If Not Low Serotonin, What’s Really Driving Depression?

DR JOHN DEMARTINI   -   Updated 1 year ago

Dr John Demartini explains why he doesn’t believe depression results from just a chemical imbalance, but rather from a comparison of your current reality to an unrealistic expectation about how life's “supposed” to be.

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DR JOHN DEMARTINI - Updated 1 year ago

This topic was initiated primarily as a result of the release of a recent study dealing with the widely held belief that serotonin and biochemical imbalances are the likely cause of depression.

In brief, the study reports that there is no evidence to support the idea that depression is caused by low levels of serotonin, one of the so-called “happy hormones”.

It also asserts that the result of 17 studies indicates that individuals with depression don’t appear to have different levels of serotonin in their brains to those without depression.

The article has since gone viral and raised a number of questions around the diagnosis and treatment of depression and so-called chemical imbalances in the brain.

This information and research presented in this recent article is actually not all that new. In fact, I attended a conference in 2008 together with over 1,000 psychiatrists, with the main topic of debate being the decrease in the effectiveness of antidepressants that was not greater than some placebo effects. I’m fascinated that it has taken 14 years for this to receive widespread attention in 2022.

Let me state my view upfront before moving on to the detail:

  • I've not been a firm believer in the biochemical model for over four decades because I've seen hundreds of individuals resolve their depression without having to take any chemical.
  • I also know that the biochemical changes in the brain can occur by changes in ratios of perceptions and expectations.

So the question is: Is depression really a condition?

This may be shocking to you if you believe that depression is a condition that needs to be treated chemically instead of feedback to let you know that your perceptions and expectations are likely imbalanced and off-center.

I have seen first-hand in thousands of cases around the world that human beings often prefer to blame or give credit to outside circumstances and solutions more than look within. They prefer false attribution biases instead of looking within to their inner resources for solutions to their daily challenges. This biased view can arise in anyone who compares themselves more to others than their own actions to their true highest values, priorities, or objectives. They put others on pedestals or in pits more than put them into their hearts. They are therefore more often outer directed more than directed authentically from within.

The whole positive thinking movement asserts that you have to be up all the time or there’s something wrong with you. This is simply not so wise to have such expectations.

Every human being has periods of cycles of ups and downs in mild or moderate degrees.

Euthymia is a term to describe these shifts on a smaller scale. Cyclothymia describes more moderate shifts, and bipolar conditions and manic and depressive states indicate even more extreme oscillations. There’s a spectrum.

Most individuals, including you, have periods of highs and lows. You also have a homeostatic mechanism in the brain that neurochemically and electronically tries to bring your physiology and psychology back into balance if you perturb it with your perceptions.

So, what throws the balance off? What results in these high and low mood swings?

They are the result of subjectively biased interpretations of reality and unrealistic expectations that have been programmed into you by injected traditions from outside authorities and moral hypocrisies.


I describe depression as a feedback system emerging where you compare your current reality to an unrealistic expectation, fantasy, or delusion about how life's “supposed” to be.

I've dealt with thousands of individuals who have been diagnosed with depression. Once I asked them some very specific questions, each of them revealed how they continuously compared their life to how they perceived it “should” have happened, was “supposed to” have happened, or wished it “would have happened”.

They also assumed that their life should have more or all upsides and less or no downsides, which is completely impossible in the same way that it’s impossible to create a one-sided magnet.

Once I worked with them to bring their perceptions into balance by finding upsides to their perceived downsides, and downsides to what they were comparing their life to about how it “should have” been, their depression dissolved.

I've seen this happen over and over again. At a recent Breakthrough Experience, my signature program that I teach, a lady said, “Well, my mother wasn't there when I was a child and I was abandoned,” – a story that she used to explain her depression, challenges, and victim-mindset in life.

I explained to her why I believe that to be a false causality. It's not because she was abandoned that was the likely “cause” of her depression – that was an EVENT that occurred. It was her expectations, perceptions, interpretations, decisions, and actions that determined what happened as a result of that event.

So, I asked her a simple question. “What did you particularly miss or did you think you missed out on in your relationship with your mom when she left?”

“Well,” she said, “I missed having somebody to be there for me, guide me, and love me unconditionally.”

I explained to her that at the level of the broader perceiving ‘soul’, nothing's missing in your life. At the level of your narrower perceiving senses, things appear to be missing.

However, if you ask the right questions, you can become aware of the new forms in which those actions are emerging.

I then asked her, “Which individuals guided and loved you when your mother left? What was the benefit of having each of them take on those roles? What would have been some of the downsides if your mother had stayed and taken on those roles?”

She explained to me that her aunt and grandmother had taken care of her and that she had experienced a financially stable childhood as a result. She had also been able to finish school and had a close-knit group of friends that she met there.

I had her stack up a detailed list of benefits of having her grandmother and aunt take on a parenting role, and the drawbacks that would have continued to occur had her mom not left.

As a result, she was able to see opportunities she had not seen before, and transform what she had originally perceived to be a negative event into something she was grateful for.

Your mind is more likely to become conscious of unconscious information when asked the right questions because the quality of your life is based on the quality of the questions you ask.

As I explained to the woman above – she had been running a story in her mind about how there would have been more positives than negatives if her mother hadn't left. Once I asked her to identify the downsides of having her mother stay and the benefit of these new individuals taking on that role, her depression dissolved.

When you have expectations that are other than what is actually happening you can set yourself up for what I call the A B C D E F G H I’s of negativity:

  • Anger and Aggression;
  • Blame and Betrayal;
  • Criticism and Challenge;
  • Despair and Depression;
  • Desire to Exit and Escape;
  • Futility and Frustration;
  • Grouchiness and Grief;
  • Hatred and Hurt: and, in a sense;
  • Insanity and Irritability.

These are byproducts of comparing your sensory reality to fantasies and unrealistic expectations.

Unrealistic expectations that your mother is “supposed to” be there at all the times and not ever missing, which is unrealistic; being positive or all upsides and no negative or downsides, which is unrealistic; or read your mind, know what you want, always be there, and do what you want, which is unrealistic.  Individuals are not one-sided and they live and perceive, decide and act according to their own higher values, not yours. Projecting your values or social ideals onto others sets you up for letdowns.

I repeatedly find one or more of these 15 common underlying unrealistic expectations or fantasies in most individuals with clinical depression.

These include:

  • An unrealistic expectation of others to be more or only one-sided where they are more positive than negative, more nice than mean, more peaceful than wrathful, more there for you than not and more kind than cruel.
  • An unrealistic expectation on others to live in your values or outside their own values.
  • The combination of the two above.
  • An unrealistic expectation on yourself to live a more or only one-sided life where you are more positive than negative, more nice than mean, more peaceful than wrathful, and more kind than cruel.
  • An unrealistic expectation that you are to be living outside your own values or in somebody else's values and be somebody you're not.
  • The combination of the two above.
  • All the above.
  • An unrealistic expectation to live in a one-sided world or that the world or society, in general, is to be more or only one-sided – more peace than war, more support than challenge, and more praise than criticism.
  • An unrealistic expectation that the world or society is to live according to your set of values.
  • The combination of the two above.
  • All the above.
  • An unrealistic expectation to have mechanical objects (computers, phones, cars, electronic gadgets…) to be more or only one-sided.
  • An unrealistic expectation that mechanical objects are to live according to your set of values.
  • The combination of the two above.
  • All the above.


Anytime you have unrealistic one-sided expectations; – for example, that the world's supposed to be peaceful and not warful, kind not cruel, or that others are to live in your values, or that you're supposed to live in other’s values (instead of communicating what you value most in terms of another individual’s value most and having them do the same) you are highly likely to experience one or more of the A B C D E F G H Is of depression as a result.

I don’t believe that depression is an illness as much as it is a feedback system. But it seems to have become a label that has allowed the pharmaceutical industry to sell drugs to individuals for so many years.

Instead, I believe that depression is a negative feedback system to let you know that you have unrealistic expectations and that you’re being inauthentic so you can get back into equilibrium, realistic expectations, and authenticity.

Something else I do during the Breakthrough Experience is to find out what the individual’s unrealistic expectations or FANTASIES are because I have not seen one depressed case, not one, that didn't have unrealistic expectations and fantasies stored inside.

As I said earlier, the quality of your life is based on the quality of the questions you ask yourself. When you ask individuals very specific questions to help make them conscious of unconscious information, they often result in tears of insight and gratitude and comments like, “No wonder I'm depressed, I’m pursuing something that’s not grounded in reality.”

I then help them crack the fantasy and find benefits of what they are currently experiencing, because anytime you compare your current reality to a fantasy of how it “should have been”, “would have been”, or “could have been”, you're not likely to appreciate your life the way it is. And, if you compare it to what it isn't, then you're likely not present with, nor appreciating what is.

So I crack their fantasies and all of a sudden the depression lifts because I’ve broken their addiction to their unrealistic expectation or fantasy about how life's “supposed to” be.

This can be both important and powerful when you realize that a one-sided life is not possible – despite what your traditions, parents, teachers, and preachers may have told you growing up.

No human being is nice without mean or kind without cruel or positive without negative all the time. These are absolute moralities that are unobtainable.

As the Buddha said, the desire for that which is unobtainable and the desire to avoid that which is unavoidable is the source of human suffering.

So, if you have a fantasy that you’re supposed to be one-sided or that individuals are supposed to be one-sided, life's not always going to match that. As such, you are more likely to feel depressed when real life doesn’t match up to your fantasy.

When you're not living your life based on your highest values, not living by priority, not doing something meaningful or creative that inspires you, not in a job or relationship that's meaningful, your blood, glucose, and oxygen go into the amygdala in your hindbrain. Your amygdala wants to avoid predators and seek prey, avoid negative and seek positive. It's the animal survival mode and mass-conscious herd instincts and impulses. This is where the one-sided expectations emerge from.

That's the area of the brain where most individuals operate from - they want to avoid any challenge and seek everything easy.

Immediate gratification costs. Long-term vision that embraces pains and pleasures, support and challenge, and all pairs of opposites has already been proven to help maximize growth.

In other words, you need prey and predator, support and challenge, praise and reprimand, to keep you authentic.

Individuals with a mission, who are doing something meaningful, who are inspired by their job, and who are inspired by their relationship, have the blood, glucose, and oxygen go into the executive center of their forebrain, As such, they tend to be more objective, reasonable, balanced, authentic, inspired and vitalized. And they tend to set more realistic expectations or objectives.

Instead of looking for a one-sided world, they are more likely to embrace both sides of life. As such, they are highly unlikely to experience the depressive states and manic states that often result from these absolute polarities of perception.

When you think about it that way, depression doesn't seem like a mystery. Instead, it’s easier to see it as a motive and mechanism to try to break your addiction to things that are unrealistic.

That’s why I'm not a believer that depression is caused by a biochemical imbalance although there are at times some correlations.

I’d also like to address the results of blood tests that indicate biochemical imbalances, including glutamate, GABA, serotonin imbalances, and dopamine imbalances.

Those imbalances are not causal but instead they are a result of present or previous, subconsciously stored distorted or lopsided perceptions.


I like to use the example of opening a door and seeing a tiger behind it. In the 200th of a millisecond, from the instant that you saw the tiger, your perception would immediately change your neurochemistry.

All of a sudden, your dopamine and serotonin would likely go down, your norepinephrine and cortisol would likely go up, your testosterone would go up, and your estrogen would go down.

Your enkephalin endorphins would also go down while your substance P would go up. All these chemistries, glutamate and GABA would go into action to try to bring those back into homeostatic balance intuitively.

So, if you were to look at your blood chemistry results and determine that you had a biochemical imbalance that required antidepressants - that conclusion would be misleading and incorrect. That would be a false attribution bias applied to a deficiency of chemical signal molecules, hormones, or transmitters inside your human brain.

No pharmaceutical company or psychiatrist can fully compete with the wisdom of the body or homeostasis of the human brain. They can assist, but that's only because the majority of people are not taking the time to find out what's going on inside human physiology and psychology. They are not being accountable for their perceptions, expectations, decisions, and actions.

Instead, they take a narrowed view without looking at the holistic aspect of the human being and how individuals can take their power back.

I'm interested in helping individuals take their power back by teaching them how to manage their state, which can also balance their correlated chemistry.

If you have a more realistic expectation, and a more objective or balanced perspective, you are less likely to have mania or depression, be infatuated or resentful, proud or ashamed.

Instead, you will tend to be centered, authentic, and empowered.

As I often say, the second you infatuate with somebody, you minimize yourself relative to them, and that's a disempowerment. The second you infatuate with others you will tend to inject their values into your life and set yourself up for unrealistic expectations of living in their values not your own.

The second you exaggerate yourself relative to somebody and resent them, you're too proud to admit what you see in them inside you, you are in a disempowered state. And you will tend to project your values onto others.

Anytime you're not authentic, you become disempowered. As such, you create symptoms in your physiology and psychology, which is a feedback system, a homeostatic feedback system, to get you back to being who you are.

The magnificence of who you truly are is far greater than any of those unrealistic expectation-based facades, volatilities and vicissitudes, and the addiction to one-sidedness and feeling one-sided or “happy” all the time is the very source of many of the depressions individuals have.

I'm a firm believer that you have way more power and control over your physiology and psychology than you might think.

If you’d love to be trained in the art of managing your perceptions then join me at my signature program the Breakthrough Experience. You’ll learn how to dissolve the unrealistic expectations and fantasies leading you to depression. You’ll be shown how to wake up a deep appreciation for life as it is.

I'm a firm believer that if individuals were educated about how their physiology and psychology worked, and how perception, unrealistic expectations and fantasies impacted their chemistry, they would be less likely to have a dependency on psychiatric drugs.

I'm not saying that medication doesn't have a place, because in some extreme cases, it may be a blessing. But it’s unwise to have medication as the first line of defense or the first choice. Instead, it’s wiser to have it as a secondary or tertiary choice.

I believe that it’s wise to take accountability, be aware of what's going on, take command of your life, and find the order that's in your so-called chaos. The disorder is in your perception. It means missing information. It means you're unconscious of one half of the equation and likely not asking the right questions, while also having false expectations about how life's “supposed” to be.

It is also wise to give yourself permission to take command of your life and learn how to master your own objectives.

I teach a program called the Breakthrough Experience most every weekend in the year. In the process of doing it, I have seen people arrive almost every week with depression, bipolar conditions, dissociative and abandonment issues, and attention deficit disorders.

They arrive with all these labels. Once they learn how to stabilize their perceptions, ask new questions, hold themselves accountable on how to perceive differently, which I call the Demartini Method, how values play a role in their behavior, and how to prioritize their life and take command of their life, they are able to be more objective and more realistic in their expectations, and their depression is dissolved and some of these other labels dissolve.

I don’t advise my students to stop taking his or her antidepressants. They stop them because they don't feel they need them anymore once they are balanced, objective and inspired by their lives again.

I am certain that your natural state is to be fulfilled and inspired.

But if you're trying to live in other individual’s values, trying to get others to live in your values, setting up fantasies of one-sidedness, having unrealistic expectations and are functioning down in your amygdala where you're avoiding pain and seeking pleasure and trying to be one-sided, you’re unlikely to have realistic expectations and objectives that are meaningful and inspiring.

That perceptual emptiness may result in you wanting to look for a quick fix and a one-sided world, which can lead to depression.

To sum up:

I'm a firm believer that you have the ability to govern your life and transcend states of depression.

I'm a firm believer that, if you ask the right questions, you can become objectively aware of things and have a balanced orientation.

You're unlikely to have balanced chemistry or balanced physiology with an imbalanced mind.

You're unlikely to have a balanced mind with imbalanced perceptions and expectations.

You’re unlikely to have a balanced perception unless you know how to ask quality questions to equilibrate the mind from your initial perceptions, which are usually subjectively biased and in a sense, causing these emotional reactions.

I'm also a firm believer you have the power to do it!

I've dedicated the last 50 years of my life to assisting individuals to master, empower and take command of their life. That's why I’m inviting you to come to the Breakthrough Experience so I can teach you how to do that - ask new questions, see things objectively, and set goals that are reasonable, really meaningful, and inspiring to you.

Many individuals who perceive they are depressed or who have been diagnosed with clinical depression, tend not to feel purposeful. There's a science on how to reclaim that. And that's what I would love to teach you in the Breakthrough Experience, including more than seven proven tools and a wealth of information to help you master your life.

So if you're interested in mastering your life and transcending this illusion of depression, then come to the Breakthrough Experience. I'm certain you can come there and learn how to take command of your perceptions, expectations, and resultant chemistry because every time you change the ratios of your perceptions, you change your chemistry.


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