The psychological effects of depression are well known. Depression also has the potential to affect the physical structure of the brain. Physical changes range from inflammation to actual shrinking.

If you’re interested in learning more about how depression can affect the physical brain, and ways to potentially avoid or reverse these changes, we’ve laid it all out for you below.

Did you know?

The National Institute of Mental Health (NIMH) estimates that 21 million U.S. adults had at least one major depressive episode in 2020.

A 2021 literature review looked into the current neuroscience research surrounding major depressive disorder (MDD). For starters, the researchers stated that there are differences in brain volume and activity when it comes to depressed brains and typical brains.

1. Brain shrinkage

A small 2018 study showed that the size of specific regions of the brain can decrease in people who experience depression.

The shrinkage may be reversible, though.

Researchers continue to debate which regions of the brain can shrink due to depression and by how much. In a 2012 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, which is the brain’s outer layer, to the brain stem.
  • Amygdala. The amygdala regulates emotion and memory.
  • Prefrontal cortices. The prefrontalcortices 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. More studies are needed to support these findings, but this is the current theory about how depression may alter brain function.

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 control emotional responses and the recognition of emotional cues in other people.

Shrinkage of those areas can potentially contribute to a reduction in empathy in individuals with postpartum depression, according to a small 2010 study. The lack of empathy could be due to other cognitive and emotional issues 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
  • dysfunction in the way you perceive emotion
  • loss of adequate emotional regulation

A 2016 study looked at animal models with chronic stress, which are often used in depression research. The study suggested 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 is not an irreversible neurodegenerative disorder. Instead, its impact on the brain may be reversible, and the brain can heal.

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 review found that when depression and anxiety occur together, the amygdala increases in size. This suggests that anxious depression may be a different outcome from other forms of depression.

3. Brain inflammation

Researchers are also making new links between inflammation and depression.

It’s known that unusual immune system activity occurs in some people with depression. But it’s still not clear whether inflammation causes depression or vice versa.

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

A small 2018 study found that people who went untreated for MDD for more than 10 years had 29 to 33 percent 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 a number of 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.

There are three main types of neurotransmitters:

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

Several neurotransmitters are associated with depression. For example, another 2018 review linked depression and anxiety in some individuals with low levels of neurotransmitters such as:

A 2017 review found evidence that an unusual balance between excitatory and inhibitory neurotransmitters may occur during depression, and that the imbalance can be reversed upon depression recovery.

The imbalance between excitatory and inhibitory neurotransmitters may be responsible for the reduction in brain volume that occurs in depression, according to a 2015 review.

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 with one another. Researchers have found evidence of both little connectivity and lots of connectivity in the brains of adolescents and adults with depression.

In a 2015 review, researchers observed hypoconnectivity, or little connectivity, in the brain’s frontoparietal network. The frontal and parietal lobes of the brain play a role in attention and the regulation of emotions.

According to another 2015 study, hyperconnectivity, or lots of connectivity, has been observed in the default mode network of adolescents with depression. The default mode network is also known as the medial frontoparietal network. A small 2020 study suggests that hyperconnectivity may increase the emotional reactivity of people with depression, among other effects.

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

  • dysphoria, or a negative mood
  • anhedonia
  • rumination

In October 2021, researchers at the University of California, San Francisco demonstrated the potential of resetting brain circuits in treatment-resistant depression by implanting a neurostimulation device into a person’s brain.

5. Oxygen restriction

Depression has been linked to reduced oxygen in the body. Reduced oxygen levels may be due to changes in breathing caused by depression — but which comes first and causes the other 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 2013 study, HIF-1 is elevated in specific immune cells found in people with MDD and bipolar disorder. More human studies are needed to support this claim, since the majority of studies finding increased HIF-1 expression are animal studies.

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.

Overall, the brain is highly sensitive to reductions in oxygen, which can lead to inflammation, brain cell injury, and brain cell death.

As we’ve learned, inflammation and cell death can lead to many 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.

However, hyperbaric oxygen chamber treatments, which increase oxygen circulation, have been shown in a small 2017 study 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 showed that interventions, 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.

Ketamine and benzodiazepine-like molecules are also promising, according to research in rats and mice, respectively. A 2017 review of human studies of ketamine was promising as well.

Research into how ketamine works has focused primarily on the activity of glutamate, a neurotransmitter, in the prefrontal cortex. According to a small 2018 study, other mechanisms related to the opioid receptor may be involved, and ketamine may activate the body’s opioid system.

More research is needed on the potential opioid-like properties of ketamine. Learn about the relationship between opioid use and mental health conditions.

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’ve 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.

Depression is a multifaceted mental health condition. A combination of approaches will most likely be necessary in order to see symptoms improve.

A combination of the strategies below can be helpful for those dealing with depression.

Going to therapy

Therapy can be an effective way to treat depression.

It works in three important ways, by helping you:

  • identify aspects of your life that have brought you chronic and intense stress
  • understand ways to process your emotions and think more reflectively and flexibly through these stressful life events, which increases insight and reduces stress during and after these life events
  • strategize better ways to navigate your life without as many stressors, or to manage the stressors with more confidence, foresight, and ease

Cognitive and group therapy, especially approaches that incorporate stress-relieving mindfulness techniques, can be a great source of support and help you overcome stigmas surrounding mental health.

Therapy techniques that are effective in depression include:

If you’re depressed, know that you’re not alone and it’s not your fault. 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 psychological symptoms of depression, too.

A combination of psychotherapy and antidepressants can be incredibly effective in both fighting the physical changes and helping you cope with your symptoms.

There are many types of antidepressant medications, including:

Remember that it can take time to find the right medication and dosage. It’s like finding the right type of therapy or therapist. There’s no one-size-fits-all antidepressant.

As such, when beginning an antidepressant, it’s vital to:

  • Be patient.
  • Track your side effects.
  • Take note of any improvement or worsening of depressive symptoms.

Talk with your doctor or psychiatrist about any concerns you may have.

Exercising regularly

Getting regular exercise can do wonders for depression. It can help with both psychological symptoms and brain changes, according to various studies in humans and animals.

A medium to large reduction in symptoms has been observed in people who exercised three times per week for 12 to 24 weeks, according to a 2019 literature review. If you have depression, regular exercise also increases your chances of the condition going into remission.

Exercise promotes brain health by:

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.

Reducing your stress

There’s considerable evidence linking psychological stress to the initiation of depressive episodes in many forms of depression, according to a 2015 review.

Trying to decrease the amount of stress in your life can seem impossible or daunting. However, there are actually some simple and quick changes you can make to help reduce your stress, such as laughing or playing with a pet. Check out 16 great examples.