The Science Behind Depression

Nyla Pirani
8 min readJan 18, 2022

Imagine waking up every morning to have little to no energy. No motivation to do the things you once used to love. Life feeling completely hopeless.

Imagine you can’t sleep or eat. You’re always in physical pain and constantly battling your mind.

In just a few sentences on a computer screen, we can begin to see what people with depression have to face every single day. But we are nowhere near the point of being able to truly understand the pain people with depression have to endure throughout their lives.

20% of all teens experience depression before they reach adulthood. But only 30% of those teens are actively being treated for depression. Suicide is also the third-leading cause of death for young people ages 15 to 24.

That’s only one, age group. Approximately 280 million people globally are suffering from the pain of depression.

These numbers are mind-blowing to me. While mental illness as a whole is beginning to be talked about more and more throughout schools and social media, the treatment of it isn’t advancing fast enough.

The first thought I had when it came to depression treatment is therapy. While therapy is great, I wanted to look at this from more of the illness standpoint and focus on the science behind depression.

This involved three main focuses:

  1. Neurotransmitters
  2. Genetics
  3. Limbic System

In this article, I’m going to cover a brief introduction to all of these areas. I’ll be publishing deeper dives into each of these sections in the next few months.


Communication from our nervous system to other parts of the body occurs in the form of electrical impulses. A cell called a neuron is what carries these messages. Our brain is full of over 100 billion of these neurons.


There are four parts of a neuron (outlined in the image above).

  1. The cell body is what directs all the activity within the neuron
  2. The dendrites receive information from other neurons
  3. The axon is was transmits messages from the cell body of its neuron to the dendrites of other neurons or other body tissues, such as muscles.
  4. The myelin is a protective covering that covers most of the neurons and helps nerve signals travel much faster and farther.

Messages within one neuron travel as electrical impulses, but as they are transferred to another neuron it becomes a neurotransmitter (a chemical such as dopamine, serotonin or oxytocin) released into the space between the axon of one neuron and the dendrites of another neuron. That space between is called the synapse.


When neurons communicate with each other, the electrical impulse triggers the release of neurotransmitters from the axon into the synapse. The neurotransmitters cross the synapse and attach to a molecule on the other side, called receptors which are located on the dendrites. They are responsible for receiving and processing the message of each neurotransmitter.

Our brain usually produces levels of neurotransmitters that keep senses, learning, movements, and moods at a stable level. But in some people who suffer from Major Depressive Disorder (MDD), the systems that accomplish this go away.

The main types of neurotransmitters that are relevant in MDD are:

  • Acetylcholine enhances memory and is involved in learning and recall.
  • Serotonin helps regulate sleep, appetite, and mood and inhibits pain. Some depressed people have reduced serotonin transmission. Low levels of serotonin can trigger a drop in norepinephrine levels, which then leads to depression.
  • Norepinephrine constricts blood vessels, raising blood pressure. This may trigger anxiety and be involved in some types of depression. It also seems to help determine motivation and reward.
  • Dopamine is essential to movement. It also influences motivation and plays a role in how a person perceives reality. Problems in dopamine transmission have been associated with psychosis, a severe form of distorted thinking characterized by hallucinations or delusions. It’s also involved in the brain’s reward system, so it is thought to play a role in substance abuse.
  • Glutamate is a small molecule believed to act as an excitatory neurotransmitter and to play a role in bipolar disorder and schizophrenia. Lithium carbonate, a well-known mood stabilizer used to treat bipolar disorder, helps prevent damage to neurons in the brains of rats exposed to high levels of glutamate. Other animal research suggests that lithium might stabilize glutamate reuptake, a mechanism that may explain how the drug smooths out the highs of mania and the lows of depression in the long term.
  • Gamma-aminobutyric acid (GABA) is an amino acid that researchers believe acts as an inhibitory neurotransmitter. It’s known to help remove anxiety.

There are multiple potential causes for these chemicals to be imbalanced. Some of the hypotheses being researched now are the short supply of molecules that help make neurotransmitters (specific enzymes), lack of receptor sites to receive the neurotransmitter, not enough molecules to build neurotransmitters or that a specific neurotransmitter isn’t being produced altogether.

The next step for researching how neurotransmitters play a role in depression is to understand how they change as people develop depression. Looking deeper into the potential causes I mentioned above will be important in identifying how we can prevent this from happening.


A person who has a relative with depression is almost five times as likely to develop it compared to someone who doesn’t have a relative with depression. Scientists also believe that approximately 40% of people with depression can trace it back to family history. That means there is a heritability genetic component to depression.

There isn’t a ton of public research done on the genetics behind depression but I’ll share what I’ve learned so far, the existing gaps and the next steps.

The heritability of depression is approximately 40% but increases to approximately 70% when twins with recurrent and severe major depression are examined.

Research from 2006 suggests that women are more likely to develop hereditary depression. However, depression in males is significantly underreported due to stigma around masculinity and showing emotions.

When I first started looking into genetics, I learned that mood is affected by dozens of genes. As a person's genetic endowments differ, so does their depression type.

The goal of understanding genetics role in depression is to pinpoint the genes involved in mood disorders and better understand their functions. This will lead to more personalized depression treatments.

Two paths are being researched in this field right now.

Chromosome 3p25–26 (Jermey)

The chromosome 3p25–26 (or Jermey) was found in more than 800 families with recurrent depression. The chromosome contains up to 40 genes and is believed to contain the genes contributing to depression.

If a person with this chromosome is raised by relatives who experience depression and also have this chromosome, their chance of developing depression is high. But they inherit the gene, not the depression itself.

Genetic Variant 5-HHTLPR (Kendall)

Another review of 19 studies found a link between a different genetic variant called 5-HHTLPR (or Kendall) and MDD.

Kendall is responsible for transporting serotonin to the synaptic cleft (the space separating two neurons)

inside the red circle is the synaptic cleft

The 5-HHTLPR variant is involved in multiple components of MDD, but there is a lot of uncertainty about its overall contributions.

Gaps + Next Steps

A lot of the research done in this area is limited and fresh. We need to dive deeper into the chromosome and genetic variant mentioned above but we also need to continue looking for other possible hereditary links.

There is a lot of uncertainty about whether the genes we’ve already identified contribute to 100% of depression genetic components so it’s important that we not only look further into the impact these have as well as broaden our understanding of the connections altogether.

The Limbic System

The limbic system is the part of the brain involved in our behavioural and emotional responses. This is especially focused on survival behaviours.


The limbic system is composed of four main parts: the hypothalamus, the amygdala, the thalamus, and the hippocampus. In the context of MDD the amygdala and hippocampus, we’re the most researched.


The amygdala is part of the limbic system, a group of structures that’s responsible for the detection of threats and fear-related behaviours in response to threatening or dangerous stimuli.

When you experience or even remember situations that spark fear the amygdala is activated.

In people with MDD, activity in the amygdala is higher and it remains increased even throughout the recovery from depression. This causes the brain to be incredibly sensitive and overreactive in frightening situations.

The amygdala is more closely associated with anxiety than depression however approximately 50% of people diagnosed with depression are also diagnosed with an anxiety disorder.

While it’s not proven to be closely related to depression alone it is a big factor in the overall development of the disorder and its symptoms.


The hippocampus is responsible for processing long-term memory and recollection. It works together with the amygdala to recall fearful moments and respond accordingly.

For example, the amygdala will register fear when a big dog starts barking aggressively by using the hippocampus to recall the memory of a previous fearful experience with a dog.

The hippocampus is smaller in some depressed people causing you to be more vulnerable to the effects of high-stress situations. Ongoing exposure to stress hormones will damage the growth of nerve cells in your hippocampus causing them to shrink even more.

In one fMRI study published in The Journal of Neuroscience, investigators studied 24 women who had a history of depression. The hippocampus was 9% to 13% smaller in depressed women compared without depression. The more intense the depression got, the smaller their hippocampus was.

Throughout this article, you can begin to see some of the initial major connections between changes within the brain and how depression can form.

This was simply a brief introduction to the science side of depression. In the next few months, I’m going to go deeper into these aspects of the brain and how we can permanently fix these problems.

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