Eli5: why is there no test for the “chemical imbalance” that is often mentioned for depression?

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Eli5: why is there no test for the “chemical imbalance” that is often mentioned for depression?

In: Chemistry

Where exactly are you getting your facts from? People used to think diseases and viruses were a chemical imbalance, that’s how bloodletting became a thing..

“Chemical imbalance” is a pretty inexact way of describing the theories for how depression is driven by body chemistry. But in any case, that chemistry is largely in the brain. The brain is separated pretty strongly from the rest of the body (only a few chemicals can move into or out of the brain into the bloodstream) meaning that it’s not something that shows up on a blood test.

It’s also not as simple as the amount of single chemicals: the brain depends on a mix of different chemicals, whose behavior depends on the concentrations of the others and whose effects depend not just on the chemicals present but on the receptors available on each cell.

If it’s any similar to some other hormones like the HPA axis, it’s because there’s only a very low amount of that chemical circulating in your body at a time. Most of it is produced in your brain and used a very short distance ‘downstream’ from there, which effectively leads to undetectable amounts in the wider circulation. So if you took a blood sample from someone’s arm like we normally do, you would hardly detect the chemical, let alone be able to tell if there’s an imbalance. You’d have to take a blood sample inside the brain between the two specific points where the chemical is produced and absorbed again, to be able to tell anything at all.

That being said, things like depression or adhd are usually caused by neurotransmitter problems. They are molecules that you find in the brain and that allow one neurone to communicate with the next, but they are not found in blood much at all. So again you’d have to somehow sample the connection between two neurones to measure the amount of neurotransmitter.

An easier way to do it is to monitor the effect of drugs that affect neurotransmitters. If you give them SSRIs (serotonin reuptake inhibitors), what you are doing is forcing serotonin to be present for a longer time before it is reabsorbed, thereby making sure the signal travels correctly from one neurone to the next. Normal people will react differently to the drug compared to depressed people with a serotonin deficiency as it were. Compare it to to adhd meds: normal people on adderall act all high, while people with adhd on adderall are able to calm down

There are several parts to an answer:

1) As somebody already mentioned. (Major) Depression is actually “the symptom”. The underlying factors causing depression are varied and cannot be reduced to a single marker, as for example with diabetes. In short, the physiological mechanisms of depression (what is malfunctioning in the brain) are not fully understood and there is a lot of active research going on.

2) The chemical imbalance that you mention refers to neurotransmitters in specific parts of the brain, meaning, you would have to test the levels of such neurotransmitter directly in those areas, since a blood test would not be enough for that. And as I mentioned, even if you test this, this would only work for a very narrow group of patients, since the physiological causes of depression are very varied.

3) Not part of the answer, but if you google “depression biomarkers” you’ll find recent research regarding the kind of tests that could allow this. Which would be helpful for, for example, knowing what kind of depression the patient has.

TLDR It is possible to test this, but its a bit more complex than a blood test

Sources:
(1) I did neuroscience research for many years, including depression

(2) https://www.sciencedirect.com/science/article/abs/pii/S0166432817318521

Neuroscientist here: Because the “chemical imbalance” theory is bullshit. It was a real theory several decades ago, which was abandoned in the field because it doesn’t make sense / doesn’t work. But it is simple and easy to explain (despite being false) and therefore continues to propagate.

To be clear, it’s not that it’s a simplification. It’s just wrong.

If it WERE a chemical imbalance, it would be something you coughs test for, you are right about that, although the test would probably not be a blood test, might require a spinal tap or PET scan (best ways to measure specific chemicals in brain). It would also be simple to treat.

Pretty much ANY neat, simple story that someone tells you about the brain is usually false.

Because it’s bs. 99% of treated depression is not for medical reasons, it’s because the world is shit, or specifically that person’s life is more shitty than normal.

I wouldn’t explain it like this to a five year old though.

It’s because the chemical balance hypothesis was something that was devised by pharmaceutical companies as a marketing ploy, and has never been substantiated by any empirical evidence.

https://www.theguardian.com/society/2018/jan/07/is-everything-you-think-you-know-about-depression-wrong-johann-hari-lost-connections

Even psychiatry is admitting to this, these days: https://www.psychiatrictimes.com/view/debunking-two-chemical-imbalance-myths-again

You’d probably need a pre- disorder reading of a test to be able to compare changes from their baseline but most depressed people don’t go to the doctor months before they feel unwell to get a baseline test just in case.

“Chemical imbalance” is an unproven theory that is embraced because it sounds nice. Much better to say, “I’m depressed because of a chemical imbalance in my brain” than, “I’m depressed because I’ve made a mess of my life.”

If we want people to seek treatment, we have to remove the shame.

So usually tests are done in blood since that’s easily accessible. The chemical imbalance that occurs in mental illness is a chemical imbalance of neurotransmitters. Basically those chemicals aren’t available in your blood, but inside your brain, and even in “normal” brains, they get reabsorbed or degraded fairly fast, so you couldn’t even really measure it in cerebrospinal fluid, since the chemicals wouldn’t be widely available there. Only way to test it would maybe doing a biopsy of a fairly large chunk of the brain and test the presence or absence of said chemicals, but for obvious reasons, that wouldn’t be a procedure that’d be useful at all. There are some tests that have been used before to sorta look at the somatic, biological side of the equation. MRI can be used to measure blood flow to certain areas of the brain, and if some areas are less or more active than others you can sorta deduce it’s degree of chemical activity, but this type of test isn’t done usually because a) it’s super expensive b) even though treating depression is hard, diagnosing it is fairly easy, and can be done in just a couple of sessions of talking to your patient, and c) said changes usually occur in very subtle ways, in quite severe depression, so at that point it has little diagnostic use. It has been used in research though, but fairly useless in clinical practice

I think a major point here is that it’s a lot of guesswork treating depression and other mental issues. This is seriously a huge gray area with a lot of unknowns. Hard to test for something when you aren’t even sure how it works. Some will say mechanism unknown. About all they know sometimes is that it works for some people. Testing on humans is hard.

Depression is as much a software issue as it is a hardware issue. The “chemical imbalance” theory implies it’s just a hardware issue. But it’s more than that.

You can measure concentrations of chemicals in the body. But you can’t measure what someone is thinking with a lab test.

Because they don’t really know how it works, they think they have an idea, but they don’t really know. In fact, they backtrack all the time all over the board on a whole range of issues because every now and then, some realize, they knew wrong, so they can still (know wrong). Just keep that in mind.

There’s a genetic test now which can be taken and conclude which will work best and which you should avoid. Why are doctors still making people be lab rats when the answers are clear?

Emotional baggage, unresolved traumas, when the mind is fed with shit the body starts feeling shit. When you are moving through life unaware of what your thinking feeling and not taking care of it stuff like this happens the power of thought is vastly underestimated

Because there is no such thing. It was a term coined by psychologists in the 80s and 90s to sell the bipolar movement and people bough it.

Neurotransmitter release not only varies in amount, but in timing, as bursts. The mix of these neurotransmitters differs in different parts of the brain and in response to different situations/actions.

So even if you COULD directly measure it, you’d have to do so over time, in various areas, in exposure to various different stimuli/situations.

And even if you could do THAT, it wouldn’t be helpful since epigenetics modifies the expression of genes in response to stress, making every human brain different.

When we think about “chemical imbalance” and depression, those chemicals are mostly neurotransmitters. Neurotransmitters are made in the brain and they work between neurons which are tiny parts of the brain.

To test the number of neurotransmitters in the brain, we would have to take samples from inside the brain, which would be very difficult and dangerous because the brain is so delicate.

Another problem is that we don’t actually know much about the “chemical imbalance” explanation. It looks like it’s one part of the bigger puzzle, because a lot of people with depression benefit from medicines that affect that balance. Not all though. So even if we could measure how many neurotransmitters someone’s brain is making, using, and breaking up, we wouldn’t know what those numbers meant.

It is a simplification that doctors use to help people understand why drugs can help treat depression. The exact mechanisms behind depression are complex and poorly understood, and likely to vary from person to person. It seems to have something to do with neurotransmitters, and the receptors they bind to, and how they work to regulate each other. But testing for that would require knowing what the baseline is for that particular patient, and getting a sample would require a brain biopsy to examine local neurotrasmitter quantities as well as the density of their respective receptors. And we don’t know from where to take the biopsy and getting enough information may mean we would need to take several. And taking brain biopsies mean you cause local brain damage.

Functional MRI could be a non-invasive tool for determining overall brain metabolism in different functional areas and may eventually lead to more clues about what is wrong in the function of a depressed brain, possibly leading to diagnostic tests and personalized treatment opportunities, but we are a long way from that.

That is my understanding, as a medical doctor.

Because it’s bullshit. You aren’t depressed because of a chemical imbalance. You are depressed because of some trauma in your life, or because you’re leading an unhappy life, possibly because we prioritise the wrong things, because we don’t have enough connection etc. The internet doesn’t make us more connected, it makes us less connected.