Is Chemical Imbalance a Useful Simplification of Mental Illness?

"Chemical imbalance": It oversimplifies mental illness, but is it still useful? - graphics of brain and neurons

We’ve all heard of the “chemical imbalance” explanation for mental illness, and in particular, depression. While this term has supported the argument that mental illness is actually an illness, it’s also a gross simplification of mental illness in terms of what’s actually going on in the brain. I wonder if perhaps this terminology is no longer serving us.

Where “chemical imbalance” came from

The idea of a chemical imbalance didn’t come about because of observations of what was happening in the brain; rather, it was an attempt to explain depression based on the way antidepressants worked.

Isoniazid and other early drugs that demonstrated antidepressant activity were known to slow the breakdown of the catecholamine neurotransmitters (serotonin, norepinephrine, and dopamine). Based on this activity of the drugs, it was hypothesized that a deficit in catecholamines led to depression. This hypothesis was first proposed in the 1960s.

The serotonin element in particular became a popular bandwagon, leading to the development of new drugs. Eventually, this led to the development of the first selective serotonin reuptake inhibitor (SSRI), Prozac, which ushered in an era marked by heavy direct-to-consumer advertising by drug companies that leaned heavily into the notion of a chemical imbalance (Pies, 2019). “Chemical imbalance” was also a handy metaphor to explain to patients that depression involved biology.

The real story

Current understanding is that depression is complex and multi-factorial. The idea that there’s a simple serotonin deficit, or catecholamine deficit more broadly, is inaccurate. Science can get a much more detailed view of what’s happening in the brain now compared to the 1960s, and there simply isn’t a shortage of neurotransmitters.

However, that doesn’t mean we throw the baby out with the bathwater. There are clearly biological elements to depression and other mental illness, and multiple factors that have been implicated.

Signalling between neurons via catecholamine neurotransmitters

This is much more complex than absolute amounts of these neurotransmitters. Regulation of neurotransmitter receptors and transporters on nerve cell membranes has a major impact on signal conduction. A potential reason the delayed onset of action of antidepressants relates to the time it takes to adapt the regulation of these receptors via changes in the expression of genes encoding for them.


The neurotransmitter glutamate can cause what’s referred to as “excitotoxicity,” and this may have a role in depression. Inflammation is suspected to be a key contributing factor. Ketamine affects the glutamate signalling system via its effect on NMDA receptors.


Speaking of ketamine, it promotes the production of brain-derived neurotrophic factor (BDNF), which is involved in neuroplasticity. BDNF’s potential role in depression continues to be investigated.

Genetic factors

Genetic variants affecting such things as serotonin transporters and methylation processes are thought to potentially play a role. Variants in the SERT (serotonin transporter) gene are associated with different patterns of response to treatment than those with the “normal” SERT gene. Significantly more research is needed in this area to gain a greater understanding of the role of genetics.

Epigenetic changes

Epigenetics refers to when and how often our genes are translated into the proteins that they code for. Multiple environmental factors are thought to affect this, and this is where adverse childhood experiences can have a huge impact. There is still much, much more to be learned in this area.

The disconnect

In Johann Hari’s book Lost Connections, he argues that the serotonin hypothesis is untrue, and therefore biology should be kicked to the curb, and depression is all psychosocial. That’s quite the leap, but the notion of a chemical imbalance is the starting point.

The idea of a chemical imbalance is sometimes described as being literally true. One way this can be done is to validate the existence of biological illness. For example, an article in VeryWellMind titled The Chemistry of Depression mentions a deficit in neurotransmitters as a contributor to depression. References to deficits in serotonin and other neurotransmitters can be seen in graphics on Pinterest and other corners of the internet, along with advice on how to “naturally” boost neurotransmitter levels.

I’m inclined to think that at this stage of the game “chemical imbalance” may have outlived its usefulness. In a time when it’s so easy for people to look things up online, if we’re using terminology that oversimplifies to the point that it’s not really accurate, we may just be shooting ourselves in the foot by hanging onto it. I’m not sure what would work better. I could suggest “complex, multifactorial, biopsychosocial illness” but that’s rather long-winded.

What do you think is the best way to characterize mental illness?

21 thoughts on “Is Chemical Imbalance a Useful Simplification of Mental Illness?”

    1. All in our head, as if there were nothing in there rather than that little old brain that is far more powerful than any computer anyone’s ever been able to come up with…

  1. i do think the argument is a little outdated. but i also believe that in some mental illnesses, like depression, there definitely is a chemical imbalance in the brain. xo

    1. Yes, there’s definitely a biological element. I’d just like to see a new description that describes it a little more accurately than chemical imbalance. I worry that people may fixate on chemical imbalance being somewhat inaccurate and then throw the baby out with the bathwater by denying that there is a biological cause. xo

  2. I agree with this, it’s extremely hard for the population to get a grip of mental illness when it is constantly being oversimplified to the point where it doesn’t really correlate with the reality of most people’s lived experiences. Yet people seem to switch off if the conversations about it become too complex. So I guess a balance is needed? Or different explanations in different contexts? I quite like your definition to be honest haha xx

  3. This is a very interesting topic! I didn’t know a whole lot about it since I’m not currently involved with a psychiatrist. Always important to remember there may be a biological component too and not as simple as assumed. Thank you for sharing!

  4. The truth of the matter is people are self centered. I don’t mean selfish. I mean focused on the demands of their own lives. My own dad has had cancer 4 times in 10 years and I still barely know what cancer is let alone what non- hodgekins lymphoma is. As long as health care is over simplified mental health will be too. Just like when someone is sick you say they’ve got the flu and don’t list symptoms or complications and we are in a society where when asked how are you all we say is fine.

  5. All the UK mental health charities do not use the chemical imbalance reason . Mind for example clearly state that this is not true, it’s come from the misunderstanding that as antidepressants influence brain chemistry then therefore it must be a chemical imbalance. The truth is we don’t really know why AD help. Being clear I am not saying there isn’t chemistry at work ( there is) just like genes, social and economic circumstances, life experiences all play a part- in essence we don’t fully understand. Which is the true complexity and why each person needs to be treated individually . What works for me may not work for you. That is where simple explanations or reasons fall down and make it so hard to explain to people who haven’t experienced it. Unfortunately it also adds to the stigma, especially around AD, where we really do not have the right research or studies, which leads to some professionals seeing medication as good, some as evil. So just like the illness is complex, the treatment is complex…which makes it harder and longer to treat. Whatever the factors that contribute to it, it is an illness, the seriousness of which people shouldn’t underestimate nor be ashamed to seek help, including medication. This is such a big topic! Chris

  6. My depression has always been triggered by psychosocial factors but surely there has to be an underlying cause within the brain that allows those factors to trigger it. Not everyone who has cancer will get depression, a high proportion will but not all, is this because they have better social means to deal with it, is it due to personality or biology? Nature or nurture? So many unanswered questions.
    Great post x

  7. I’m guilty of oversimplifying. I refer to bipolar as a “brain disorder”. The world lacks the proper words for describing MI, because as you point out the biology of it isn’t understood yet. I have hopes that one day they will actually figure it out, at which point I believe the stigma will get better once it is proven that it’s physical.

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