Risk Factors

Depression is a very complex illness and no there is no single cause of depression.

Biological, psychological, and social factors all play a part, as do lifestyle choices, relationships, and coping skills. According to a Special Report on Depression published by Harvard Medical School, researchers have identified a number of different factors that may put a person at risk for depression, including faulty mood regulation by the brain, genetic predisposition, stress, medical problems, and medications.[1] It’s believed that several of these forces interact, often – but not always – in the context of some triggering event, to bring on depression.

Below is a list, adapted from the Harvard Special Report on Depression, of various factors that researchers believe play a role in depression.

Faulty mood regulation

Researchers believe that disruptions in the complex brain systems involved in mood regulation have a major impact on depression.[2] While evidence points to imbalances in particular chemical messengers in the brain playing a role in depression,[3] this is typically complicated by other factors and is rarely considered a cause on its own.

Genetic predisposition

Depression is known to be influenced by a person’s genetic make-up.[4]  If something in the genes goes awry, they can alter your biology in a way that results in your mood becoming unstable.

In a genetically predisposed person, different stressors (such as relationship conflict or the loss of a job) can then push this system off balance and lead to depression.  While a history of depression in your family does not mean that development of depression is a certainty, it is associated with an increased risk. If a close relative has experienced depression, you should be aware of what depression is, how it can be treated, and how to gauge your own health.


Your genetic makeup influences how sensitive you are to stress. When genetics, biology, and stressful life situations come together, depression can result. But stress has its own consequences. It triggers a chain of chemical reactions and responses in the body.

If the stress is short-lived, the body will usually return to normal. But when stress is long-lasting or the system gets stuck in overdrive, changes in the body and brain can occur that lead to depression. Certain stressors can have lasting emotional and physical consequences. Studies have found that early losses and emotional trauma could leave a person more susceptible to depression later in life.

Medical problems

Certain medical problems have been linked to depression.[5] These include:

  • Hypothyroidism
  • Degenerative neurological conditions, such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease
  • Stroke
  • Certain nutritional deficiencies, such as a lack of vitamin B12
  • Other endocrine disorders, such as problems with the parathyroid or adrenal glands that cause them to produce too little or too much of particular hormones
  • Particular immune system diseases, such as lupus
  • Specific viruses and other infections, such as mononucleosis, hepatitis, and HIV
  • Cancer
  • Erectile dysfunction
  • Low testosterone


Sometimes, symptoms of depression may be a side effect of certain drugs, such as steroids or blood pressure medication.  Some medications in the following drug categories have been reported to have depression-like side effects:

  • Antimicrobials, antibiotics, antifungals, and antivirals
  • Heart and blood pressure drugs
  • Hormones
  • Tranquilizers, insomnia aids, and sedatives

It’s important to keep in mind that:

  • Most people who take these types of medications will not experience depressive symptoms, although having a family or personal history of depression may make you more susceptible to experiencing such symptoms.
  • Some of the drugs cause symptoms like malaise (a general feeling of being ill or uncomfortable) or appetite loss that may be mistaken for depression.


  1. Miller, M. (2020). Understanding Depression: The many faces of depression – and how to find relief. Harvard Health Publishing. https://www.health.harvard.edu/mind-and-mood/understanding-depression
  2. Anand, A., Li, Y., Wang, Y., Wu, J., Gao, S., Bukhari, L., Mathews, V., Kalnin, A., & Lowe, M. (2005). Activity and connectivity of brain mood regulating circuit in depression: A functional magnetic resonance study. Biological Psychiatry, 57(10), 1079-1088. https://doi.org/10.1016/j.biopsych.2005.02.021
  3. Werner, F., & Coveñas, R. (2013). Classical neurotransmitters and neuropeptides involved in major depression in a multi-neurotransmitter system: A focus on antidepressant drugs. Current Medicinal Chemistry, 20(38), 4853-4858. 10.2174/09298673113206660280
  4. Levinson, D. (n.d.). Major depression and genetics. Stanford Medicine. https://med.stanford.edu/depressiongenetics/mddandgenes.html
  5. The National Institute of Mental Health. (2021). Chronic illness and mental health: Recognizing and treating depression. National Institute of Mental Health. https://www.nimh.nih.gov/health/publications/chronic-illness-mental-health/

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