Depression may cause some structural changes to the brain. Depending on the area affected, you may have different symptoms, including issues with how you perceive and regulate emotion.

Depression, while often thought of for its emotional symptoms, has the potential to affect the physical structure of the brain. Physical changes may range from inflammation to actual shrinking.

We discuss how depression affects your brain physically and ways to potentially avoid or reverse the changes.

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Researchers in a 2021 research review looked into the current neuroscience research surrounding major depressive disorder (MDD). They noticed differences in brain volume and activity when it comes to the brains of people with depression.

Structural brain changes, changes in brain size, and inflammation have all been noted in other research.

1. Brain shrinkage

A small 2018 study suggests that the size of specific regions of the brain can decrease in people who experience depression. Researchers continue to debate which regions of the brain can shrink due to depression and by how much.

In a 2012 research review, studies showed that the following parts of the brain can be affected:

  • Hippocampus: The hippocampus supports memory, learning, navigation, and perception of space.
  • Thalamus: The thalamus relays information from the cerebral cortex (the brain’s outer layer) to the brain stem.
  • Amygdala: The amygdala regulates emotion and memory.
  • Prefrontal cortices: The prefrontal cortices control cognitive functions. They manage attention, impulse control, and emotional reactions.

The amount these areas shrink is linked to the severity and length of the depressive episode. But, more studies are needed to support these findings.

When a section of the brain shrinks, your ability to perform the functions associated with that particular section declines.

For instance, the amygdala and prefrontal cortices work together to manage emotional responses and the recognition of emotional cues in other people.

Shrinkage of those areas can potentially contribute to a reduction of empathy in people who have had depressive episodes. The lack of empathy could also be due to other cognitive and emotional symptoms caused by depression.

An older 2008 study found that amygdala-prefrontal cortical dysfunction may cause the following symptoms in nearly all people with depression:

  • anhedonia, or the loss of interest in activities you once enjoyed
  • a dysfunction in the way you perceive emotion
  • loss of adequate emotional regulation

2. Brain size in co-occurring depression and anxiety

The amygdala is directly linked to emotions, and it’s also in charge of the body’s fight-or-flight response to perceived threats.

A 2020 research review suggests that when depression and anxiety occur together, the amygdala increases in size. This suggests that anxiety and depression together may have a different outcome from other forms of depression.

3. Brain inflammation

Researchers are also making new links between inflammation and depression.

Unusual immune system activity occurs in some people with depression. But it’s not clear whether inflammation causes depression or vice versa.

Brain inflammation during depression is related to the amount of time someone has been depressed. As a result, significant brain inflammation is more likely to be relevant in persistent depressive disorder, a chronic form of depression.

A small 2018 study found that people who went untreated for MDD for more than 10 years had 29–33% more “translocator protein total distribution volume” when compared with people who were depressed and untreated for less time. “Translocator protein total distribution volume” is an indicator of brain inflammation.

Because brain inflammation can cause brain cells to die, it can lead to complications. These include shrinkage and reduced neuroplasticity, which is the ability of the brain to change as a person ages.

Brain inflammation can also lead to reduced functioning of neurotransmitters, the body’s chemical messengers.

4. Structural differences

The central nervous system uses neurotransmitters to relay messages between neurons and other cells within the body.

These molecules control everything from breathing to mood. According to a 2018 review of research, scientists have identified over 100 types.

Several neurotransmitters have been associated with depression.

For example, other 2018 research looked at people with anxiety and depression. They linked these conditions with low levels of neurotransmitters, such as:

  • serotonin
  • dopamine
  • norepinephrine

A 2016 review found evidence that an unusual balance between different types of neurotransmitters may occur during depression. They suggest this imbalance can be reversed upon depression recovery.

The imbalance between neurotransmitters may be responsible for the reduction in brain volume that occurs in depression, according to 2015 research.

In recent years, there’s been an interest in identifying brain circuits involved in depression. A brain circuit is essentially a network of neurons. Too much or too little activity in a given circuit may play a role in the onset of depression and other mental health symptoms, according to 2021 research.

The term “connectivity” refers to the ways that different regions of the brain interact. Researchers have found evidence of both little connectivity and lots of connectivity in the brains of adolescents and adults with depression.

In a 2019 study, researchers observed hypoconnectivity, or little connectivity, in the brain’s frontoparietal network in people with symptoms of depression. The frontal and parietal lobes of the brain play a role in attention and emotional regulation.

A small 2020 study suggests that hyperconnectivity, or lots of connectivity, may increase the emotional reactivity of people with depression, among other effects.

According to a 2018 research review, connectivity changes may also result in symptoms such as:

  • dysphoria, or a negative mood
  • anhedonia
  • rumination

In October 2021, researchers demonstrated the potential of resetting brain circuits in people with treatment-resistant depression by implanting a neurostimulation device into a person’s brain.

5. Oxygen restriction

Depression may also be linked to reduced oxygen in the body. Reduced oxygen levels may be due to changes in breathing caused by depression — but which comes first remains unknown.

The body produces a specific protein in response to hypoxia, a condition in which the brain is not getting enough oxygen. This protein is known as hypoxia-inducible factor-1 (HIF-1).

According to a 2019 study in rats, elevated HIF-1 in specific immune cells appears to be associated with depression-like behaviors.

More human studies are needed to support this claim. However, the researchers suggest that targeting HIF-1 may provide future treatment opportunities for depression.

Another theory that needs further study involves the retention of carbon dioxide. Carbon dioxide retention occurs in conditions such as sleep apnea, and people with sleep apnea have high rates of depression.

It’s uncertain what has a greater impact on this increased depression risk: inflammation or the disruption of sleep-related circadian rhythms (aka 24-hour sleep-wake patterns).

The brain is highly sensitive to reductions in oxygen, which can lead to:

Inflammation and cell death can lead to symptoms associated with development, learning, memory, and mood. Even short-term hypoxia can lead to confusion, much like what’s observed in high-altitude hikers.

In a small 2017 study, hyperbaric oxygen chamber treatments, which increase oxygen circulation, were shown to relieve symptoms of depression in humans.

Research suggests that some of the physical brain changes caused by depression can be reversed.

A 2016 study looked at animal models with chronic stress, which are often used in depression research. The research suggests that brain shrinkage in depression was likely the result of weakened dendrites — not the loss of brain cells. Dendrites are cellular extensions found in the neurons, or nerve cells.

This suggests that depression changes may be reversible and the brain can heal.

Treatments — such as antidepressants and cognitive behavioral therapy — may help reduce inflammation caused by depression. They may also help the brain form new synaptic connections that were compromised during depression.

A 2023 study looked at people with treatment-resistant depression who were treated with low doses of ketamine. They found that the drug not only reduced depression severity but also improved some aspects of neurocognitive functioning, including:

  • processing speed
  • episodic memory
  • working memory
  • attention

However, more research is needed on the potential opioid-like properties of low doses of ketamine.

Benzodiazepine-like molecules are also promising, according to research in mice.

Exercise can also help improve the structure of the hippocampus in people with depression, according to a 2020 study.

Did you know?

In 2019, the Food and Drug Administration (FDA) approved esketamine (Spravato), the first ketamine-based antidepressant. Spravato is a nasal spray intended for people with treatment-resistant depression who have tried at least two antidepressants.

It’s taken in combination with an oral antidepressant and must be administered in the presence of a healthcare professional.

Spravato begins to reduce the symptoms of depression in as little as 24 hours after administration.

The National Institute of Mental Health (NIMH) estimates that 21 million U.S. adults had at least one major depressive episode in 2021.

Depression is a complex mental health condition. Doctors may need to use a combination of approaches to help symptoms improve.


Therapy can help treat depression. It works by helping you:

  • identify aspects of your life and thinking processes that cause stress
  • understand ways to process your emotions
  • learn to think more reflectively and flexibly through stressful life events
  • strategize better ways to navigate your life without as many stressors or to manage the stressors better

Cognitive and group therapy, especially approaches that incorporate stress-relieving mindfulness techniques, can provide support and help you overcome stigma surrounding mental health.

If you’re depressed, you’re not alone. There are a number of helpful resources out there. Check out:

Taking antidepressants

If you’re currently experiencing a depressive episode, antidepressants may help prevent the physical changes that can occur. They can be effective aids in managing the symptoms of depression, too.

A combination of psychotherapy and antidepressants can be incredibly effective for managing physical changes and helping you cope with your symptoms.

There are many types of antidepressant medications, including:

  • selective serotonin reuptake inhibitors (SSRIs)
  • serotonin-norepinephrine reuptake inhibitors (SNRIs)
  • tricyclic antidepressants
  • tetracyclic antidepressants
  • dopamine reuptake blockers

It can take time to find the right medication and dosage. There’s no one-size-fits-all antidepressant. Talk with a doctor or psychiatrist about any concerns you may have.

Exercising regularly

Regular exercise or movement can help with both psychological symptoms and brain changes, according to various studies in humans and animals.

According to a 2019 research review, a medium to large reduction in symptoms has been observed in people who exercised 3 times per week for 12–24 weeks.

If you have depression, regular exercise also increases your chances of the condition going into remission.

Exercise promotes brain health by:

  • decreasing inflammation
  • restoring the balance toward parasympathetic activity after the exercise ends
  • improving metabolic functioning
  • improving cardiovascular activity

In addition, a 2020 study suggests exercise can help improve the structure of the hippocampus and activate brain function, among other benefits.

The best forms of exercise for people with depression include aerobic, resistance, and mind-body exercise.

While exercise is important, it can also be challenging when you’re depressed. Be gentle with yourself.

Reducing your stress

There’s considerable evidence that links stress to the start of depressive episodes in many types of depression.

Trying to lower your stress levels can often seem impossible or daunting at times. But there are some simple and quick changes you can make to reduce stress, like taking a few deep breaths or playing with a pet.