The causes of depression are complex and not clearly defined, but chemical imbalances might be only one factor that plays a role.

Depression is a common mental health condition but also a complex one. While symptoms may be similar, the underlying cause of depression — and therefore what treatments may be effective — can vary from person to person.

Some theorize that chemical imbalances in the brain may explain the onset of depression.

Because many chemical reactions influence your mood, it’s not as simple as pegging symptoms of depression on one chemical being too low or another being too high.

There are also many factors, such as genetics and environment, that can contribute to depression. Brain chemistry is only one factor that scientists have examined to better understand depression and its onset.

The exact cause of depression is not known. But increased access to brain imaging technology has allowed a closer look at the brain, giving scientists a better understanding of mood disorders such as depression than ever before.

A 2019 review shows that images of the brains of people with depression may look different than those of people without depression. Whether this results from depression or if depression causes these differences is unclear.

There’s been a decades-long debate on the role of chemical imbalances in the development of mental health conditions like depression. While some research points to low levels of certain chemicals as the possible cause, this has been challenged many times in research.

Chemical imbalances occur in the brain when there aren’t enough or excessive amounts of neurotransmitters — the brain’s messengers.

The theory that chemical imbalances cause depression is outdated and has been seen more as a brain circuitry issue.

Structural differences in the brain

Some research suggests that changes in certain parts of the brain may contribute to depression symptoms. Parts of the brain that may be affected help regulate mood and emotions. These can include the following:

  • frontal lobe
  • parietal lobe
  • hippocampus
  • thalamus

This study also reported that lower gray matter volume was found in people with major depressive disorder than those without it. Other parts of the brain, including the basal ganglia and the caudate nucleus, also have lower volumes.

Neurotransmitters are chemical messengers in the brain that allow neurons to communicate throughout the body. They’re essential for keeping the brain functioning and automatic responses like breathing.

Neurotransmitters are vital for various functions, including regulating mood and emotions.

You have many different neurotransmitters in your body, but the ones most associated with depression are dopamine, serotonin, and norepinephrine.


Dopamine is mostly associated with pleasure, though it’s also essential for functions such as memory, learning, motor skills, and more.

Anhedonia, the inability to feel pleasure, is a symptom of major depressive disorder. Some research suggests that the dopamine system plays a role in this symptom.

Often dubbed the “happy hormone,” low levels of dopamine may contribute to feelings of depression and sadness.


Serotonin helps to stabilize your mood. It’s thought to help regulate happiness, though it can also affect anxiety and sleep.

The theory that low serotonin levels correlate to depressive symptoms is decades old. While this 2015 study suggests that there’s not enough evidence to support this theory, it does acknowledge that serotonin does play a role in how emotions are processed.

Low serotonin levels have also been associated with the following:


The hormone and neurotransmitter norepinephrine increases your heart rate. It plays a vital role in your body’s fight, flight, or freeze response, adrenaline, and stress levels.

Not enough or too much norepinephrine is associated with depression and mania. It’s unlikely, however, that low levels of norepinephrine alone can contribute to depression.

What causes low levels?

Neurotransmitters work by traveling between neurons, aka nerve cells, and attaching to receptor sites. Once they reach the receptor site, their message has been relayed. This triggers an action in the target cells.

It’s unclear whether low levels of neurotransmitters cause depression, but they can decrease the amount of nerve cell communication in the brain. This disconnects the brain and signals to know when to experience certain emotions and responses.

There are several possible explanations for low levels of neurotransmitters:

  • lack of receptor sites to receive messages
  • not enough are being produced
  • shortage of molecules that help produce the neurotransmitter
  • termination of the signal before the neurotransmitter reaches the receptor site

There are many treatments for depression, but they aren’t one-size-fits-all. What may work for one person may not work for you.

Treatment options can include various types of psychotherapy, such as cognitive behavioral therapy (CBT) and interpersonal therapy (IPT).

Antidepressant medications are also often used to help treat depression. These medications work by regulating the levels of neurotransmitters in your brain. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed, which help by regulating serotonin levels.

Self-care strategies — such as exercise and a nutrient-dense diet — can also help.

A combination of therapy, medication, and home remedies may work best for you. Talking with a healthcare or mental health professional about your symptoms is a good first step.

Depression is a complex condition. Researchers are still not sure of the exact cause but suggest that brain chemistry is one piece of the puzzle.

However, the imbalance of one or several neurotransmitters is not likely the sole culprit for your symptoms. While brain chemistry may play a part, depression can be caused by many factors.

If you or someone you know is living with depression, there are resources that may help. You can check out Psych Central’s resource guide for helpful tips.

If you want more information or are concerned that you may have depression, consider taking our depression quiz. It will help you determine if you might benefit from a mental health professional evaluation. But if you’re concerned or want more information, consider speaking with a healthcare or mental health professional.