Many factors may play a role in depression, including genetics, brain biology and chemistry, and life events such as trauma, loss of a loved one, a difficult relationship, an early childhood experience, or any stressful situation.

Depression can happen at any age, but often begins in the teens or early 20s or 30s. Most chronic mood and anxiety disorders in adults begin as high levels of anxiety in children. In fact, high levels of anxiety as a child could mean a higher risk of depression as an adult.  More than twice as many women report experiencing depression than men.

Depression can co-occur with other serious medical illnesses such as diabetes, cancer, heart disease, and Parkinson’s disease. Depression can make these conditions worse and vice versa. Sometimes medications taken for these illnesses may cause side effects that contribute to depression. A doctor experienced in treating these complicated illnesses can help work out the best treatment strategy.

Research on depression is ongoing, and one day these discoveries may lead to better diagnosis and treatment. To learn more about current research, visit the NIMH website at

Courtesy, National Institute of Mental Health

The Following By Dr. Dana Steidtmann and Dr. Sam Hubley
University of Colorado, Helen and Arthur E. Johnson Depression Center

Below you will find the following brief articles on Causes:

  • The Interaction of Nature and Nurture
  • Stress
  • Loss
  • Trauma
  • Biological Causes – The Brain
  • Biological Causes – Genetics



What is understood about the causes of depression is often oversimplified in popular media descriptions. In doing so, theories about people’s biological makeup or so-called “nature” and their life experiences, “nurture” may be portrayed as opposing or distinct explanations and pitted against one another.  Examples of this include overemphasizing that depression is caused by particular brain abnormalities a person inherits or that it is caused by major life changes. Indeed, both of these things have been associated with increased risk for depression. However, there is now widespread agreement among scientists these relationships are complex and that one’s biology can interact with life experiences in order to contribute to overall depression risk. Scientists are only beginning to understand the complex ways that biology and life experience interact. However, one example of this type of interaction is described below.

Caregiver Response to Children’s Temperament

Temperament can be thought of a person’s innate personality. For example, are people inherently more inclined to be shy or outgoing?  Temperament is a relatively stable feature of personality that emerges early in infancy, is surprisingly stable across the lifespan and is heavily influenced by genetic factors. In addition, different types of temperament in infants and young children have been shown to elicit particular ways of responding from caregivers (Sroufe, 1985). For example, young children who are more fussy or have particular difficulty sleeping may elicit or bring out higher levels of frustration in responses by caregivers. By contrast, relatively easygoing children may tend to elicit higher amounts of affection and positive attention. Over time, the net impact of these caregiver interactions may contribute to differences in bonding and early life stress, both of which are associated with later risk for developing depression.

Sroufe, L. A. (1985). Attachment classification from the perspective of infant-caregiver relationships and infant temperament. Child Dev, 56(1), 1-14.



There are multiple factors that contribute to causing depression. However, very often, the first time a person experiences depression, it is during or following a stressful life event such as a death of a loved one, breakup, move or job loss. In some cases, if a person’s depressed mood is primarily due to a life stressor, and the mood improves as the situation begins to resolve itself, that person may be diagnosed with something called an Adjustment Disorder, rather than a depressive disorder. Adjustment Disorder implies that a person is having a difficult time coping with a specific stressor or stressors and that distress will decrease and no longer interfere with daily life once a person gets used to or “adjusts” to the new situation.

However, when the depressed mood persists over time or when lots of little things add up to create high stress, it may be associated with depression.  Some researchers have speculated the association with life stress is because depressive symptoms result from an overreaction of the body’s stress response. Is also appears that some people are biologically prone to depression, but that even those who are biologically-prone may not experience depression until a stressful life event occurs. Interestingly, the association between life stress and depression becomes weaker as a person experiences more periods of depression.

What Kinds of Life Stressors Are Associated with Depression?

When people think of big stressors, they usually think of things like the breakup of a relationship, losing a job, or the death of a loved one. Indeed, these types of events commonly precede the first experience of depression. However, any kind of major life change, even if it is desired, can be experienced as stressful. Thus, events that people typically think of as “positive” events, such as going off to college, getting married, the birth of a child or a job promotion can also be experienced as very stressful and are sometimes associated with symptoms of depression.

Another type of stress – the pile up of daily hassles – can also be associated with feeling depressed. Daily hassles are things all people have to deal with in their daily lives that create some amount of stress.  For example, hassles might include things like paying bills, home and auto repairs, getting a cold, and routine disagreements with friends or family. When the daily hassles of life pile up, people may begin to feel overwhelmed.  It is a bit tricky to say if a pile up of such hassles can cause depression, because people may be more likely to perceive everyday tasks as hassles, and to let them pile up, when they are feeling depressed.  However, there is an association between daily hassles and depressed mood. The association may be somewhat more common among people with Persistent Depressive Disorder type of depression than other types (Ravindran et al, 1995).

Does Depression Usually Occur Following Increased Stress?

No. Although being depressed is typically experienced as quite stressful in itself, and major depression often occurs for the first time following a major life stressor, life stress does not always occur before someone becomes depressed. In fact, the strength of the association between depression and life stress decreases as people experience a greater number of depressive episodes. For example, if someone is experiencing a 3rd or 4th depressive episode, there may be relatively little change in life stress prior to the occurrence of that episode. One of the theories to explain why stress becomes less associated with depression over time is that the very experience of being depressed changes the brain in ways that makes is more prone to depression in the future. This theory is sometimes referred to as the “kindling hypothesis” (Monroe & Harkness, 2005). There is some support for this idea because depression is associated with certain changes in the brain.



It is common that a stressful life event triggers a person’s first episode of depression. Although the death of a loved one can be one of the most stressful experiences a person goes through, not everyone experiences depression after a loss and the relationship between loss and depression is complex. When someone dies, surviving loved ones often go through a grief process that involves mourning and letting go. Although a grieving period usually includes feeling sad and may include other symptoms that look similar to depression, most experts acknowledge that grieving is a normal and expected reaction to loss, and a distinct process from depression. However, in some cases, loss of a loved one can trigger thoughts and feelings that are not part of a normal grieving process. In those cases, loss may bring about depression or other health conditions.

What Is The Difference Between Grief and Depression?

This is a complicated and sometimes controversial question to answer. Although researchers are studying this issue, it is not yet well understood. In prior versions of the Diagnostic and Statistical Manual of Mental Disorder (DSM), which is the manual used to diagnose depression and other mental health conditions in the United States, it was indicated that people should not be diagnosed with depression if they have experienced the death of a loved one within the past 8 weeks, and did not have any symptoms of depression prior to the loss. The most recent version of the DSM removes that guideline, but encourages health care providers to distinguish between normal grief and depression (APA, 2013). Some of the differences between sadness and grief include:

  • In grief, sadness tends to come in waves and usually includes positive memories or emotions mixed in with the negative ones. In depression, thoughts and feelings tend to be mainly sad and negative.
  • Feelings of low self-esteem and worthlessness are common in depression but not in grief.

Further complicating this question is that researchers have identified a type of grief that looks different than both normal grief and depression. This type of grief has been termed Persistent Complex Bereavement or Prolonged Grief and it occurs in about 10% of those who lose a close loved one. Prolonged Grief is different from other grief in that it is more intense, lasts longer and causes disruption to daily life that does not fade over time. In addition, a person may feel intense concern about the future and personal safety. Prolonged Grief is different from depression in that is it more personal and closely tied to a loss whereas depression is more characterized by sadness (Tay et al., 2016).

If Grieving is Normal, Do People Seek Treatment for Grief?

It can be difficult to distinguish between grief, prolonged grief and depression. Sometimes an assessment by a professional can help to sort out what is going on. If the loss has prompted depression or complicated grief, treatment may be helpful. Even in cases of normal grief, receiving supportive therapy to help make sense of the loss may be beneficial.



Traumatic events are events in which individuals perceive the physical and/or emotional safety of themselves or loved ones to be threatened. Traumatic events can be single-events such as a serious car accident or being robbed at gunpoint. They may also be longer lasting events that unfold over weeks, months or years; for example being present in a war zone or living with an abusive parent or spouse.  Depression is commonly triggered by life stressors and experiencing traumatic events is, by definition, a major stressor. However, trauma is often considered separately from other life stressors in depression research because there is a particularly high likelihood that someone who has experienced trauma may eventually experience depression.  There is also evidence to show that a history of trauma may influence how helpful (or unhelpful) particular treatments may be. Experiencing trauma may also bring about Post-Traumatic Stress Disorder, a condition that is separate from depression but closely related to it.

What is the Association Between Trauma and Depression?

Researchers have shown a particularly strong link between childhood trauma and risk for developing depression. The increased risk for depression lasts all the way into adulthood, well after a person may have escaped the traumatic circumstances. For example, adults who report that they were exposed to physical, sexual, or emotional abuse or neglect as children are more than two times as likely to develop depression than those without childhood trauma exposure {Chapman, 2004 #4}. In addition, trauma during childhood appears to be associated with a more chronic course of depression {Negele, 2015 #5}. One theory to account for these associations is that exposure to trauma during childhood impacts the developing brain in important ways that make a person more vulnerable to depression in the future. People with depression and a history of trauma may benefit from specialized treatments. For example, there is evidence that people with a history of childhood exposure to trauma are more likely to benefit from psychotherapy than medication as a treatment for depression {Nemeroff, 2003 #7}.

How Is Depression Different Than Post-Traumatic Stress Disorder (PTSD)?

Post-Traumatic Stress Disorder (PTSD) is a diagnosis and a grouping of symptoms that can occur in response to trauma. The four groups or clusters of symptoms in PTSD are unwanted thoughts or memories about the trauma, avoidance of situations or things that remind one of the trauma, changes in thoughts and moods (like feeling numb), and changes in physiological arousal.  Depression and PTSD look similar in some ways. For example, in both cases a person may withdraw socially, have a loss of interest in activities, have difficulty sleeping and feel emotionally numb. However, in contrast to PTSD, depression does not require the occurrence of a traumatic stressor to be diagnosed. In addition, PTSD often includes a strong sense of being on the lookout for danger, and sometimes a person may re-live the trauma in the form of nightmares or vivid recurring memories. These symptoms are not characteristic of depression. Although PTSD and depression are distinct syndromes, many people who have symptoms of PTSD will also experience symptoms of depression.  In a large study, depression was 3 to 5 times more likely in those with PTSD than those without PTSD {Kessler, 1995 #6}.

Chapman, D. P., Whitfield, C. L., Felitti, V. J., Dube, S. R., Edwards, V. J., & Anda, R. F. (2004). Adverse childhood experiences and the risk of depressive disorders in adulthood. J Affect Disord, 82(2), 217-225. doi:10.1016/j.jad.2003.12.013

Kessler, R. C., Sonnega, A., Bromet, E., Hughes, M., & Nelson, C. B. (1995). Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry, 52(12), 1048-1060.

Negele, A., Kaufhold, J., Kallenbach, L., & Leuzinger-Bohleber, M. (2015). Childhood Trauma and Its Relation to Chronic Depression in Adulthood. Depress Res Treat, 2015, 650804. doi:10.1155/2015/650804

Nemeroff, C. B., Heim, C. M., Thase, M. E., Klein, D. N., Rush, A. J., Schatzberg, A. F., . . . Keller, M. B. (2003). Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Proc Natl Acad Sci U S A, 100(24), 14293-14296. doi:10.1073/pnas.2336126100



The story of depression and the brain began with two common sense ideas.  First, there was idea that there was a problem with the part of the brain that controlled our feelings. Second, a newer idea shifted focus from parts of the brain to the chemical messengers that help different parts of the brain communicate with each other. Currently, scientists believe that the story of depression and the brain is much more complex than those original ideas. The new story paints a picture with many different brain parts organized into whole brain networks and multiple different chemical messengers (not just one).

The “Broken” Brain and Lobotomies. Scientists from the early 1900s believed that “overactive nerves” were responsible for causing depression. To cure depression based on this logic, it was necessary to remove these parts of the brain. Patients received lobotomies which meant that physicians surgically removed parts of their brains.  Lobotomies were relatively common until the late 1960s. Although they are still used today on rare occasions, scientists have developed much better treatments for depression that don’t require brain surgery.

Serotonin and the “Chemical Imbalance Theory”. The next famous theory of depression and the brain suggested that depression was caused by a “chemical imbalance”. According to this theory, people with depression didn’t have enough serotonin. Serotonin is one of the brain’s chemical messengers or neurotransmitters that is involved in influencing mood, sleep, appetite, and pain. We often hear the logic of this theory in “There is research indicating that depression is related to low levels of serotonin. Antidepressants increase your serotonin levels and can help you get rid of your depression.” Although researchers have since shown this theory does not fully explain how serotonin is related to depression, the chemical imbalance theory that explains depression as problem of low serotonin is still very common.

            The “Neural Network” of Depression. Today’s researchers argue that the story of depression and the brain is very complex.  They do not believe that depression is caused by a problem in one single brain region or in the overall levels of one single neurotransmitter.  Instead, they think different brain regions are connected to each other in what are called “neural networks”.  Small problems in each brain region that make up just one part of the network can end up causing big problems when you start to add them all together.  For example, a common neural network described by depression scientists includes three major regions:

  • The amygdala, which plays a big part in creating emotional experiences.
  • The hippocampus, which plays a big part in storing memories and remembering them.
  • The prefrontal cortex, which plays a big part in organizing and making sense of all the information coming into and out of our brains.  It also has the ability to control other parts of the brain by making them become more active or less active.

Scientists are conducting research every day that is helping us understand how small problems in each of these brain regions can add up to cause depression. They are also very interested in how one brain region influences another region through the release of neurotransmitters of all kinds. According to this story, many people with depression have an overactive amygdala and hippocampus which is related to experiencing a lot of memories that have strong emotions attached to them.  An overactive amygdala and hippocampus are associated with too much activation in one part of the prefrontal cortex that combines information from all different parts of the brain into our “sense of self”.  This “sense of self” is how we think and feel about ourselves and when we have too much activation in this network, that picture of our self tends to be more negative than positive. At the same time, a different part of the prefrontal cortex is showing signs of too little activation.  This is a problem because this other part of the prefrontal cortex helps decrease activation in the amygdala and hippocampus, and it is hard to do its job of watching over the amygdala and hippocampus when it is not active enough. Each of these smaller problems all combine together to influence our behavior and there is one of type of behavior that is very common with this pattern of brain activity: rumination. Rumination is the tendency to think about negative things over and over again and is one of the key features of depression.  When people ruminate a lot it becomes very difficult to experience joy, problem-solve effectively, and feel satisfied in our relationships with other people. It then becomes easy to imagine how being trapped inside your head creates a whole bunch of other problems that all contribute to the overall experience of depression.

To learn more about depression and the brain, check out the resources listed below. Three important findings from research on depression and the brain are:

  1. The hippocampus does appear to be smaller in some depressed people, and the hippocampus seems to decrease in size as the number of depressive episodes increases.
  2. Antidepressant medications immediately increase the amount of serotonin in the brain but people taking antidepressants don’t typically feel better until several weeks later.  Several weeks after taking antidepressants, we begin to see an increase in the number of new nerve cells in the hippocampus.
  3. Newer treatments that attempt to directly target specific neural networks are being developed.  There is a good reason to be optimistic about this approach to treatment, but there is still a lot of work to do in terms of making sure they are safe, effective, and accessible.



If you ask someone with depression if they have a family member with a history of a depression, the answer will most likely be, “Yes.”  That’s because depression tends to run in families.  The question then becomes one of Nature vs. Nurture, “Does depression run in families because family have similar genes or because family members grow up in similar environments?” It turns out that the answer is a little bit of both.

Nature vs. Nurture in Depression

To understand the “Nature” of depression, it is important to know that we inherit half our genes from our biological mother and half our genes from our biological father.  Genes are like the “blueprints” of life and tell the cells in our bodies what to build and how to work.  They determine our height and eye color and also help to create our personalities.  However, our environments can influence our genes.  For example, a son of two basketball players may have genes that tell his cells to grow his adult body to 6’6”, but if he doesn’t have regular access to food or his mother drank alcohol excessively during her pregnancy, he may only grow up to be 5’10”.  These “gene by environment” interactions are very common so it is very unusual for experts in the genetics of depression to say that it’s one or the other.

Is there a gene for depression?


Just as researchers have identified single genes that are responsible for certain diseases such as Cystic Fibrosis or Down Syndrome, researchers have attempted to identify a “depression gene.” So far they have not found consistent results.  Because mental health disorders like depression are complex and look very different from one person to the next, it is almost certainly the case that there are multiple genes acting together that contribute to a person’s overall genetic vulnerability to depression.

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