Biological Theories Part That One: Depression

Hello! And welcome to the fun part! Let’s dive right on in, ladies and gents.

Depression and Anxiety share some very common roots, especially in the biological arena. If you already read Part This One, you will notice some repeat of information, but press on anyway, please. Repetition is key to learning! If you didn’t read it, I recommend reading it anyways because learning is cool and helps your brain!  If ever there’s something that you didn’t quite get (either it’s more complicated than I estimated, I explained it poorly, or my sources suck…) don’t hesitate to bring it up in the comments and I’ll do my best to address it!

Depression is a terribly complex thing. I’m creating individual posts between biological, psychological, and evolutionary theories of the causes, as well as environmental relationships, yet not one single thing is the cause of Depression. Most researchers and doctors agree that Depression results from a combination of factors. Nevertheless, it’s important to understand the different roots to weed out what could be affecting you specifically. I also believe understanding what is happening in the body will help you connect to your specific symptoms, to give you a better edge on combating them. Some of these roots could be seen as less of what’s causing your depression and more of what’s happening when you’re depressed.

The biological causes of depression are often summed up as an imbalance of chemicals in the brain, and that is a part of it, but it doesn’t tell the whole story. A good quick primer for Depression is in this video here. (It also covers Bipolar as well as Depression.)

Recent studies have found a multitude of factors as possible sources of Depression. These can be your genetics, which results in the physical makeup of your brain and how it functions, if your nervous system is at the correct level of sensitivity to neurotransmitters, if your circadian rhythm is running smoothly, or if other factors like disease, and lifestyle, including long-term stress, contribute. Some researchers have found certain regions of the brain operating at a lower capacity, or even having less mass than those with non-depressed brains. Some theories cite long-term inflammation in the brain, leading to cell death with no neurogenesis (simple article, and more complex article), or recovery of cells. More and more evidence points to suspects like faulty circadian rhythms leading to the whole system falling out.

The simplest way to put Depression (and by putting it simply I know I risk leaving out some things.) is that your brain is in a state of degeneration, or faulty activation, and lacks the resources to return to a baseline level of function. Researchers are looking for the mechanisms behind the initial lapse in functionality, and why it is so hard for the depressed body to catch back up. All the theories I present to you operate around that presupposition.

Let’s start with the basics; Depression is a type of mood disorder and is located biologically in the nervous system, so let’s look at what is called The Central Nervous System, or CNS. For those of you who want to read stuff, here’s a great article covering CNS basics from Though Co. Even if you’re reading, checking out the Crash Course episode on the Nervous System, which starts with this episode, and goes 8 specific episodes in total (about 10 minutes each.) (You’ll be seeing a lot of Crash Course here. I think they are a wonderful project that conveys a significant amount of information in a quick, entertaining and easy to understand way.), will be very helpful, as they do the heavy lifting of learning for you, as learning anatomy can easily go over one’s head. The following episodes of Crash Course cover how the nerves themselves work, and transmit messages. This Thought Co. article covers the same information. Again, I recommend going through both sources!

Jumping from this information, we head into what is likely the most prevalent theory, The Monoamine Deficiency theory. Monoamines are complex little things and if you really want to understand them it takes a bit of understanding of biochemistry. (The link above is really one of the simplest explanations of them I could find!) The tl;dr of it is that Monoamines are the type of neurotransmitters involved in cognitive processes related to movement, emotion, and psychological arousal. These are serotonin, dopamine, and norepinephrine. The Monoamine Hypothesis essentially states that a depletion of these neurotransmitters, or an improper sensitivity to them, leads to depressive symptoms, and possibly a Major Depressive episode/disorder. The Monoamine Hypothesis is the lead idea used by pharmaceutical companies in the formulation of anti-depressants.

For decades though, this theory has been challenged by scientists and is no longer seen as the leading cause of Depression. More and more scientists are discovering other roots, some that are more psychologically and environmentally based than chemically. But this doesn’t mean it’s all bunk. Monoamine levels ARE low in depressed patients. This is why antidepressants can be helpful. It’s just not all there is, which could be why they don’t help everyone, or why so many patients find their medications need frequent adjusting.

There is little easy reading on the Monoamine Hypothesis, but if this is something that has sparked your interest, I dug up some links for you all to check out: (I just recommend keeping Google open in a separate tab to look up information that is outside your realm of current knowledge!) A very simple overview. A Report called Looking Beyond The Monoamine Hypothesis, by Johan A den Boer. Evidence for a biochemical lesion in depression by Leonard BE Department of Pharmacology, National University of Ireland, Galway. The Discrediting of The Monoamine Hypothesis. Depression, The Case for A Monoamine Deficiency.


Your diet and current metabolic state also can influence how you feel.

Certain nutrients are vital to the formulation of proteins, hormones, and neurotransmitters, which the body requires to function. When certain nutrients are not present, your body lacks the ability to form these vital chemicals. This is a pretty neat 5-minute video primer on how your diet affects your brain.

The science of diet and nutrition is so complicated that there are at least hundreds of schools of thought on the “best” way to eat. (Just walk into the food and lifestyle-related sections of Barnes and Noble and you get a glimpse.) That being said, I’ll do my best to give you enough information in future posts that you can make more educated decisions for yourself, or discuss with your doctor about your diet! (But please, always listen to your doctor before you listen to me. Cuz I’m not a doctor.)


Another frequently cited source of depression is prolonged stress. The common perception of stress is that state one is in when your mother in law is about to show up, but the house is in a state of disaster, the children aren’t dressed, the dog just peed, and your partner has yet to put on pants. And while that is a very valid perception of stress, it doesn’t quite tell you what stress is.

Stress, quite simply put, is a state your nervous system places your body into to combat “threat”. This system is known as your Sympathetic Nervous system (Youtube link) and is what most people know as your “Fight or Flight or Freeze” response. Luckily, we have a system, called the Parasympathetic System (more youtube) to calm you back down and ensure what is called Homeostasis.

Overactivation of the SNS relates more to Anxiety disorders than Mood Disorders (if you can’t tell by the list of symptoms.) But it does have significant relevance as the long-term state leads to a decreased ability to produce new cells, remove cellular waste from the body, lack of sleep, and absorb nutrients properly. This decline can eventually lead to a Depressive disorder that is incredibly difficult to climb out of as it requires tackling unconscious responses as well as bad habits one has formed.

The interplay between the CNS and your Endocrine system (the hormone-producing side of your body) of the stress response is known as the HPA Axis. (youtube) (shortened because the hypothalamic-pituitary-adrenal axis is really hard to say!) This system is normally self-regulating, however, as is the nature of complex things, the system can go awry. When this system does go wrong, elevated levels of the hormone cortisol stay in the bloodstream and can wreak havoc on your body. The malfunctioning of the HPA Axis is implicated in multiple disorders including; anxiety disorder, bipolar disorder, insomnia, posttraumatic stress disorder, borderline personality disorder, ADHD, major depressive disorder, burnout, chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and alcoholism. But before you go screaming that you need to get rid of your cortisol, remember that it is important for every day functioning under normal circumstances! (It wakes you up and can keep you at an even level of alertness throughout the day!)

The most simple and best explanation for how all of this ties together comes from this four-minute TED-ED video.

Studies have linked decreased brain mass- particularly in the hippocampus– with depression. I personally am not sure if the interplay is causal, or looped. Some suggest that a smaller hippocampus can lead to depressive states, and others suggest that the MDD can lead to decreased mass. Sort of like a nasty feedback loop.

Other studies have found that centers like the medial prefrontal cortex, the “Me Center” of the brain, and the amygdala are influencing other centers of the brain negatively. The amygdala has been shown to have increased mass in those with depression as opposed to those never having been depressed, as well as being hyper-responsive to “negatives” and under responsive to “positives”.


The possibly least mind-bending topic of today’s post is to do with the Circadian Rhythm. Your Sleep Cycle is sort of like a master control, decreasing certain hormones and increasing others. This is a part of a system that allows your mind and body to reset, and recover from the day. Memories are processed and logged away, and cellular repair and production occur on a higher level, allowing us to heal and the brain to function in the most efficient way.

One of the core defining symptoms of Depression is disrupted sleep- either too much or too little. This can be causal, as the lack of sleep can lead to a decrease in cellular reproduction in the brain, as well as inhibiting our ability to process thoughts, memories, and emotions, or it can be a by-product of the disease itself. Some researchers have found that people with depressed brains have a faulty sleep-wake cycle wired in their system. Disrupted circadian rhythms can also be caused by poor habits, late-night exposure to blue light, and insufficient exposure during the daylight hours, and numerous diseases.

Women are often cited as being more prone to mood disorders and other such things- such as insomnia, part of which is related to the way the menstrual cycle interacts with the normal circadian rhythm. (Though it’s posited that women are simply diagnosed more often than men and classic symptoms are more attributed to women than men.)

Regardless of the cause, as with many symptoms of depression, it can be a vicious cycle that is difficult to break.


A huge question in Depression research is if it is inheritable- do we get it from our parents? Are depressed people hardwired to become depressed? Do our genes make us more or less susceptible to depressed states? The tentative answer is “yes”.

Geneticists are uncovering genes found to be active in people with depression- suggesting a link. Some of these genes, when expressed in certain ways, help or inhibit one’s ability to feel pleasure or reward. Other genetic links were found to play a roll in the ability to efficiently produce energy. Another series of studies have linked a gene regulating the way serotonin is transported through our system, making one more or less susceptible to stress.

But simply having these genes doesn’t guarantee one way or another that you will or won’t experience depression. Genes flip on and off throughout our lifetime, being triggered by various internal and external sources. Some genes regulate the activation and suppression of other genes even. The manifestation of these genes is correlated through early life nurture, as well as our current environment and behaviors, so I’ll be talking about them more in-depth gradually as we go through this blog!


In addition, chronic health conditions or a dramatic change to one’s body can also lead to Depression, either by inducing symptoms through the damage the disease does to the body or by affecting one psychologically. (but that’s another show.) Cancer is one of the most commonly cited, as well as chronic conditions like heart disease, lupus, and arthritic conditions. Dramatic changes like the onset of paralysis, or stroke (to name only a few) can also lead to Depression or depressive episodes. If you suffer from a chronic or life-changing condition and have not discussed the possible comorbidity of depression with your doctor, it may be helpful to do so!

A fascinating condition I just stumbled upon with a high Comorbidity of depression is temporal lobe epilepsy. This is especially relevant as the seizure passes through the amygdala.


While not a machine, in reality, the human body can be viewed as one in the sense that we are an amalgamation of finely tuned systems that can be thrown out of balance quite easily, and it can be easy to slip into the mentality that the biological reasons for our depression our out of our control completely. While we can’t change the bodies we have been born into, we can, however, learn how they specifically need to be taken care of. The responsibility of our reactions to this situation we find ourselves in is in our own hands.

Next week we’ll come back and talk specifically what medical science has come up with to combat these deficiencies in our systems, and what we can do in our daily lives to minimize the negative outcomes of these awry systems

“”But you haven’t put yourself forward; you’ve been put forward. And as for not being the right and proper person, why, Mr. Frodo wasn’t, as you might say, nor Mr. Bilbo. They didn’t choose themselves.’ …

And then he bent his own neck and put the chain upon it, and at once his head was bowed to the ground with the weight of the Ring, as if a great stone had been strung on him. But slowly, as if the weight became less, or new strength grew in him, he raised his head, and then with a great effort got to his feet and found that he could walk and bear his burden.”

J. R. R. Tolkien, The Lord of The Rings, The Return of The King.

Please note that some of the links provided may lead to websites that want to sell you products. I am not affiliated with any of these websites and am not attempting to push you towards certain brands or products. I have simply used those links for the information they contain.

Again, this blog is for informational purposes. I am not a professional. It should not be an exclusive source to diagnose, treat, cure, or prevent disease.

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