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How Does Depression Affect the Brain?

Published by Dr. Venn-Watson
Dr. Eric Venn-Watson’s Highlights
    • Depression is a condition that affects as many as one in 15 people, and is characterized by feelings of sadness, hopelessness, and a general loss of interest in activities that were once enjoyed. 
    • Left untreated, depression can result in physical brain changes like smaller brain size, less brain plasticity, and inflammation. 
    • Treatments for depression are available, and can help protect the quality of life and brain function of people with this mental health condition. 

The World Health Organization reports that mental health issues are on the rise. Understanding what depression is and how it affects the brain will be key in developing new therapies and treatments for people who suffer. 

Let’s talk about what depression is and what we know about how it affects the brain. 

What Is Depression?

If someone says they’re depressed, you might assume they’re just having a bad day. Feeling low, sad, or hopeless can be normal from time to time, with or without a specific cause for the feelings. 

However, someone who is truly depressed experiences more than just feelings of sadness. 

Depression, also known as major depressive disorder, is a serious medical condition that, if left untreated, can negatively impact someone’s quality of life and may even become life-threatening. 

What Are the Symptoms of Depression?

People who suffer from depression have frequent feelings of sadness, loneliness, and hopelessness. They may also lose interest in activities they once enjoyed. 

Other symptoms include:

  • Changes in appetite
  • Unexplained weight gain or loss
  • Feeling fatigued or tired all the time
  • Sleeplessness, or the desire to sleep more than usual
  • Difficulty concentrating
  • Feelings of self-harm or suicide 

These feelings may come and go or may last for weeks and months. Usually, a person is not diagnosed with depression unless they experience these feelings for longer than two weeks. 

How Common Is Depression?

Although depression can feel isolating, it is extremely common. An estimated one in 15 adults suffers from depression at some point during their lifetime. Depression may begin in childhood but usually presents in teenage years or early adulthood. 

Women are at higher risk for developing depression than men, and it’s also considered a hereditary disease, meaning if your parents or grandparents had it, you’re at a higher risk of developing it, too. 

Who Is at Risk?

Anyone can suffer from depression, but some factors can increase your likelihood of developing depression:

  • A family history of depression, anxiety, or other mental illness.
  • Environmental factors. If you are exposed to violence, physical or mental abuse, poverty, or neglect, you may be more likely to develop depression.
  • The biomechanics of your brain. Depression affects the levels of important regulatory chemicals in your brain, like serotonin, dopamine, and norepinephrine. If you naturally have higher or lower levels of these chemicals, you may be at higher risk of mental illnesses like depression. 

Although depression can't be predicted, knowing your risk factors can help you be aware of symptoms if they present so you can get the help and treatment you need. Treatment is important because depression can have a physical impact on the brain. 

Depression’s Impact on the Brain

The feelings produced by depression are hard to manage, but the physical impact it has on your brain (if left untreated) can be irreversible. First, let’s look at a few parts of healthy brain function and then discuss how depression can alter these functions. 

Gray Matter

You’ve probably heard of “gray matter” inside your brain. This is a part of your brain that is dense with neurons and contains a lot of important information. Gray matter interacts with white matter, located deeper within your brain, and is filled with nerve fibers (axons). 

Gray matter processes movements, memories, and emotions. It probably goes without saying that gray matter is important and helps contribute to brain size. Gray matter volume (GMV) is the amount of gray matter a person has in their brain. 

In a patient with depression, gray matter volume appears to decrease in several areas of the brain:

  • Hippocampus. Within the temporal lobe of your brain is the hippocampus, a structure responsible for memories and learning. The hippocampus is malleable, which is important to your brain’s neuroplasticity but is also easily damaged by psychiatric and neurological disorders. 
  • Prefrontal cortex. This part of your brain is responsible for expressing personality, complex cognitive behavior, social behavior, and executive function. 
  • Thalamus. This structure is like a relay center, sending messages from your senses (except smell) to other parts of your brain for processing. 
  • Caudate nucleus. Movement, motivation, romantic feelings, and emotions are processed in this part of your brain. 
  • Insula. This important structure helps you process feelings, determine risk versus reward, enact auditory and vestibular functioning, and also plays a key role in developing pain pathways. 

While it’s unclear how much GMV a person with major depression will lose if their condition is untreated, studies show that brain shrinkage does occur. Interestingly, activity in the amygdala, the part of your brain that processes your fight or flight response, may increase with depression. 

Unfortunately, that’s not necessarily a good thing. Enlarged amygdalas are frequently associated with anxiety and behavioral disorders.


Studies have shown that people who experience major depressive episodes have higher translocator proteins, a protein frequently observed with inflammation. 

Chronic, low-level inflammation is associated with negative metabolic health conditions like:

  • High blood pressure
  • Unhealthy cholesterol
  • Excess eight
  • Unregulated blood sugar levels

Inflammation is an immune response by our bodies to a foreign invader, like a virus or bacteria, or an injury. Unfortunately, the system doesn’t always work properly, and underlying health conditions can cause inflammation constantly, which can have a detrimental impact on overall health. 

Brain inflammation can cause damage to the brain, like loss of brain cells, cognitive problems, and increased brain aging. 

Left untreated, the level of these inflammatory proteins rises, leading to brain changes that are more significant and can lead to personality changes and difficulty with decision-making. 

Cell Communication

The cells in your brain are divided into two major groups, neurons (brain and nerve cells) and glia (non-neuron cells that are still inside your brain). 

Neurons operate by communicating information with each other. They do this through a series of neurotransmitters. Neurotransmitters are brain chemicals released from one neuron and received by another. 

At the end of every neuron is an axon terminal, where neurotransmitters are located. When a neuron fires, one of the resulting actions can be to release neurotransmitters from one neuron to be received by a neighboring neuron's dendrites (a tree branch-like structure). The completed transmission has numerous purposes that help maintain homeostasis in your brain and body. 

When your neurons communicate properly, neural pathways are formed. In healthy brains, there is a high level of plasticity, which means that neural pathways can be rerouted when new things are learned, or to restore connections after an injury or trauma. 

The brain chemistry of someone with depression is different. New studies point to problems with the way brain cells communicate as an underlying cause of depression itself. The issue may not be with the hormones usually thought to affect depression but rather with excitatory signals between cells that are transferred abnormally. 

What About Stress?

Sometimes it seems that depression and stress go hand in hand. While it’s true that chronic stress can lead to depression, the two are both separate conditions.

Stress can be both good and bad. When you have a deadline or are in danger, stress is a tool your body uses to motivate you and help you get the job done or get out of harm’s way. However, chronic stress can lead to neurological disorders. 

When It’s More Than Stress

Stress includes feelings of worry, irritation, and anger and may even have physical components like an upset stomach, sleeplessness, or changes in appetite. However, if you experience stress for longer than two weeks without an obvious stressor in your life, you could suffer from an anxiety disorder. 


Like depression, someone who experiences anxiety has these feelings for a longer period of time, and may not be able to pinpoint a specific reason for experiencing the feelings. Like depressed patients, people with anxiety may experience changes in their level of social engagement and loss of interest in things they once enjoyed. They may also experience physical symptoms like increased heart rate, muscle cramping, digestive issues, backaches, and headaches. 

Cortisol and Your Brain

When you experience a mental health condition like anxiety, your body naturally produces more stress hormones. One of these hormones is cortisol. 

Cortisol is useful in the short term: it heightens fight or flight response, increases blood sugar to give you a burst of energy, and suppresses certain systems to send all your energy into taking care of the urgent alarm you are facing. 

However, cortisol can have negative side effects if it hangs around for too long, especially when produced continually. It can cause your brain to use more glucose, and activate the parts of the brain that control mood and fear. This can lead to changes in the brain that result in mood disorders and dysfunctions. 

What Are the Treatments for Depression?

Thankfully, there are numerous options for the treatment of depressed people. Depression treatment is essential in re-establishing a person’s quality of life and protecting their brain's physical structure. 


An entire class of medications has been developed to help people who suffer from depression. Antidepressant medications generally work to help rebalance or more efficiently utilize the levels of various mood-regulating neurotransmitters in the brain. 

Cognitive Behavioral Therapy

In addition to medication, cognitive behavioral therapy, also known as CBT, can help a person suffering from depression learn new coping skills, recognize triggers, and identify feelings and symptoms of depression when they arise. A form of psychotherapy, CBT focuses on giving a person a safe place to discuss their depression, and helps them find unique ways to manage it and maintain their quality of life. 

Lifestyle Changes

Understanding the importance of diet and exercise is important to undergirding other treatments for depression. A person’s diet and physical activity level can help elevate their mood and keep them healthy. 

In addition, relaxation techniques like meditation or yoga can help alleviate ancillary feelings of stress or worry, which can help a person feel more centered and balanced. 

Learning More

Depression is a common mental illness, and it has direct physical impacts on the brain. Learning more about how depression affects the brain can help us develop new treatments and therapies to relieve suffering. 

Genetics plays a role in depression, but just because you are related to someone with depression doesn’t mean you will develop depression. Knowing your risks can help you become aware of symptoms of depression if they arise and can help you get treatment faster. 

In addition to these treatments, leading a healthy lifestyle, maintaining a healthy weight, and managing stress are crucial elements in keeping mentally healthy. 

If you or someone you know may be experiencing depression, you can check out these resources from SAMHSA’s National Helpline on where and how to get help. 

You can find more information about maintaining a healthy life by checking out our website and exploring our blog



Mental health|WHO.int

Psychiatry.org - What Is Depression?

Neuroanatomy, Gray Matter - StatPearls - NCBI Bookshelf

Hippocampus in health and disease: An overview - PMC

Yale team discovers how stress and depression can shrink the brain | YaleNews

Larger Amygdala Volume Mediates the Association Between Prenatal Maternal Stress and Higher Levels of Externalizing Behaviors: Sex Specific Effects in Project Ice Storm

The Role of Inflammation in Depression and Fatigue - PMC

Depression stems from miscommunication between brain cells; Study challenges role of serotonin in depression -- ScienceDaily

What’s the difference between stress and anxiety?|APA.org

Chronic stress puts your health at risk - Mayo Clinic

Treatments for depression - InformedHealth.org - NCBI Bookshelf

Profile photo for Eric Venn-Watson

Eric Venn-Watson M.D.

Eric is a physician, U.S. Navy veteran, and Co-founder and COO of Seraphina Therapeutics. Eric served over 25 years as a Navy and Marine Corps physician, working with the special forces community to improve their health and fitness. Seraphina Therapeutics is a health and wellness company dedicated to advancing global health through the discovery of essential fatty acids and micronutrient therapeutics.

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