How Depression Affects the Brain

March 11, 2022

Nue Life

Nue Life

Top points

  • Depression causes brain changes that emphasize negative thoughts, resulting in difficulty regulating mood.
  • Advances in neurobiology show that the neurotransmitters glutamate and GABA are affected by depression.
  • Ketamine acts on glutamate, which may improve brain function faster than traditional antidepressants.

French psychiatrist Louis Delasiauve was the first to identify depression as a psychiatric condition in the 1850s, yet anecdotal descriptions of the disease go back to ancient Greece and beyond.

While we’ve known about the impact of depression on our lives for centuries, we’ve only recently had the technology to study depression’s physical impact on our brains. This knowledge has helped us evolve treatments to address the disease’s long-term toll on our neurobiology.

In this article, we’ll explore how depression impacts the brain, how treatment can help, and which ones might be right for you.

The Complexities of Depression

The first thing that we need to understand is that depression is not a simple disease. The causes and effects of depression are vast and difficult to nail down. Many of the changes in the brain of a person with depression could be either the cause or the result of depression.

Hundreds of factors contribute to regulating your mood and emotions, from chemicals to your brain’s efficiency, to genetics, to life events. Your mood is an incredibly complex system.

To get a bigger picture, we’re going to break it down into two main sections: things that put your brain at risk for developing depression and changes that depression makes to your brain.

What Is Depression?

Before we dive into the nuances of the effects of depression on the brain, let’s define what depression is.

Depression, or major depressive disorder, is not just a lowered mood. It’s not just grieving or sadness. Depression is characterized by a long-term state of depressed mood that affects your level of functioning and brings about negative changes to your lifestyle. It is a common but serious medical illness that can be treated.

The Symptoms

Depression can rear its head in various ways, and everybody experiences it differently. For many people, depression is characterized by intense feelings of sadness and dread and even thoughts of suicide. For others, depression looks like a complete lack of emotion altogether.

Here are some common symptoms of depression according to the American Psychiatric Association that range from minor to severe:

  • Feelings of sadness or depressed mood
  • Loss of interest in hobbies
  • Changes in appetite
  • Changes in sleeping habits
  • Increased fatigue
  • Feelings of worthlessness, hopelessness, or guilt
  • Difficulty concentrating

Potential Causes

Depression can be caused by a variety of situations. For many, depression is caused by an extremely stressful or sad event: losing a loved one, ending a relationship, or getting fired from a job.

But it doesn’t have to be brought on by an event. Sometimes depression is caused by an imbalance of hormones in the body or a medication with depression as a side effect.

Sometimes, there seems to be no cause. But in any case, these symptoms can be overcome. It’s your right to feel good, and that can be achieved. We’ll talk more about how to get there shortly, but first, let’s go into more of the biology behind this mental illness.

Risk Factors For Depression

Several different factors can put you at risk of developing depression. Not all of these factors are related to physical aspects of the brain. Still, they all play a role in how your brain changes from depression, so it’s important to understand them in order to fully grasp depression and move forward on the healing journey.


There is a link between mood disorders and inflammatory responses in the brain. According to new research from Emory University, this physical response can lead to a chain reaction of events in the brain that could lead to depression.

A variety of factors can cause inflammation in the brain. A poor diet could be a major contributor, but people with a sedentary lifestyle are also at risk of inflammation in the brain.

When your brain gets inflamed, its priorities have to shift, and its energy output needs to alter slightly. To reduce brain inflammation, your brain may take energy away from the part of your brain that regulates mood. Inflammation requires a lot of energy from your brain, and the effects can be severe.

This tends to primarily affect the part of your brain that is in charge of motivation. If enough inflammation occurs, you may experience a loss of motivation characteristic of depression. This may be what causes the loss of interest and willingness to work that so many depressed people experience.


Your genetics can also increase the risk of developing depression. While there is not one particular gene that causes depression in many people, various accumulations of certain genetic factors can indeed make a person more at risk of developing depression.

We know this based on studies of twins. If one identical twin has depression, it is very likely the other twin will also. But with fraternal twins, this same link does not exist, suggesting that genetics play a big role in depression.


Stress seems to be one of the biggest precursors to depression that we know about. This seems to come in two different forms: negative thought patterns and stressful life events.

Stress isn’t just any old emotion. A particular hormonal response comes with stress that can cause serious harm to your brain. And although short bouts of stress are normal and harmless, when stress happens long-term, changes can start to happen in the brain.

When you get stressed, your body releases cortisol: the stress hormone. When released in a normal amount, it helps get your body back to normal after a stressful event. It regulates the heart rate, plays a role in blood sugar, and has a great deal of value in the hippocampus.

But when chronic stress occurs, cortisol levels get too high, and it eventually causes some harm to the natural functions of the brain.

First of all, high cortisol can keep your synapses in the hippocampus from being properly regulated. Cortisol can cause damage to specific proteins that help to maintain synaptic function. This can reduce social interaction and make you susceptible to more stress and really increase your risk for depression.

Of even greater concern, extended periods of stress can even cause damage to brain cells and reduce the size of the brain. Particularly, it affects the prefrontal cortex, which plays a role in memory and learning. This can reduce neuroplasticity and increase your risk of depression.

But it goes even further. Not only can stress shrink your prefrontal cortex, but it can also increase the size of the amygdala, which makes your brain more susceptible to future stress. This vicious cycle can put your brain at risk for various mental illnesses.

Depression and the Brain

Now that we’ve delved into some of the causes and risk factors for depression, let’s walk through some of the ways that depression affects your brain to take the next step towards getting your mental wellness back.

Brain Biochemistry

Your brain is an incredible machine, constantly working to regulate your body. Neurons are firing millions of times a minute, sending signals to other parts of the brain and throughout the entire body.

One piece that keeps these neurons firing properly is a chemical called neurotransmitters. There are hundreds of neurotransmitters in your brain, and they are responsible for keeping those signals traveling from neuron to neuron.

But depression causes your brain to get an imbalance of these chemicals. The predominant theory is that your brain reuptakes your neurotransmitters too quickly, resulting in a smaller amount of available neurotransmitters for your brain.

But the effectiveness of neurotransmitters could also be affected by neurons not being receptive to them or that the brain does not produce enough.

The lowered amount of mood-related neurotransmitters obviously has negative effects on your mood, and it can contribute to a reduction in your brain’s neuroplasticity. This makes it difficult for your brain to break out of the negative thought patterns that come from depression, keeping you in a state of lowered mood.

For many years, doctors thought that the neurotransmitters that depression affected most were the mood-related transmitters, specifically serotonin, and norepinephrine. That is why most antidepressants target these neurotransmitters.

But as time goes on, it seems that these particular brain chemicals don’t quite contribute to all of the symptoms of depression.

Scientists at Yale University, among others, have begun to look into other potential contributors to depression. Their research has led them to look at the two most common neurotransmitters in the brain: glutamate and GABA.

These two neurotransmitters are present between the neurons in the higher regions of the brain relating to mood. And those connections are being broken. So it seems that, although serotonin and norepinephrine are affected by depression, they are not the only piece of the complex neurochemical puzzle that depression is.

Neuron Damage

Depression can also cause damage to nerve cells in different brain regions related to functions like mood and memory.

In particular, depression can cause a lot of damage to the hippocampus. One study took a look at the brains of women with depression compared with normal brains. On average, their hippocampus was 9 to 13 percent smaller than the average brain. And they found that the longer the women had struggled with depression, the smaller the hippocampus was.

In addition to causing damage to neurons, depression and stress can slow down your brain’s ability to create new ones. This seems to suggest that improving your brain’s neurogenesis abilities can have very positive effects on mood regulation and treating depression.

The Amygdala

While depression causes reduced size in places like the hippocampus and thalamus, it causes an increase of activity in the amygdala. The amygdala is a part of the brain that helps regulate specific emotions, and it is activated when you recall particularly emotional memories.

The amygdala works with positive emotions like pleasure and even sexual arousal, but it also deals with many negative emotions such as anger, sorrow, or fear.

In a person with depression, the amygdala is very active. Sad, stressful, or fearful memories are brought up in the brain.

How To Treat Depression

Now that we have a better grasp of the biology of depression let’s turn to treatment options. Don’t believe the lie that you can’t overcome depression. Some solutions can help you find the wholeness you deserve.

Here are some of the treatment options available and some lifestyle habits to get into in order to help set you up for success in mental health.


For starters, it’s good to get your sleep schedule on track. Sleep is a great regulator of your body’s functions. During sleep, your brain gets a chance to reset and heal. But it can be difficult to get good sleep. Depression causes insomnia for many people.

But there are things you can do to help your body sleep better. Set up a nightly routine and a consistent bedtime and wake time. Getting your body into a rhythm can help cue your body to wind down when it’s time.

Getting sunshine every day can also help align your body’s internal clock to help get your sleep schedule on track. And it’s also important to remember that alcohol is not sleep’s friend. It can be tempting to drink to help you wind down. But alcohol actually makes it harder for your body to stay asleep. So it’s best to avoid it.

A Healthy Diet

Eating right can really help you when it comes to depression. As we mentioned before, unhealthy eating habits can contribute to inflammation in the brain, a major risk factor for depression. Eating healthy can help to reduce your risk of inflammation.

But eating healthy will also keep your body’s energy healthy and clean. It can make a big difference on how you feel, so make sure you eat right.


Exercise is incredibly effective at reducing symptoms of depression. One study found that all forms of exercise could help promote a healthy mood and reduce depression.

Getting active every day, or even a few times a week, can help improve your mood. Depression can make it difficult to want to get up and get your body moving, but exercise can make a big difference in your mental health


Therapy is an integral part of depression treatment. It is necessary for holistic, person-focused care.

There are several different types of therapy out there, and one of the most effective methods for treating depression is called cognitive behavioral therapy, or CBT.

CBT is a particular type of therapy that focuses on thought pattern change. A therapist guides the patient, helping them identify the negative thought patterns present in their brain. Once the patient learns to identify these patterns, they can replace them.

The therapist helps the patient learn better-coping methods with their psychological problems. This method can improve a person’s daily functioning and quality of life.


Depression is commonly treated with antidepressants. There are several different kinds of antidepressants.

  • SSRIs (selective serotonin reuptake inhibitors)
  • SNRIs (serotonin and norepinephrine reuptake inhibitors)
  • MAOIs
  • Tricyclic antidepressants

The two most common are SSRIs and SNRIs, targeting serotonin and norepinephrine. But, as we mentioned before, recent research has shown that these two neurotransmitters don’t play as big of a role in depression as we thought.

As a result, these types of medical treatment prove ineffective for many people. In fact, one study looked into the effectiveness of SSRIs and SNRIs, and depression symptoms only improved in about 20 percent of the people studied.

Not to mention, antidepressants, when they do work, act very slowly. It can take up to eight weeks for many of these medicines to make a meaningful difference in a person’s mood, making the process of finding effective treatment difficult and slow.

This ineffectiveness leads to people trying multiple antidepressants without seeing any success. When this happens, it is called “treatment-resistant depression,” and it’s a plight that affects many people.

Clearly, there are many people out there looking for a better solution.

The Ketamine Alternative

Fortunately, there have been new advancements in depression treatment that have delivered massive improvements in symptoms. The psychedelic therapy of ketamine can make a difference for so many people.

This treatment is based on the new findings that glutamate and GABA are some of the main players in depression. Ketamine’s main method of action is on the glutamate in the brain.

Ketamine was originally used as an anesthesia medication. It has a unique ability to induce sleep and reduce pain without greatly altering cardiovascular function, making it a very effective anesthetic.

But recently, scientists at Yale have discovered its effectiveness as a treatment for major depressive disorder.

Ketamine triggers the production of glutamate in the brain. This creates a big chain reaction, affecting the NMDA receptors in the brain. The result of this chain reaction is a big increase in neuroplasticity, prompting the brain to make new neural connections, restoring the neural pathways lost from depression.  

These researchers at Yale have conducted studies with small doses of ketamine, too low to induce anesthesia. Their results have been nothing short of incredible. About half of the people they’ve studied showed massive improvements in their depression within 24 hours of their first treatment.

So not only is ketamine more effective than traditional antidepressants, but it works incredibly fast. Ketamine seems to be a solution that provides many people with substantive healing and a new-found feeling of wholeness.


Depression is an intense battle that so many people face. But for the 280 million people in the world who are fighting, there is still hope.

Whether it’s lifestyle changes, CBT or ketamine therapy (or a combination of all three), there are treatments that can help your brain recover from the debilitating effects of depression. As Christopher Reeve once said, “Once you choose hope, anything is possible.”

Treatment at Nue Life

At Nue Life, we offer at-home ketamine experiences that are virtually supervised so that you can have your treatment in the comfort of your own home. Nue Life is also committed to whole-person care, offering personalized ketamine treatment and after-treatment care in the form of integration group sessions and health ccoaching. For more information, visit our programs page.

Depression | WHO

Depression and Sleep | Sleep Foundation

Depression: How effective are antidepressants? | Informed Health

Effect of exercise on depression | American Psychological Association

How Depression Affects the Body | University of Washington Medicine

How Depression Affects the Brain | Yale Medicine

How New Ketamine Drug Helps with Depression | Yale Medicine

Major Depression and Genetics | Genetics of Brain Function | Stanford Medicine

Researchers outline the connection between inflammation and depression | Emory University School of Medicine  

The Mind and Mental Health: How Stress Affects the Brain | Touro University

What causes depression? | Mind and Mood | Harvard Health Publishing

What is Cognitive Behavioral Therapy? | American Psychological Association

What Is Depression? | American Psychiatric Association

Melancholia and Depression During the 19th Century | British Journal of Psychiatry

Join the Beckley Academy
Mailing List

Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.

Have you made up your mind to change your mind?

Need further advice?

Speak with our Welcome team.

Get Started
Begin your journey with us.
Sign up to the Nue Life newsletter.

Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.
© 2024 NueCo Holdings, P.B.C. All Rights Reserved Reserved

NueCo Holdings, P.B.C. is a technology platform that provides services to affiliated independently owned and operated medical practices, and does not own, direct, or control the medical professionals providing the standard of care to their patients.
The Instagram logo.The Facebook logoThe Twitter, or X, logoThe LinkedIn logo
Thank you! Your submission has been received!
Oops! Something went wrong while submitting the form.