Physical Effects of Depression on the Brain

Medically Reviewed by Smitha Bhandari, MD on August 25, 2022
3 min read

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.

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.

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

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.

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:

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.

Show Sources


Molecular Psychiatry: “Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.”

Translational Psychiatry: “Profound and reproducible patterns of reduced regional gray matter characterize major depressive disorder.”

Neural Plasticity: “The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex.”

Proceedings of the National Academy of Sciences of the United States of America (PNAS): “Depression, antidepressants, and the shrinking hippocampus.”

Frontiers in Immunology: “The Role of Inflammation in Depression and Fatigue.” 

The Lancet Psychiatry: “Microglia and major depression: not yet a clear picture,” “Association of translocator protein total distribution volume with duration of untreated major depressive disorder: a cross-sectional study.” 

Journal of Psychiatry & Neuroscience: “Adult neuroplasticity: A new ‘cure’ for major depression?” “Lifetime major depression and grey-matter volume.”

Translational Neurosciences: “Longitudinal brain volume changes in major depressive disorder.”

Nature Medicine: “Synaptic plasticity and depression: New Insights from stress and rapid-acting antidepressants.”

Current Neuropharmacology: “Brain Structural Effects of Antidepressant Treatment in Major Depression.”

PeerJ: “Brain structural and functional changes in patients with major depressive disorder: a literature review.”

JAMA Psychiatry: “Increased Translocator Protein Distribution Volume, A Marker of Neuroinflammation, in the Brain During Major Depressive Episodes.”

Frontiers in Molecular Neuroscience: “Cannabinoid 1 Receptor Signaling on Hippocampal GABAergic Neurons Influences Microglial Activity.”

British Medical Bulletin: “The neurobiology of depression.”

Frontiers in Psychology: “Psychotherapy and brain plasticity,” “Mindfulness and Symptoms of Depression and Anxiety in the General Population: The Mediating Roles of Worry, Rumination, Reappraisal and Suppression,” “Thought Control Ability Is Different from rumination in Explaining the Association between Neuroticism and Depression: A Three-Study Replication.”  

National Institute of Mental Health: “Depression.”

Frontiers in Psychiatry: “Physical Exercise in Major Depression: Reducing Mortality Gap While Improving Clinical Outcomes.”

BMC Medicine: “A randomized controlled trial of dietary improvement for adults with major depression (the ‘SMILES’ trial).”

National Suicide Prevention Lifeline: “National Suicide Prevention Lifeline.”

View privacy policy, copyright and trust info