Do Depression and Anxiety Result from a Chemical Imbalance in the Brain?

Another Great Question from Rob, an Enthusiastic and Thoughtful Fan

Hi David,

I’m listening to your old face book video.  You are describing bi-polar disorder which you mention is a biological disorder.

I’m curious, what is the difference between a biological disorder (which obviously exists) and a “chemical imbalance”? If I understood some of your previous talks, there is no evidence of any “chemical imbalances” in the brain?  Perhaps that is something you can address in a future podcast if you see fit?

As always, I appreciate all the wisdom you share!


Hi Rob,

Sure, I can address this in a podcast, but here’s a quick answer so you won’t have to wait.

The concept of “imbalances” was used for hundreds of years, unsuccessfully, to explain how nature works. For example, balances and imbalances in these four elements—earth, air, fire, and water—were thought to explain nature, but the theory just didn’t work. Nature cannot be explain by a hydraulic system of “balances” or “imbalances” of earth, air, fire, and water.

For example, the massive fires in Northern and Southern California right now are likely the result of global warming, and the lack of rain, and not by some kind of “imbalance” of earth, air, fire, and water. Well, I guess you COULD say the fires are due to too much fire and not enough water! But that’s not much of an explanation–because it’s just a tautology! It’s like saying “fire is the cause of fire.” Duh!

Global warming appears to be caused by burning fossil fuels and dumping millions of tons of hydrocarbons into the atmosphere, causing the “greenhouse effect.”

For two thousand years, medicine tried unsuccessfully to use the “balances” and “imbalances” model to explain medical illnesses, which were seen as due to an imbalance of four “humors”—black bile, yellow bile, blood, and phlegm. So when George Washington had a severe throat infection, his doctors thought it was the result of an “imbalance,” namely, too much blood, so they bled him. This so-called “treatment” contributed to his death. Again, the balance and imbalance theory did not explain anything in a valid way, and did nothing to advance medicine. It was not a sound or useful theory.

Very few medical illnesses are due to “chemical imbalances.” For example, a broken leg is not usually due to a “chemical imbalance” in the bones, but rather from a fall and the physical forces that cause the fracture. Similarly, a heart attack has a biological but it is not caused by a “chemical imbalance” in most cases, but rather from the narrowing or closure of one or more arteries that supply blood and oxygen to the heart, as well as other causes, such as electrical conduction disorders. A heart attack is not the result of a chemical imbalance, and cardiologists rarely talk about “chemical imbalances,” although in some cases electrolyte abnormalities can cause cardiac problems.

Hydraulic imbalances of basic elements or humors, as you can see, is a primitive way of thinking that goes back at least two thousand years, to the time of Hippocrates, an early physician. And hydraulic imbalances in brain chemicals do not explain most brain disorders, emotional upsets, or behavioral problems, either.

Still, psychiatrists have tried to use the “chemical imbalance” theory to explain psychiatric disturbances for the past 60 years or so; but this effort has not been helpful, in my opinion, because the brain is not a hydraulic system of balances and imbalances. The brain is some kind of super computer, an massively complex electronic system that we are just beginning to understand.

There are many biological abnormalities in the brain, but are rarely “chemical imbalances.” For example, Alzheimer’s Disease is a true biological brain disorder, but it is not due the result of a chemical imbalance. The same is true of brain tumors, as well as encephalitis (an infection of brain tissue) or meningitis. These are true biological problems, but they do not result from “chemical imbalances.”

Schizophrenia is a tragic and severe psychiatric disorder–it is not a variant of normal thinking or behavior, and it has a yet-unknown biological cause, which partially involves genetic causes. We will likely know the cause of schizophrenia fairly soon–but it likely will NOT be a “chemical imbalance.”

The brain can have all kinds of biological abnormalities that are not “chemical imbalances”—hemorrhages, strokes, malformations from genetic abnormalities, traumatic injuries from concussions, infections, and so forth, but these do not usually involve “chemical imbalances.” Neuropathology was one of the few courses I excelled in as a medical student at Stanford, and received one of the highest scores ever on the final exam, but I cannot recall using the term “chemical imbalance” in that class.

We do not yet know the cause of most (or arguably any) psychiatric / psychological “disorders.” I used to do full time research on the “chemical imbalance” theory of depression, but left biological psychiatry to focus on new forms of psychotherapy when I realized that the chemical imbalance theory was not a productive or valid.

The theory holds that depression is due to a deficiency of serotonin, one of the many neurotransmitter substances in the brain, and that mania is due to an excess of serotonin. But I am not aware of any consistent or convincing evidence for this theory.

The research my colleagues and I did on this theory, which we published in the top psychiatry journal, Archives of General Psychiatry, did not support this theory.

This is the article:

Mendels, J., Stinnett, J. L., Burns, D. D. & Frazer, A. (1975). Amine precursors and depression. Archives of General Psychiatry, 32: 22 – 30.

Essentially, we flooded the brains of depressed veterans with massive increases in serotonin–but there was no effect on their moods. The depression levels did not improve from the increases in serotonin. This was, to my way of thinking, a simple and direct test of the “chemical imbalance” theory, and the result were crystal clear.

That was a clinical study. I was also involved in basic brain research on the chemical imbalance theory. I won the A. E. Bennett Award from the Society for Biological Psychiatry for the next article:

Burns, D. D., London, J., Brunswick, D., Pring, M., Mendels, J., Garfinkel, D. & Rabinowitz, J. L. (1976). A kinetic analysis of 5 – hydroxyindoleacetic acid excretion from rat brain and CSF. Biological Psychiatry, 11(2): 125 – 147.

I mention this not to brag, but to emphasize that I was not an “outsider,” but someone working very successfully within the system of biological psychiatry. I also wrote chapters on the chemical imbalance theory for textbooks, such as this one, which was based on a review of the entire world literature on the chemical imbalance theory:

Burns, D. D., & Mendels, J. (1979). Serotonin and affective disorders. Chapter 3 in Current Developments in Psychopharmacology, Vol. 5 (Essman, W. B. and Valzelli, L., eds. ), New York: Spectrum Publications, Inc., pp. 293 – 360.

Much recent suggests that antidepressants–which boost brain serotonin systems, have very few true antidepressant effects above and beyond their placebo effects. Of course, a placebo effect can itself be fairly strong. That’s why some people do appear to improve when treated with antidepressants. In many cases, they attribute their improvement to the medication, when the improvement may actually be due to changes in their won behavior and thinking.

Everything about being human results from biological (genetic) and environmental influences—such as IQ, personality, height, hair color, and the proclivity to being naturally more negative in outlook (depression, anxiety, shyness, anger) or more naturally positive (happy, confident, outgoing). However, we do not yet have much understanding of the brain systems that are involved. To what extent is depression the result of problems with our hardware (tissue level brain abnormalities or damage) vs. software (learning, neural circuitry, etc.)? We just don’t know.

Here’s one final analogy that may work. The brain is an incredibly complex super computer, involving billions and billions of neurons. I suspect you’ve had many problems with your computer over the years. We all encounter this. The computer freezes up, crashes, won’t connect to the internet, or whatever. Were any of these problems ever due to a “chemical imbalance” in the chip?

I don’t think so! So, it is true that humans are biological, and that biological factors contribute to our emotions, positive or negative. But this does not mean that psychiatric problems are due to “chemical imbalances.”

Let me know if I’ve made this clear.

Finally, because I am sometimes misquoted by individuals who may not understand what I’m saying, I am NOT saying that medications should never be used for individuals with psychiatric problems. Far from, sometimes medications can be helpful, even lifesaving.

And I’m NOT saying that people who take any kind of psychiatric drugs should suddenly stop taking them. That can be dangerous or even a disaster in some cases. All drug decisions must be made on a personal basis, based on a dialogue with your physician.

Some people may feel that a wrong theory is better than no theory at all. This is not my thinking. I am an agnostic on the causes of depression and anxiety. Some day we will know much more about causes. For this day, I am simply grateful and excited that we have so many new and powerful treatments for depression and anxiety, including TEAM-CBT and other new treatment methods, and that so many people can now be treated quickly and effectively without any medication at all. And to me, that’s good news!

One last thing. I get tons of positive emails, which I deeply appreciate, but I occasionally get hostile emails from people who don’t like what I say or write about. They scold me! A therapist recently emailed me to let me know she would never again recommend any of my books to her patients because of my position that we have perhaps been oversold by drug companies on the safety and efficacy of the antidepressants.

Remember to take what I say with a grain of salt. Sometimes, in fact often, I am wrong. But I always try to convey my honest take on things, thinking “the truth shall make you free.” For years I suppressed my thinking, fearing it would hurt or anger some people. Now I’m being more open. If you ever want more scientific references, I’d be happy to send you tons of them.

I still struggle with this issue of how open to be with all of you, and I still don’t know the “correct” answer. I don’t want to hurt anyone’s feelings, and I think the prognosis for fast, effective treatment of depression and all of the anxiety disorders has never been brighter.

Let me know what YOU think!



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