Depression Isn’t a Chemical Imbalance

November 28, 2010 Natasha Tracy

While depression is commonly thought of as a chemical imbalance, research shows it's much more. Depression also involves physiological and genetic components.

What I know about the brain is a fragment of what is known about the brain. What we know about the brain is a fragment of what there is to know about the brain. That being said, what we do know is worth taking a look at.

In the 1960s, scientists discovered that increasing levels of dopamine, norepinephrine, and serotonin in the brain reduced depressive symptoms. This suggested that a depressed brain didn’t have enough of these chemicals and this is where the chemical imbalance theory came from. It was quite reasonable and made perfect sense, but we’ve learned a lot since the 1960s.

Balancing Chemicals in the Brain Doesn’t Explain Depression Treatment

Of course, as we all know, many people are not helped by antidepressants. If it was simply a case of increasing the levels of these chemicals in the brain, we would all get better. Additionally, the brain’s level of neurotransmitters can be dramatically increased in a few days but antidepressants typically take weeks to work. People didn’t miss these points; however, scientists have been working at increasing their knowledge for the last 50 years.

The Great Chemical Imbalancer: Stress Leads to Depression

One issue that has been brought forward is the issue of stress and depression. It is known that inducing long periods of stress will often induce depression.

Stress sends a reaction through four brain systems ending up with the adrenal glands secreting substances like cortisol which interacts with the serotonin receptors in the brain. This cortisol is useful in acute stress as it prepares the body to take action against the stress, i.e. fight, flight, or nothing (yes, there is a “status quo” option). Fear and anxiety are closely linked here. Once the stress has been dealt with, cortisol levels return to normal.

However, in the depressed, it seems that the brain does not successfully regulate the cortisol levels and thus the depressed person continues to show elevated cortisol levels. (FYI, cortisol levels can be measured in the blood.)

Increased cortisol alters serotonergic receptors in the brain; it alters receptors differently in different parts of the brain. (This brain alteration can be seen in the brains of those who have committed suicide.) Antidepressants work to revert these changes and reduce cortisol levels. (Stress systems seen below, provided by McGill University.)

Stress also alters the response of other receptors in the brain. (It’s complicated; see more on serotonin and other molecules involved in depression.)

Stress Physically Alters the Brain

One important takeaway is that stress alters the brain physically and that this is not indicative of a particular individual’s psychological ability to deal with stress. These physical alterations then interact with other neurotransmitters and systems in the brain. (That being said, improving one’s ability to deal with stress is often part of successful depression treatment.)

So Depression Is an Imbalance Caused by Stress Then?

Well, not exactly. We do know about the above relationship but we know about other relationships too. We know that the hippocampus seems smaller in depressed people and that successfully treating the depression increases the cell creation (or slows cell death) in this part of the brain. However, we don’t know if the smaller hippocampus leads to depression or the depression leads to the smaller hippocampus.

We also know that depression is related to parts of the brain involving planning, meaning, pleasure, motivation, focus and pain.

Depression Isn’t Just a Chemical Imbalance

In short, depression just isn’t a chemical imbalance. Yes, chemicals play a role but so do physical changes and genetics. A chemical imbalance is just too simplistic to explain everything seen in the brain.

Why Does This Matter?

It’s okay if you don’t understand the specifics; people spend their whole lives looking at this stuff. The reason why the basics matter though is twofold:

  1. It refutes a lot of antipsychiatry, anti-mental illness folks out there constantly asking for evidence of a chemical imbalance. It’s more complicated than that. A simple spreadsheet of blood levels is just never going to be the answer.
  2. It’s worth understanding the complexity because it sheds light on why drugs sometimes don’t work. Drugs do what they do and they represent what we can do with the knowledge that we have, but it’s impossible to design a drug (at the moment) to address all the linkages we know about in the depressed (not to mention the bipolar) brain. No matter what the drug ads say, you can’t just turn a dial and expect for it to fix everyone.

If you want to learn more about the brain check out The Brain From Top to Bottom provided by the McGill University. It allows you to dial up or dial down the complexity of the explanation of a variety of brain topics.

APA Reference
Tracy, N. (2010, November 28). Depression Isn’t a Chemical Imbalance, HealthyPlace. Retrieved on 2024, April 18 from

Author: Natasha Tracy

Natasha Tracy is a renowned speaker, award-winning advocate, and author of Lost Marbles: Insights into My Life with Depression & Bipolar. She's also the host of the podcast Snap Out of It! The Mental Illness in the Workplace Podcast.

Natasha is also unveiling a new book, Bipolar Rules! Hacks to Live Successfully with Bipolar Disorder, mid-2024.

Find Natasha Tracy on her blog, Bipolar BurbleX, InstagramFacebook, and YouTube.

Dr Musli Ferati
December, 4 2010 at 9:15 pm

The causes of mental illness are a complex interweaving of organic and psychosocial factors. In this respect no exception even depression. Moreover, depression as the worrying symbol of humanity is something more than psychiatric problem. With depressive reactions we meet every day and everywhere: at home, at school, at the plant, on the road... In a word, depressive disorders are our major account to modern civilization. As regard of chemical imbalance, as the cause of depression, we can freely say that the same is just an implication on the complex mechanisms that take place in brain which needs to customize our global functioning. Obstacles in this are are larger, and it is hard to believe that antidepressant drugs alone can solve the depression completely.

Natasha Tracy
December, 1 2010 at 8:50 am

Hi Donna,
Thanks. I think the insulin example is actually useful in explanations to people in terms of diabetics needing the medication to function, you're right, we are more complex in what we need to function differs per person.
And yes, I like to think the "we all need different treatments" thing would become obvious. I like to think eventually it will just be something that we all (society at large) understand.
- Natasha

November, 30 2010 at 3:58 pm

You made a simple statement that really puts mental illness under the microscope. "If it was simply a case of increasing these levels of chemicals in the brain, we would all get better." So often, the easy explanation - the insulin illustration - is enlightening to the listening person. The fact that there are many causes mingled together to bring on mental illness is a great explanation to those of us,(most), who have had to try different medications and dosages thereof. We are all different in makeup and personal history that it becomes obvious there is no "one pill fits them all" answer.
I enjoyed your blog.

Natasha Tracy
November, 30 2010 at 7:57 am

Hi Jake,
I'm sorry to hear that, many people have stories like yours. I have my own nasty-doctor stories to tell myself, so I understand. I think it's really hard to trust doctors, especially if you end up with a new one or seeing a series of new ones. They don't know you and their decisions may just not be the best of you.
Of course, in their defense, many of them are doing the best they can, it's just that medicine's best isn't all that great in the area of mental illness. But we do learn more every day, and I do believe treatment improves every year, particularly for those doctors that specialize and keep up with specific types of literature.
I'm glad you're doing what it takes for you to be stable, for your sake and the sake of your family.
And yes, I would never suggest medications are flat-out "safe", just better than the alternative that many of us face.
Thanks for your comments. I know they speak to many people's experiences.
- Natasha

November, 30 2010 at 7:24 am

Just a side note. I am very thorough. I read all your blogs, I appreciate your journey. I am very cynical about the psychiatric system or to be more precise the hierarchical/paternal nature of it.
I have had treatment involuntarily administered to me, from my Mum medicating my food, to forcible committment(which started with an ugly arrest).
I am not "Tom Cruise" anti-psychiatry, I am "ooops" anti-psychiatry.
I am someone who rarely has bone-crushing depression, but I get ugly mania. Think dipped in gas set on fire, hit the ground running on glass mania. I like you rapid cycle and have experienced ultra-rapid when a replacement doctor thought topomax would be the drug for me.
I have a lot of mistrust.
With all that said and like you I am adament, if you have this illness you require treatment, how much depends on the severity of a persons illness.
I have five kids. I have to stay relatively stable or they are screwed. If it means meds I will take them, I just don't want to be told they are perfectly safe.
So again, there you have it.
cheers Natasha

Natasha Tracy
November, 30 2010 at 6:22 am

Hi Jake,
Sorry, I wasn't trying to be sensitive just informed. I'm a scienc-y and link-y kind of gal and there are always new things to learn.
I didn't think you were attacking me :)
I completely agree that questioning is healthy, and absolutely, that means questioning me :)
Thank-you for your compliments and your comments are welcome any time.
- Natasha

November, 29 2010 at 8:38 pm

Ouch! I forget how perilous the internets are.
Competing science?
Oh well. You need not be so sensitive.
I certainly was not attacking you I like your blog.
This blog is great!!! You rock!!!!!
I just meant in general as with all humans I do not agree with all they say,
or all you say.
It makes sense to be just the slightest bit autonomous.
I am experienced with the psychiatric system.
I am forty six almost forty seven.
I went on psychotropic drugs when I was nine.
Questioning everything makes sense to me

Natasha Tracy
November, 29 2010 at 6:05 am

Hi Jake,
Well, a pill is a Band-Aid for some, and more for others. I can honestly say that there was a time that a particular medication brought me pretty close to a "normal" state. That's more than a Band-Aid. Unfortunately at this time my medication situation is considerably more complicated.
I agree on not dwelling on the "why", as in, why did this happen to me. I'm a person that's pretty interested in the science behind the disease and the treatment, but that's me.
But you are absolutely right, no matter what the cause, the result is the same and you have to focus on dealing with that.
If you feel like discussing what you disagree with, feel free. Pretty much everything I've said comes directly from McGill university (except why I think it matters) so if you have competing science, I'd love to see the links.
- Natasha

November, 28 2010 at 9:31 pm

A pill is like a band-aid.
A band-aid does prevent the blood that has already been spilled. Medication for me is like a band-aid and for the moment it has staunched the flow of sanity from my brain(barely).
I have no illusions that it is going to fix me, I gave up on that notion years ago.
The key for me is not to dwell on "why do I have this shitty illness" but rather how can I mitigate the pain I do to myself and the damage I do to relationships.
Maybe I have a chemical imbalance, maybe it is hormones, maybe I am a malingering bum but it does not change the reality on the ground.
You have raised some interesting points. I dont' agree with you on everything but thats what I like about you, so there you have it.
regards Jake

Natasha Tracy
November, 28 2010 at 2:06 pm

Hi Maggie,
These are good points.
You'll note that I was clear in stating that just because a stress hormone contributes to depression, that doesn't mean it's any more the person's fault than a "chemical imbalance" theory. Nothing in our current knowledge indicates depression is a personal failing.
See, I don't believe in lying to people so that they'll get treatment. If you really want to distill the information the truth is this: your brain is sick and you need treatment for that illness. It's similar to cancer, I (and doctors) have no idea why people get cancer but I know that when you get sick you need treatment.
I don't believe that any reputable doctor believes that one thing causes a mental illness. We've known about the complexity for so long it would be impossible for them to miss it. Of course that doesn't mean they will tell patients that. Doctors speak down to their patients out of course. They don't really have an hour to explain mental illness (or any other illness) to the average person.
I'm thinking PCP means family doctor (not sure what country you're in). I have to say for the vast majority of garden variety depression a family doctor can prescribe an SSRI or two and the problem is solved. All those people don't need psychiatrists. They just don't. It's after you've failed several treatments or if you have a more serious disorder that you need a psychiatrist, which is reasonable as they are specialists.
I agree with you with regard to suicide and antidepressants, but the truth is family doctors are often in a _better_ position to stop this from happening than psychiatrists are. Family doctors generally know the person better and can see them more frequently, which is what they need.
Yup, you're right, the headline is strong, but anyone who bases their opinion on a headline can easily be disarmed with the most obvious of facts. I'm actually hoping more people will read the article because of the title, not less.
I believe that knowledge is power. I believe that people make better decisions with better information.
- Natasha

Natasha Tracy
November, 28 2010 at 1:50 pm

In my experience anti-psych people don't want any explanation that involves psychiatry at all, they are anti-everything.
However, I think education in this matter is important so people can at least know what the science is currently telling us.
Yes, chem imbalance is simple and convenient but that doesn't make it beneficial in the long run; it really just fuels straw-man arguments about how the chemical imbalance theory can't be proven.
- Natasha

The Maggie
November, 28 2010 at 1:39 pm

I think that the chemical imbalance explanation is a necessary evil in some cases. Because I know that for some people, the only way you are going to get them to try psych meds that may very well save their lives, is if you can assure them that it is no way a failing on their part and blaming the brain's chemistry is the most sure-fire way of convincing someone of that.
It relates back to the "would you take insulin if you were diabetic?" argument for people who are reluctant to take psych meds. When i was non-med compliant that argument never worked with me, but after hitting bottom, i accepted that i need my meds, and thus, have accepted this analogy.
My point being, a lot of people (including doctors) cannot wrap their mind around the idea that there isn't one thing that causes depression and thus not one thing that fixes it. so yes, in that sense, the imbalance explanation is most convenient.
HOWEVER, it also probably contributes to the number of people who will see their PCP for pscyh meds and expect the pills to make them all better.
I believe that is why suicidality can increase when some people take antidepressants: the pills make you feel better just enough to give you the energy to complete the act. OR people think “i'm still depressed even though i'm on medication, I must be unfixable and end or attempt to end their lives. I think it is incredibly irresponsible for PCP's to prescribe psych medication. I was going to qualify that sentence with “at least initially, but maybe okay for med management” but even then, things can go wrong very fast any time you are on a psych medication.
I think the danger with this information is that in a headline/sound bite/tweet centered world 90% of people will only read “depression not a chemical imbalance” and base an opinion (a strong one) just on that information. We've all known at least once person who will form and stand by an opinion despite having no basis for that opinion whatsoever. So for that reason, I think this is one of those situations where for most people, this little bit knowledge can be a very dangerous thing.

November, 28 2010 at 12:40 pm

Nice explanation. My understanding of the anti-psych ppl is that they would also support a more "it's complicated" view whereas the media and even a lot of psychiatrists pass along the imbalance explanation because its simpler and more convenient.

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