Written by: THE BALANCE
Medically reviewed by Dr. Sarah Boss, MD
Last updated: January 19, 2026
Fact checked
Quick Summary
  • But the question that often arises is, What exactly is going on inside a depressed brain?
  • Recent researches and evidence show that brain connections play an important role in depression.
  • If you are interested in knowing about the "depression brain" then keep reading this article and you'll get answers to all your questions about how depression affects the brain.
Reading time: 8 min

Depression is one of the most common mental health disorders. Over 350 million people are affected by depression worldwide. Without any doubt, we can say it is an incredibly serious illness. But the question that often arises is, What exactly is going on inside a depressed brain? 0r, is there any biological basis for this sadness?

The answer is, Yes!.. Recent researches and evidence show that brain connections play an important role in depression. If you are interested in knowing about the “depression brain” then keep reading this article and you’ll get answers to all your questions about how depression affects the brain. (source: WHO, 2023)

Depression is assumed to be caused by the “monoamine deficiency hypothesis”-which means that one of three neurotransmitters in the brain is deficient or underactive. Neurotransmitters can be thought of as chemical messengers within the brain. It’s what helps one cell in the brain communicate with another to pass that message along. The reality is there are more than a hundred neurotransmitters in the brain and billions of connections between neurons. 

For decades, it was thought that the primary cause of depression was some abnormality in these neurotransmitters, specifically serotonin and norepinephrine. However, norepinephrine and serotonin did not seem to be accountable for the symptoms of depression in people who have major depression, Instead, the chemical messengers between the nerve cells in the higher centers of the brain involved in regulating mood and emotion which include glutamate and GABA were possibilities as alternative causes for the symptoms of depression (source: NIMH, 2024)

When people with depression are exposed to stress they lose the connection between the nerve cells and the communication between them becomes inefficient and noisy. Because the noisy communication in the circuits involved in regulating mood and emotions contributes to the biology of depression. (source: APA, n.d.)

According to scientists, there are subtle but many important distinctions between a normal brain and a depressed brain. These differences can include a more active amygdala in the depressed brain, gray matter abnormalities, and brain shrinkage. Below is a brief overview of these differences;

  1. Amygdala, a brain structure, is associated with regulating emotions. Depression patients may have a more active amygdala than the normal brain. Also, in depressed people, the amygdala becomes more active if exposed to a stimulus like sad situations, as compared to the normal brain. 
  1. Gray matter is brain tissue made up of cell bodies and nerve cells located in different brain parts. Most importantly, in the cerebrum and cerebellum. It play role in controlling sensory and muscular, activity precision, and coordination. 

Depressed people, according to studies were shown to have thicker gray matter in parts of the brain involved in self-perception and emotions. That may result in depression.  (source: NHS, 2023)

  1. A depressed brain may be realizing an increased amount of cortisol. A stress hormone in the brain. As a result of this long-term exposure parts of the brain start shrinking including the hippocampus and the prefrontal cortex. In fact, a study reveals 9-13% of the women with depression had smaller hippocampi as compared to those who don’t have a depression history.

Depression is primarily known for the sadness it causes and all the non-physical symptoms including guilt, irritability, feelings of hopelessness, and trouble focusing or concentrating on tasks. Nevertheless, depression is a mental illness but it also causes physical symptoms. The physical symptoms caused by depression can also affect brain functioning. These physical symptoms include;

  • Pain: Those with depression often report vague aches and pains in their limbs, joints, or in back. Even some people report chronic and debilitating pain in their full body. Researchers are still finding a link between physical pain and depression.
  • Weight changes: Sometimes depression may cause you to eat less or more than you usually eat. As a result, depressed people may report weight gain or loss. Overeating during depression can be linked to “emotional eating” to self-medicate feelings of depression. Whereas loss of appetite can result due to low energy, and motivation which can cause low weight and eventually not a good physical symptom.
  • Gastrointestinal problems: Depression patients may have frequent stomach problems, such as nausea, bloating, diarrhea, or constipation. The most accurate explanation for these symptoms could be low levels of serotonin that are frequently reported in depression patients. Although serotonin helps regulate mood, researchers think that it also plays a role in maintaining digestive function.
  • Blood pressure: Depression also leads to chronic stress.  Long-term or chronic stress has been known to contribute to high blood pressure (hypertension). 
  • Affected immunity: Increase stress can cause a person’s immune system to work less optimally. That means they’re more likely to get sick.  Moreover, when someone with a weak immune system does get sick, it may take longer for them to get better.
  • Psychomotor symptoms: psychomotor symptoms refer to symptoms that make a person feel as though they are thinking and moving at a different pace than usual. Depressive people may perceive their thoughts as sluggish and their movements seem heavy. 
  • Fatigue: People with depression feel tired and lazy more often. They have low energy and a hard time getting out of bed. This causes less physical activity.

Now it’s time to have your hands on the information you’ve been looking for. As per the previously mentioned information you might have got an idea about the physical effects of depression. So, depression has a physical impact and symptoms, but can depression cause brain depression? The answer you’ll find below. The long-term effects of depression on the brain include the following. (source: MedlinePlus, 2024)

Brain Size

There is a growing debate on the notion that depression may shrink specific areas of the brain. Noticeably, the affected areas lose gray matter volume. Especially people who experience long-term or frequent depression may have a higher loss of gray matter volume. Some studies also have evidence supporting the idea that the size of specific brain regions can shrink in people who have depression. However, the amount of shrinkage depends on the severity of the symptoms of depression. The following parts of the brain can be affected by depression: (source: NICE, 2022)

  1. Hippocampus
  2. Thalamus
  3. Amygdala
  4. Frontal part
  5. Prefrontal cortices

Brain Inflammation

People with major depressive disorder may have a high level of translocator proteins and these proteins are linked to inflammation. Moreover, people with untreated depression(such as 10 years or longer) are shown to have a higher level of these proteins. One thing that expert aren’t sure about is whether inflammation cause depression or depression cause inflammation. The effects of inflammation in brain areas can cause;

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

Reduce Oxygen

Depression may cause reduce oxygen in your body. These changes in oxygen level may be caused by changes in breathing due to depression. In people with major depressive disorder, cellular factor produced in response to the brain not getting enough oxygen (hypoxia) is elevated in specific immune cells.  (source: NIDA, 2020)

Related: Mental Health luxury Inpatient Rehab (source: Psychiatry.org, n.d.)

Like brain inflammation, the relation between depression and a low oxygen level is vague. It’s still not confirmed either depression causes reduced oxygen or vice versa. However, reduce oxygen in the brain can lead to inflammation, brain cell death, and brain cell injury.

Other Changes In Brain Structures

Long-term depression can also lead to structural and connective changes in the brain. These changes include (source: NCBI Bookshelf, 2025)

  • Reduced/disturbed function of the hippocampus that causes memory impairment.
  • Reduced/disturbed function of the prefrontal cortex can prevent the patient from getting executive function done and affect their attention.
  • Reduced/disturbed function of the amygdala that can directly affect mood and emotional regulation.

Depression is a serious mental illness that can lead to physical effects. So, the only way to save yourself from the worst outcomes of long-term depression is through timely and proper treatment. In case you or your loved one have symptoms of depression consult a mental health professional as soon as possible.

FAQs 

What part of the brain controls depression?
According to a study, the amygdala, hippocampus, and dorsomedial thalamus are the brain structures linked with depression.
What happens in the brain when you have depression?
Long-term depression affects three core areas and their functioning.
1-Amygdala: depression: Problems in sleep and behavior
2-Hippocampus: poor moods and memories
3-Thalamus: mood and motivation
Can untreated anxiety and depression cause brain damage?
Yes! If left untreated both anxiety and depression can affect or damage brain functioning. To know how depression affects the brain read the above-mentioned information.   

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