Depression and the brain

What Does Depression Physically Do to My Brain?

Written by Keri Wiginton

In this Article

  • Brain Size
  • Brain Inflammation
  • Are the Changes Permanent?
  • How to Get Help

Depression is more than feeling down. It may physically change your brain.

This can affect how you think, feel, and act. Experts aren’t sure what causes these changes. They think genetics, stress, and inflammation might play a role.

It’s important to get help for your depression. That’s because repeat episodes seem to damage your brain more and more over time. Early treatment might help you avoid or ease some of the following changes.

Brain Size

There’s some debate about which areas are affected and how much. There’s growing evidence that several parts of the brain shrink in people with depression. Specifically, these areas lose gray matter volume (GMV). That’s tissue with a lot of brain cells. GMV loss seems to be higher in people who have regular or ongoing depression with serious symptoms.

Studies show depression can lower GMV in these areas:

Hippocampus. That part of your brain is important for learning and memory. It connects to other parts of your brain that control emotion and is responsive to stress hormones. That makes it vulnerable to depression.

Prefrontal cortex. This area plays a role in your higher-level thinking and planning.

There’s also evidence these parts of your brain get smaller:

  • Thalamus
  • Caudate nucleus
  • Insula

Results are mixed on how depression affects the amygdala. That’s your fear center. Some studies show it gets smaller. Others found that stress and depression might boost its GMV. The more severe the depression, the higher the GMV.

When these areas don’t work the right way, you might have:

  • Memory problems
  • Trouble thinking clearly
  • Guilt or hopelessness
  • No motivation
  • Sleep or appetite problems
  • Anxiety

You might also move or talk slowly, or overreact to negative emotions.

Brain Inflammation

Experts aren’t sure if depression or inflammation comes first. But people who have a major depressive episode have higher levels of translocator proteins. Those are chemicals linked to brain inflammation. Studies show these proteins are even higher in people who’ve had untreated major depressive disorder for 10 years or longer.

Uncontrolled brain inflammation can:

  • Hurt or kill brain cells
  • Prevent new brain cells from growing
  • Cause thinking problems
  • Speed up brain aging

Are the Changes Permanent?

Scientists are still trying to answer that question. Ongoing depression likely causes long-term changes to the brain, especially in the hippocampus. That might be why depression is so hard to treat in some people. But researchers also found less gray matter volume in people who were diagnosed with lifelong major depressive disorder but hadn’t had depression in years.

While more research is needed, there’s hope that current or new treatments might help reverse or ward off some brain changes.

Here’s what research says about two common depression treatments:

Antidepressants. These work on the chemicals in your brain that control stress and emotions. There’s evidence these drugs can help your brain form new connections and lower inflammation.

Cognitive behavior therapy (CBT). Experts think CBT promotes neuroplasticity. That means you can change your brain in a way that helps your depression.

How to Get Help

Tell your doctor if you have symptoms of depression. They’ll want to rule out other health conditions so they can find you the right treatment. You might need to make some lifestyle changes, take medicine, or talk to a mental health specialist. Some people benefit from a mix of all three.

Some treatments for mild or serious depression include:

  • Talk therapy
  • Antidepressants
  • Short-term use of ketamine
  • Brain stimulation
  • Exercise
  • Meditation
  • Healthy diet change

Suicide is a serious symptom of depression. Get help right away if you’re thinking about hurting yourself. You can reach someone at the National Suicide Prevention Lifeline at 1-800-273-8255. They’re available anytime, day or night.

How Depression Affects the Brain > News > Yale Medicine

When we think about depression, what comes to mind are feelings and emotions – or, for some, the absence of feelings and emotions. In order to really understand depression, however, it’s important to be aware that the condition has physical aspects as well. Most people understand what depression looks like on the outside, in terms of a person’s behavior, but our medical understanding of the actual progression of the disease and its treatments continues to evolve.  

What we know right now is that, on a chemical level, depression involves neurotransmitters, which can be thought of as the messengers that carry signals between brain cells, or neurons.  

“The current standard of care for the treatment of depression is based on what we call the ‘monoamine deficiency hypothesis,’ essentially presuming that one of three neurotransmitters in the brain is deficient or underactive,” says Rachel Katz, MD, a Yale Assistant Professor of Clinical Psychiatry.  

But according to Dr. Katz, this is only part of the story. There are about 100 types of neurotransmitters overall, and billions of connections between neurons in each person’s brain.  

There remains much to learn.

For years and years, doctors and researchers assumed that depression stemmed from an abnormality within these neurotransmitters, particularly serotonin or norepinephrine. But over time, these two neurotransmitters did not seem to account for the symptoms associated with major depression. As a result, doctors began to look elsewhere.  

The search proved fruitful.  “There are chemical messengers, which include glutamate and GABA, between the nerve cells in the higher centers of the brain involved in regulating mood and emotion,”  says John Krystal, MD, chair of Yale’s Department of Psychiatry, noting that these may be alternative causes for the symptoms of depression.  

These two are the brain’s most common neurotransmitters. They regulate how the brain changes and develops over a lifetime. When a person experiences chronic stress and anxiety, some of these connections between nerve cells break apart. As a result, communication between the affected cells becomes “noisy,” according to Dr. Krystal. And it’s this noise, along with the overall loss of connections, that many believe contribute to the biology of depression.  

This “neurobiology of depression” is important to understand. First, it helps doctors understand how the disease develops and evolves. Also important, though, is that those same doctors can then use their new understanding of depression’s mechanisms to build targeted treatment plans. And, since depression is often a long-term disease, people needs long-term treatments for it.  

“There are clear differences between a healthy brain and a depressed brain,” Dr. Katz says. “And the exciting thing is, when you treat that depression effectively, the brain goes back to looking like a healthy brain. ”  

We have entered a new era of psychiatry, Dr. Katz adds. As we shift away from a single hypothesis about what causes depression, we are also learning more about the brain as a whole, in all of its complexities.  

In this video, Drs. Katz and Krystal explain how depression affects the brain.

Read more Yale Medicine news

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