Understanding How Depression Is Formed

April 1st, 2021

Summarized from this excellent article.

Depression and depressive episodes are the result of several process that happen in your body. To understand how this works, we have to take a step back.

You may have heard before that the brain changes over time. This is called neuroplasticity. According to Wikipedia, neuroplasticity is "the ability of neural networks in the brain to change through growth and reorganization". Neuroplasticity can be helpful for us to engage in new activities that result in our well-being -- something particularly important for people with depression.

Naturally, dysfunctional neuroplasticity would mean that the brain is no longer malleable and doesn't change over time. If this happens, it's also more likely that depression and anxiety are an outcome. If your brain can't change it's state, it can get caught in a bad state.

So then we look at the causes of dysfunctional neuroplasticity. It turns out that neuroplasticity is affected by the regulation and birth of neurons in our brain. If neurons are being regulated and birthed at a proper rate, our brain remains malleable. And if neurons aren't being created at a healthy rate, and are instead dying (which is termed atrophy), dysfunctional neuroplasticity ensues. Atrophy -> dysfunctional neuroplasticity.

Okay, so: depression & anxiety are often causes by dysfunctional neuroplasticity, and dysfunctional neuroplasticity is when the brain is no longer malleable, and a common cause of dysfunctional neuroplasticity is neuron atrophy.

So what causes the brain to atrophy? It appears there are several causes, but one of them that's most relevant to us are these molecules called neurotrophic factors.

Neurotrophic factors are biomolecules in the brain, and they regulate the survival and birth of several types of cells including neurons, synapses and dendrites. These neurotrophic factors essentially are the "fertilizer" for the birth of neurons, synapses and dendrites, and they are vital to the creation of those cells. Examples of neurotrophic factors are BDNF (brain-derived neurotrophic factor), NGF (nerve growth factor), and GDNF (glial cell line-derived neurotrophic factor).

If the levels of neurotrophic factors are lowered, fewer neurons (and synapses and dendrites) will be created because they have less "fertilizer. And if that happens, there's a higher likelihood that the brain will enter a dysfunctional neuroplastic state. And if that happens, it's more likely that depression and anxiety are an outcome.

Now, depression & anxiety can be set off by a number of things, but a common root cause is a stressful event like losing a loved one. These stressful events often lead to increased levels of stress hormones such as glucocorticoids. (In a name you might actually recognize, cortisol is a type of glucocorticoid).

Glucocorticoids cause atrophy in the brain by, you guessed it, lowering neurotrophic factors. (Glucocorticoids also cause atrophy through a dysregulated HPA-axis, which I have to read more about). But basically this is how we get from -a stressful event- to -depression-.

An important part of treating depression and anxiety is figuring out to change the inputs earlier in the process, by either lowering stress or raising neurotrophic factors. This is because if you can raise those back to healthy levels, they will create neurons again and lead to healthy neuroplasticity. And mostly, this is what the current drug treatments try to do.


I have lots more to write about in regards to mental health and psychedelic treatments, but I want to get something published sooner rather than later. Something something working in public. Sign up for my newsletter for updates.  

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