Depression
What Causes Depression?
Depression does not have one single cause.
Written by Sanjida Ahmed, PhD, Cellular and Molecular BiologyChief Operating Officer and Lead Scientist, Personalized Prescribing. Last reviewed October 2, 2026.
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Depression does not have one single cause. It appears to develop from a combination of life experiences, stress, genetics and changes in the way different brain systems work together. Researchers have studied several possible contributors, including neurotransmitters, the body’s stress-response system and inflammation.
How Brain Chemicals May Be Involved
The brain uses chemical messengers called neurotransmitters to help nerve cells communicate. Several are important in mood and mental health:
- Serotonin helps regulate mood, anxiety, sleep and appetite.
- Dopamine is important for motivation, reward and pleasure.
- Norepinephrine helps with energy, alertness, attention and the response to stress.
- Glutamate and GABA help maintain the balance between brain activity and calmness. Depression is not simply a matter of having “too little serotonin.” Different people may have different patterns of these systems, which may help explain why depression can feel very different from one person to another.
Stress Can Affect the Brain
Long-term stress may place the body’s stress-response system under constant pressure. Over time, this can affect hormones, inflammation and neurotransmitter activity, including serotonin, dopamine and norepinephrine. Genetics may influence how strongly an individual responds to these changes.
This may help explain why one person develops mainly: sadness and anxiety, while another experiences loss of motivation and pleasure, and another struggles with fatigue, poor concentration or feeling constantly on edge.
Why Genetics Matter
Our genes help control many of the systems involved in mood, stress and brain communication. Small genetic differences may influence how easily these systems become disrupted and how well they recover.
This does not mean that genes determine whether someone will become depressed. Rather, genetics may influence a person’s underlying vulnerability and the way their brain responds to stress and treatment.
Depression Is More Than a “Chemical Imbalance”
A better way to think about depression is as a dysregulation of several connected brain systems.
These can include:
- Stress + genetics
- Changes in brain signaling
- Serotonin, dopamine, norepinephrine, glutamate and GABA systems may become dysregulated
- Mood, motivation, energy, concentration and anxiety may change
- Symptoms of depression may develop
Research also suggests that depression can involve changes in how well brain cells communicate and adapt over time. This process is often described as neuroplasticity.
Why This Matters for Treatment
Not everyone with depression has the same symptoms or the same underlying biological pattern.
That is one reason why:
A medication that works well for one person may not work as well for another.
Understanding a person’s symptoms, genetics and medication response may help healthcare professionals make treatment more personalized rather than relying only on trial and error.
In Brief, depression is not caused by one single chemical or one single problem. Stress, genetics and changes in brain systems involved in serotonin, dopamine, norepinephrine, glutamate and GABA may all play a role. Because these systems can be affected differently from one person to another, people with the same diagnosis can have very different symptoms and may respond differently to treatment. Understanding these differences can help support more personalized care.
This article is educational. It does not diagnose, and it does not replace advice from your prescriber or pharmacist. Never start, stop or change a medication based on a web page.