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There is still a lot to know about how depression affects the brain. Evidence suggests that it can alter the size of certain areas, affect communication between structures, and lead to changes in neurotransmitters and inflammation.

Depression is a severe mental disorder and a leading cause of disability around the world. It is estimated that 8.4% of all U.S. adults had at least one major depressive episode.

While the symptoms of depression are well known, there is still a lot to learn about the underlying mechanisms of this disorder, namely how it can physically affect the brain. Magnetic resonance imaging (MRI) has been used to investigate changes in depressive patients. Evidence shows significant alterations in specific brain regions, as well as in how they work.

Understanding these changes is crucial to develop more effective treatments and improving the lives of those struggling with depression.

If you are dealing with depression, early treatment will help you prevent (and even reverse) the damage to your brain. Untreated depression can affect the brain more and more over time.

How Depression Affects our Brain

Depression affects the brain in multiple ways, impacting different regions and structures.

1. Brain shrinkage

There’s an ongoing debate about how depression affects the brain. Still, research tells us that several regions can decrease in size:


This complex brain structure has a central role in learning, long-term memory, and recollection. It connects other parts of the brain that process emotion and stress. While the reason for the shrinkage is not fully understood, it seems to be related to chronic stress and inflammation.

Prefrontal Cortex:

This region is responsible for high-level thinking, planning, decision-making, and social behavior. Brain images of people with depression suggest abnormally low activity in this area, which may contribute to difficulties in cognitive tasks and social interaction.


Known as the brain’s central station for sensory information (except smell). One of its main functions is to filter the vast amount of information it receives and decide where to focus attention. As depression is involved in how sensory input is perceived, there may be a reduction in the thalamus size.

Caudate Nucleus:

Plays a critical role in various high-level functions, including, planning movement, learning, memory, reward, motivation, emotion, and romantic interactions. Studies show that it reduces size in people with depression.


Its main purpose is to connect our sensory experiences to our emotional responses. It is involved with a wide range of functions from feelings of love, pain, emotions, cravings, and addiction to taste and also regulating our immune system.

2. Changes in the brain circuits

When a person is exposed to severe stress and anxiety — as one experiences when depressed —  some of the connections between nerve cells are affected and even lost. As a result, the communication between the circuits becomes inefficient. And it is this loss of synaptic connections that might be contributing to the biology, and consequently, the symptoms of depression.

3. Neurotransmitters

The predominant care for depression is still based on the monoamine deficiency hypothesis. This presumes that depression is caused by a chemical imbalance in the brain, specifically a deficiency in one of three neurotransmitters: serotonin, dopamine, or norepinephrine.

Neurotransmitters are commonly known as the body’s chemical messengers. It’s what helps one cell in the brain communicate with another to pass a message along. 

However, researchers concluded that these neurotransmitters did not account for all the symptoms involved with depression. In fact, one alternative cause that is being studied has to do with two of the brain’s most abundant neurotransmitters — glutamate and GABA. These neurotransmitters are involved in regulating mood and emotion, as well as how the brain changes and adapts over time.

While these findings may represent a possible shift in our understanding of depression, it doesn’t mean people should stop taking their medication. There’s a need for further research on the causes of depression and what treatments may be more effective.

4. Brain Inflammation

While depression and brain inflammation are still one “the chicken or the egg” situation (experts are not sure of which came first), inflammation definitely plays a role in the development and maintenance of depression.

We know that inflammation is the body’s natural reaction against injury or infection, but it can also be a response to chronic stress or other environmental factors.

Studies show that people with depression have higher levels of inflammatory markers. These chemicals seem to be even higher in people who had untreated depression for the last 10 years or longer.

5. The role of stress

Our ability to cope with chronic stress can lead to changes in our brain’s structure and function, which may contribute to the development of depression.

Our stress response is regulated by the hypothalamic-pituitary-adrenal (HPA) axis — a complex neuroendocrine mechanism that mediates the effects of stressors to maintain our physiological homeostasis. When our HPA axis is chronically activated it can cause brain inflammation and changes in neurotransmitters (which, as we discussed, are relevant factors in depression).

In addition, a study found an increase in the amygdala size in adults with depression and high levels of anxiety, which is consistent with anxiety-related amygdala hyperactivity.

The amygdala is a region of the brain responsible for processing physiologic and behavioral responses to stress. It is closely linked to emotions, fear, and motivation. 

An overactive amygdala can create a cognitive bias that leads us to view the world and ourselves in negative way. Moreover, this increase in negative thoughts and emotions seems to happen at the same time as a decrease in the effects of dopamine — which plays a primary role in our brain’s reward system.

Does Depression Permanently Affect the Brain?

While this question needs further research, some evidence suggests that the damage in the structures and functions of the brain can be reversed with treatment for depression. 

Early and effective treatment for depression is crucial to managing depression symptoms and avoiding changes to the brain. If you have depression or want to help a loved one with depression seek help from a therapist at the first signs.

Depression Treatment in Baltimore, MD

Are you wondering how depression affects the brain? Do you notice an aggravation of other functions such as cognitive tasks, memory, or social interaction?

Therapy for depression can alleviate your symptoms and prevent damage to your brain. Our therapists at New Connections can help you process your emotions while exploring better ways to cope with stress and anxiety (which can worsen these changes).

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About the Author:

Cathy Sullivan-Windt

Psychologist (Ph.D.) & Owner

Cathy is a licensed counseling psychologist with almost 20 years of experience. She specializes in women’s counseling, anxiety treatment, sexual assault recovery, life transitions, and relationship issues.

In her free time, she enjoys spending time in nature, traveling, reading, and being with her family and friends.

Read More About Cathy

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