21/10/2025
Even if we accept the idea of a chemical imbalance, we still have to ask: "what’s causing that imbalance in the first place?" The latest understanding suggests it may actually stem from nervous system dysregulation - meaning medication might manage symptoms, but not address the true root cause.
A major study published in Molecular Psychiatry titled “The serotonin theory of depression: a systematic umbrella review of the evidence” examined decades of research involving tens of thousands of people. The scientists found that serotonin levels and their breakdown products in the blood or brain fluids were no different between people diagnosed with depression and those without it. This is striking, considering that up to 90% of the public still believes depression is caused by “low serotonin” or a “chemical imbalance.”
The serotonin theory of depression was first proposed in the 1960s, but it gained mainstream traction in the 1990s when pharmaceutical companies began marketing a new generation of antidepressants - SSRIs (Selective Serotonin Reuptake Inhibitors) like Prozac. These drugs were promoted on the premise that they corrected an underlying chemical deficiency.
The study’s lead author, Dr. Joanna Moncrieff, a professor of psychiatry at University College London, explained:
“Many people take antidepressants because they have been led to believe their depression has a biochemical cause, but this new research suggests this belief is not grounded in evidence….It is high time to inform the public that this belief is not grounded in science.”
The researchers also reviewed experiments where serotonin levels were deliberately lowered in hundreds of healthy participants. The result? No one developed depression simply from reduced serotonin levels.
This raises serious concerns, especially since antidepressants alter normal brain chemistry. They often blunt both negative and positive emotions, and several studies suggest they may work primarily through placebo effects, by creating a sense of hope rather than correcting a measurable chemical imbalance.
As Moncrieff and her team put it:
“Our view is that patients should not be told that depression is caused by low serotonin or by a chemical imbalance, and they should not be led to believe that antidepressants work by targeting these unproven abnormalities. We do not understand what antidepressants are doing to the brain exactly, and giving people this sort of misinformation prevents them from making an informed decision about whether to take antidepressants or not.”
All of this points to a deeper truth: depression may not begin as a problem with brain chemistry at all. Instead, it may arise from life experiences, trauma, chronic stress, and nervous system dysregulation - factors that then influence the brain and body, rather than the other way around. Mainstream medicine often misses this perspective, but it may hold the key to understanding and healing depression at its source.