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Causes and Risk Factors for MDD

Reviewed by: HU Medical Review Board | Last reviewed: September 2023

The exact cause of major depressive disorder (MDD) is not known. Experts think it is a combination of internal and external factors.1

Some possible internal factors are biological. Biological causes of a health condition are changes that happen within the body. An example of a biological cause is the genes we inherit from our parents (genetics). Brain function or structure changes are also biological factors.1

External factors are things we experience socially or in our environment. An example of an external causal factor is experiencing severe trauma or stress. Access to support from friends and family is an example, too.1

Some of the most common potential causes of MDD and factors that increase risk are described below.


Genes are passed down (inherited) from parents to children. Our genes control things like the color of our hair or how tall we are. Some genes also increase the risk of developing certain health conditions.2

Studies on MDD have found that depression may run in families. If a person has a first-degree relative with depression (like a parent or sibling), they are 3 times more likely to have depression, too. While experts do not know the exact genes involved, this finding points toward an underlying genetic factor as a cause of depression.1,2

Changes in brain chemistry and function

Our brain uses chemicals to send signals to the rest of our body. These chemicals are called neurotransmitters. Our body naturally makes them, and they play a role in many different bodily functions. Neurotransmitters affect mood, digestion, movement, and more.3

Changes in certain neurotransmitters may lead to symptoms of depression. Most medicines used to treat depression target these chemicals. Neurotransmitters thought to be involved in depression include serotonin, dopamine, norepinephrine, glutamate, and gamma-aminobutyric acid (GABA).1

Specific processes in the brain (pathways) rely on neurotransmitters. Some of these pathways control the way we think, concentrate, or experience pleasure. Experts are not sure whether changes in neurotransmitters impact these pathways or whether changes in the pathways impact neurotransmitters. Many believe it is a combination of both.1,4

Some areas of the brain may be different sizes or have different activity levels in people with depression, too. For example, people with depression may have a more active amygdala than those without. Or it could be the amygdala is activated by traumas. The amygdala plays a role in the perception of emotions like anger, fear, pleasure, and sadness. Much more research is needed to understand the brain changes involved in MDD.1,4

Other health issues and hormone changes

Other medical or mental health conditions can cause depression-like symptoms. These issues include thyroid function problems, Parkinson’s disease, or bipolar disorder. When diagnosing or treating your depression, your doctor will monitor you for these conditions as well.1

Hormone changes may also play a role in developing depression. For example, women are at risk of developing symptoms during or right after pregnancy. Symptoms may also occur at different stages of the menstrual cycle. Some women develop depression symptoms only during these times. This points toward a potential hormone-related cause.5,6

Stress and trauma

External environmental or social issues may also lead to depression developing. The exact way these factors affect symptoms is not known. They may impact the balance of neurotransmitters. They might also impact the way people process information.1,5,7

Social or environmental factors can also impact self-esteem and how people cope with challenges in the future. Experts are currently studying these relationships. But it is clear that many of these experiences are linked with depression.1,5,7

Exposure to childhood abuse or trauma and experiencing financial distress are examples of external causal factors. Lacking social support and using drugs or alcohol are also external factors that may increase a person’s chance of developing depression.1,5,8

Personality traits, self-esteem, and coping

Some aspects of a person’s personality may make them more likely to develop depression. Examples of these traits include being easily overwhelmed by stress or being more pessimistic than others. They cannot control some of these traits. Other traits may stem from environmental stressors like having lower income, employment problems, or strained relationships with loved ones.1,8

Factors that increase the risk for MDD

Having qualities that are linked to these potential causes of depression puts people at higher risk of developing MDD. Risk factors include:1,8

  • Having a sibling or parent with depression
  • Having a history of past depression symptoms or episodes
  • Being exposed to severe stress
  • Lacking a support system (friends, family, or professional support)
  • Being divorced, separated from a partner, or widowed
  • Experiencing abuse, trauma, poverty, or neglect (especially as a child)
  • Having other medical or mental health conditions
  • Being pregnant or having given birth recently
  • Going through or nearing menopause
  • Using recreational drugs or alcohol
  • Having low self-esteem or a low tolerance for stress
  • Being physically inactive

This is not a complete list of all potential risk factors for MDD. It is also possible for a person to not have clear risk factors and still develop MDD. If you are concerned about your risk, talk with your doctor. They can help screen and monitor you for symptoms. They also may be able to recommend support options like therapy to help with general mental well-being and coping.

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