Research fascinates me for a lot of reasons. It gives us important information, it challenges things we thought we knew, and sometimes it changes what I do clinically.
But I've started noticing which research actually makes its way into everyday prescribing conversation.
A lot of it is medication research. This medication had this effect size. This receptor or neurotransmitter may be involved. A new drug may work through a pathway nobody has targeted before. That is what lands in my inbox and what gets presented at the meetings I go to.
All useful.
But there is a pattern built into a lot of it. We isolate a biological target. We change it with a medication. Symptoms change. Then we start asking what that target might tell us about the disorder itself.
And I have started wondering what seeing that pattern over and over does to the way I think.
Not whether it makes me think biologically. Everything happening in the person is biological.
I mean whether it trains me to think about biology one piece at a time. It can start to become: find the receptor, neurotransmitter, circuit or pathway that is abnormal. Connect it to the symptoms. Then find something that corrects it.
I prescribe these medications every day and I watch them help people, sometimes dramatically. The research is useful. But that last step, where changing one biological process turns into an explanation for the disorder, has always made me scratch my head a little.
Not because that process could not have caused the problem. It absolutely could have. The problem is that the treatment response does not tell us that it did.
And there is another way of thinking about the biology that I almost never see put in front of me, or hear people talk about much. But that research is out there. What if the important unit is not always the individual part? What if sometimes it is the state of the whole system?
That is not a brand-new thought for me. It is probably part of why medication research built around a receptor or a neurotransmitter has never landed completely cleanly for me. What was new was finding research that described the biology in a way that fit the intuition.
Psychiatric diagnoses are mostly descriptions of patterns of symptoms. They tell me what the person is experiencing, not how this particular person arrived there.
Take depression. Think about five people on your own panel who all carry that diagnosis. One of them got there after years of trauma, insomnia and isolation. Another has recurrent episodes with a strong family history and no obvious trigger. Another has chronic pain, stopped doing the things that gave their life meaning, and slid into it gradually. Another is postpartum. Another has substance use mixed into all of it.
Same diagnosis. Potentially very different roads in.
A neurotransmitter system, a hormonal process, a genetic vulnerability, a circuit-level difference, or several of those interacting, could absolutely play a causal role in one person's depression. The point is not that those things cannot cause depression. The point is that the label does not tell us which processes mattered in this person, how much they mattered, or how they interacted.
Now give all five of them the same SSRI and ask the same question.
Some improve a lot.
Some improve somewhat.
Some do not improve at all.
Some feel worse. And when the person you started on sertraline six weeks ago comes back worse, we say it pretty quickly: maybe they're actually bipolar.
Sometimes the bipolar answer is the right one, and a concerning response to an antidepressant absolutely can be part of the evidence. But notice the move we are tempted to make. The medication produced an unexpected response, and we immediately start working backward from that response toward a different explanation of the underlying illness. Maybe this is not unipolar depression after all. Maybe it is bipolar, and now we start assuming there must be a different underlying biology.
Sometimes that conclusion turns out to be right. But the response itself did not prove it.
Did they sleep? Did they get activated, restless, unable to sit still? Was there akathisia that nobody named? Was there substance use nobody asked about again? Did anything in their life change across those six weeks? Was medication ever the thing that mattered most for this person in the first place?
And when those questions get skipped, I wonder how much the story we already have is narrowing what we think to ask.
What interests me is how natural that first move feels. The drug behaved differently than expected, so there must be a different underlying disease process. We are using a response to a medication to infer what must be happening biologically underneath.
That is the same habit of thought I am starting to notice in the research I read. Work backward from what happened after we changed one biological variable, and use that response to tell a story about what must have been wrong underneath.
Now run that same move in the other direction, on the cases where the treatment works.
Suppose a medication changes glutamate signaling and somebody's OCD gets better. That is genuinely useful and worth knowing. But what have we learned about the OCD?
One possibility is that glutamate was directly involved in producing the OCD. Another is that it was helping keep it going.
But there is a third possibility, and it gets discussed least of all. Glutamate may not have been contributing to the problem at all. The medication may have changed a part of the system that was never abnormal, and changing it may have compensated for something happening somewhere else, or strengthened a competing process, or interrupted a pattern that had become self-sustaining, or simply pushed the whole system into a different state.
On that third reading, glutamate was not the problem, was not maintaining the problem, and may have been perfectly ordinary until we deliberately changed it. It just happened to be somewhere we could push.
Someone has anaphylaxis and we give epinephrine. The reaction was not caused by an epinephrine deficiency or a broken adrenergic system. We deliberately push a system that was working normally, hard enough to counteract what is happening elsewhere, and the person's whole state changes.
That distinction feels easy to see there. In psychiatry, though, the same distinction gets blurred, and a drug that works has a way of turning into a theory of the illness.
I said at the start that everything happening in the person is biological, and I want to be precise about what I mean by that.
I do not mean that receptors, neurotransmitters, hormones and brain circuits are one kind of biology, while attention, learning, fear, memory and emotion are some other kind.
They are the same thing described at different levels.
When somebody feels fear, that fear is a biological state involving neural activity, chemical signaling, autonomic activity, memory and attention. Learning is biological change. A shift in attention is a shift in biological activity. An intrusive thought is not sitting outside the biology. The thought is something the biological system is doing, and so is the relief somebody feels after checking the lock one more time.
So there is not biology over here and psychology over there. There is one biological organism constantly changing state in response to what is happening inside it and around it.
And that matters for medication. If a drug changes one receptor system, it has not changed one isolated biological thing while everything else stays put. It has changed one part of a system made entirely of interacting biological processes.
That change may alter activity elsewhere. Those changes may feed back on the system we started with, affect other networks, alter attention, change learning, shift autonomic activity, or change what gets remembered or expected next. Some of them may reinforce each other. Some may cancel each other out.
The point is not that medication changes biology. Everything was biology already.
The point is that changing one part of the biology can change the state of the whole biological system.
So the end result may be a biological state that looks very different from the one we started with, even though the thing we initially changed was never abnormal and may never have been part of the problem. In that possibility we perturbed one part of the system and the system reorganized.
That is a different thing from proving we found the broken part.
Then I found a 2024 two-part review in JAMA Psychiatry that described almost exactly what I had been trying to put into words.
The authors use something called dynamical systems theory. The basic idea is actually pretty simple. A complicated system with a lot of interacting parts can settle into a pattern and stay there.
In psychiatry, that could mean that what we call a disorder is not always one broken part causing everything else. It may sometimes be a whole biological system that has settled into a particular state and is having trouble getting out of it.
That was the part that felt so familiar to me. Because if that is true, then treatment does not necessarily have to go back and fix whatever originally caused the problem. Sometimes changing one part of the system may be enough to disturb the pattern and push the whole thing into a different state.
That is essentially what I had been wondering about. The papers gave me a framework for it, and they even discuss the possibility that a relatively short intervention can sometimes have a lasting effect if it pushes the system into a different stable state.
None of that proves this is how any particular psychiatric medication works. It does not prove that memantine helps OCD by pushing the brain from one state into another. But it gives a legitimate scientific framework for a possibility I think we overlook: the thing we changed may not have been the thing that was wrong. Changing it may simply have been enough to make the whole system behave differently.
We have been treating psychiatric disorders pharmacologically for a long time, and no medication reliably produces the same outcome across everyone carrying the same diagnosis.
Maybe that is not only because we have not found the right receptor yet. Maybe there is not one thing under the diagnosis waiting to be found.
Maybe some treatments work because they correct something that really was central to the problem. Maybe some work on something that was helping keep it going. And maybe some work on something that was never wrong at all, and simply happened to be a place where we could interrupt the system hard enough that it reorganized into something better.
Those three possibilities lead to very different conclusions. A treatment working does not tell us which one we are looking at.
Which brings me back to where I started.
The research we read does more than tell us whether a treatment works. It also gives us ways of thinking about why it worked. And if most of what reaches me has that same shape, change one part and see what happens and then ask what that part tells us about the disorder, it becomes very easy to keep looking for the answer in one part of the system.
That is why the dynamical systems paper caught my attention. It was still talking about biology. It was just looking at the biology differently. Instead of asking only which part is abnormal, it asks what the whole system is doing, how the parts are interacting, and whether changing one of them might shift the system even if that part was never the original problem.
I do not think one way of looking at this makes the other useless. Sometimes we may actually identify something central to the problem and treat it directly. But I think we also need room for the possibility that a treatment worked simply because we found somewhere in the system where we could effectively push.
Medication can absolutely be one way into that system. I just do not think the place where we entered necessarily tells us why the system was in that state to begin with.