That Neuroscience Guy - Depression and the Brain

Episode Date: April 11, 2021

Depression is a prevalent yet complex condition, and there are multiple ways it can affect the brain. In today's episode, we discuss the neuroscience of Depression. 

Hi, my name is Olof Kregolsen, and I'm a neuroscientist at the University of Victoria. And in my spare time, I'm that neuroscience guy. Welcome to the podcast. Have you ever felt down or sad? Well, of course you have. We all have. But some of us experience this to a greater extent, what we call depression. On today's podcast, we're going to be talking about the neuroscience of depression. Depression is really complex to unpack. There are several possible

causes of depression, and the story is still being figured out. It's possible it's faulty mood regulation by the brain. There's definitely a genetic component that makes us vulnerable. There is the impact of stressful events in life, the impact of medications we take, and even medical problems. All of these forces interact to bring on depression. Early research into the neural basis of depression was focused on neurotransmitters, either a lack of neurotransmitter or an imbalance in neurotransmitter production. Just as a reminder, what does a neurotransmitter do? Well, when a neuron fires, if you remember previous episodes, an electrical

signal is sent down the axon of a neuron, and when it reaches the end, neurotransmitter is what's released. And that allows a neuron to communicate with other neurons. And this, of course, makes up all of brain communication and function, the ability of neurons to communicate with each other. So if you have a problem with neural communication or an imbalance in the sense that the system is firing irregularly, you're going to have problems. So in line with this, a lot of research is focused on the role of dopamine, one neurotransmitter that plays a role in depression. For instance, if you have people that are depressed play a simple reward gambling game, so a game in which they sometimes win money and sometimes they lose money, you find that their

brain's response to reward is reduced relative to people who are not depressed. Why this is important here is it's become quite clear that dopamine plays quite an important role in the reward signal that's generated by these gambling outcomes. So you might be able to conclude just from this that dopamine is the underlying cause of depression, and it's true that certain antidepressants target the midbrain dopamine system. But like I said at the outset, it's a little bit more complicated than that. There's no doubt that chemicals are involved in this process but like I said it's not just a matter of one chemical being too high or another being too low or an overall sort of fluctuation in the release of these neurotransmitters but there's millions and even billions of chemical reactions that make up the brain.

And there's other neurotransmitters that come into this. So you have to remember, it's not just dopamine. We'll talk a little bit more about neurotransmitters in the sense that you have to realize that these things are responsible for our sensation, for learning, for movements, moods. So if your neurotransmitter system is off, then all of these things will be impacted. And that's the way it works. When neurotransmitter is released, it goes across a neural synapse and it binds. Well, that might stop functioning correctly, which impacts neural communication. Or you can imagine that the amount of neurotransmitter that's being released is inadequate. In all of these instances, this will lead to a problem.

And neural firing, like we've said a couple of times now, is the basis for the way the brain works. In terms of thinking about specific brain regions, it's quite common in people that experience depression to see irregularities in the function and firing of the amygdala, the thalamus, and the hippocampus. The amygdala is a brain structure. You have two, one on each side, attached to the front of the hippocampus that's been shown to play a key role in emotion and emotional processing. Typically, when people are experiencing depression, the amygdala is more active. In other words, it has a greater response when people are presented with an emotional experience, for instance. What's interesting is that the firing the amygdala stays at an

enhanced level even when people have clinically recovered from depression. So what is the amygdala doing? We've talked about this before, but essentially, like I've just said, it adds the emotional content to things. So for instance, if you see a significant other or something you really like, the amygdala will fire and add the emotional response. Interestingly, in people who are just overtired or haven't slept enough, you typically see more activity in the amygdala, and people that are sleep deprived also tend to be more sad, and sleep deprivation or lack of sleep is also being tied to depression. So you can see how it sort of begins

to fit together. Another area of the brain that's impacted by depression, like I've said, is the thalamus. The thalamus is typically called the relay station of the brain. It's located in the central midbrain region, and it plays a crucial role in processing and integrating sensory information. Most information that comes into the brain goes through the thalamus. And one of the prominent theories about the dysfunction in the thalamus in people with depression is that if this region is impacted and isn't functioning correctly,

people that are experiencing depression have a hard time linking incoming sensory information and life experience, in other words, with positive and negative emotions. The third brain region I mentioned that is impacted by depression is the hippocampus. The hippocampus plays a crucial role in memory. In a previous episode, we talked about how the hippocampus is responsible for linking together all the parts of a memory. So for instance, if you were out for dinner last night, the hippocampus plays a role in linking together the location, the food you had, the people you're with, and the way you were feeling. Interestingly, the hippocampus has been

shown to be smaller in people who are experiencing depression, although it's not tied specifically to having a smaller hippocampus in general. What's thought is that the stress on the brain that's brought about by depression basically suppresses the production of new neural cells so that the hippocampus isn't able to regenerate, if you will. And there's an interesting fact about antidepressants that sort of supports this. People have wondered for quite some time while antidepressants take some time to kick in. For instance, if you begin taking most antidepressants, it takes a couple of weeks or longer before they start to do their job. And if depression was solely linked to the release and imbalance of neurotransmitters, then antidepressants should act more quickly because medications do exist that can change

the release of neurotransmitter within the brain on a very rapid timescale. Yet, that's not what's seen. Typically, antidepressants, as we've said, take some time. Why is this, and how do you explain this in terms of the hippocampus and the production of new neural cells? Well, one working theory right now is that antidepressants specifically promote neurogenesis, in other words, neural reproduction, and that does take some time. It takes time for new nerve cells to grow and for new connections to form. And thus, mood only begins to improve after this neural regenesis has taken place. So we've talked about neurotransmitters and we've talked about specific brain regions, but in terms of depression, you also have to look at genetics. I don't want to do a massive deep dive on genetics within this episode,

but a simple way to think about the way genes work is that throughout your life, genes turn on and off. And when they turn on, they're making proteins, for instance, at a time that you need them. And when they turn off, they're not making proteins because you don't need them. But what happens if the genes get it wrong? Imagine that the depression and its impact on the brain sort of messes up the firing of the genetic production cycle. Well, in this case, you'd have proteins being created when you don't need them, and you would be missing proteins when you did need them. And this could result in a mood imbalance, for instance, because your brain is literally lacking the things it needs in certain situations. Therefore, some people might actually be genetically predisposed to depression because the way their genetic production cycle isn't

perfectly timed with the needs of their body. But more recent theories sort of tie this to actual instances in life. For instance, a stressful event at work or a medical illness is far more likely to offset the timing of the genetic production cycle. So, the important message I wanted to make on this episode is depression isn't a simple syndrome you can't just tie it to one neurotransmitter or one part of the brain depression is brought on by an imbalance in a range of neurotransmitters we talked about dopamine specifically but there are any number of research studies that look at acetylcholine and serotonin and other neurotransmitters. Depression also doesn't involve one brain region. It involves multiple brain regions. Now, on this episode, we mentioned the amygdala, the thalamus, and the hippocampus

specifically, but there are studies that show that other brain regions are impacted by depression. For instance, people that are experiencing depression typically have trouble within the prefrontal cortex, and that's an area that plays a crucial role in goal setting and working memory and any number of executive functions. And finally, I mentioned the genetic piece. Our genes and our genetic makeup are responsible for keeping our body doing what it's supposed to be doing. And if life events upset this sort of genetic balance, if you will, then that can also lead to depression. My name is Olof Kregolsen and I'm that neuroscience guy. You can check out more on my website at www.olofkregolsen.com

or you can follow me on Twitter at that neuroscience guy. Thanks for listening and I'll see you on the next episode.