Depression is a hot-button topic in the field of mental health. It’s often discussed and readily highlighted in popular media, but still frequently misunderstood. What are the causes of depression, and how do people get depression in the first place? The answers are as complex as the human brain, but professional research into what causes depression offers actionable clues.
According to the National Alliance on Mental Illness, nearly a quarter of American adults experienced mental illness in 2024: 23.4 percent, or 61.5 million people. According to a Gallup poll from the same year, much of that manifests as depression, which reportedly affects more than 18% of American adults. With so many people affected by this illness, determining what causes major depressive disorder has never been more important for treatment.
The problem with pinpointing those roots is that depression manifests differently for each person, often influenced by their experiences and environment as much as their biology. Many factors can cause it, such as genetic propensity, a medical illness, the death of a loved one or other traumatizing or emotional events. The Mayo Clinic notes that depression most frequently occurs in the teens, 20s and 30s, but also cautions that depression can still appear at any age.
A person suffering from depression usually experiences persistent sadness or loss of interest. The disease can affect how a person thinks, feels and behaves, leading to a variety of physical and emotional symptoms, including:
- Lack of appetite
- Difficulty falling or staying asleep
- Inability to concentrate
- Low energy / fatigue
- Self-esteem issues
Because these symptoms can all carry harmful stigmas, it’s important to remember that depression isn’t a weakness, but rather a serious disease that may require long-term treatment. Most people feel better with therapy or medication, but even successful treatment may still leave those affected wondering “where does depression come from?” Because it’s impossible to account for every variable in social, cultural or personal experiences, turning to biology is the most reliable path to useful answers.
Brain Function as a Depression Factor
As the ‘biological computer’ that runs our entire body, the brain is a delicate instrument that carries as much capability to hurt as it does to heal. The components of the brain each react differently to depression, both functionally and physically. A 2022 Harvard Health Publishing article discusses some of the most well-known brain structures, and how depression affects the brain.
The amygdala is small, no larger than a shelled peanut in most cases, but it does a lot of heavy lifting where memory is concerned. This small bit of gray matter is responsible for emotions ranging from sexual arousal to fear and anger, which means it activates when our most emotionally-charged memories are recalled. It works harder when we’re struggling with sadness or depression, and may enlarge to cope with the added demand of doing so.
The hippocampus joins the amygdala near the base of the brain, and is roughly 2 to 3 times larger, though it may increase in size with exercise or decrease due to illness or advanced age. When processing unpleasant memories, such as an aggressive dog in childhood, it works with the amygdala to introduce caution around dogs later in life. When observed in some people with depression, this brain structure is found to be smaller than normal, pointing to a potential link.
Finally, the basal ganglia, roughly the size of a gum ball and located in the front center of the brain, aids in emotional processing as well. And, much like observations on the hippocampus, sometimes appears to be smaller than average when studied in people with depression. While these instances of shrinkage aren’t always a cause-and-effect relationship, they may be used as important diagnostic criteria in the future to help targeted depression treatment.
Genetics as a Depression Factor
In 2025, King’s College of London published a groundbreaking article on the effect of genetics on depression. The cited study pointed out that most previous studies on the link between depression and genetic code—DNA—used almost exclusively study participants of white European ancestry. By consciously including a more diverse set of study participants, they were able to identify 308 specific genes related to depression. This identification and isolation is a crucial step in not only future diagnoses of depression, but ultimately effective treatments as well.
While research isn’t fully clear, two people with different genetic codes can experience the same traumatic event, with one person developing depression while the other doesn’t. Different genes may also lead to different types of depression, such as psychotic depression, dysthymia or bipolar disorder.
No one explicitly inherits depression, but you can inherit a genetic combination from either or both parents, predisposing you to the mental illness.
Substance Use as a Depression Factor
Mood disorders such as depression or bipolar disorder can sometimes appear hand-in-hand with substance use. While sometimes these substances are what causes depression in the first place, in other cases they may be used to self-medicate after depression has already occurred. Struggling with both a substance use and a mood disorder at the same time is a medical condition known as comorbidity, and these issues are typically treated simultaneously.
For example, if someone is dealing with a lot of stress or emotional pain they don’t know how to treat, they may turn to alcohol or drugs to self-medicate. Drugs and alcohol provide temporary relief and a sense of euphoria, usually followed by a crash once they wear off that can include feelings of anxiety, irritability or low energy, making the initial depression worse. As they increase the dosage to avoid these crashes, it leads to dependency on the substance to feel good. The psychological aspect of addiction can be just as hard to overcome as the physical withdrawals. Thankfully, treating the depression can sometimes reduce substance cravings, helping someone recover from both disorders.
Childhood Experiences as a Depression Factor
Traumatic early childhood experiences can put individuals at an increased risk for depression. Undergoing a lot of stress in early childhood can also lead to high amounts of stress and mental health disorders later in life. Examples of these traumatic experiences include:
- Direct physical, emotional or sexual abuse
- Emotional or medical neglect
- Conflict within the family dynamic
- Overly critical commentary and expectations
- Death of a loved one
- Being raised by a mentally ill parent
Talking to a therapist about potentially traumatic childhood experiences and family dynamics may help to better understand how they affect you. Understanding and working through learned negative thought patterns and coping behaviors may also help lessen the severity of depression symptoms over time.
Major Life Events as a Depression Factor
Immediate and prolonged major life events can cause stress that may trigger depression, especially in individuals already at risk for the disease. Immediate major life events that can cause immense levels of stress and affect mental health include:
- Losing a job
- Losing a friend or family member to death
- Divorce from a spouse or a breakup
- Suffering a serious physical injury
- Childbirth-related trauma manifesting as postpartum depression
- Living through a natural disaster
High stress from prolonged major life events can potentially cause more severe symptoms of depression and may include:
- Stress related to a job or loss of one
- An abusive or unhealthy personal relationship
- Homelessness or home insecurity
- Chronic pain or illness
Experiencing multiple stressful life events simultaneously can increase your risk of depression. Since depression can often go undiagnosed and untreated, tracking your mental health during times of immense stress can help identify warning signs of the disease. Daily journaling, confiding in a loved one or seeing a licensed therapist for regular appointments are all excellent steps to take when mitigating depression symptoms.
Depression Can Come in Many Forms
If none of the main causes fit your specific case, then what is the cause of depression affecting you? Many other causes to consider may answer this question:
- Gender: According to a 2025 paper published by the Center for Disease Control, women are 10% more likely to be diagnosed with depression, though the cause for the gender gap is still being researched.
- Medications: In a 2023 article published by the American Associate for Retired Persons, a study notes that nearly a third of Americans are currently taking some form of medication with depression side effect risks.
- Age: Older adults are at a higher risk of depression. Lacking social support or living alone can increase that risk even further.
- Other social problems: Social isolation because of mental illness or being shunned by family or friends can potentially cause depression.
No matter the reason, depression should always be treated seriously. Medication and therapy can be used to reduce associated symptoms and help individuals take back their lives.
Seek Mental Health Treatment for Depression
If you or a loved one is struggling with depression, Restore Mental Health is here to ensure you aren’t alone. Treatment is available to help with your specific mental health needs. Contact us today to speak with a trained mental health professional and take the first step toward reclaiming your life from mental illness.
