Remember when we were told that depression is caused by a chemical imbalance?

Quieting the Signal

There is a particular relief in the first hour after a painkiller takes hold. The ache that organized your whole morning recedes, and for a while you can almost believe the problem left with it. Then the pill wears off, and you discover that what you bought was time.

Medicine draws a useful line here, though it rarely gets said out loud. Some treatments are symptomatic: they quiet the signal. Others are causal: they go after whatever is producing the signal in the first place. Both have their place. Trouble starts when we mistake one for the other.

Consider angina, the chest pain that comes when narrowed arteries can’t deliver enough blood to the heart. A strong enough opioid would dull that pain. The patient would feel better, measurably and genuinely less miserable. Few physicians would conclude from this that the patient had been suffering from an opioid deficiency. The pain was information about a blocked vessel, and the drug turned down the volume on the message. The causal treatments look very different: a procedure to reopen the artery, or the slower and far less glamorous work of changing how someone eats and moves. Those are harder. Some of them hurt. They are also the ones that touch the problem.

Back pain follows the same shape. Pain pills can make a bad week survivable, and nobody deserves shame for taking them. But the weakened muscles and the hips that stopped moving well years ago are still there when the prescription runs out. Rehab is tedious. It asks for months of small, unrewarding repetitions before anything feels different. The person who chooses it is choosing the cause over the symptom, and paying for that choice up front.

Now hold that frame up against depression.

For roughly three decades, many people were told that depression is a chemical imbalance, usually low serotonin, and that an SSRI works by topping it back up. By some estimates, 85 to 90 percent of the public came to believe this. The appeal is easy to see. The story locates the problem somewhere neutral and offers a clean fix. It may also be the opioid-deficiency error wearing a lab coat: someone takes a drug that raises serotonin activity, feels better, and the improvement gets read backward as proof of what was missing.

In 2022, a team led by psychiatrist Joanna Moncrieff at University College London published an umbrella review in Molecular Psychiatry, gathering the major lines of serotonin research into one picture. They found no consistent evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies showed no difference in serotonin between people with depression and people without it. The review drew sharp pushback. More than thirty researchers, led by Sameer Jauhar at King’s College London, argued that the serotonin system is still implicated in depression in more complicated ways. Notably, even those critics said they don’t hold the simple low-serotonin explanation. The live scientific argument is about whether serotonin plays some part. The popular version, the one many patients were handed in an exam room, has very few defenders left.

None of this makes antidepressants useless. Plenty of people find real relief from them, and relief matters. Pain medication is what lets some people get through physical therapy at all, and an SSRI might take the edge off enough for someone to show up to harder work. (If you take one now, this is no reason to stop on your own; changes are safest made gradually, with whoever prescribes it.) The question is whether we describe the medication honestly, as something that can quiet the signal, rather than as the replacement of a missing part.

If depression isn’t a deficiency, what is it? A more interesting possibility is that the chemistry does shift, but in response to something. Prolonged stress changes the body. So does grief. So do years in a relationship that keeps confirming you don’t matter, or sleep you keep sacrificing, or the drink that quietly became nightly, or the reflex of withdrawing whenever things get hard. Brains are adaptive organs. They reshape themselves around what we live through and what we repeatedly do. Seen this way, an “imbalance” looks less like a defect and more like an accurate record.

This is also where the picture gets wider than one person. A low mood rarely sustains itself alone. Someone who withdraws gets fewer invitations, and fewer invitations confirm the sense of being unwanted, which justifies more withdrawal. Partners and families adapt around a depressed person’s silence in ways that quietly keep it in place. The culture adds its own loop, offering a fast explanation and a fast fix to people who are exhausted and would like both. None of these pieces needs a villain. Together they can hold someone in place long after the original injury has passed.

You might feel some resistance here. If what happened to me shaped my brain, and my own habits deepened it, that can start to sound like blame. I’d read it in the opposite direction. A brain shaped by experience can be reshaped by experience, and what changed once can change again. The deficiency story, for all its comfort, never offered that.

This is the territory psychodynamic therapy was built for. Instead of aiming at the symptom directly, it looks for what the symptom is organized around: the expectations you carry into relationships, or the feelings you learned early were too much to show. Much of that sits outside ordinary awareness, which helps explain why people keep arriving at familiar outcomes without quite choosing them. The work is to notice those patterns as they surface, including in the room with the therapist, until they become something you can see rather than something that quietly runs you. The evidence here is better than its reputation. A 2010 review by Jonathan Shedler in American Psychologist found effect sizes for psychodynamic therapy as large as those for other evidence-based treatments, along with a detail worth sitting with: people tended to keep improving after therapy ended. That is roughly what you would expect from a treatment aimed at the cause. A painkiller tends to stop working when you stop taking it. Understanding has a way of continuing on its own.

The difficult part is the timeline. A pill works in weeks, and part of its promise is that you won’t have to do much. Causal work moves at the speed of rehab, with long stretches where nothing seems to happen before something finally gives. People leave it because it feels like standing still, when what is actually happening is the slow laying down of new patterns. Making peace with that pace may be the hardest part of getting better.

The pain was trying to tell you something. It may be worth staying long enough to hear what.

Sources: Moncrieff J, et al. “The serotonin theory of depression: a systematic umbrella review of the evidence.” Molecular Psychiatry, 2022. Jauhar S, et al. “A leaky umbrella has little value: evidence clearly indicates the serotonin system is implicated in depression.” Molecular Psychiatry, 2023. Shedler J. “The efficacy of psychodynamic psychotherapy.” American Psychologist, 2010.