Major Depressive Disorder

Learning Objectives

  • Describe the symptoms and risk factors of major depressive disorder

Jacob cries all day and, feeling that he is worthless and his life is hopeless, he cannot get out of bed. Ava stays up all night, talks very rapidly, and went on a shopping spree in which she spent $3,000 on furniture, although she cannot afford it. Maria recently had a baby and she feels overwhelmed, teary, anxious, and panicked, and believes she is a terrible mother for practically every day since the baby was born. All these individuals demonstrate symptoms of a potential mood disorder.

Types of Mood Disorders

Mood disorders are characterized by severe disturbances in mood and emotions—most often depression, but also mania and elation (Rothschild, 1999). All of us experience fluctuations in our moods and emotional states, and often these fluctuations are caused by events in our lives. We become elated if our favorite team wins the World Series and dejected if a romantic relationship ends or if we lose our job. At times, we feel fantastic or miserable for no clear reason. People with mood disorders also experience mood fluctuations, but their fluctuations are extreme, distort their outlook on life, and impair their ability to function.

A photograph shows a person sitting in a fetal position.

Figure 1. Mood disorders are characterized by massive disruptions in mood. Symptoms can range from the extreme sadness and hopelessness of depression to the extreme elation and irritability of mania. (credit: Kiran Foster)

The DSM-5 lists two general categories of mood disorders. Depressive disorders are a group of disorders in which depression is the main feature. Depression is a vague term that, in everyday language, refers to an intense and persistent sadness. Depression is a heterogeneous mood state—it consists of a broad spectrum of symptoms that range in severity. Depressed people feel sad, discouraged, and hopeless. These individuals lose interest in activities once enjoyed, often experience a decrease in drives such as hunger and sex, and frequently doubt personal worth.

The DSM-5 identifies several depressive disorders: major depressive disorder, persistent depressive disorder, disruptive mood dysregulation disorder, premenstrual dysphoric disorder, substance/medication-induced depressive disorder, depressive disorder due to another medical condition, unspecified depressive disorder, or unspecified mood disorder. Depressive disorders vary by degree, but this module highlights the most well-known ones.

Bipolar and related disorders are a group of disorders in which mania is the defining feature. Mania is a state of extreme elation and agitation. When people experience mania, they may become extremely talkative, behave recklessly, or attempt to take on many tasks simultaneously. The most recognized of these disorders is bipolar disorder.

What Is Major Depressive Disorder?

According to the DSM-5, the defining symptoms of major depressive disorder (MDD) include “depressed mood most of the day, nearly every day” (feeling sad, empty, or hopeless or appearing tearful to others), and loss of interest and pleasure in usual activities (APA, 2013). In addition to feeling overwhelmingly sad most of each day, people with depression will no longer show interest or enjoyment in activities that previously were gratifying, such as hobbies, sports, sex, social events, time spent with family, and so on. Friends and family members may notice that the person has completely abandoned previously enjoyed hobbies; for example, an avid tennis player who develops major depressive disorder no longer plays tennis (Rothschild, 1999).

To receive a diagnosis of major depressive disorder, one must experience at least a total of five symptoms of the following symptoms for at least a two-week period (in addition to having a depressed mood and a loss of interest in activities); these symptoms must cause significant distress or impair normal functioning, they must be a change from previous functioning, and they must not be caused by substances or a medical condition. These symptoms include:

  1. significant weight loss (when not dieting) or weight gain and/or significant decrease or increase in appetite;
  2. difficulty falling asleep or sleeping too much;
  3. psychomotor agitation (the person is noticeably fidgety and jittery, demonstrated by behaviors like the inability to sit, pacing, hand-wringing, pulling or rubbing of the skin, clothing, or other objects) or psychomotor retardation (the person talks and moves slowly, for example, or talks softly, very little, or in a monotone voice);
  4. fatigue or loss of energy;
  5. feelings of worthlessness or guilt;
  6. difficulty concentrating and indecisiveness; and
  7. suicidal ideation: thoughts of death (not just fear of dying), thinking about or planning suicide, or making an actual suicide attempt.

Additionally, to receive a diagnosis of major depressive disorder, an individual must experience distress or impairment of normal functioning, the depressive episode(s) should not be attributed to substances or other medical conditions, there should be no manic episodes, and the major depressive episode(s) should not be better accounted for by schizoaffective, or some other, disorder.

Major depressive disorder (MDD) is considered episodic: its symptoms are typically present at their full magnitude for a certain period of time and then gradually abate. Approximately 50–60% of people who experience an episode of major depressive disorder (MDD) will have a second episode at some point in the future; those who have had two episodes have a 70% chance of having a third episode, and those who have had three episodes have a 90% chance of having a fourth episode (Rothschild, 1999). Although the episodes can last for months, a majority of people diagnosed with this condition (around 70%) recover within a year. However, a substantial number do not recover; around 12% show serious signs of impairment associated with major depressive disorder after five years (Boland & Keller, 2009). In the long term, many who do recover will still show minor symptoms that fluctuate in their severity (Judd, 2012).


Major depressive disorder affected approximately 163 million people in 2017 (2% of the global population).[1] The percentage of people who are affected at one point in their life varies from 7% in Japan to 21% in France. In most countries, the number of people who have depression during their lives falls within an eight to 18% range. In North America, the probability of having a major depressive episode within a year-long period is 3%-5% for males and eight to 10% for females. Major depression is about twice as common in women as in men, although it is unclear why this is so and whether factors unaccounted for are contributing to this. The relative increase in occurrence is related to pubertal development rather than chronological age, reaches adult ratios between the ages of 15 and 18, and appears associated with psychosocial more than hormonal factors. Depression is a major cause of disability worldwide.

People are most likely to develop their first depressive episode between the ages of 30 and 40, and there is a second, smaller peak of incidence between ages 50 and 60. The risk of major depression is increased with neurological conditions such as stroke, Parkinson’s disease, or multiple sclerosis, and during the first year after childbirth. It is also more common after cardiovascular illnesses and is related more to those with a poor cardiac disease outcome than to a better one. Studies conflict on the prevalence of depression in the elderly, but most data suggest there is a reduction in this age group. Depressive disorders are more common in urban populations than in rural ones and the prevalence is increased in groups with poorer socioeconomic factors, e.g., homelessness.

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Causes of Depression

MDD is believed to be a combination of genetic, environmental, and psychological factors. Risk factors include a family history of the condition, major life changes, certain medications, chronic health problems, and substance abuse. About 40% of the risk appears to be related to genetics.[2]

Three overlapping circles. The first is labeled, "Biology" and includes physical health, genetic vulnerabilities and drug effects. The second circle is labeled, "Psychological" and includes coping skills, social skills, family relationships, self-esteem, and mental health. The third circle is labeled, "Social" and includes peers, family circumstances, and family relationships.

Figure 2. The biopsychosocial model shows that a variety of factors may influence mental health.

The diathesis-stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The pre-existing vulnerability can be either genetic, implying an interaction between nature and nurture, or schematic, resulting from views of the world learned in childhood.

The biopsychosocial model is an interdisciplinary model that looks at the interconnection between biological, psychological, and social-environmental factors. The model specifically examines how these aspects play a role in topics ranging from health and disease models to human development. Childhood abuse, whether physical, sexual, or psychological, are all risk factors for depression, among other psychiatric issues that co-occur such as anxiety and drug abuse. Childhood trauma also correlates with the severity of depression, lack of response to treatment, and length of illness. However, some are more susceptible to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.

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Research shows us that the neurotransmitter serotonin plays a role in depression, but that role may not be as clear-cut as once hypothesized. The monoamine theory, derived from the efficacy of monoaminergic drugs (such as SSRIs) in treating depression, was the dominant theory until recently. Studies have shown that depletion of tryptophan, a necessary precursor of serotonin, a monoamine, can cause depression in those in remission or relatives of depressed patients; this suggests that decreased serotonergic neurotransmission is important in depression. There is also a correlation between depression risk and polymorphisms in the 5-HTTLPR gene, which codes for serotonin receptors. This and other research suggest a link between serotonin and depression. However, the monoamine theory is inconsistent with the fact that serotonin depletion does not cause depression in healthy persons, the fact that antidepressants instantly increase levels of monoamines but take weeks to work, and the existence of atypical antidepressants, which can be effective despite not targeting this pathway.

This video explains a little bit of the research and explains other theories that help to explain depression.

You can view the transcript for “Why Depression Isn’t Just a Chemical Imbalance” here (opens in new window).

Results of Major Depressive Disorder

Major depressive disorder is a serious and incapacitating condition that can have a devastating effect on the quality of one’s life. The person suffering from this disorder lives a profoundly miserable existence that often results in unavailability for work or education, abandonment of promising careers, and lost wages; occasionally, the condition requires hospitalization. The majority of those with major depressive disorder report having faced some kind of discrimination and many report that having received such treatment has stopped them from initiating close relationships, applying for jobs for which they are qualified, and applying for education or training (Lasalvia et al., 2013). Major depressive disorder also takes a toll on health. Depression is a risk factor for the development of heart disease in healthy patients, as well as adverse cardiovascular outcomes in patients with preexisting heart disease (Whooley, 2006).

Risk Factors for Major Depressive Disorder

Major depressive disorder is often referred to as the common cold of psychiatric disorders. Around 6.6% of the U.S. population experiences major depressive disorder each year; 16.9% will experience the disorder during their lifetime (Kessler & Wang, 2009). It is more common among women than among men, affecting approximately 20% of women and 13% of men at some point in their lives (National Comorbidity Survey, 2007). The greater risk among women is not accounted for by a tendency to report symptoms or to seek help more readily, suggesting that gender differences in the rates of major depressive disorder may reflect biological and gender-related environmental experiences (Kessler, 2003).

Lifetime rates of major depressive disorder tend to be highest in North and South America, Europe, and Australia; they are considerably lower in Asian countries (Hasin, Fenton, & Weissman, 2011). The rates of major depressive disorder are higher among younger age cohorts than among older cohorts, perhaps because people in younger age cohorts are more willing to admit depression (Kessler & Wang, 2009).

A number of risk factors are associated with major depressive disorder: unemployment (including homemakers); earning less than $20,000 per year; living in urban areas; or being separated, divorced, or widowed (Hasin et al., 2011). Comorbid disorders include anxiety disorders and substance abuse disorders (Kessler & Wang, 2009).

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WAtch It

This video explains depression from the viewpoint of a clinical provider. Doctors, nurses, and other medical professionals should be aware of the signs of major depression (and other depressive disorders such as persistent depressive disorder) in order to ensure that individuals get the appropriate help they need.

You can view the transcript for “Depressive Disorders: Presentation & Treatment” here (opens in new window).

Key Takeaways: Major Depressive Disorder


depressive disorder: one of a group of mood disorders in which depression is the defining feature

major depressive disorder: commonly referred to as depression or major depression, characterized by sadness or loss of pleasure in usual activities, as well as other symptoms

mood disorder: one of a group of disorders characterized by severe disturbances in mood and emotions; the categories of mood disorders listed in the DSM-5 are bipolar and related disorders and depressive disorders

suicidal ideation: thoughts of death (not just fear of dying), thinking about or planning suicide, or making an actual suicide attempt

  1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators (10 November 2018). "Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017". Lancet. 392 (10159): 1789–1858. doi:10.1016/S0140-6736(18)32279-7. PMC 6227754. PMID 30496104. Retrieved 23 June 2020.
  2. American Psychiatric Association (2013), Diagnostic and Statistical Manual of Mental Disorders (5th ed.), Arlington: American Psychiatric Publishing, pp. 160–68, ISBN 978-0-89042-555-8, retrieved 22 July 2016