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How Does Depression Affect the Brain?

How Does Depression Affect the Brain?

Published: March 22, 2022

The brain is one of the most complex neurochemical organs we have in our body. It enables us to think, make decisions, sleep, eat, regulate our emotions, and keep our bodily systems operating. Every activity we complete in our daily life, every feeling or thought we have, and every automatic operation of our organs starts or passes through the brain.

We know that depression affects our brain by triggering sadness and pessimistic thoughts. But did you know that depression also has the power to affect the neuroanatomy of our brain? That's right! Depression can do more harm than just affecting our emotions - it can change our brain's structure and neurochemistry.

Read more: TMS Therapy

Thankfully we are in an era that provides us with technology and a body of knowledge to take a deeper look into the physical symptoms of depression. In addition, understanding how depression affects brain regions is essential to developing more effective depression treatments.

This may help you or a loved one follow a solid recovery path with long-lasting change. So, let's embark upon the science behind depression and the brain.

What Is Major Depression?

In the mental health field, major depression or major depressive disorder is the technical term to refer to what we generally call clinical depression. Major depression is a psychological condition that causes significant and persistent low feelings, negative thoughts, and a series of physical symptoms.

Major depressive disorder symptoms can be worse than just feeling drained for days or even weeks. In fact, in the case of severe depression, the symptoms may be so excruciating that they impair almost all aspects of our life, like engaging in basic activities such as eating or taking a shower.

We may all be aware that depression causes feelings of sadness or hopelessness, but what are the other signs we may want to look for? Some of the other symptoms of depression include:

  • Ongoing fatigue or low energy
  • Insomnia
  • Sleeping too much
  • Significant changes in eating patterns that result in weight gain or loss
  • Lack of concentration or attention issues not associated with another mood disorder, mental illness, or substance abuse
  • Experiencing a lack of pleasure in most activities or relationships
  • A weakened immune system that is not related to other health conditions
  • Physical pain or aches (i.e., headaches and stomach aches) that are not associated with another health condition or mood disorder
  • Suicidal thoughts or suicide attempts

According to the American Psychiatry Association (APA) guidelines, if you experience most of these depressive symptoms for two weeks or more, you may be suffering from major depression or major depressive disorder. If you are encountering thoughts of taking your life, please reach out to the National Suicide Prevention Lifeline to receive immediate support.

As you may recognize, all of these symptoms are pretty perceivable. But what about the parts of our body we cannot see? What impact does depression have on our brain?

Depression and the Brain's Anatomy

The brain is a super elaborate organ formed of blood vessels, nerves, neurons, glial cells, white matter, and gray matter. All these elements work in alignment to guarantee that our bodies and minds work appropriately at all times. When one of these tiny parts does not function as it should, the brain and body may suffer. The result can be a wide variety of physical effects or mental health illnesses.

Inside the brain, there are chemical messengers called neurotransmitters. Neurotransmitters transmit messages from one neuron to another or from neurons to muscles. Neurotransmitters can send three types of messages: they may ask the neuron to increase its activity, decrease it, or modulate it. But why are neurotransmitters important?

Relationship of Neurotransmitters to Depression

Scientists have studied the connection between low or excessive neurotransmitters' activity and mood disorders, like depression. In turn, they have found that some neurotransmitters have a direct link to depression, including:

  • Dopamine. Dopamine influences our capacity to experience pleasure and motivation.
  • Norepinephrine. Norepinephrine sends signals to the brain and the whole body when there is a stressful event, activating the body's 'alarm' system.
  • Serotonin. This neurotransmitter influences different activities, such as our emotional responses, sleeping patterns, and eating cycles, involved in mood regulation.

Some people refer to serotonin, dopamine, and norepinephrine as the 'happy hormones.' When these three work appropriately, depression symptoms may significantly decrease or go away. New research has found two more neurotransmitters involved with depression - glutamate and gamma-aminobutyric acid (GABA).

Glutamate is the most important excitatory neurotransmitter in the entire nervous system as it helps the brain develop normally. But when there is a high glutamate concentration, nerve cells may die due to overactivation.

Unlike glutamate, which may kill brain cells with its excitatory power, GABA has a calming effect on the nervous system. This calming effect occurs thanks to GABA's inhibitory power, which may reduce your brain cells' overactivity during stress or anxiety.

Many pieces of research show that untreated major depressive disorder causes an imbalance in the activity of these five neurotransmitters. During a major depressive disorder episode, the level of dopamine, serotonin, and GABA decreases, while norepinephrine and glutamate activity increases. This under and over-activity of brain chemicals may cause damaging effects to the brain cells and even modify the structure of some brain areas.

Depression and Brain Shrinkage

Thanks to neuroimaging and medical technology, scientists have observed that untreated major depressive disorder causes structural brain changes. Researchers have discovered that some brain areas shrink when depression becomes a long-term mental illness, while others become amorphous.

One of the reasons for this is that these brain areas lose or modify their gray matter volume (GMV). But which brain regions are most affected during depressive episodes?

Prefrontal Cortex

The prefrontal cortex plays a vital role in a wide variety of functions, including planning, decision-making, working memory, behavior control, rule learning, expressing your personality, and social emotions.

The prefrontal cortex is highly susceptible to stress hormones (think about those moments when stress has influenced you to make impulsive decisions). Scientists have found abnormalities in some prefrontal cortex areas in most individuals experiencing a major depressive disorder.


The hippocampus is perhaps one of the most studied areas concerning depression and brain changes - this is partly due to its higher level of malleability or neuroplasticity.

Even when we get older, the hippocampus neuroplasticity allows us to keep learning and storing information in our memory by creating new neural networks. But unfortunately, long-term depression causes atrophy and shrinkage of this brain area.


The amygdala is the part of the brain responsible for regulating behavioral, physiological, and emotional responses to threats or stressful events. In other words, the amygdala activates our 'fight-flight-freeze' alarm system.

Recently, research has highlighted that a major depressive episode physically changes the size of the amygdala. Acute depression increases the size of the amygdala, while permanent major depressive disorder causes the opposite effect.

Brain Inflammation

Last but not least, some people with clinical depression may experience brain inflammation as an immune response to this mental illness. While a low level of brain inflammation may not be concerning, research shows that prolonged or higher levels of brain inflammation can undoubtedly increase the risk of experiencing other mental health and physical issues.

Are Brain Changes Permanent?

Not in most cases, as long as the person follows appropriate major depression treatment.

As we mentioned earlier, the brain has this great tool called neuroplasticity, meaning that it can regenerate itself by allowing new brain cells to grow and connect with others. However, finding the proper treatment on time is crucial to help the brain heal before it experiences more severe damage.

Brain-Focused Treatment for Clinical Depression

There are different treatments to help you overcome major depression. Some effective treatments include psychotherapy and antidepressant treatment. However, in some cases, major depression becomes resistant to these treatments. In these cases, transcranial magnetic stimulation (TMS) therapy has proven effective.

Transcranial magnetic stimulation is a Food and Drug Administration (FDA) approved treatment for treatment-resistant depression. It is a non-invasive and painless form of brain stimulation.

The goal of TMS is to target affected brain areas and reawaken or calm the brain cells' activity in specific areas. Compared to other types of brain stimulation, TMS only targets the affected part of your brain and does not require anesthesia or hospitalization.

How Can I Get Help?

At GIA Miami, we welcome you to use our experience, knowledge, and technology to design an individualized treatment plan for you. Major depressive disorder is a tormenting mental health condition, but it is treatable!

We believe that anyone deserves to grow their mental wellness, including you. So, whenever you feel ready, call us at 561.462.4099 to let us know about your mental or emotional needs. We would be honored to offer you a helping hand and walk with you during your healing journey.

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