Psychiatry’s most convenient myth? This doc just reignited the chemical imbalance debate
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We looked at all the different areas of research on serotonin and showed that none of them provided convincing or consistent evidence for there being an abnormality of serotonin in people with depression.
—Joanna Moncrieff, MD
For decades, many of us have relied—explicitly or implicitly—on a simple story to help patients understand depression: Your brain chemicals are out of balance.
It’s been clinically convenient, emotionally reassuring for some patients, and tightly woven into how antidepressants have been explained in exam rooms, textbooks, and pharma ads.
But at the 2025 Inner Compass Conference, British psychiatrist Joanna Moncrieff, MD, reignited a long-simmering controversy: What if that story was never supported by solid evidence in the first place?
Revisiting the serotonin hypothesis
Dr. Moncrieff is best known for her work questioning the serotonin hypothesis of depression—the idea that depressive symptoms stem from a deficiency or dysfunction in serotonin signaling.
In her remarks, she summarized years of research reviews examining multiple lines of evidence: serotonin levels, receptors, metabolites, genetic studies, and depletion experiments.
The conclusion, she said, was consistent and uncomfortable: None of these research areas produced convincing or reliable evidence that people with depression have a serotonin abnormality.
"We looked at all the different areas of research on serotonin and showed that none of them provided convincing or consistent evidence for there being an abnormality of serotonin in people with depression," she said in an Instagram Reel of the conference.
That finding alone wasn’t new. What was new was how forcefully it challenged psychiatry’s public-facing narrative. "Of course, one of the responses to that was 'oh, well, you know, maybe it’s not serotonin, maybe it’s something else.' And there are, of course, numerous hypotheses about possible biological causes of depression. But the trouble is none of them have been established either. So the psychiatric establishment were furious that they had been exposed by the publication of this paper. And they tried to neutralize it," she said.
For clinicians trained to value falsifiability, that should give pause.
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Here’s where nuance matters. Discrediting the chemical imbalance explanation is not the same as saying antidepressants are ineffective. Drugs can alleviate symptoms without correcting an underlying biological defect—much like how alcohol reduces social anxiety without treating a “GABA deficiency.”
Dr. Moncrieff’s argument is less about clinical outcomes and more about intellectual honesty. If we don’t actually know the biological cause of depression, should we keep telling patients that we do?
As Dr. Moncrieff’s work reminds us, psychiatry still lacks definitive biological explanations for depression—and that’s okay.
For clinicians, the challenge moving forward is to explain treatments clearly, acknowledge uncertainty honestly, and resist the urge to oversimplify a condition that remains profoundly complex.