets made

To feel why any of this touches your mood, you have to see what a mitochondrion is really doing with energy, because it is stranger and more precise than burning.

When you eat, your body tears electrons off the food. Those electrons get fed into the mitochondria and passed down a chain of proteins like a bucket brigade, hand to hand, until at the very end they are handed to the oxygen you just breathed. That flow of electrons is not a bonfire. It is a current. And Picard’s key move, the one that reorganizes everything, is to stop thinking of the mitochondrion as a furnace and start thinking of it as a resistor in a circuit.

Picture a fire hydrant cracked wide open. The water comes out with so much raw violence it tears up the street and puts out nothing. Useless. Now screw a nozzle on it. Same water, same pressure, but now it is a shaped, aimed, usable stream. The mitochondria are the nozzle. The raw energy pouring in from the universe is the open hydrant, and these little machines hold that chaos inside a narrow, exact band, converting a violent current into clean, structured signals the rest of the cell can actually use.

Now you can see what a struggling mitochondrion might do to a mood. If the nozzle is clogged, you do not get a clean stream. You get sputter. The signals come out wrong. The hormones bottleneck at that first cholesterol step. And the engine, running dirty, leans on cheaper, messier chemistry, and one of the things that can pile up is lactate. Lactate is not evil, your brain and heart actually burn it as fuel. But when it builds past a certain point, in certain conditions, it can nudge the brain circuits tied to fatigue and even panic. So inefficient energy production does not just leave you low on power. It can tilt the very systems that color a whole day with dread. The feeling is real. It may simply start in the cell.

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They put a number on the cost of a bad mood

This is where we leave the metaphors and get to the measurements, because Picard is not out here reading auras. He is calculating energy with heavy isotopes and sealed chambers, and the numbers are brutal.

Back to that chamber. He and his team brought in people with rare, genetically confirmed mitochondrial diseases, folks whose engines are built inefficient from birth, and compared them to healthy controls. Common sense says a broken engine burns less fuel. The opposite is true. To keep the lights on with a bad engine, the body has to run backup generators all day, and it burns hot. Just to lie still on that twin bed and exist, these patients burned about a hundred and eighty more calories a day than healthy people. A graduate student in the lab called it the pizza tax. Every single day, before you sit up, before you do one useful thing, your body has quietly burned off a slice of pizza just to stay alive.

Then they let them out. For nine days the participants lived normally while drinking water spiked with traceable heavy atoms, so the team could measure exactly what they burned out in the world. The healthy people, walking and working and seeing friends, burned about sixteen percent more than they had in the chamber. The patients with bad mitochondria burned only about five percent more. Sit with that. Out in the whole wide world, they barely moved more than they had in a room the width of their shoulders. Not because they were lazy. Because there was little power left to spend. When the grid is failing, the body imposes rolling blackouts, and one of the first things it cuts is you, walking around, living. Their behavior in the world was being quietly shaped by the charge left in their cells.

Think of the phone again. A hidden app, draining fifteen percent in the background, all day. The chip is fine. The screen is fine. But everything is sluggish, nothing new will open, and you cannot for the life of you figure out why. That is close to what a struggling mitochondrion does to a human being. And most of the people living it have been told, for years, that they just need more willpower.

You do not have a rare disease, so here is the study that puts this on your street. In 2018, Picard’s group worked with a group nobody could accuse of imagining their stress. Mothers who are the full-time caregivers of children with severe autism, one of the most relentless chronic stressors we can measure. They compared their cells to mothers of neurotypical kids. The trick was a new tool Picard built, because the old way of judging mitochondria was to just count them, and counting is a trap. A struggling cell often mass-produces cheap, broken mitochondria to compensate, the way a failing factory fills the floor with jammed machines. Lots of machines. No output. So he built an index that measures quality instead of quantity, the actual horsepower of the engines, not how many are crammed in. And the high-stress mothers did not have fewer mitochondria than the calm controls. They had a similar number, running worse. The weight of years of stress tracked with a measurable drop in the quality of their cellular engines. The burden of the mind showed up, in the cell.

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Here is the twist that changes everything

Up to now the arrow points one way. Struggling mitochondria, struggling mood. Fix the cell, help the mind. That alone would be a revolution in how we treat depression and burnout, and it is coming.

But the same study caught the arrow pointing the other way, and this is the part I cannot stop thinking about.

They tracked these women’s moods every morning and every night for a week, right up against their blood draws. And they found something that should give you pause if you believe mood is just a puff of smoke rising off the biology. A woman’s mood on a given evening was associated with the measurable health of her mitochondria the next morning. The mood came first in time, the cellular reading followed. That does not prove the feeling caused the change, an honest scientist stops short of that. But it points, at least, to a two-way street rather than a one-way one. And it is hard to look at and still call the mind a passive passenger.

Her positive mood on one night accounted for a meaningful slice of the variation in her cellular energy the following day, enough that the researchers could see it clearly in the data. Between the women reporting the brightest moods and the darkest, the difference in raw respiratory capacity ran as high as sixteen or eighteen percent. Treat that as illustrative, not a dial you turn with one good evening. But let the size of it land. If your car lost eighteen percent of its horsepower overnight, you would feel it the instant you touched the gas. That is the gap between waking up clear and capable and waking up underwater.

So the street runs both ways, even if not evenly. Energy shaping mood is on firm ground. Mood shaping energy is newer, softer, still correlational, but real enough to show up in the data. Mind moves the machine, and we can measure the tracks.

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So why do they keep pushing antidepressants?

Because for forty years we were told a story, and the story turned out to be thin.

You know the story. Depression is a chemical imbalance, your serotonin is low, the pill tops it back up. It is clean and simple. And in 2022, a team led by Joanna Moncrieff went looking, in a large umbrella review in Molecular Psychiatry, for the actual evidence that low serotonin causes depression. They could not find it. Not in the blood, not in the receptors, not in the genes. The imbalance millions of us were medicated for was never really established in the first place.

So if it is not simply low serotonin, what is it? Here is the hypothesis quietly gaining ground, and it is the one this whole piece has been walking toward. Depression may be an energy crisis. Look at a depressed brain and whole regions are running cold, low fuel in exactly the areas that carry mood and drive. The cells make less ATP, and the deeper the deficit, the heavier the depression. Researchers now call it a bioenergetic model of depression. Some, staring at the reward circuits, call it flat out a dopaminergic energy crisis. Not a chemical missing from the soup. A power shortage in the machine.

And now look at where the pills actually act, because this is the part that made me take notice. The very first antidepressants ever discovered, the MAO inhibitors, work by blocking an enzyme called monoamine oxidase, the enzyme that chews up your serotonin and dopamine. That enzyme does not float loose in the brain. It sits bolted to the outer wall of the mitochondrion. The original antidepressants were mitochondrial drugs. We just never called them that.

And here is the thing about those chemicals: you make them yourself. Your body builds serotonin and dopamine from scratch, out of the food you eat, using enzymes that run on mitochondrial energy and mitochondrial cofactors. The mitochondria are the factory that manufactures these molecules, and they hold the machinery that clears them away. They sit on both ends of every mood chemical you have. The pills reach into the middle and nudge one narrow step. The engine that runs the whole line, the making and the breaking, nobody is treating.

That is the answer to the question in the title. They keep pushing antidepressants because the pill works on the one piece we learned to target seventy years ago, and because the deeper target, your own energy, is harder to sell and easier to ignore.

Now hear me clearly, because I am a clinician and this next part is not optional. If you are on a mood medication, do NOT come off it. Not on your own, and certainly not because an article on Substack stirred something in you. Never ever make a change in medication like that without your doctor walking you through it every step. These medicines keep people alive, and stopping them suddenly can be extremely dangerous.

But this is the hopeful part, and it is a real one. If your mood truly runs on your mitochondria, then the things that heal your mitochondria, the sleep and the light and the movement and the food and the way you carry stress, may make your medication work better while you are on it. And for some people, over time, and only ever with a doctor supervising it, that same work might mean needing less. Maybe, for some, one day, needing none. I am not promising you that. I am telling you where the science points, and that it is a conversation worth having with the doctor who knows you, rather than a life sentence you quietly assume.

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The question everyone is stepping around

Now go one step further than the scientists usually will in print.

We have been told, for a century, that the mind is a product of the body. Bottom up. Neurons fire, chemistry happens, and out the top, like steam, comes the feeling. Mood is the exhaust of the machine. That is the assumption baked into almost everything.

But notice two things, side by side. First, we have never explained where the felt experience itself comes from. We can map every neuron and every molecule and still not find the place where it starts to feel like something to be you. That gap has a name in philosophy, the hard problem, and it is not fringe, it is unsolved in every serious room where people think about this. Second, the mind is measurably reaching down and moving the machine. The caregiver’s evening mood tracks her cells by morning. And think about the strangest, most ordinary event in all of medicine, the placebo. We hand someone a sugar pill with no drug in it, we tell them with confidence it will heal them, and their body launches a real, measurable healing response. Nothing pharmacological entered them. The trigger was belief and expectation, and that trigger set off the body’s own chemistry, dopamine, endorphins, real molecules made on the inside. A shift in the mind became a shift in the body.

Put those two facts in the same hand. We have never shown that the felt mind is made of matter, that remains a philosophical position and not a settled result, and meanwhile the mind is measurably steering the matter. At the very least, that should make you slow down before calling the mind a byproduct. At the very least, it reopens a question we may have shut too early.

Here is my one flag, and I will only plant it once. From this line forward, this is a reach. It is a philosophical hypothesis, not an established biological model, and it could be completely wrong. Good. Now that it is said, let me tell you where I think this goes.

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Maybe the mitochondria don’t make your mind. Maybe your mind plays them.

I have written before that the brain might not be the source of consciousness so much as its receiver, the way a radio is not where the music is made, only where it is caught. I want to drop that same idea one level deeper, down into the cell.

Picard calls the mitochondria the consilience point, the place where psychology and biology and physics all jump together into one thing. He points out that the flow of electrons from your food to your breath is, at bottom, the most fundamental signature of being alive. Stop that flow and there is no emotion, no thought, no you. So the mitochondria sit exactly at the seam, the border crossing between the felt world and the physical one, translating one into the other in both directions at once.

If mind were only a fume rising off that machinery, the machinery would not sit and wait for the mind’s instructions. But it does. So walk out onto the ice with me. What if the mitochondria are not the factory that manufactures your consciousness, but the antenna it tunes into? The nozzle is not just shaping the energy from your last meal. Maybe it is also the place where something larger, call it mind, call it awareness, call it whatever your tradition calls it, reaches in and takes hold of matter. The organelle you inherited from an ancient bacterium, humming in every cell, might be the exact spot where the immaterial grabs the wheel. That is a wild thing to say, and I am saying it as a hypothesis, not a finding. I also think it is a reasonable thing to entertain, given how quickly science dismisses anything still unproven. And yet materialism, the belief that matter is all there is and mind is only its shadow, is itself a philosophical stance, not a proven fact. It is a faith of its own, just a quieter one.

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What to do with this

If your mitochondria are listening to your mind, and shifting by morning, then the question of what drives them has an answer, and most of it is yours. Not consciousness first. You first. The way you sleep is charging or draining the battery. Light in the morning, cold on the body, real movement, one slow deep breath that floods the system with oxygen, the people you choose to sit near, the story you run on a loop in your own skull. None of that is soft. Every bit of it is you, walking to the panel and setting the resistors, tuning the exact machines that will help build tomorrow’s moods out of tonight’s inputs.

Which means the next time you wake up in the wet-sand morning, you get to hold two true things at once. It is not a character flaw, and it is not only in your head. It is, in part, an energy state. And an energy state can be changed, and it will change you back.

One last thing, because it moves me every time. You did not get these engines from both parents the way you got the rest of your DNA. Mitochondria pass down one line only, mother to child, unbroken, all the way back. The little machines helping decide whether you panic or stay steady today are the same lineage that powered your mother, and hers, and hers, down a chain that does not skip. When you steady your own energy, you are tending something a thousand generations old. You were told the genes were in charge. They were never the whole story. Something older and stranger has been helping run the lights the whole time, and a surprising amount of it is yours to set tonight.

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PS: Learning to tend that energy on purpose, your sleep, your stress, your light and movement and the state you keep yourself in, is most of what I do with people. If you want help charging the battery instead of only fighting the mind, this is where I do that work: www.nextlevelhuman.com/human-coaching

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References:

Chalmers, D. J. (1995). Facing up to the problem of consciousness. Journal of Consciousness Studies, 2(3), 200–219.

Hollis, F., van der Kooij, M. A., Zanoletti, O., Lozano, L., Cantó, C., & Sandi, C. (2015). Mitochondrial function in the brain links anxiety with social subordination. Proceedings of the National Academy of Sciences, 112(50), 15486–15491.

Kelly, C., Trumpff, C., Acosta, C., Assuras, S., Baker, J., Basarrate, S., ... & Picard, M. (2024). A platform to map the mind–mitochondria connection and the hallmarks of psychobiology: The MiSBIE study. Trends in Endocrinology & Metabolism, 35(10), 884–901.

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2023). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry, 28(8), 3243–3256.

Nuwer, R. (2026, July 17). Martin Picard’s mitochondrial theory of mind. Quanta Magazine.

Picard, M., McEwen, B. S., Epel, E. S., & Sandi, C. (2018). A mitochondrial health index sensitive to mood and caregiving stress. Biological Psychiatry, 84(1), 9–17.

Ruby, J. G., Wright, K. M., Rand, K. A., Kermany, A., Noto, K., Curtis, D., ... & Ball, C. A. (2018). Estimates of the heritability of human longevity are substantially inflated due to assortative mating. Genetics, 210(3), 1109–1124.

Sercel, A. J., Sturm, G., Shaulson, E. D., Gallagher, D., St-Onge, M.-P., Kempes, C. P., Pontzer, H., Hirano, M., & Picard, M. (2023). Hypermetabolism and energetic constraints in mitochondrial disorders. Nature Metabolism, 5(11), 1875–1891.

Wellen, K. E., Hatzivassiliou, G., Sachdeva, U. M., Bui, T. V., Cross, J. R., & Thompson, C. B. (2009). ATP-citrate lyase links cellular metabolism to histone acetylation. Science, 324(5930), 1076–1080.