The Causes of Clinical Depression - Insight Into Genetic, Psychological, Environmental and Medical Factors

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The causes of clinical depression include genetic/biological factors, psychological issues, environmental triggers, medical conditions, and some medications. In most cases, no single cause is sufficient for depression to occur; rather a combination of factors make it more likely that a person will develop depression.

Causes of Clinical Depression: Genetic/Biological Factors

Clinical depression often runs in families, and researchers have identified several genes that may interact to influence the likelihood that depression will develop. It is unlikely that a single gene causes depression, but rather a combination of genes creates a greater risk for the disorder.

A 2003 study identified a serotonin transporter gene (5-HTT) that influenced the rate of depression in response to stress (Caspi et al., 2003). Each person receives two copies of this gene (one from each parent) in either a short or long variant. The study tracked 800 young adults over five years, and results showed that 33% of people with at least one “short” variant became depressed after stressful experiences such as job loss or divorce. In contrast, only 17% of people with two “long” variants became depressed when faced with the same circumstances. People with two “short” variants were the worst off, and their risk of becoming depressed increased steadily with more stressful life events.

In 2008, a protective gene (CRHR1) was identified that when present, reduced the risk of depression following childhood abuse (Bradley et al., 2008). Study researchers found that the CRHR1 gene is the blueprint for corticotrophin-releasing hormone (CRH) - a hormone involved in dealing with stress. Interviews were conducted with 621 adults, and among those who had experienced childhood abuse, people with protective variants of the CRHR1 gene experienced half the amount of depressive symptoms as those without the protective version.

In addition to identifying genes that create a risk for depression, brain chemistry and brain structures have been shown to play a role. Improper functioning of the neurotransmitters serotonin, norepinephrine, and dopamine have been linked to depression; many antidepressant medications act by restoring imbalances and aiding in the generation of new nerve connections in the brain. Differences in brain structures such as the amygdala and hippocampus have also been observed in those with clinical depression.

Psychological Factors

Psychological risk factors for depression are those aspects of your temperament that make you susceptible to the disorder. Some personality patterns that increase risk for depression include low self-esteem, a pessimistic attitude about the future, and difficulty handling stress, loss or rejection. People with these personality traits are more likely to engage in negative thought patterns, which can contribute to the development of depression and maintain depressive symptoms. For example, someone with depression might have recurrent thoughts such as: “Things will never get better for me” or “There is no hope for the future”.

Causes of Clinical Impression: Environmental Factors

Although not sufficient to trigger depression on their own, stressful life events may play a role in the development of depression if you are already susceptible. Difficult life circumstances such as illness or death, divorce, job loss, and financial difficulties are all potential triggers for a depressive episode. In addition, early traumatic events such as childhood abuse or the loss of parent have been linked to later development of depression. Those who are already susceptible to depression due to genetic vulnerability or negative thought patterns, may find themselves pushed into a major depressive episode when faced with difficult life events.

Medical Conditions

Certain medical conditions have been linked to depression, such as hypothyroidism, heart disease, neurological disorders such as multiple sclerosis, cancer, and prolonged pain. When evaluating the causes of clinical depression that co-exist with a medical condition, physicians work to determine which symptoms appeared first. If symptoms of depression began after the appearance of a medical condition, the disorder is more than likely secondary to the physical issue. People suffering with a medical condition and depression are doubly at risk - due to the direct effects of the medical issue and the secondary stress that comes with poor health.


There are also medications that are known to increase risk for depression such as heart and blood pressure drugs, beta blockers, hormones, and tranquilizers. If you are taking any of these medications and also experiencing feelings of low mood, it is important to talk with your doctor about whether medication may be causing your symptoms.

None of the above causes of clinical depression is likely to trigger the disorder alone. If you suffer with depression, chances are you have a combination of risk factors, such as a genetic vulnerability, low self-esteem, and a stressful life trigger. Although the causes may be out of your control, depression is readily treatable through therapy and/or medication.

NB: The content of this article is for information purposes only and is not intended to replace sound medical advice and opinion.


Bradley, RG. et al. “Influence of Child Abuse on Adult Depression: Moderation by the Corticotrophin-Releasing Hormone Receptor Gene” Archives of General Psychiatry. American Medical Association, 2008.

Caspi, A. et al. “Influence of Life Stress on Depression: Moderation in the 5-HTT Gene” Science. American Association for the Advancement of Science, 2003.

Harvard Medical School “What Causes Depression?",

Medline Plus. “Major Depression”,

National Institute of Mental Health. “Depression”,

University of Maryland Medical Center. “Causes of Depression”,