Is depression caused by a chemical imbalance in the brain?

last updated: Apr 13, 2022

4 min read

It’s not uncommon for people to experience depression at some point in life. If you or a loved one live with depression, you might wonder what caused it. One popular theory involves a chemical imbalance of neurotransmitters in the brain.


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How do neurotransmitters affect the brain?

Neurotransmitters are chemicals released by nerve cells that transfer messages between neurons. Often called the body’s chemical messengers, neurotransmitters allow neurons to communicate with each other.

Scientists theorize that neurotransmitters are linked with depression and other mental health conditions. Unfortunately, there aren’t any accurate tests yet that measure neurotransmitter levels in a living brain, so it’s hard for researchers to make a clear connection between these chemicals and mood changes (Liu, 2018). 

Here are three main neurotransmitters that may affect your mood, actions, and emotions:

  • Serotonin: Studies show that low serotonin levels might enhance negative emotions like depression, fear, anxiety, and irritability. 

  • Norepinephrine: Norepinephrine is typically released as a stress hormone. It may play a role in mood since lower levels have been linked to reduced energy, confidence, and positive feelings in people with depression.

  • Dopamine: This brain chemical is involved in motivation and experiencing pleasure. Dopamine also affects how well you regulate emotions.

Keep in mind that these neurotransmitters don’t operate separately. They interact in multiple ways, so it’s possible that a chemical imbalance in one can influence the balance of another. 

Do chemical imbalances cause depression?

While researchers have theories about connections between chemical imbalances and depression, science still can’t pinpoint an exact cause of depression. But since depressive symptoms often respond to medications that raise serotonin and norepinephrine, we can say chemical imbalances are at least partly responsible (Park, 2019).

Other factors that may affect your risk of developing depression include (aan het Rot, 2009; Shadrina, 2018):

  • Genetics or family history of depression 

  • Chronic stress (grief, relationship difficulties, illness)

  • Adversity or trauma in childhood

  • Disturbances in sleep cycle

Your risk for depression is the combined impact of any or all of these things. Researchers have found that your genetic makeup and environment are better predictors of depression than one thing alone (aan het Rot, 2009).

Can a chemical imbalance cause other conditions?

Dopamine, serotonin, and norepinephrine all play a significant role in regulating areas of your brain that control how you feel, think and act (Grace, 2016). 

Researchers are trying to find out if imbalances in brain chemistry are connected to other mental conditions like the ones below. 


Research suggests that chemical imbalances of serotonin and norepinephrine associated with depression are also connected to anxiety disorders. These two conditions also tend to respond to the same types of medication, such as SSRIs (Liu, 2018).


There is evidence that an overactive dopamine system in the brain is involved with schizophrenia. Additionally, scientists have found drugs that increase dopamine levels (such as amphetamines) can make psychosis worse in those with schizophrenia (Grace, 2016).

Chronic pain

Chronic pain, defined as sustained or intermittent pain that lasts for more than 12 weeks, is closely associated with feelings of depression. People with clinical depression often report having chronic pain and are treated with similar medications to increase the concentration of serotonin in the brain (Haleem, 2019).

Symptoms of depression

The criteria for major depression, according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), is experiencing at least five of these symptoms in a two week period (Park, 2019):

  • Depressed mood most of the day or nearly every day (feeling sad, empty, or hopeless) 

  • Diminished interest or enjoyment in daily activities 

  • Changes in appetite or noticeable weight loss or weight gain

  • Insomnia or hypersomnia nearly every day

  • Feeling restless or sluggish

  • Fatigue or lack of energy nearly every day

  • Persistent feelings of worthlessness or excessive guilt 

  • Diminished ability to think, concentrate, or make decisions

  • Recurrent thoughts of death, recurrent suicidal ideation without a specific plan, or a suicide attempt 

To be diagnosed with clinical depression, these symptoms have to be severe enough to interfere with daily functioning at home, work, or school (Park, 2019).

If symptoms like the ones above affect your happiness and quality of life, talk to a healthcare provider or mental health professional. There are treatment options that can alleviate symptoms and improve how you feel. 

Treatment for depression

The two main treatments for depression are psychotherapy and medications. You’re likely to get the most benefit from combining the two. Keep in mind that it may take some trial and error to discover what works best for your situation.


Antidepressant medications have been a standard treatment for depression for decades. First-line drugs include selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). These work by increasing the amount of serotonin and norepinephrine in the brain (Park, 2019).

You may start to see symptoms improve as early as two weeks, though the full effects don’t usually kick in for at least 8–12 weeks (Park, 2019).


Either alone or in combination with medication, therapy is another common recommendation for treating mental health conditions. Talk therapy has been well studied and is effective for people with depression. 

There are multiple therapies you can try, including cognitive behavioral therapy (CBT). This type teaches you to identify thoughts and beliefs that aren’t helping you.

No one therapy is significantly better than another for treating depression––it all depends on what works for you. A skilled therapist can help you choose the type that best meets your needs and can combine treatments (Park, 2019).


If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

  • aan het Rot, M., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. Canadian Medical Association Journal, 180 (3), 305–313. doi:10.1503/cmaj.080697. Retrieved from

  • Grace, A. A. (2016). Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nature Reviews. Neuroscience , 17 (8), 524–532. doi:10.1038/nrn.2016.57. Retrieved from

  • Haleem, D. J. (2019). Targeting serotonin1A receptors for treating chronic pain and depression. Current Neuropharmacology , 17 (12), 1098–1108. doi:10.2174/1570159X17666190811161807. Retrieved from

  • Liu, Y., Zhao, J., & Guo, W. (2018). Emotional roles of mono-aminergic neurotransmitters in major depressive disorder and anxiety disorders. Frontiers in Psychology, 9,

  1. doi:10.3389/fpsyg.2018.02201. Retrieved from

  • Park, L. T., & Zarate Jr., C. A. (2019). Depression in the primary care setting. The New England Journal of Medicine, I(6), 559–568. doi:10.1056/NEJMcp1712493. Retrieved from

  • Shadrina, M., Bondarenko, E. A., & Slominsky, P. A. (2018). Genetics factors in major depression disease. Frontiers in Psychiatry, 9,

  1. doi: 10.3389/fpsyt.2018.00334. Retrieved from

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Current version

April 13, 2022

Written by

Ellyn Vohnoutka, BSN, RN

Fact checked by

Felix Gussone, MD

About the medical reviewer

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.